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3.A.1.1:  The Carbohydrate Uptake Transporter-1 (CUT1) Family

Maltooligosaccharide porter. The 3-D structure has been reported by Oldham et al. (2007). An altering access mechanism has been suggested for the maltose transporter resulting from rigid-body rotations (Khare et al., 2009). Bordignon et al. (2010) and Schneider et al. (2012) have reviewed the extensive knowledge available on MalEFGK2, its mode of action and its regulatory interactions.  The transporter sequesters the MalT transcriptional activator at the cytoplasmic surface of the membrane in the absence of the transport substrate (Richet et al. 2012).  The crystal structures of the transporter complex MBP-MalFGK2 bound with large malto-oligosaccharide in two different conformational states have also been determined. In the pretranslocation structure, Oldham et al. 2013 found that the transmembrane subunit MalG forms two hydrogen bonds with malto-oligosaccharide at the reducing end. In the outward-facing conformation, the transmrembrane subunit MalF binds three glucosyl units from the nonreducing end. These structural features explain why large modified malto-oligosaccharides are not transported by MalFGK2 despite their high binding affinity to MBP. In the transport cycle, substrate is channeled from MBP into the transmembrane pathway with a polarity such that both MBP and MalFGK2 contribute to the overall substrate selectivity of the system (Oldham et al. 2013).  Stabilization of the semi-open MalK2 conformation by maltose-bound MBP is key to the coupling of maltose transport to ATP hydrolysis in vivo, because it facilitates the progression of the MalK dimer from the open to the semi-open conformation, from which it can proceed to hydrolyze ATP (Alvarez et al. 2015). Both the binding of MalE to the periplasmic side of the transmembrane complex and binding of ATP to MalK2 are necessary to facilitate the conformational change from the inward-facing state to the occluded state, in which MalK2 is completely dimerized (Hsu et al. 2017).

MalEFGK of E. coli
MalE (receptor [R])
MalF (membrane [M])
MalG (membrane [M])
MalK (cytoplasmic [C])

The galactooligosaccharide (transports the di, tri and tetrasaccharides) uptake porter GanOPQ (MalEFG) functioning with the energizing ATPase MsmX (see 3.A.1.1.26).  These oligosaccharides are derived from galactans and arabinogalactans, compenents of pectins in plant cell walls.  The energizing ATPase is probably MsmX (see 3.A.1.1.26) (Watzlawick et al. 2016).

GanOPG of Bacillus subtilis
YufK, GanO or GanS (R) (O07009)
YufL or GanP (M) (O32261)
YufM or GanQ (M) (O07011) MsmX (C) (see 3.A.1.1.26)

Glycerol-phosphate porter. Transports both glycerol-3-P and glycerol-3-P diesters including glycerophosphocholine but not glycerol-2-P (Yang et al. 2009; Wuttge et al. 2012).  UgpB (the receptor) binds glycerol 3-P with high affinity, but not glycerol 2-P (Wuttge et al. 2012).  UgpB (the receptor) binds glycerol 3-P with high affinity, but not glycerol 2-P (Wuttge et al. 2012).

UgpABCE of E. coli
UgpB (R)
UgpA (M)
UgpE (M)
UgpC (C)

Lactose porter
LacEFGK of Agrobacterium radiobacter
LacE (R)
LacF (M)
LacG (M)
LacK (C)

Hexitol (glucitol; mannitol) porter
SmoEFGK of Rhodobacter sphaeroides
SmoE (R)
SmoF (M)
SmoG (M)
SmoK (C)

Cyclodextrin porter
CymDEFG of Klebsiella oxytoca
CymE (R)
CymF (M)
CymG (M)
CymD (C)

Maltose/trehalose porter
MalEFGK of Thermococcus litoralis
MalE (R)
MalF (M)
MalG (M)
MalK (C) (not sequenced)

Sucrose/maltose/trehalose porter (sucrose-inducible)
AglEFGK of Sinorhizobium meliloti
AglE (R)
AglF (M)
AglG (M)
AglK (C)

The oligosaccharide (glucuronate-linked to a xylo-oligosaccharide) ABC uptake porter, GuoEFGK in AguEFGK. GuoE binds with high affinity a four sugar aldotetrouronic
acid [2-O-α-(4-O-methyl-α-D-glucuronosyl)-xylotriose] (Shulami et al., 1999; S.Shulami, personal communication)

GuoEFGK of Geobacillus stearothermophilus
AguE or GuoE (R) (C9RT46)
AguF or GuoF (M) (Q09LY7)
AguG or GuoG (M) (Q09LY6)
AguK or GuoK (C) (not identified)

Alginate (MW 27,000 Da) (and Alginate oligosaccharides) uptake porter. Sphingomonas species A1 is a 'pit-forming' bacterium that directly incorporates alginate into its cytoplasm through a pit-dependent transport system, termed a 'superchannel' (Murata et al., 2008). The pit is a novel organ acquired through the fluidity and reconstitution of cell surface molecules, and through cooperation with the transport machinery in the cells. It confers upon bacterial cells a more efficient way to secure and assimilate macromolecules (Murata et al., 2008).  The substrate-transport characteristics and quaternary structure of AlgM1M2SS with AlgQ1 have been determined (Maruyama et al. 2015). The addition of poly- or oligoalginate enhanced the ATPase activity of reconstituted AlgM1M2SS coupled with one of the periplasmic solute-binding proteins, AlgQ1 or AlgQ2. External fluorescence-labeled oligoalginates were specifically imported into AlgM1M2SS-containing proteoliposomes in the presence of AlgQ2, ATP, and Mg2+. The crystal structure of AlgQ2-bound AlgM1M2SS adopts an inward-facing conformation. The interaction between AlgQ2 and AlgM1M2SS induces the formation of an alginate-binding tunnel-like structure accessible to solvent. The translocation route inside the transmembrane domains contains charged residues suitable for the import of acidic saccharides (Maruyama et al. 2015).

AlgSM1M2Q1Q2 of Sphingomonas sp.A1
AlgS (C)
AlgM1 (M)
AlgM2 (M)
AlgQ1 (R)
AlgQ2 (R)

Saturated and unsaturated oligogalacturonide transporter, TogMNAB (transports di- to tetrasaccharide pectin degradation products which consist of D-galacuronate, sometimes with 4-deoxy-L-threo-5-hexosulose uronate at the reducing end of the oligosaccharide) (Hugouvieux-Cotte-Pattat et al. 2001). Regulated by pectin utilization regulator KdgR (Rodionov et al. 2004)

Oligogalacturonide transporter TogMNAB of Erwinia chrysanthemi
TogM (M)
TogN (M)
TogA (C)
TogB (R)

Palatinose (isomaltulose; 6-O-α-D-glucopyranosyl-D-fructose) uptake porter
PalEFGK of Erwinia rhapontici
PalE (R)
PalF (M)
PalG (M)
PalK (C)

Glucose, mannose, galactose porter
GlcSTUV of Sulfolobus solfataricus
GlcS (R)
GlcT (M)
GlcU (M)
GlcV (C)

Arabinose, fructose, xylose porter
AraSTUV of Sulfolobus solfataricus
AraS (R)
AraT (M)
AraU (M)
AraV (C)

Trehalose porter
TreSTUV of Sulfolobus solfataricus
TreS (R)
TreT (M)
TreU (M)
TreV (C)

Maltooligosaccharide porter (Maltose is not a substrate, but maltotriose is.)
PF1933, 1936, 1937, 1938 of Pyrococcus furiosus
PF1938 (R)
PF1937 (M)
PF1936 (M)
PF1933 (C)

Trehalose/maltose/sucrose porter (trehalose inducible)
ThuEFGK of Sinorhizobium meliloti
ThuE (R)
ThuF (M)
ThuG (M)
ThuK (C)

N-Acetylglucosamine/N,N'-diacetyl chitobiose porter (NgcK (C) not identified)
NgcEFG of Streptomyces olivaceoviridis
NgcE (R)
NgcF (M)
NgcG (M)

Platinose (isomaltulose) (6-O-α-D-glucopyranosyl-D-fructofuranose) porter
PalEFGK of Agrobacterium tumefaciens
PalE (R)
PalF (M)
PalG (M)
PalK (C)

The fructooligosaccharide porter, MsmEFGK (Barrangou et al., 2003)
MsmEFGK of Lactobacillus acidophilus
MsmE (R) AAO21856
MsmF (M) AAO21857
MsmG (M) AAO21858
MsmK (C) AAO21860

The xylobiose porter; BxlEFG(K) (Tsujibo et al., 2004)
BxlEFGK of Streptomyces thermoviolaceus
BxlE (R) CAB88161
BxlF (M) CAB88162
BxlG (M) CAB88163
BxlK (C) Unknown

The maltose, maltotriose, mannotetraose (MalE1)/maltose, maltotriose, trehalose (MalE2) porter (Nanavati et al., 2005). For MalG1 (823aas) and MalG2 (833aas), the C-terminal transmembrane domain with 6 putative TMSs is preceded by a single N-terminal TMS and a large (600 residue) hydrophilic region showing sequence similarity to MLP1 and 2 (9.A.14; e-12 & e-7) as well as other proteins.

MalE1E2FGK of Thermotoga maritima
MalE1 (R) (binds maltose, maltotriose and mannotetraose) (AAD36279)
MalE2 (R) (binds maltose, maltotriose and trehalose) (AAD36901)
MalF1 (M) (AAD36278)
MalG1 (M) (AAD36277)
[MalG2 (M) (AAD36899]
MalK (C) (AAD36351)

The cellobiose/cellotriose (and possibly higher cellooligosaccharides), CebEFGMsiK [MsiK functions to energize several ABC transporters including those for maltose/maltotriose and trehalose] (Schlösser et al., 1997, Schlösser et al., 1999)

CebEFGMsiK of Streptomyces reticuli
CebE (R) (CAB46342)
CebF (M) (CAB46343)
CebG (M) (CAB46344)
MsiK (CAA70125)

The glucose/mannose porter TTC0326-8 plus MalK1 (ABC protein, shared with 3.A.1.1.25) (Chevance et al., 2006).
TTC0326-8 MalK1 of Thermus thermophilus
TTC0326 (M) - Q72KX4
TTC0327 (M) - Q72KX3
TTC0328 (R) - Q72KX2
MalK1 or TTC0211 (C) - Q72L52

The trehalose/maltose/sucrose/palatinose porter (TTC1627-9) plus MalK1 (ABC protein, shared with 3.A.1.1.24) (Chevance et al., 2006).
TTC1627-9 + MalK1 of Thermus thermophilus
TTC1627 (R) (Q72H68)
TTC1628 (M) (Q72H67)
TTC1629 (M) (Q72H66)
MalK1 (TTC0211) (C) (Q72L52)

The maltose porter, MdxEFG and MsmX (Ferreira and Sá-Nogueira, 2010)

The maltose porter of Bacillus subtilis, MalEFG/MsmX.
MalE (R) - O06989
MalF (M) - O06990
MalG (M) - O06991
MsmX (C) - P94360

Maltose/Maltotriose/maltodextrin (up to 7 glucose units) transporters MalXFGK (MsmK (3.A.1.1.28) can probably substitute for MalK; Webb et al., 2008).

MalXFGK of Streptococcus mutans:
MalX (R) (Q8DT28)
MalF (M) (Q8DT27)
MalG (M) (Q8DT26)
MalK (C) (Q8DT25)

The raffinose/stachyose transporter, MsmEFGK (MalK (3.A.1.1.27) can probably substitute for MsmK; Webb et al., 2008).

MsmEFGK of Streptococcus mutans:
MsmE (R) (Q00749)
MsmF (M) (Q00750)
MsmG (M) (Q00751)
MsmK (C) (Q00752)

Aldouronate transporter, LplA,B,C (Chow et al., 2007)
LplABC of Paenibacillus sp. JDR-2:
LplA (R)(A9QDR6)
LplB (M)(A9QDR7)
YtcP (M)(A9QDR8)
LplC - not identified

Glucose porter, GtsABCD (del Castillo et al., 2008).  The orthologue of GtsA (receptor) in P. aeruginosa (64% identical to the P. putida GtsA has been biochemically characterized (Stinson et al. 1977) and corresponds to the sequence with UniProt acc# Q9HZ48 (Friedhelm Pfeiffer, personal communication).

The glucose porter of Pseudomonas putida, GtsABCD:
GtsA (R) (Q88P38)
GtsB (M) (Q88P37)
GtsC (M) (Q88P36)
GtsD (C) (Q88P35)

The trehalose-recycling ABC transporter, LpqY-SugA-SugB-SugC (essential for virulence) (Kalscheuer et al., 2010).

LpqY-SugA-SugB-SugC of Mycobacterium tuberculosis
LpqY (R) (Q7D8J9)
SugA (M) (O50452)
SugB (M) (O50453)
SugC (C) (O50454)  

The glucosylglycerol uptake transporter (functions in osmoprotection and also transports sucrose and trehalose (Mikkat and Hagemann, 2000) (most similar to 3.A.1.1.8).
GgtABCD of Synechocystis sp. strain PCC6803
GgtA (C) (Q55035)
GgtB (R) (Q55471)
GtC (M) (Q55472)
GgTD (M) (Q55473)

The N,N'-diacetylchitobiose uptake transporter, DasABC/MsiK (MsiK energizes several ABC transporters (see 3.A.1.1.23)) (Saito et al., 2008).

DasABC MsiK of Streptomyces coelicolor
DasA (R) (Q8KN19)
DasB (M) (Q8KN18)
DasC (M) (Q8KN17)
MsiK (C) (Q9L0Q1)

The arabinosaccharide transporter AraNPQMsmX. Transports α-1,5-arabinooligosaccharides, at least up to four L-arabinosyl units; the key transporter for α-1,5-arabinotriose and α-1,5-arabinotetraose, but not for α-1,5-arabinobiose which is transported by AraE. MsmX is also used by the MdxEFG-MsmX system (3.A.1.1.36) (Ferreira and Sá-Nogueira, 2010). Involved in the uptake of pectin oligosaccharides with either MsmX or YurJ as the ATPase (Ferreira et al. 2017).

AraNPQ-MsmX of Bacillus subtilis 
AraN (R) (P94528) 
AraP (M) (P94529)
AraQ (M) (P94530)
MsmX (C) (P94360) 

Glycerol uptake porter, GlpSTPQV (Ding et al., 2012).

GlpSTPQV of Rhizobium leguminosarum 
GlpS (C) (G3LHY8)
GlpT (C) (G3LHY9)
GlpP (M) (G3LHZ0)
GlpQ (M) (G3LHZ1)
GlpV (R) (G3LHZ3) 

Putative transport system


Q93J94 (R)
Q93J93 (M)
Q93J92 (M)
Q9L0Q1 (C?)

Predicted arabinoside porter. Regulated by arabinose-responsive regulator AraR (Rodionova et al. 2012).

AraEFG of Thermotoga maritima
AraE (R) (TM0277) -
AraF (M) (TM0278) Q9WYB4
AraG (M) (TM0279) Q9WYB5

Inositol phosphate porter (Rodionova et al. 2013). Binds inositol phosphate with low Kd and inositol with a lower affinity.

InoEFGK of Thermotoga maritima
InoE (R) TM0418 (Q9WYP9)
InoF (M) TM0419 (Q9WYQ0)
InoG (M) TM0420 (Q9WYQ1)
InoK (C) TM0421 (Q9WYQ2)

Alpha-1,4-digalacturonate porter (Nanavati et al., 2006). Regulated by pectin utilization regulon UxaR (Rodionova et al. 2012).

AguEFG of Thermotoga maritima
AguE (R) (TM0432) (Q9WYR3)
AguF (M) (TM0431) (Q9WYR2)
AguG (M) (TM0430) (Q9WYR1)

Predicted chitobiose porter. Regulated by chitobiose-responsive regulator ChiR (Kazanov et al., 2012).

ChiEFG of Thermotoga maritima
ChiE (R) (TM0810) (Q9WZR7)
ChiF (M) (TM0811) (Q9WZR8)
ChiG (C) (TM0812) (Q9WZR9)

Trehalose porter. Also binds sucrose (Boucher and Noll, 2011). Induced by glucose and trehalose. Directly regulated by trehalose-responsive regulator TreR (Kazanov et al., 2012).

TreG (M) (ThemaDRAFT_1378) G4FGN6 TreF (M) (ThemaDRAFT_1379) G4FGN7 TreE (R) (ThemaDRAFT_1380) G4FGN8

α-glucoside uptake permease, Agl3E/Agl3F/Agl3G. Plays a role in normal morphogenesis and antibiotic production. Strongly induced by trehalose and melibiose, and weakly induced by lactose and glycerol but not glucose (Hillerich and Westpheling 2006).The operon is controlled by a GntR homologue, Agl3R, and downstream of the gntR gene is a gene encoding an extracellular carbohydrase.

Agl2E/3F/3G of Streptomyces coelicolor
Agl3E (R); 425aas (Q9FBS5)
Agl3F (M) 6TMSs; 310aas (Q9FBS6)
Agl3G (M) 7TMSs; 303aas (Q9FBS7)
(ABC protein (C) not identified) 

Agl3E, Agl3F and Agl3G ABC porter. Induced by trehalose and melibiose using a GntR-like transcription factor (Hillerich and Westpheling 2006).  The ATPase subunit, Agl3K, may be the MsiK (Sco4240; see 3.A.1.1.33) protein (Saito et al. 2008).

Agl3EFG (Sco7167-5) of Streptomyces coelicolor.
Agl3E (R)
Agl3F (M)
Agl3G (M)
Agl3K (unknown)  

MalEFG (K unknown), involved in maltose and maltodextrin uptake (van Wezel et al. 1997).  The MalK protein may be the MsiK (Sco4240; Q9L0Q1; see 3.A.1.1.33) protein.

MalEFG (Sco2231-29) of Streptomyces coelicolor.
MalE (R)
MalF (M)
MalG (M)

Maltose transporter, MusEFGKI.  All five genes have been reported to be essential for uptake activity (Henrich et al. 2013).  The MusI gene product is of 215 aas with 5 TMSs and comprises the founding member of a distinct family of poorly characterized protein in TC family 9.B.28. 

MusEFGKI of Corynebacterium glutamicum

Probable glucoside uptake porter, YcjNOPV.  Encoded in an operon or gene cluster with a glucosyl hydrolase and two oxidoreductases (Moussatova et al. 2008).

YcjNOPV of E. coli
YcjN (R) (430 aas)
YcjO (M) (293 aas)
YcjP (M) (280 aas)
YcjV (C) (360 aas)

ABC-type fucose uptake porter FucABCD.  The ATPase subunit, FucD, has not been identified (Manzoor I., Shafeeq S., Afzal M. and Kuipers OP, JMMB, in press, 2015).

FucABCD of Streptococcus pneumoniae
FucA, (R)
FucB, (M)
FucC, (M)

The lacto-N-biose I (LNB; Gal β-1,3-GlcNAc)/galacto-N-biose (GNB; Gal β-1,3-GalNAc) transporter.  The solute-binding protein crystallizes only in the presence of LNB or GNB, and it was therefore named GNB/LNB-binding protein (GL-BP) (Wada et al. 2007; Suzuki et al. 2008; Asakuma et al. 2011). Isothermal titration calorimetry measurements revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and 0.010 μM, respectively, and the binding process is enthalpy-driven. The crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose (Galbeta1-3GlcNAcbeta1-3GaSuzuki et al. 2008; Asakuma et al. 2011). Isothermal titration calorimetry measurements revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and 0.010 μM, respectively, and the binding process is enthalpy-driven. The crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) were determined.  The MalF and MalG membrahe proteins arAsakuma et al. 2011). Isothermal titration calorimetry measurements revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and 0.010 μM, respectively, and the binding process is enthalpy-driven. The crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) were determined.  The MalF and MalG membrahe proteins are encoded adjacent to the gene for GL-BP, but the ATPase was not identified.

The LNB/GNB uptake transporter of Bifidobacterium longum
MalE homologue
MalF homologue
MalG homologue
MalK homologue, not identified.

The polyol (mannitol, glucitol (sorbitol), arabitol (arabinitol; lyxitol)) uptake porter, MtlEFGK (Brünker et al. 1998).

MtlEFGK of Pseudomonas fluorescens
MtlE, R, 436 aas
MtlF, M, 296 aas
MtlG, M, 276 aas
MtlK, C, 367 aas

Probable glycerophosphocholine (GPC) uptake porter (Chandravanshi et al. 2016). The system may include a receptor and three membrane proteins (of 378 aas and 6 TMSs, 299 aas and 7 TMSs, and 113 aas and 3 TMSs (?). The ATPase has not been identified.

GPC uptake porter of Thermus thermophilus

Maltose - maltoheptose transporter, MalEFGK (based on sequence similarity with the E. coli ortholog; 3.A.1.1.1).  MalEF is a R-M fusion protein with the MalE domain N-terminal and the MalF domain C-terminal. The protein, of 733 aas, has 8 TMSs, one N-terminal to MalE (a signal sequence for export of the MalE domain to the periplasm), an extra TMS at the N-terminus to bring the N-terminus to the periplasmic side of the inner membrane, and then the usual 6 TMSs observed for most ABC membrane proteins.  MalG (M, 272 aas, 6 TMSs) and MalK (C, 374 aas) are of normal size and composition.

MalEF/MalG/MalK of Bdellovibrio bacteriovorus
MalEF, R-M, 733 aas, 8 TMSs
MalG, M, 272 aas, 6 TMSs
MalK, C, 374 aas


Sugar (sucrose, maltose, glucose, fructose, esculin (coumarin β-glucoside)) uptake system possibly consisting of 5 or 6 proteins (see below) (Nieves-Morión and Flores 2017). These proteins are all implicated in sugar uptake, but they may include components of multiple transporters.

Sugar uptake porter of Nostoc (Anabaena) strain PCC7120
GlsR, MalE-like, All1916, 418 aas and 1 N-terminal TMS (R) (Q8YVQ8)
GlsQ, MalF-like, Alr2532, 301 aas and 6 TMSs (M) (Q8YU29)
GlsP, MalG-like, All0261, 276 aas and 6 TMSs (M) (Q8Z042)
GlsC, MalK-like, Alr4781, 432 aas and 0 TMSs (C) (Q8YMZ3)
GlsD, MalK-like, All1823, 366 aas and 0 TMSs (C) (Q8YVZ3)
3.A.1.2:  The Carbohydrate Uptake Transporter-2 (CUT2) Family

Ribose porter.  RbsA has two ATPase domains fused together; RbsB is the substrate receptor; RbsC has 10 TMSs with N- and C-termini in the cytoplasm and forms a dimer (Stewart and Hermodson, 2003).  ABC importers can be divided into two classes. Type I importers follow an alternating access mechanism driven by the presence of the substrate. Type II importers accept substrates in a nucleotide-free state, with hydrolysis driving an inward-facing conformation.  RbsABC2 seems to share functional traits with both type I and type II importers, as well as possessing unique features, and employs a distinct mechanism relative to other ABC transporters (Clifton et al. 2014).

RbsABC of E. coli
RbsA (C)
RbsB (R)
RbsC (M)

Arabinose porter (Horazdovsky and Hogg 1989).

AraFGH of E. coli
AraF (R)
AraG (C)
AraH (M)

Galactose/glucose (methyl galactoside) porter
MglABC of E. coli
MglA (C)
MglB (R)
MglC (M)

Xylose porter
XylFGH of E. coli
XylF (R)
XylG (C)
XylH (M)

Multiple sugar (arabinose, xylose, galactose, glucose, fucose) putative porter
ChvE, GguAB of Agrobacterium tumefaciens
ChvE (R)
GguA (C)
GguB (M)

D-allose porter.  The structure of AlsB has been solved at 1.8 Å resolution (Chaudhuri et al. 1999). Ten residues from both the domains form 14 hydrogen bonds with the sugar. 6-Deoxy-allose, 3-deoxy-glucose and ribose bind with reduced affinity so AlbP can function as a low affinity transporter for D-ribose (Chaudhuri et al. 1999).

AlsABC of E. coli
AlsB (R)
AlsA (C)
AlsC (M)

Fructose/mannose/ribose porter
FrcABC of Sinorhizobium meliloti
FrcA (C)
FrcB (R)
FrcC (M)

Autoinducer-2 (AI-2, a furanosyl borate diester: (3aS,6S,6aR)-2,2,6,6a-tetrahydroxy-3a-methyltetrahydrofuro[3,2-d][1,3,2]dioxaborolan-2-uide) uptake porter (Taga et al., 2001, 2003)

LsrACDB of E. coli
LsrB (R) AAC74589
LsrA (C) AAC74586
LsrC (M) AAC74587
LsrD (M) AAC74588

Rhamnose porter (Richardson et al., 2004) (Transport activity is dependent on rhamnokinase (RhaK; AAQ92412) activity (Richardson and Oresnik, 2007) This could be an example of group translocation!)
RhaSTP of Rhizobium leguminosarum bv. trifolii
RhaS (R) AAQ92407
RhaT (C) AAQ92408
RhaP (M) AAQ92409

The purine nucleoside permease (probably transports guanosine, adenosine, 2'-deoxyguanosine, inosine and xanthosine with decreasing affinity in this order) (Deka et al., 2006)
PnrA-E of Treponema pallidum
PnrA (R) (TmpC; Tp0319) (P29724)
PnrB (?51 aas; 1 TMS; Tp0320) (O83340)
PnrC (C) (533 aas; duplicated; Tp0321) (NP_218761)
PnrD (M) (400 aas; 10 TMSs; Tp0322) (NP_218762)
PnrE (M) (316 aas; 10 TMSs; Tp0323) (NP_218763)

The erythritol permease, EryEFG (Geddes et al., 2010) (probably orthologous to 3.A.1.2.16)

EryEFG of Sinorhizobium meliloti
EryE (C) (CAC48737)
EryF (M) (CAC48738)
EryG (R) (CAC48735)

The (deoxy)ribonucleoside permease; probably takes up all deoxy- and ribonucleosides (cytidine, uridine, adenosine and toxic analogues, fluorocytidine and fluorouridine tested), but not ribose or nucleobases (Webb and Hosie, 2006)
RnsABCD of Streptococcus mutans
RnsA (R) (AAN58814)
RnsB (C) (AAN58813)
RnsC (M) (AAN58812)
RnsD (M) (AAN58811)

The probable autoinducer-2 (AI-2;, a furanosyl borate diester: 3aS,6S,6aR)-2,2,6,6a-tetrahydroxy-3a-methyltetrahydrofuro[3,2-d][1,3,2]dioxaborolan-2-uide) uptake porter (Shao et al., 2007) (50-70% identical to RbsABC of E. coli; TC# 3.A.1.2.1)

RbsABC of Aggregatibacter actinomycetemcomitans (Actinobacillus succinogens)
RbsA (C) (A6VKS8)
RbsB (R) (A6VKT0)
RbsC (M) (A6VKS9)

Putative L-arabinose porter (Rodionov et al. 2010).

AraUVWZ of Shewanella oneidensis
AraU (R) (Q0HIQ8)
AraV (C-C) (Q0HIQ7)
AraW (M; 10 TMSs) (Q0HIQ6)
AraZ (M; 9 TMSs) (Q0HIQ5)

The putative xylitol uptake porter, XltABC (Rodionov et al., 2010)

XltABC of Shewanella pealeana
XltA (C) (A8H4W7)
XltB (M; 9 TMSs) (A8H4W6)
XltC (R) (A8H4W5)

The erythritol uptake permease, EryEFG (Yost et al., 2006) (probably orthologous to 3.A.1.2.11)

EryEFG of Rhizobium leguminosarum
EryE (C) (Q1M4Q7)
EryF (M) (Q1M4Q8)
EryG (R) (Q1M4Q9)

General nucleoside uptake porter, NupABC/BmpA (transports all common nucleosides as well as 5-fluorocytidine, inosine, deoxyuridine and xanthosine) (Martinussen et al., 2010) (Most similar to 3.A.1.2.12). NupA is 506aas with two ABC (C) domains. NupB has 8 predicted TMSs, NupC has 9 or 10 predicted TMSs in a 4 + 1 (or 2) + 4 arrangement.

NupABC/BmpA of Lactococcus lactis
BmpA (R) (D2BKA1)
NupA (C) (A2RKA7)
NupB (M) (A2RKA6)
NupC (M) (A2RKA5)

Xylose porter (Nanavati et al. 2006). Regulated by xylose-responsive regulator XylR (Kazanov et al., 2012).

XylFEK of Thermotoga maritima
XylF (M) (TM0112) (Q9WXW7)
XylE (R) (TM0114) (Q9WXW9)
XylK (C) (TM0115) (Q9WXW0)

D-ribose porter (Nanavati et al., 2006). Induced by ribose (Conners et al., 2005).

RbsABC of Thermotoga maritima
RbsA (C) (TM0956) (Q9X051)
RbsB (R) (TM0958) (Q9X053)
RbsC (M) (TM0955) (Q9X050)  

Glucose porter. Also bind xylose (Boucher and Noll 2011). Induced by glucose (Frock et al. 2012). Directly regulated by glucose-responsive regulator GluR (Kazanov et al., 2012).

GluEFK of Thermotoga maritima
GluE (     GluE (R) (ThemaDRAFT_1377) (G4FGN5)
GluF (M) (ThemaDRAFT_1376) (G4FGN4); 9 TMSs
GluK (C) (ThemaDRAFT_1375) (G4FGN3)  

The myoinositol (high affinity)/ D-ribose (low affinity) transporter IatP/IatA/IbpA. The structure of IbpA with myoinositol bound has been solved (Herrou and Crosson 2013).

IatP/IatA/IbpA of Caulobacter crescentus
IatP (M) (B8H230)
IatA (C) (B8H229)
IbpA (R) (B8H228)

ABC sugar transporter that plays a role in the probiotic benefits through acetate production (Fukuda et al. 2012).

Sugar transporter of Bifidobacterium longum
BL1694, 385 aas (R) (Q8G3R1)
BL1695, 517 aas (C) (Q8G3R0)
BL1696, 405 aas (M) (Q8G3Q9)

ABC sugar transporter important for the probiotic effect of Bifidobacterium longum; involved in producing acetate (Fukuda et al. 2012).

Sugar transporter of Bifidobacterium longum
BL0033 of 327 aas (R) (Q8G848)
BL0034 of 513 aas (C) (Q8G847)
BL0035 of 356 aas (M) (Q8G846)
BL0036 of 340 aas (M) (Q8G845)

XylFGH downstream of characterized transcriptional regulator, ROK7B7 (Sco6008); XylF (Sco6009); XylG (Sco6010); XylH (Sco6011)) (Świątek et al. 2013).

XylFGH of Streptomyces coelicolor 
XylF (R)
XylG (C)
XylH (M; 12 TMSs) 

Putative sugar uptake porter, YtfQRT/YjfF (Moussatova et al. 2008).

YtfQRT/YjfF of E. coli
YtfQ (R)
YtfR (C)
YtfT (M)
YjfF (M)

Xylose transporter, XylFGH (XylF (R), 359 aas; XylG (C), 525 aas; XylH (M), 389 aas.  Controlled by a 3 component sensor kinase/response regulator system (XylFII, sensor, A6LW07; LytS, SK, A6LW08; YesN, RR, A6LW09) (Sun et al. 2015). The XylFII-LytS complex provides the molecular basis for D-xylose utilization and metabolic modification (Li et al. 2017).

XylFGH of Clostridium beijerinckii
XylF (R)
XylG (C)
XylH (M; 12 TMSs)

Sugar (pentose?) transport system, YphDEF

YphDEF of E. coli
YphD (M) 332 aas, 10 TMSs
YphE (C) 503 aas
YphF (R) 327 aas

Riboflavin uptake ABC transporter, RfuABCD.  The periplasmic binding protein (RfuA) has been crystallized at 1.3 Å resolution with riboflavin bound (Deka et al. 2013). Similar systems are found in other spirochetes such as Treponema denticola, and Borrelia burgdorferi (Deka et al. 2013).

RfuABCD of Treponema pallidum
RfuA, R, 343 aas and 1 N-terminal TMS
RfuB, C, 586 aas and 0 TMSs
RfuC, M, 377 aas and 9 or 10 TMSs
RfuD, M, 313 aas and 9 TMSs (may be N-terminally truncated)

High affinity fructose uptake porter, FrtABC, Km (fructose) = ~100μM; expression of the frtABC operon is regulated by the product of the upstream gene, frtR, FrtR, a LacI/GalR-type repressor that allows activation in the presence of fructose (Ungerer et al. 2008). When FruR is eliminated, the cells become hypersensitive to fructose, and the level of fruABC expression is much higher than in the presence of wild type cells grown on fructose (Ungerer et al. 2008).

FrtABC of Anabaena (Nostoc) variabilis
FrtA, Ava2171, Q3MB45, 341 aas with 1 N-terminal TMS (R)
FrtB, Ava2172, Q3MB44, 517 aas and 0 TMSs (C)
FrtC, Ava2173, Q3MB43, 332 aas and 8 TMSs (M)
3.A.1.3:  The Polar Amino Acid Uptake Transporter (PAAT) Family

Histidine; arginine/lysine/ornithine porter (Heuveling et al. 2014)

HisJ (histidine receptor)-ArgT (arg/lys/orn receptor)-HisMPQ of Salmonella typhimurium
HisJ (R)
ArgT (R)
HisM (M)
HisQ (M)
HisP (C)

Glutamine porter
GlnHPQ of E. coli
GlnH (R)
GlnP (M)
GlnQ (C)

Arginine porter
ArtI (arginine receptor #1)/ArtJ (arginine receptor #2)-ArtMQP of E. coli
ArtP (C)
ArtQ (M)
ArtM (M)
ArtJ (R)
ArtI (R)

Glutamate/aspartate porter.  Similar in sequence to 3.A.1.3.19 which is specific for Glu, Asp, Gln and Asn (Singh and Röhm 2008).

GltIJKL of E. coli
GltI (R)
GltJ (M)
GltK (M)
GltL (C)

Octopine porter
OccQMPT of Agrobacterium tumefaciens
OccT (R)
OccQ (M)
OccM (M)
OccP (C)

Nopaline porter
NocQMPT of Agrobacterium tumefaciens
NocT (R)
NocQ (M)
NocM (M)
NocP (C)

Glutamate/glutamine/aspartate/asparagine porter
BztABCD of Rhodobacter capsulatus
BztA (R)
BztB (M)
BztC (M)
BztD (CC)

General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux) (Prell et al. 2009; Hosie et al. 2002Hosie et al. 2002).

AapJQMP of Rhizobium leguminosarum
AapJ (R)
AapQ (M)
AapM (M)
AapP (C)

Glutamate porter
GluABCD of Corynebacterium glutamicum
GluA (C)
GluB (R)
GluC (M)
GluD (M)

Cystine/diaminopimelate transporter, CysXYZ; these proteins are also designated FliY/YecS/YecC.  Note, another transporter is designated CysZ in E. coli (TC# 2.A.121.1.1).  CysXYZ also transports the toxic amino acid analogues, L-selenaproline (SCA; L-selenazolidine-4-carboxylic acid) and L-selenocystine (SeCys) (Deutch et al. 2014).

Cys/Dap porter of E. coli
CysX or FliY (R)
CysY or YecS (M)
CysZ or YecC (C)

Arginine/ornithine (but not lysine) porter
AotJQMP of Pseudomonas aeruginosa
AotJ (R)
AotQ (M)
AotM (M)
AotP (C)

Arginine/lysine/histidine/glutamine porter
BgtAB of Synechocystis PCC6803
BgtA (C)
BgtB (R-M)

Uptake system for L-cystine (Km=2.5 μM), L-cystathionine, L-djenkolate ( 2-amino-3-[(2-amino-3-hydroxy-3-oxopropyl)sulfanylmethylsulfanyl] propanoic acid), and S-methyl-L-cysteine (Burguière et al., 2004, Burguière et al., 2005)

TcyJKLMN (YtmJKLMN) of Bacillus subtilis
TcyJ (R) (NP_390816)
TcyK (R) (O34852)
TcyL (M) (O34315)
TcyM (M) (O34931)
TcyN (C) (O34900)

Uptake system for L-cystine (Burguière et al., 2004)

TcyABC (YckKJI) of Bacillus subtilis
TcyA (R) (P42199)
TcyB (M) (P42200)
TcyC (C) (P39456)

Putative uptake system for arginine, YqiXYZ (Sekowska et al., 2001)

YqiXYZ of Bacillus subtilis
YqiX (R) (P54535)
YqiY (M) (P54536)
YqiZ (C) (P54537)

Uptake system for glutamate and aspartate (Leon-Kempis et al., 2006)
PEB1 transport system Campylobacter jejuni
PEB1a (R) (Q0P9X8)
PED1b (M) (A1VZQ3)
PEB1c (C) (A3ZI83)

Basic amino acid uptake transporter, BgtAB (BgtA is shared with NatFGH/BgtA; 3.A.1.3.18; Pernil et al., 2008)
BgtAB of Anabaena sp. PCC7120
BgtA (C) (Q8YPM6)
BgtB (R-M) (Q8YSA2)

Acidic and neutral amino acid uptake transporter NatFGH/BgtA. BgtA is shared with BgtAB (3.A.1.3.17; Pernil et al., 2008)
NatFGH-BgtA of Anabaena sp. PCC7120
BgtA (C) (Q8YPM6)
NatF (R) (Q8YPM9)
NatG (M) (Q8YPM8)
NatH (M) (Q8YPM7)

Acidic amino acid uptake porter, AatJMQP (Singh and Röhm, 2008).  It is the sole system that  transports glutamate and glutamine, but it can also transport aspartate and asparagine (Singh and Röhm 2008).

AatJMQP of Pseudomonas putida
AatJ (R) Q88NY2
AatM (M) Q88NY3
AatQ (M) Q88NY4
AatP (C) Q88NY5

The putative lysine uptake system, LysXY

LysXY of Streptococcus pyogenes
LysX (R-M) (Q9A1H0)
LysY (C) (Q9A1H1)

Hydroxy L-proline uptake porter, HprABC (Johnson et al. 2008).

HprABC of Pseudomonas aeruginosa
HprA (C) (Q9I488)
HprB (M) (Q9I487)
HprC (R) (Q9I484)

Amino acid transporter, AatJMQP. Probably transports L-glutamic acid, D-glutamine acid, L-glutamine and N-acetyl L-glutamic acid (Johnson et al. 2008). Very similar to 3.A.1.3.19 of P. putida

AatJMQP of Pseudomonas aeruginosa
AatJ (R) (Q9I402)
AatM (M) (Q9I403)
AatQ (M) (Q9I404)
AatP (C) (Q9I405)

Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR.

PA5152-PA5144 of Pseudomonas aeruginosa
PA5152 (C) (Q9HU32)
PA5153 (R) (Q9HU31)
PA5154 (M) (Q9HU30)
PA5155 (M) (Q9HU29)

Putative methionine uptake porter, Sco_5260, 5259, 5258. Defects cause impaired sporulation, reduced growth and reduced production of actinorhodin and undecylprodigiosin. Induced by S-adenosylmethionine (Shin et al. 2007).

Sco_5260, 5259, 5258 of Streptomyces coelicolor
Sco5260 (R) 320aas (Q9F3K5)
Sco5259 (M) 316aas (Q9F3K6)
Sco5258 (C) 253aas (Q9F3K7) 

Glutamine transporter, GlnQP. Takes up glutamine, asparagine and glutamate which compete for each other for binding both substrate and the transmembrane protein constituent of the system (Fulyani et al. 2015). Tandem substrate binding domains (SBDs) differ in substrate specificity and affinity, allowing cells to efficiently accumulate different amino acids via a single ABC transporter. Analysis revealed the roles of individual residues in determining the substrate affinity (Fulyani et al. 2013).

GlnPQ of Lactococcus lactis subsp. cremoris (Streptococcus cremoris)

The putative polar amino acid uptake porter, YhdWXYZ.  Probably under NtrBC transcriptional control (Jiang et al. 2006).

YhdWXYZ of E. coli
YhdW (R)
YhdX (M)
YhdY (M)
YhdZ (C)

Basic amino acid uptake porter, ArtIQ2N2. Transports Arginine, lysine and histidine.  Several 3-d structures have been solved (4YMS, 4YMT, 4YMU, etc., Yu et al. 2015).

ArtIQ2N2 of Caldanaerobacter subterraneus subsp. tengcongensis (Thermoanaerobacter tengcongensis)
ArtI (R)
ArtQ (M)
ArtN (C)

Putative amino acid uptake porter, YckIJK; deletion of YckK (substrate binding protein) increases sensitivity to the antimicrobial peptide, cecropin (Chen et al. 2015). 

YckIJK of Haemophilus psarasuis
YckI (C)
YckJ (M)
YckK (R)

Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential (Paul et al. 2016).

Basic amino acid transporter of E. coli
3.A.1.4:  The Hydrophobic Amino Acid Uptake Transporter (HAAT) Family

Leucine; leucine/isoleucine/valine porter (also transports phenylalanine and tyrosine; Koyanagi et al., 2004)
LivK (leucine-specific receptor)-LivJ (Leu/Ile/Val receptor)-LivHMGF of E. coli
LivJ (R)
LivK (R)
LivH (M)
LivM (M)
LivG (C)
LivF (C)

Leucine/proline/alanine/serine/glycine (and possibly histidine) porter
NatA-E neutral amino acid porter of Synechocystis sp.PCC6803
NatA (C)
NatB (R)
NatC (M)
NatD (M)
NatE (C)

General L- (and D-)amino acid uptake porter (transports acidic, basic, polar, semipolar and hydrophobic amino acids). The amino and carboxyl groups do not need to be α since γ-aminobutyric acid (GABA) is a substrate. The system may function with additional binding proteins since L-alanine uptake is not dependent on BraC.
BraCDEF of Rhizobium leguminosarum
BraC (R)
BraD (M)
BraE (M)
BraF (C)

The high-affinity (<1 μM) urea porter
UrtA-E urea porter of Anabaena sp. PCC7120
UrtA (R)
UrtB (M)
UrtC (M)
UrtD (C)
UrtE (C)

The high affinity urea/thiourea/hydroxyurea porter (Beckers et al., 2004)
UrtA-E of Corynebacterium glutamicum
UrtA (R) CAF19637
UrtB (M) CAF19636
UrtC (M) CAF19638
UrtD (C) CAF19639
UrtE (C) CAF19640

The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB) (Picossi et al., 2005)
NatA-E of Anabaena sp. strain PCC7120
NatA (C) BAB73003
NatB (R) BAB73533
NatC (M) BAB73004
NatD (M) BAB73241
NatE (C) BAB74611

The protocatechuate (3,4-dihydroxybenzoate) uptake porter, PcaMNVWX (Maclean et al., 2011)

PcaMNVWX of Sinorhizobium (Ensifer) meliloti
PcaM (R) (Q92TN0)
PcaN (M) (Q92TN1)
PcaV (M) (Q92TN2) 
PcaW (C) (Q92TN3) 
PcaX (C) (Q92TN4) 

Branched chain amino acid uptake transporter. Transports alanine (Hoshino and Kose 1990).

BraC-G of Pseudomonas aeruginosa
BraG (C) (P21630)
BraE (C) (P21629)
BraE (M) (P21628)
BraD (M) (P21627)
BraC (R) (P21175)

Uptake transporter, CamABCD of cholate (steroid) metabolites, 1β(2'-propanoate)-3aα-H-4α(3"(R)-hydroxy-3"-propanoate)-7aβ-methylhexahydro-5-indanone and a desaturated analog (Swain et al. 2012).

CamABCD of Rhodococcus jostii
CamA, R, 405 aas (Q0S717)
CamB, M, 285 aas, 8 TMSs (Q0S718)
CamC, M-C, 607 aas, 10 TMSs in a 5 + 5 arrangement followed by the C domain (Q0S719)
CamD, C, 245 aas (Q0S720)

The branched chain hydrophobic amino acid transporter, LivJFGHM (Basavanna et al. 2009).

LivJFGHM of Streptococcus pneumoniae
LivJ (R) 286 aas
LivF (C) 236 aas
LivG (C) 254 aas
LivH (M) 292 aas, 7 TMSs
LivM (M) 318 aas, 9 TMSs

The phenylpropeneoid uptake porter, CouPSTW.  The purple photosynthetic bacterium Rhodopseudomonas palustris is able to grow photoheterotrophically under anaerobic conditions on a range of phenylpropeneoid lignin monomers, including coumarate, ferulate, caffeate, and cinnamate. RPA1789 (CouP) is the periplasmic binding-protein component of the ABC uptake system (CouPSTU).  CouP binds a range of phenylpropeneoid ligands with K d values in the nanomolar range. The crystal structure of CouP with ferulate as the bound ligand shows H-bond interactions between the 4-OH group of the aromatic ring with His309 and Gln305. H-bonds are also made between the carboxyl group on the ferulate side chain and Arg197, Ser222, and Thr102 (Salmon et al. 2013).

CouPSTW of Rhodopseudomonas palustris 
CouP (R) 385 aas
CouS (C) 239 aas
CouT (M-C) 590 aas
CouW (M) 346 aas

ABC-type uptake porter for pyruvate and monocarboxylate 2-oxo acids.  Pyruvate uptake has been measured and is inhibited by monocarboxylate 2-oxo-acids such as 2-oxobutyrate, 2-oxovalerate, 2-oxoisovalerate, 2-oxoisocaproate and 2-oxo 3-methylvalerate which are probably substrates (Pernil et al. 2010). 

ABC porter of Anabaena (Nostoc) strain 7120
Alr2535, Q8YU26, 268 aas, 1 N-terminal TMS (R)
Alr2536, Q8YU25, 316 aas, 9 TMSs, (M)
Alr2538, Q8YU24, 308 aas and 8 TMSs (M)
Alr2539, Q9YU22, 259 aas and 0 TMSs (C)
Alr2541, Q9YU20, 264 aas and 0 TMSs (C)
3.A.1.5:  The Peptide/Opine/Nickel Uptake Transporter (PepT) Family

Oligopeptide porter (also takes up amino glycoside antibiotics such as kanamycin, streptomycin and neomycin as well as cell wall-derived peptides such as murein tripeptide). It transports substrate peptides of 2-5 amino acids with highest affinity for tripeptides. Also transports δ-aminolevulinic acid (ALA). [May be regulated by PTS Enzyme INtr-aspartokinase.] ATP-binding to OppDF may result in donation of peptide to OppBC and simultaneous release of OppA (Doeven et al., 2008).
OppABCDF of Salmonella typhimurium
OppA (R)
OppB (M)
OppC (M)
OppD (C)
OppF (C)
MppA (R) (in E. coli)

Dipeptide porter. Also transports δ-aminolevulinic acid (ALA) and heme (Létoffé et al., 2008).
DppABCDE of Bacillus subtilis
DppA (C)
DppB (M)
DppC (M)
DppD (C)
DppE (R)

Nickel porter. Histidine 416 of NikA is essential for nickel uptake (Cavazza et al., 2011).

NikABCDE of E. coli
NikA (R)
NikB (M)
NikC (M)
NikD (C)
NikE (C)

Agrocinopine (an opine)/Agrocin 84 (an antibiotic) porter (Kim and Farrand, 1997)
AccABCDE of Agrobacterium tumefaciens
AccA (R)
AccB (C)
AccC (C)
AccD (M)
AccE (M)

Probable cationic peptide porter (may also take up peptide antibiotics and protamine; implicated in K+ homeostasis) [SapD can stimulate the K+ uptake activities of TrkH and TrkG (TC #2.A.38.1.1) in the presence of ATP] (Mason et al., 2006)
SapABCDF of Salmonella typhimurium
SapA (R)
SapB (M)
SapC (M)
SapD (C)
SapF (C)

The β-glucoside (cellobiose (β-1,4), cellotriose, cellotetraose, cellopentaose, laminaribiose (β-1,3), laminaritriose, sophorose) uptake porter, CbtABCDF
The β-glucoside uptake porter of Pyrococcus furiosus, CbtABCDF
CbtA (R)
CbtB (M)
CbtC (M)
CbtD (C)
CbtF (C)

The α-galactoside (melibiose, raffinose) uptake porter, AgpABCDF
The α-galactoside uptake porter of Rhizobium meliloti
AgpA (R)
AgpB (M) (not identified)
AgpC (M) (not identified)
AgpD (C) (not identified)
AgpF (C) (not identified)

Maltose and maltooligosaccharide porter

MalEFGK of Sulfolobus solfataricus
MalE (R)
MalF (M)
MalG (M)
MalK (C-C)

Cellobiose and cellooligosaccharide porter
CbtABCDF of Sulfolobus solfataricus
CbtA (R)
CbtB (M)
CbtC (M)
CbtD (C)
CbtF (C)

Oligopeptide porter (transports peptides of 4-35) amino acyl residues; di- and tripeptides are not transported; hydrophobic basic peptides are preferred). OppA determines the specificity of the system (Doeven et al., 2004). A large cavity in OppA binds proline-rich peptides preferentially (Berntsson et al., 2009). Two crystal structures of OppA with different nonapeptides show binding in different registers (Berntsson et al., 2011).

OppABCDF of Lactococcus lactis
OppA (R) (Q9CEK0)
OppB (M) (P0A4N7)
OppC (M) (P0A4N9)
OppD (C) (Q07733)
OppF (C) (P0A2V4)

Glutathione porter, YliABCD or GseABCD (Suzuki et al., 2005)

YliABCD of E. coli
YliA (GsiA) (C-C) (P75796)
YliB (GsiB) (R) (P75797)
YliC (GsiC) (M) (P75798)
YliD (GsiD) (M) (P75799)

Probable rhamnose oligosaccharide porter. Induced by rhamnose (Conners et al., 2005).

RtpEFGKL of Thermotoga maritima
RtpE (R) (TM1067) Q9X0F7
RtpF (M) (TM1066) Q9X0F6
RtpG (M) (TM1065) Q9X0F5
RtpK (C) (TM1064) Q9X0F4
RtpL (C) (TM1063) Q9X0F3

Probable xylan oligosaccharide porter (Conners et al., 2005). Induced by xylan and xylose. Regulated by xylose-responsive regulator XylR (Kazanov et al. 2012).

XloEFGKL of Thermotoga maritima
XloE (R) (TM0071) Q9WXS6
XloF (M) (TM0072) Q9WXS7
XloG (M) (TM0073) Q9WXS8
XloK (C) (TM0074) Q9WXS9
XloL (C) (TM0075) Q9WXT5

Probable cellobiose porter. Induced by barley, glucomannan (Conners et al., 2005)

CelEFGKL of Thermotoga maritima
CelE (R) (TM1223) Q9X0V0
CelF (M) (TM1222) Q9X0U9
CelG (M) (TM1221) Q9X0U8
CelK (C) (TM1220) Q9X0U7
CelL (C) (TM1219) Q9X0U6

Probable mannose/mannoside porter. Induced by beta-mannan (Conners et al., 2005). Regulated by mannose-responsive regulator manR (Kazanov et al., 2012).

MtpEFGKL of Thermotoga maritima
MtpE (R) (TM1746) Q9X268
MtpF (M) (TM1747) Q9X269
MtpG (M) (TM1748) Q9X270
MtpK (C) (TM1749) Q9X271
MtpL (C) (TM1750) Q9X272

β-glucoside porter (Conners et al., 2005). Binds cellobiose, laminaribiose (Nanavati et al. 2006). Regulated by cellobiose-responsive repressor BglR (Kazanov et al. 2012).

BglpEFGKL of Thermotoga maritima
BglE (R) (TM0031) Q9WXN8
BglF (M) (TM0030) Q9WXN7
BglG (M) (TM0029) Q9WXN6
BglK (C) (TM0028) Q9WXN5
BglL (C) (TM0027) Q9WXN4

The proline betaine uptake porter (Alloing et al., 2006)

PrbABCD of Sinorhizobium meliloti
PrbA (R) (Q92NF1)
PrbB (M) (Q92NF0)
PrbC (M) (Q92NE9)
PrbD (C-C) (Q92NE8)

The oligopeptide transporter OppA1-5, B1, C1, DF (functions with five binding proteins of differing induction properties and peptide specificities; OppA1-3 are chromosomally encoded; OppA4 and 5 are plasmid encoded.) (Medrano et al., 2007)
OppA1-5,B1,C1,D,F of Borrelia burgdorferi
OppA1 (R): O51307
OppA2 (R): O54584
OppA3 (R): O51308
OppA4 (R): O31315
OppA5 (R): O50927
OppB1 (M): O31307
OppC1 (M): O51310
OppD (C): O31309
OppF (C): O31310

The major oligopeptide uptake porter, Opp-3 (of four paralogues, this is the only one that mediates nitrogen nutrition (Hiron et al., 2007).
Opp-3 of Staphylococcus aureus
OppB (M) = (Q2FZR7)
OppC (M) = (Q2FZR6)
OppD (C) = (Q2FZR5)
OppF (C) = (Q2FZR4)
OppA (R) = (Q2FZR3)

5-6 amino acyl oligopeptide transporter AppA-F (Koide and Hoch, 1994).
AppABCDF of Bacillus subtilis
AppA(R) (P42061)
AppB(M) (P42062)
AppC(M) (P42063)
AppD(C) (P42064)
AppF(C) (P42065)

The Microcin C/peptide uptake porter, YejABEF (Novikova et al., 2007).  The 'Trojan horse' antibiotic, microcin C, consists of a nonhydrolyzable aspartyl-adenylate that is efficiently imported into bacterial cells owing to a covalently attached peptide. Once inside the cell, the peptide "carrier" is removed by proteolytic processing to release a potent aspartyl tRNA synthetase inhibitor (Severinov and Nair 2012).

YejABEF of E. coli:
YejA (R) (P33913)
YejB (M) (P0AFU1)
YejE (M) (P33915)
YejF (C-C) (P33916)

The peptide transporter OppA,B,C,D,F (influences biofilm formation; Lee et al., 2004). Similar to 3.A.1.5.1, OppA is similar to the Vibrio furnissii OppA that provides several functions: hemolysis, antibiotic resistance, and virulence (Wu et al., 2007).
OppABCDF of Vibrio fluvialis:
OppA (R) (Q5V9S2)
OppB (M) (Q5V9S1)
OppC (M) (Q5V9S0)
OppD (C) (Q5V9R9)
OppF (C) (Q5V9R8)

The Ethylene diamine tetraacetate (EDTA) uptake porter, EppABCD (Zhang et al., 2007).

EppABCD of EDTA-degrading bacterium BNC1:
EppA (R) (Q9F9T7)
EppB (M) (Q9F9T6)
EppC (M) (Q9F9T5)
EppD (C-C) (Q9F9T4)

The antimicrobial peptide (protamine, melittin, polymyxin B, human defensin (HBD)-1 and HBD-2 exporter, YejABEF (Eswarappa et al., 2008). Prefers N-formyl methionine peptides, such as Microcin C (of prokaryotic origin) to non formylated peptides (of eukaryotic origin) (Novikova et al., 2007).

YejABEF of Salmonella enterica
YejA (R) (Q8ZNK0)
YejB (M) (Q7CQ74)
YejE (M) (Q8ZNJ9)
YejF (C-C) (Q8ZNJ8)

The ABC peptide/signalling peptide transporter. OptA binds peptides of 3-6 aas; OptS binds dipeptides. OptB,C,D are most similar to 3.A.1.5.19.

The OptASBCDF transport system of Lactococcus lactis
OptS (R) (Q64K09)
OptA (R) (Q9CIL2)
OptB (M) (Q9CILI)
OptC (M) (Q9CIL0)
OptD (C) (Q9CIK9)
OptF (C) (Q9CIK8)

The glutathione transporter, OppA (Dasgupta et al., 2010). OppA binds glutathione and the nanopeptide, bradykinin. Also regulates cytokine release, apoptosis and the innate immune response of macrophages infected with M. tuberculosis (Dasgupta et al., 2010).

Peptide transporter of Mycobacterium tuberculosis
OppA (R) (P66771)
OppD (C) (P63395)
OppC (M) (P66964)
OppB (M) (P66966)

The glutathione uptake porter, DppBCDF with the glutathione binding protein, DppA (GbpA; HbpA). Takes up reduced (GSH) and oxidized (GSSG) but not bulky glutathione S conjugates or glutathione derivatives with C-terminal modifications (Vergauwen et al., 2010).

DppABCDF of Haemophilus influenzae
DppA (R) (P33950)
DppB (M) (P45096)
DppC (M) (P51000)
DppD (C) (P45095)
DppF (C) (P45094)

The Nickel (Ni2+) uptake porter, NikZYXWV (Howlett et al., 2012).

NikZYXWV of Campylobacter jejuni 
NikZ (R) (Q0P844)
NikY (M) (Q0P845)
NikX (M) (Q0P846)
NikW (C) (Q0P847)
NikV (C) (Q0P848) 

Probable xylan oligosaccharide porter (Conners et al. 2005). Induced by cylan and xylose. Regulated by xylose-responsive regulator XylR (Kazanov et al. 2012).

XtpELKGF of Thermotoga maritima
XtpE (R) (TM0056) (Q9WXR2)
XtpL (C) (TM0057) (Q9WXR3)
XtpK (C) (TM0058) (Q9WXR4)
XtpG (M) (TM0059) (Q9WXR5)
XtpF (M) (TM0060) (Q9WXR6)

Putative fucose-glucose oligosaccharide porter. Binds xyloglucan hepta-, octa-, nonasaccharides with beta-1,4- tetraglucosyl backbones (Conners et al., 2005)

GloEFGKL of Thermotoga maritima
GloE (R) (TM0300) (Q9WYD6)
GloF (M) (TM0301) (Q9WYD7)
GloG (M) (TM0302) (Q9WYD8)
GloK (C) (TM0303) (Q9WYD9)
GloL (C) (TM0304) (Q9WYE0)  

Predicted galactoside porter. Induced by lactose (Conners et al., 2005)

LtpE (R) (TM1199) Q9X0S6 LtpF (M) (TM1198) Q9X0S5 LtpG (M) (TM1197) Q9X0S4 LtpK (C) (TM1196) Q9X0S3 LtpL (C) (TM1194) Q9S5X6

ABC α-galactoside uptake porter.  Most highly induced by stachyose (Andersen et al. 2012).

ABC α-galactoside uptake porter of Lactobacillus acidophilus
F0TFS5 (R)
F0TFS6 (R)
F0TFS7 (M)
F0TFS8 (M)
F0TFS9 (C)
F0TFT0 (C)

The Nickel (Ni2+) uptake porter, NikABCDE (Hiron et al. 2010)

NikABCDE of Staphylococcus aureus 
NikA (R) (G8V0I4)
NikB (M) (I0C488)
NikC (M) (I0C487)
NikD (C) (I0C7E8)
NikE (C) (I0C7E7) 

Putative oligopeptide uptake porter. Induced by S-adenosylmethionine. Deletion caused impaired sporulation and impaired the enhancing activity of S-adenosylmethionine on actinorhodin (but not undecylprodigiosin) production (Shin et al. 2007).

Putative oligopeptide uptake porter of Streptomyces coelicolor
Sco_5476 (M) (O86571)
Sco_5477 (R) (O86572)
Sco_5478 (M) (O86573)
Sco_5479 (C) (O86574)
Sco_5480 (C) (O86575) 

Putative peptide transporter encoded adjacent to the putative transport system with TC#3.A.1.5.36. The orthologue controls aerial mycelium formation in S. griseus (Akanuma et al. 2011).

Sco_5117-Sco_5121 of Streptomyces coelicolor
Sco_5117 (R) (Q9F353)
Sco_5118 (M) (Q9F352)
Sco_5119 (M) (Q9F351)
Sco_5120 (C) (Q9F350)
Sco_5121 (C) (Q9F349)

Peptide transporter encoded adjacent to the putative transport system with TC#3.A.1.5.35 (Akanuma et al. 2011). Induced by exogenous S-adenosylmethionine (SAM) at a concentration of 2muM which also enhanced antibiotic production and inhibited morphological development (Park et al. 2005). SAM can be imported into cells. Mutants in the bldK genes confer resistance to the toxic tripeptide, bialaphos (Nodwell et al. 1996).

BldKA-D and Sco_5116 of Streptomyces coelicolor 
BldKA (Sco_5112) (M) (Q93IU3)
BldKB (Sco_5113) (R) (Q93IU2)
BldKC (Sco_5114) (M) (Q93IU1)
BldKD (Sco_5115) (C) (Q93IU0)
Sco_5116 (C) (Q8CJS2) 

The ABC BldKA-E (SGR_2418-2414) oligopeptide transport system. It controls aerial mycelium formation on glucose media. Probably involved in extracellular peptide signalling (Akanuma et al. 2011).  Probably orthologous to 3.A.1.5.35.

BldKA-E of Streptomyces griseus
SGR_2417; BldKA (M) (B1W1M1)
SGR_2418; BldKB (R) (B1W1M2)
SGR_2419; BldKC (M) (B1W1M0)
SGR_2420; BldKD (C) (B1W1L9)
SGR_2421; BldKE (C) (B1W1L8) 

The putative D-alanyl-D-alanyl dipeptide permease, DdpABCDF; encoded within an operon that includes the D-ala-D-ala peptidase, DdpX (VanX, YddT). May also interact with the YegQ peptidase (P76403).

DdpABCDF of E. coli
DdpA (R)
DdpB (M)
DdpC (M)
DdpD (C)
DdpF (C)  

Di- and tri-peptide transporter, DppBCDF with periplasmic substrate binding receptors, A1, A3, A5, A7 and A9, each with differing specificities for peptides (Pletzer et al. 2014).

Dpp transporter of Pseudomonas aeruginosa
DppB, (M)
DppC (M)
DppD (C)
DppF (C)
DppA1 (R)
DppA3 (R)
DppA5 (R)
DppA7 (R)
DppA9 (R)

Nickel uptake porter, NikAB(CD)E (Benoit et al. 2013).

NikAB(CD)E of Helicobacter hepaticus
NikA (R)
NikB (M)
NikCD (M-C)
NikE (C)

Oligopeptide transporter, OppABCDF/MppA/YgiS.  MppA is a murein peptide receptor, and YgiS is a bile acid (e.g., cholate, deoxycholate) receptor that may use the Opp system for uptake.  YgiS mRNA is degraded by the toxin MgsR which is regulated by the antitoxin, MgsA and this loss of the mRNA protects the cell against bile acid stress (Kwan et al. 2015).

OppABCDF/MppA/YgiS system of E. coli
OppA (R)

OppB (M)
OppC (M)
OppD (C)
OppF (C)
MppA (R)
YgiS (R)

Peptide transporter, SapABCDF

SapABCDF of E. coli
SapA (R)
SapB (M)
SapC (M)
SapD (C)
SapF (C)

The metal-staphylopine (nicotianamine-like metalophore) complex uptake system, CntABCDF.  Staphylopine binds divalent nickel, cobalt, zinc, copper and iron (Ghssein et al. 2016).

Metal-staphylopine uptake system, CntABCDF of Staphylococcus aureus

Peptide transporter, SapABCDF. Mutants are more sensitive than the wild type to wheat alpha-thionin and to snakin-1, which is the most abundant antimicrobial peptide from potato tubers. They were also less virulent than was the wild-type strain in potato tubers: lesion areas were 37% that of the control, and the growth rate was two orders of magnitude lower. Thus, the interaction of antimicrobial peptides from the host with the sapA-F operon from the pathogen plays a similar role in animal and in plant bacterial pathogenesis (López-Solanilla et al. 1998).

SapABCDF of Dickeya chrysanthemi (Pectobacterium chrysanthemi) (Erwinia chrysanthemi)
SapA, 540 aas, R
SapB, 313 aas, M
SapC, 296 aas, M
SapD, 330 aas, C
SapF, 269 aas, C
3.A.1.6:  The Sulfate/Tungstate Uptake Transporter (SulT) Family

Sulfate/thiosulfate porter

Sbp (sulfate receptor)-CysP (thiosulfate receptor)-CysTWA of E. coli
Sbp (R)
CysP (R)
CysT (M)
CysW (M)
CysA (C)

Tungstate porter. (TupA, the receptor, exhibits an extremely high affinity for tungstate (Kd <1 nM) and discriminates between tungstate and molybdate (Andreesen and Makdessi, 2007))

TupABC of Eubacterium acidaminophilum
TupA (R)
TupB (M)
TupC (C)

Sulfate porter
CysAWT SubI-sulfate porter of Mycobacterium tuberculosis
CysA (C)
CysW (M)
CysT (M)
SubI (R)

Vanadate porter (Pratte and Thiel, 2006) (most similar to TupABC (3.A.1.6.2))
VupABC of Anabaena variabilis ATCC29413
VupA (R) (ABA23645)
VupB (M) (ABA23644)
VupC (C) (ABA23643)

Tungsten (KM=20pM)/molybdate (KM=10nM) porter (Bevers et al., 2006)
WtpABC of Pyrococcus furiosus
WtpA (R) (Q8U4K5)
WtpB (M) (Q8U4K4)
WtpC (C) (Q8U4K3)

The Molybdate/Tungstate Transporter, ModA-C (Zhang and Gladyshev, 2008).
ModABC of Pyrobaculum calidifontis
ModA (R) (A3MW02)
ModB (M) (A3MW01)
ModC (C) (A3MW00)

The chloroplast sulfate transporter, SulP/SulP2/Sabc/Sbp (Melis & Chen et al., 2005).

Chloroplast sulfate uptake permease of Chlamydomonas reinhardtii
SulP (M) (Q8RVC7)
SulP2 (M) (Q6QJE2)
Sabc (C) (Q6QJE1)
Sbp (R) (Q6QJE0)

Molybdate/tungstate transport system, ModABC (WtpABC) (ModA binds to ModBC with high affinity (0.11%u03BCM) and dissociates slowly; the complex is destabilized by nucleotide and substrate binding (Vigonsky et al. 2013).

ModABC of Archeoglobus fulgidus
ModB (M; 12 TMSs; type I fold) (O30143)
ModC (C) (O30144)
ModA (R) (O30142)

The putative molybdate, tungstate, selenite transporter, WtpBC (Kim and Whitman 1999).
WtpB of 249 aas (M) (Q58763)
WtpC of 297 aas (C) (Q58762)
WtpA of 346 aas (R) (Q58586)

WtpBC of Methanocaldococcus jannaschii (Methanococcus jannaschii)
3.A.1.7:  The Phosphate Uptake Transporter (PhoT) Family

Phosphate porter, PhoSPstABC.  Serves as both a transporter and a sensor for transcriptional activation of the pho regulon in the presence of low external phosphate.  The unphosphorylated EIIANtr protein of the PTS (TC# 4.A) activates PhoR, the senor kinase that phosphorylates the response regulator, PhoB, that activates the pho regulon (Lüttmann et al. 2012).

PhoS (phosphate receptor)-PstABC of E. coli
PhoS (R)
PstA (M)
PstC (M)
PstB (C)

Phosphate transporter, PstSCAB (Gebhard and Cook, 2007).
PstSCAB of Mycobacterium smegmatis
PstS (R) (Q7WTY8)
PstC (M) (Q7WTY7)
PstA (M) (Q7WTY6)
PstB (C) (P0C560)

High-affinity phosphate-specific permease, PstAB/PhoS. The 3-d structure of PhoS = (PBP) = PfluDING) has been solved at high resolution by x-ray crystallography (Ahn et al. 2007) with phosphate bound (4F1U and 4F1V; 0.95Å resolution) and with arsenate bound (4F18 and 4F19; 0.88Å resolution) (Elias et al. 2012). Phosphate binds with 500-fold higher affinity than arsenate due to a dense and rigid network of ion-dipole interactions (Elias et al. 2012). The PBP from Halomonas sp. GFAJ-1 has a phosphate affinity 5000-fold higher than that of arsenate (Elias et al. 2012).

PstAB/PhoS of Pseudomonas fluorescens
PstA (C) (C3KCB5)
PstB (M) (C3KCB6)
PstC (PBP) (R) (D0VWY2) 

High specificity inorganic phosphate porter, PstABCS (Sarin et al. 2001).

PstABCS of Mycobacterium tuberculosis 
PstA2 (M) (P0A627)
PstB2 (C) (P95302)
PstC2 (M) (P0A630)
PstS2 (R) (O05870) 

The phosphate transporter, PstABCS.  The structure of PstS is known to 1.3Å resolution (Brautigam et al. 2013).

PstABCS of Borrelia burgdorferii
PstA (M) (O51235)
PstB (C) (O51236)
PstC (M) (O51234)
PstS (R) (O51233)
3.A.1.8:  The Molybdate Uptake Transporter (MolT) Family

Molybdate porter
ModABC of E. coli
ModA (R)
ModB (M)
ModC (C)

The molybdate/tungstate ABC transporter, ModABC. The trans-inhibited 3-d structure of ModABC, is available (3D31.A and 3D31.B)(Gerber et al., 2008)

ModABC of Methanosarcina acetivorans
ModA (Q8TTV0)
ModB (M) (Q8TJ86)
ModC (C) (Q8TTV2)
3.A.1.9:  The Phosphonate Uptake Transporter (PhnT) Family

Phosphonate/organophosphate ester porter (broad specificity). Reviewed by Hinz & Tampé (2012).

PhnCDE of E. coli
PhnC (C)
PhnD (R)
PhnE (M)

Phosphonate/phosphate porter, PhnDCE (Gebhard and Cook, 2007)
PhnDCE of Mycobacterium smegmatis
PhnC (C) (A0QQ70)
PhnD (R) (A0QQ71)
PhnE (M) (A0QQ68)
3.A.1.10:  The Ferric Iron Uptake Transporter (FeT) Family

Ferric iron (Fe3+) porter
SfuABC of Serratia marcescens
SfuA (R)
SfuB (M)
SfuC (C)

Ferric iron (Fe3+) porter
Fut A1A2BC of SynechocystisPCC6803
FutA1 (R)
FutA2 (R)
FutB (M)
FutC (C)

Ferric iron (Fe3+) porter (selective for trivalent cations, Fe3+, Ga3+ and Al3+) (Anderson et al., 2004)

FbpABC (HitABC) of Haemophilus influenzae
FbpA (R) (AAC21773)
FbpB (M) (AAC21774)
FbpC (C) (AAC21775)

The Fe-hydroxamate-type siderophore uptake porter (transports Fe+3 bound to ferrioxamine, ferrichrome or pyoverdine siderophores) (Vajrala et al., 2010).

NitABC of Nitrosomonas europaea
NitA (R) (Q82VN7)
NitB (M) (Q82VN6)
NitC (C) (Q82VN5)

Siderophore-independent iron uptake system, AfuABC (Saken et al. 2000).

AfuABC of Yersinia enterocolitica
AfuA (R)
AfuB (M)
AfuC (C)
3.A.1.11:  The Polyamine/Opine/Phosphonate Uptake Transporter (POPT) Family

Polyamine (putrescine/spermidine) uptake porter.  Plays a role in biofilm formation (Zhang et al. 2013).  Spermidine-preferring (Igarashi and Kashiwagi 1996).

PotABCD of E. coli
PotA (C)
PotB (M)
PotC (M)
PotD (R)

Putrescine porter (Igarashi and Kashiwagi 1996).

PotGHIF of E. coli
PotG (C)
PotH (M)
PotI (M)
PotF (R)

Mannopine porter
MotABCD of Agrobacterium tumefaciens plasmid pTi15955
MotA (R)
MotB (C)
MotC (M)
MotD (M)

Chrysopine porter
ChtGHIJK of Agrobacterium tumefaciens
ChtG (C)
ChtH (R)
ChtI (R)
ChtJ (M)
ChtK (M)

2-aminoethyl phosphonate porter
PhnSTUV of Salmonella typhimurium
PhnS (R)
PhnT (C)
PhnU (M)
PhnV (M)

The γ-aminobutyrate (GABA) uptake system, GtsABCD (White et al., 2009).
GtsABCD of Rhizobium leguminosarum
GtsA (R) (Q1M7Q4)
GtsB (M) (Q1M7Q3)
GtsC (M) (Q1M7Q2)
GtsD (C) (Q1M7Q1)

PotABCD of Streptococcus pneumoniae
PotA (C) 385 aas
PotB (M) 275 aas (also called PotH)
PotC (M) 257 aas
PotD (R) 356 aas

The spermine/spermidine uptake porter, PotABCD.

PotABCD of Staphylococcus aureus
PotA (C)
PotB (M)
PotC (M)
PotD (R)  

Putative polyamine (spermidine/putrescine) uptake porter, YdcSTUV (Moussatova et al. 2008).

YdcSTUV of E. coli
YdcS (R; 381 aas)
YdcT (C; 337 aas)
YdcU (M; 313 aas)
YdcV (M; 264 aas)
3.A.1.12:  The Quaternary Amine Uptake Transporter (QAT) Family (Similar to 3.A.1.16 and 3.A.1.17)

Glycine betaine/proline porter, ProU or ProVWX (also transports proline betaine, carnitine, dimethyl proline, homobetaine, γ-butyrobetaine and choline with low affinity).  Contributes to the regulation of cell volume is response to osmolarity.  A reconsituted system shows osmotic strength-gating (Gul and Poolman 2012).

ProVWX of E. coli
ProW (M)
ProX (R)
ProV (C)

Glycine betaine OpuAA/AB/AC porter (also transports dimethylsulfonioacetate and dimethylsulfoniopropionate).  The system has been reconstituted in nanodiscs and shows substrate-dependent ionic stringth-gated gating and energy coupling dependent on anionic lipids (Karasawa et al. 2013).

OpuAA, AB, AC of Bacillus subtilis
OpuAA (C)
OpuAB (M)
OpuAC (R)

Choline porter
OpuBA, BB, BC, BD of Bacillus subtilis
OpuBA (C)
OpuBB (M)
OpuBC (R)
OpuBD (M)

Uptake system for choline, L-carnitine, D-carnitine, glycine betaine, proline betaine, crotonobetaine, γ-butyrobetaine, dimethylsulfonioacetate, dimethylsulfoniopropionate, ectoine and choline-O-sulfate
OpuCA, CB, CC, CD of Bacillus subtilis
OpuCA (C)
OpuCB (M)
OpuCC (R)
OpuCD (M)

Uptake system for glycine-betaine (high affinity) and proline (low affinity) (OpuAA-OpuABC) or BusAA-ABC of Lactococcus lactis). BusAA, the ATPase subunit, has a C-terminal tandem cystathionine β-synthase (CBS) domain which is the cytoplasmic K+ sensor for osmotic stress (osmotic strength)while the BusABC subunit has the membrane and receptor domains fused to each other (Biemans-Oldehinkel et al., 2006; Mahmood et al., 2006; Gul et al. 2012). An N-terminal amphipathic α-helix of OpuA is necessary for high activity but is not critical for biogenesis or the ionic regulation of transport (Gul et al., 2012).

BusAA-AB of Lactococcus lactis
BusAB (M-R)

Uptake system for hisitidine, proline, proline-betaine and glycine-betaine
HutXWV of Sinorhizobium meliloti
HutX (R)
HutW (M)
HutV (C)

High affinity (3 μM) choline-specific uptake system (Dupont et al., 2004)
ChoXWV of Sinorhizobium meliloti
ChoX (R) (AAM00244)
ChoW (M) (AAM00245)
ChoV (C) (AAM00246)

A proline/glycine betaine uptake system. Also reported to be a bile exclusion system that exports oxgall and other bile compounds, BilEA/EB or OpuBA/BB (required for normal virulence) (R.D. Sleator et al., 2005).
OpuBA/BB or BilEA/EB of Listeria monocytogenes
OpuBA (C) (Q93A35)
OpuBB (M-R) (Q93A34)

The salt-induced glycine betaine OtaABC transporter (Schmidt et al., 2007)
OtaABC of Methanosarcina mazei Go1
OtaA (C) Q8U4S5
OtaB (M) Q8U4S4
OtaC (R) Q8U4S3

The OpuC transporter selective for glycine betaine > choline, acetylcholine, carnitine and proline betaine (contains tandem cystathionine-β-synthase (CBS) domains in the ABC component of OpuC that are required for osmoregulatory function (Chen and Beattie, 2007)).
OpuCA, CB, CC of Pseudomonas syringae
OpuCC (R) (Q87WH3)
OpuCB (M) (Q87WH4)
OpuCA (C) (Q87WH5)

The glycine betaine uptake porter, GbpABCD (Saum et al., 2009).
GbpABCD of Methanosarcina mazei
GbpA (R) (Q8Q040)
GbpB (M) (Q8Q043)
GbpC (M) (Q9Q042)
GbpD (C) (Q8Q041)

The CbcWV/CbcX (choline)/CaiX (carnitine)/BetX (betaine) transporter with 3 binding receptors for distinct quaternary ammonium compounds. Only the ligand-bound receptor binds to the transporter with high affinity (Chen et al., 2010; Thomas et al., 2010).

CbcWV/CbcX/CaiX/BetX of Pseudomonas aeruginosa
CbcW (M) (Q9HTI7)
CbcV (C) (Q9HTI8)
CbcX (R) (Q9HTI6)
CaiX (R) (Q9HTH6)
BetX (R) (Q9HZ04)

High affinity (2mμM) choline uptake porter. The choline binding receptor exhibits a venus fly trap mechanism of substrate binding. (ChoX binds acetyl choline and betaine with low affinity (80μM and 470μM, respectively) (Aktas et al., 2011) (most similar to 3.A.1.12.7)

ChoVWX of Agrobacterium tumefaciens 
ChoX (R) (Q7CXG0)
ChoW (M) (Q7CXG1)
ChoV (C) (A9CI32)

OsmU (OsmVWXY) transporter for glycine betaine and choline-O-sulfate uptake. Induced by osmotic stress (0.3M NaCl) (Frossard et al., 2012).

OsmU or OsmVWXY of Salmonella enterica 
OsmV (STM1491) (C) (Q8ZPK4)
OsmW (STM1492) (M) (Q8ZPK3)
OsmX (STM1493) (R) (Q8ZPK2)
OsmY (STM1494) (M) (Q8ZPK1) 

Putative osmoprotectant (glycine/betaine/choline) uptake transporter, YehWXYZ.  Induced by osmotic stress and growth into the stationary phase; under RpoS (σS) control (Ibanez-Ruiz et al. 2000; Checroun and Gutierrez 2004).  YehZ is also called OsmF.

YehWXYZ of E. coli
YehW (M) 243 aas
YehX (C) 308 aas
YehY (M) 385 aas
YehZ or OsmF (R) 305 aas
3.A.1.13:  The Vitamin B12 Uptake Transporter (B12T) Family (Similar to 3.A.1.14)

Vitamin B12 porter. The 3-D structure of BtuCDF has been solved to 2.6 Å (Hvorup et al., 2007). The conformational transition pathways of BtuCD has been revealed by targeted molecular dynamics simulation (Weng et al., 2012). Asymmetric states of BtuCD are not discriminated by its cognate substrate binding protein BtuF (Korkhov et al., 2012).  ATP hydrolysis occurs at the nucleotide-binding domain (NBD) dimer interface, whereas substrate translocation takes place at the translocation pathway between the TM subunits, which is more than 30 angstroms away from the NBD dimer interface.  Hydrolysis of ATP appears to facilitate substrate translocation by opening the cytoplasmic end of translocation pathway (Pan et al. 2016).

BtuCDF of E. coli
BtuC (M)
BtuD (C)
BtuF (R)

Putative cobalamin (vitamin B12) uptake porter, BtuFCD (Rodionova et al. 2015).

BtuFCD of Chloroflexus aurantiacus
BtuF (R; 1 TMS)
BtuC (M; 9 TMSs)
BtuD (C; 0 TMSs)
3.A.1.14:  The Iron Chelate Uptake Transporter (FeCT) Family (Similar to 3.A.1.13 and 3.A.1.15)

Iron (Fe3+) or ferric-dicitrate porter (Braun and Herrmann, 2007)
FecBCDE of E. coli
FecB (R)
FecC (M)
FecD (M)
FecE (C)

Iron (Fe3+)-enterobactin porter

FepBCDG of E. coli
FepB (R) (C8U2V6)
FepC (C) (P23878)
FepD (M) (P23876)
FepG (M) (P23877)

Iron (Fe3+)-hydroxamate (ferrichrome, coprogen, aerobactin, ferrioxamine B, schizakinen, rhodotorulic acid) porter, albomycin porter
FhuBCD of E. coli
FhuB (M-M; 20 TMSs; 10+10)
FhuC (C)
FhuD (R)

Iron-chrysobactine porter
CbrABCD of Erwinia chrysanthemi
CbrA (R)
CbrB (M)
CbrC (M)
CbrD (C)

Heme (hemin) uptake porter. The receptor, HmuT, binds two parallel stacked heme molecules, and two are transported per reaction cycle (Mattle et al., 2010).

HmuTUV of Yersinia pestis
HmuT (R) (Q56991)
HmuU (M) (Q56992)
HmuV (C) (Q56993)

The iron-vibriobactin/enterobactin uptake porter
ViuPDGC of Vibrio cholerae
ViuP (R)
ViuD (M)
ViuG (M)
ViuC (C)

Iron (Fe3+)-hydroxamate porter (transports Fe3+-ferrichrome and Fe3+-ferrioxamine B with FhuD1, and these compounds plus aerobactin and coprogen with FhuD2).  FhuB may function with FhuG (A6QEV8) together with FhuD2 to form a ferrichrome transporter where FhuB and FhuG have conserved arginine residues (R71 and R61, respectively) that form essential salt bridges with FhuD2 (Vinés et al. 2013).

FhuBCD1D2 of Staphylococcus aureus
FhuB (M)
FhuC (C)
FhuD1 (R)
FhuD2 (R)

The iron-vibrioferrin uptake porter (Tanabe et al., 2003)
PvuBCDE of Vibrio parahaemolyticus
PvuB (R) (BAC16540)
PvuC (M) (BAC16541)
PvuD (M) (BAC16542)
PvuE (C) (BAC16543)

The Corrinoid porter, BtuCDE (Woodson et al., 2005)
BtuCDE of Halobacterium sp. strain NRC-1
BtuC (M) (AAG19698)
BtuD (C) (NP_444218)
BtuE (R) (AAG19697)

The heme porter, Shp/SiaABC (HtsABC). Shp is a cell surface heme binding protein that transfers the heme directly to HstA (Nygaard et al., 2006). The crystal structure of the heme binding domain of Shp has been solved (Aranda et al., 2007). HtsABC is required for the uptake of staphyloferrin A (Beasley et al. 2009). The Shp cell surface heme receptor feeds iron-heme to the transporter in preparation for uptake (Sun et al. 2010; Ouattara et al., 2010). 

Shp/HtsABC of Streptococcus pyogenes
Shp (R1) (291 aas; Q1J548)
HtsA (R2) (294 aas; Q99YA2)
HtsB (M) (340 aas; Q99YA3)
HtsC (C) (278 aas; Q99YA4)

The molybdate/tungstate ABC transporter, MolABC.  For MolC; HI1470(C)/MolB; HI1471(M), the 3D structure is known at 2.4 Å resolution; Pinkett et al., 2007).  MolA binds to MolBC with low affinity (50 - 100μM), forming a transient complex that is stabilitzed by ligand binding (Vigonsky et al. 2013).

MolABC of Haemophilus influenzae
MolC; HI1470 (C) (Q57399)
MolB; HI1471 (M; 10 TMSs; type II fold) (Q57130)
MolA; HI1472 (R) (E3GUW2)

Desferrioxamine B uptake porter, DesABC (Barona-Gomez et al., 2006)

DesABC of Streptomyces coelicolor
DesA (R) (1 TMS) (Sco7499; Q9L178)
DesB (M-M) (18 TMSs; 9 9 TMSs) (Sco7498; Q9L179)
DesC (C) (0 TMSs) (Sco7400; Q9L177)

Ferric iron-coelichelin uptake porter, CchCDEF (Barona-Gomez et al., 2006).

CchCDEF of Streptomyces coelicolor
CchC (M) (Sco0497) (Q9RK09)
CchD (M) (Sco0496) (Q9RK10)
CchE (C) (Sco0495) (Q9RK11)
CchF (R) (Sco0494) (Q9RK12)

The Fe3+ /Fe3+ferrichrome/Fe3+heme uptake porter; SiuABDG (FTSABCD) (Montañez et al., 2005; Hanks et al. 2005; Li et al. 2013).  A similar system has been characterized in S. iniae (Wang et al. 2013).

SiuABDG (FtsABCD) of Streptococcus pyogenes
SiuA; FtsA (C) (Q9A197)
SiuD; FtsB (R) (Q9A199)
SiuB; FtsC (M) (Q9A198)
SiuG; FtsD (M) (Q06A41) 

Uptake transporter for the catecholic trilactone (2, 3-dihydroxybenzoate-glycine-threonine)3 siderophore bacillibactin (for ferric iron scavenging), FeuABC (Gaballa and Helmann, 2007; Miethke et al., 2006).

FeuABC of Bacillus subtilis
FeuA (R) (P40409)
FeuB (M) (P40410)
FeuC (M) (P40411)

The heme-specific uptake porter, HemTUV (Létoffé et al., 2008).

HemTUV of Serratia proteamaculans
HemT (R) - (A8GDS8)
HemU (M) - (A8GDS7)
HemV (C) - (A8GDS6)

Heme acquisition ABC uptake transporter, IsdDEF (Liu et al., 2008)
IsdDEF of Staphylococcus aureus
IsdD (?) (358aas, 2TMSs) (Q5HGV2)
IsdE (R) (295aas, 1TMS) (Q7A652)
IsdF (M) (273aas; 8TMSs) (Q7A651)

The heme uptake porter, ShuTUV (Burkhard and Wilks, 2008). Transports a single heme per reaction cycle (Mattle et al., 2010). (3-d structure of ShuT is known (2RG7).

ShuTUV of Shigella dysenteriae
ShuT(R) (Q32AX9)
ShuU(M) (Q32AY2)
ShuV(C) (Q32AY3)

Heme uptake porter, HugBCD (Villarreal et al., 2008); also called HmuTUV.
HugBCD of Plesiomonas shigelloides
HugB (R) (Q93SS3)
HugC (M) (Q93SS2)
HugD (C) (Q93SS1)

Heme-iron (hemin) utilization transporter BhuTUV ( Brickman et al., 2006; Vanderpool and Armstrong, 2004).  The crystal structures of BhuUV with or without the periplasmic haem-binding protein BhuT have been solved (Naoe et al. 2016). The TMSs show an inward-facing conformation, in which the cytoplasmic gate of the haem translocation pathway is completely open. Since this conformation is found in both the haem- and nucleotide-free form, the structure of BhuUV-T provides the post-translocation state and the missing piece in the transport cycle of type II importers.

BhuTUV of Bordetella pertussis
BhuT (R) (Q7VSQ6)
BhuU (M) (Q7W024)
BhuV (C) (Q7W025)

The heme uptake porter, PhuTUV (transports one heme per reaction cycle) (Mattle et al., 2010).

PhuTUV of Pseudomonas aeruginosa
PhuT (R) (Q9HV90)
PhuU (M) (O68878)
PhuV (C) (O68877)

The putative ferric iron-desferrioxamine E uptake porter, DesEFGH.  The DesE binding receptor has been characterized (Barona-Gómez et al. 2006).  The remaining three (desFGH) genes cluster together without a gene encoding a receptor (R).  They are believed to function with DesE based on sequence similarity and phylogenetic analyses (Getsin et al., 2013).

DesEFGH of Streptomyces coelicolor
DesE (Sco2780) (R) (349 aas; 1 TMS) (Q9L074)
DesF (Sco1785) (C) (301 aas; 0 TMSs) (Q9S215)
DesG (Sco1786) (M) (375 aas; 9 TMSs) (Q9S214)
DesH (Sco1787) (M) (345 aas; 9 TMSs) (Q9S213)
3.A.1.15:  The Manganese/Zinc/Iron Chelate Uptake Transporter (MZT) Family (Similar to 3.A.1.12, 3.A.1.14 and 3.A.1.16)

Manganese (Mn2+) porter
MntABC of Synechocystis 6803
MntA (C)
MntB (M)
MntC (R)

Manganese (Mn2+) and zinc (Zn2+) porter
ScaABC of Streptococcus gordonii
ScaA (R)
ScaB (M)
ScaC (C)

Zinc (Zn2+) porter, AdcABC/AII

AdcABC of Streptococcus pneumoniae
AdcA (R)
AdcB (M)
AdcC (C)
AdcAII (Lmb) (R)

Iron and manganese porter
YfeABCD of Yersinia pestis
YfeA (R)
YfeB (C)
YfeC (M)
YfeD (M)

Zinc (Zn2+) porter.  Required for Zn2+ homeostasis and virulence of Salmonella enterica (Ammendola et al., 2007).

ZnuABC (YebLMI) of E. coli
ZnuA (R)
ZnuC (C)
ZnuB (M)

Iron (Fe2+)/Zinc (Zn2+)/Copper (Cu2+) porter
MtsABC of Streptococcus pyogenes
MtsA (R)
MtsB (C)
MtsC (M)

Manganese (Mn2+) (Km=0.1 μM) and iron (Fe2+) (5 μM) porter (inhibited by Cd2+ > Co2+ > Ni2+, Cu2+) (most similar to YfeABCD of Yersinia pestis (TC #3.A.1.15.4)). Important for virulence in Salmonella (Karlinsey et al., 2010).

SitABCD of Salmonella typhimurium
SitA (R)
SitB (C)
SitC (M)
SitD (M)

Manganese (Mn2+), zinc (Zn2+) and possibly iron (Fe2+) uptake porter, TroABCD (Hazlett et al., 2003).  Transcription of the operon is controlled by the Mn2+-activated (not Zn2+- or Fe2+-activated) repressor, TroR (153 aas, acc# F7IW50;) TroR contains a metal-binding domain homologous to the YtgC-R protein (3.A.1.15.12) which has the membrane domain of this ABC transporter (N-terminus) fused to the repressor domain (C-terminus) (Liu et al. 2013).  TroA (Tromp1), the periplasmic metal binding protein, was originally reported to be an outer membrane porin (Zhang et al. 1999), but this proved to be incorrect.

TroABCD of Treponema pallidum
TroA (R) P96116
TroB (C) P96117
TroC (M) P96118
TroD (M) P96119

Manganese (Mn2+) and Iron (Fe2+) porter, SitABCD (Davies and Walker, 2007)
Sit ABCD of Sinorhizobium meliloti
SitA (R) - (Q92LL5)
SitB (M) - (Q92LL4)
SitC (C) - (Q92LL3)
SitD (M) - (Q92LL2)

The Mn2+/Zn2+ transporter MntABC (KB of Mn2+ and Zn2+ is 0.1μM which bind with equal affinity to the same site (Lim et al., 2008)
MntABC of Neisseria meningitidis:
MntA (C) (A1IQK5)
MntB (M) (A1IQK4)
MntC (R) (Q5FA63)

The zinc uptake porter, YcdHI-YceA (Gaballa et al., 2002).
YcdHI-YceA of Bacillus subtilis
AdcA (YcdH) (R) (O34966)
AdcC (YcdI) (C) (O34946)
AdcB (YceA) (M) (O34610)

Metal ion (probably iron) uptake permease , YtgABC-RD. The third gene in the ytg operon is fused, the N-terminal membrane domain being fused to the C-terminal transcriptional regulator homologous to the diphtheria toxin repressor, DtxR. These two domains may be proteolitically processed yielding the two active proteins (Thompson et al. 2012). 

Chlamydiae/Verrucomicrobia group
YtgABC-RD of Chlamydia trachomatis 
YtgA (R) (O9S529)
YtgB (C) (084071)
YtgC-R (M-R) (084072)
YtgD (M) (084073) 

The ZnuA18/ZnuA08/ZnuB/ZnuC zinc (Zn2+) uptake system (Hudek et al. 2013).  ZnuB (M) and ZnuC (C) can function with either of two zinc ion receptors, ZnuA18 (R) which is encoded in the znuACB operon, and ZnuA08 (R) which is encoded elsewhere on the chromosome.  ZnuA18 is more efficient that ZnuA08 in promoting uptake (Hudek et al. 2013).

Zn2+ uptake system of Nostoc punctiforme
ZnuA18 (R) (B2IWS9)
ZnuA08 (R) (B2J0B7)
ZnuB (M) B2IWT1)
ZnuC (C) (B2IWT2)

High affinity Mn2+ uptake complex, PsaABC (Lisher et al. 2013).

PsaABC of Streptococcus pneumoniae
PsaA (R; 309 aas)
PsaB (C; 240 aas)
PsaC (M; 282 aas)

High affinity Mn2+ uptake complex, MntABC.  The 3-d structure of MntC has been  solved to 2.2Å resolution (Gribenko et al. 2013).

MntABC of Staphylococcus aureus 
MntA of 247 aas (C)
MntB of 278 aas (M)
MntC of 309 aas (R)

ZnuABC Zinc/Manganese/iron uptake porter

ZnuABC of Leptospira sp.
ZnuA (R) 345 aas
ZnuB (M) 275 aas
ZnuC C) 210 aas

ZnuABC Zinc/Manganese/Iron uptake porter

  ZnuABC of Bdellovibrio bacteriovorus
ZnuA (R)
ZnuB (M)
ZnuC (C)
3.A.1.16:  The Nitrate/Nitrite/Cyanate Uptake Transporter (NitT) Family (Similar to 3.A.1.12 and 3.A.1.17)

Nitrate/nitrite porter
NrtABCD of Synechococcus sp. (PCC 7942)
NrtA (R)
NrtB (M)
NrtC (C)
NrtD (C)

Bispecific cyanate/nitrite transporter (functions in both cyanate and nitrite assimilation; Maeda and Omata, 2009).
CynABD of Synechococcus PCC7942
CynA (R)
CynB (M)
CynD (C)

Bicarbonate porter (activated by low [CO2] mediated by CmpR; (Nishimura et al., 2008))
CmpABCD of Synechococcus sp.
CmpA (R)
CmpB (M)
CmpC (C)
CmpD (C)

Nitrate uptake system, NrtABCD (Frías et al., 1997)

NrtABCD of Anabaena (Nostoc) sp. PCC 7120
NrtA (R) (Q44292)
NrtB (M) (Q8YRV7)
NrtC (C-R) (Q8YRV8)
NrtD (C) (Q8YZ25)
3.A.1.17:  The Taurine Uptake Transporter (TauT) Family (Similar to 3.A.1.12 and 3.A.1.16)

Taurine (2-aminoethane sulfonate) porter
TauABC of E. coli
TauA (R)
TauB (C)
TauC (M)

Aromatic sulfonate porter
SsuABC of Pseudomonas putida
SsuA (R)
SsuB (C)
SsuC (M)

Putative hydroxymethylpyrimidine transport system, ThiXYZ (Rodionov et al., 2002). Regulated by TPP (thiamin) riboswitch. Potentially takes up a pyrimidine moiety of thiamin.

ThiXYZ of Haemophilus influenzae
ThiZ (C) (P44656)
ThiX (M) (Q57306)
ThiY (R) (P44658)

The taurine uptake system, TauABC (Krejcík et al., 2008).

TauABC of Neptuniibacter caesariensis
TauA (R) (Q2BM68)
TauB (C) (Q2BM69)
TauC (M) (Q2BM70)

The phthalate uptake system, OphFGH (Chang et al. 2009).
OphFGH of Burkholderia capacia
OphF (R) (C0LZR7)
OphG (M) (C0LZR8)
OphH (C) (C0LZR9)

Putative hydroxymethylpyrimidine transport system, ThiXYZ (Rodionov et al., 2002). Regulated by TPP (thiamin) riboswitch. Potentially takes up a pyrimidine moiety of thiamin. ThiY is homologous to the yeast THI5 HMP-P synthase (P43534) (Bale et al., 2010).

ThiXYZ of Pasteurella multocida
ThiX (M) (Q9CLG9)
ThiY (R) (Q9CLH1)
ThiZ (C) (Q9CLG8)

Putative riboflavin transport system, RibXY. Regulated by FMN riboswitch (Vitreschak et al. 2002)

RibXY of Roseiflexus castenholziiRibX (M) (A7NLS3)RibY (R) (A7NLS2)

Putative thiamine transport system, ThiXYZ (Rodionov et al., 2002). Regulated by TPP (thiamin) riboswitch.

ThiXYZ of Roseiflexus castenholziThiX (M) (A7NH43)ThiY (R) (A7NH44)ThiZ (C) (A7NH45)

Uncharacterized membrane protein of 733 aas and 12 TMSs. The other constituents of the system have not been identified.

UP of Chondrus crispus

Aliphatic sulfonate (alkanesulfonate) import permease, SsuABC (YcbOEM) and is regluated by the transcriptional activator, Cbl (van Der Ploeg et al. 1999; Eichhorn and Leisinger 2001).

SsuABC of E. coli
SsuA (YcbO), (R), 319 aas
SsuB (YcbE), (C), 255 aas
SsuC (YcbM), (M), 263 aa  

Putative ABC transporter specific for riboflavin, RibXYZ. RibY is called "NMT1/THI5 like domain protein" (Anderson et al. 2015).

Riboflavin transporter, RibXYZ, of Thermobaculum terrenum
RibY, 1 N-terminal TMS; R (D1CEG8)
RibX, 7 TMSs, M (D1CEG9)
RibZ, unknown

Sulfonate and sulfonate ester uptake transporter, SsuABC (Koch et al. 2005).

SsuABC of Corynebacterium glutamicum
SsuA (R)
SsuB (C)
SsuC (M)

Putative thiamine (vitamin B1)-specific transporter, ThiXYZ (Rodionova et al. 2015).

ThiXYZ of Chloroflexus aurantiacus
ThiX, (M, 5 TMSs) (A9WDS0)
ThiY, (R, 1 TMS) (A9WDR9)
ThiZ, (C, 0 TMSs) (A9WDR8)

Riboflavin uptake porter, RibXY (RibX, 168 aas and 6 TMSs; RibY, 351 aas) (Gutiérrez-Preciado et al. 2015).

RibXY of Chloroflexus aurantiacus
3.A.1.18:  The Cobalamin Precursor/Cobalt (CPC) Family

The putative cobalamin precursor/cobalt (CPC) transporter family includes proteins of about 190 aas with 4-6 TMSs. These proteins are encoded in operons that are subject to regulation by vitamin B12 (Rodionov et al. 2003).


Putative ECF transporter, EcfSTA; regulated by a cobalamin riboswitch.

EcfSTA of Roseifluxes sp. RS-1
EcfS (S) (A5UXW2)
EcfT (T) (A5UXW1)
EcfA (A) (A5UXW0)

Putative Co2+ ECF transporter, EcfSTA

EcfSTA of Gloeobacter violaceus
EcfS (S) (Q7NIY0)
EcfT (T) (Q7NIX9)
EcfA (A) (Q7NIX8)

Putative Co2+ ECF transporter, EcfSTA

EcfSTA of Syntrophobotulus glycolicus
EcfS (S) (F0SWZ4)
EcfT (T) (F0SWZ5)
EcfA (A) (F0SWZ6)
3.A.1.19:  The Thiamin Uptake Transporter (ThiT) Family (Most similar to 3.A.1.10, 3.A.1.6 and 3.A.1.8 in that order)

Thiamin, thiamin monophosphate and thiamin pyrophosphate porter. The 2.25 Å structure of ThiB (TbpA) has been solved (Soriano et al., 2008).
ThiBPQ of Salmonella typhimurium (functionally characterized and partially sequenced) and E. coli (fully sequenced but not functionally characterized)
ThiB; TbpA (R)
ThiP; YabK (M)
ThiQ; YabJ (C)

The thiamine pyrophosphate (TPP) uptake porter (Bian et al., 2011).

TPP transporter of Treponena denticola TDE0143/TDE0144/TDE0145
TDE0143 (R) (Q73RE6)
TDE0144 (M) (Q73RE5)
TDE0145 (C) (Q73RE4)

ABC transporter of unknown function. The three genes encoding this system are adjacent to a gene homologous to a mycothiol maleylpyruvate isomerase.

ABC transporter of Streptomyces hygroscopicus
Periplasmic binding protein (R) (H2JXL4)
Permease (M) (H2JXL5)
ATPase (C) (H2JXL6)

The putative sulfate/thiosulfate transporter, YnjBCD. YnjB has 12 TMSs. The three genes encoding this system are adjacent to one encoding a thiosulfate:sulfur transferase or a rhodanese (B7L6N1).  Also considered to be a thiamine transporter (Moussatova et al. 2008).

YnjBCD of E. coli
YnjB (possible receptor, R) (B7L6M8)
YnjC (M) (B7L6M9)
YnjD (C) (B7L6N0)

Putative ABC transporter

ABC transporter of Deinococcus deserti
Permesae (M) (C1CWI2)
ATPase (C) (C1CWI3)
Possible periplasmic receptor (R) (C1CWI4)
3.A.1.20:  The Brachyspira Iron Transporter (BIT) Family (Most similar to 3.A.1.6, 3.A.1.8 and 3.A.1.11)

The iron transporter, BitABCDEF (Dugourd et al. 1999).

BitABCDEF of Brachyspira (Serpulina) hyodysenteriae
BitA (R)
BitB (R)
BitC (R)
BitD (C)
BitE (M)
BitF (M)

Hexose-phosphate transporter.  Transports glucose-6-phosphate (Km = 0.3 υM) and fructose-6-phosphate (1.3 υM).  Sugar phsophates can be used as both carbon and phosphate sources (Moisi et al. 2013).

Sugar phosphate uptake permease, FbpABC of Vibrio cholerae
FbpA 344 aas (R) (Q9KLQ7)
FbpB 700 aas (M) (Q9KLQ6)
FbpC 351 aas (C) (Q9KLQ5)

Iron (Fe3+) uptake porter, AfuABC (FbpABC) (Chin et al. 1996).

AfuABC (FbpABC) of Actinobacillus pleuropneumoniae
AfuA (R)
AfuB (M)
AfuC (C)


Putative glycerol phosphodiester uptake transporter.  The three genes encoding this system are in an operon with a gene encoding a glycerophosphodiester phosphodiesterase, providing the evidence that this transporter might function to take up such substrates.

Putative glycerol phosphodiester uptake porter of Bdellovibrio exovorus A11Q_2445 (R), 344 aas and 1 TMS
A11Q_2446 (M), 541 aas and 12 TMSs
A11Q_2447 (C), 245 aas and 0 TM  
3.A.1.21:  The Siderophore-Fe3+ Uptake Transporter (SIUT) Family

The Fe3+-Yersiniabactin uptake transporter, YbtPQ (Brem et al., 2001; Fetherston et al., 1999)
YbtPQ of Yersinia pestis
YbtP (M-C)
YbtQ (M-C)

The Fe3+-carboxymycobactin transporter, IrtAB (Rodriguez and Smith, 2006). IrtA contains an FAD-binding domain (Ryndak et al., 2010).

IrtAB of Mycobacterium tuberculosis
IrtA (M-C) (P63391)
IrtB (M-C) (P63393)
3.A.1.22:  The Nickel Uptake Transporter (NiT) Family

Nickel (Ni2+) porter
CbiKMQO of Actinobacillus pleuropneumoniae
CbiK (R)
CbiM (M)
CbiQ (M)
CbiO (C)
3.A.1.23:  The Nickel/Cobalt Uptake Transporter (NiCoT) Family

Nickel (Ni2+) porter (Chen and Burne, 2003)

UreMQO of Streptococcus salivarius
UreM (M) (Q79CJ1)
UreQ (M) (Q79CJ0)
UreO (C) (Q79CI9)

Putative cobalt (Co2+) porter (Chen and Burne, 2003)
CbiMQOK of Clostridium acetobutylicum
CbiM (M) (AAK79333)
CbiQ (M) (AAK79335)
CbiO (C) (AAK79336)
CbiK (Auxiliary?) (AAK79334)

Cobalt (Co2+) porter 

Cbi M(N)OQ of Geobacter sulfurreducens 
Cbi M(N) (D7AE13)
CbiO (D7AE10)
CbiQ (D7AE11) 

The NikM2 (230 aas; 5 TMSs)/NikN2 (110 aas; 2 TMSs) pair is part or all of a nickel transporter.  The crystal structure of NikM2 is known (PDB 4M5C; 4M58).  It possesses an additional TMS at its N-terminal region not present on other ECF transporter of known structure, resulting in an extracellular N-terminus. The highly conserved N-terminal loop inserts into the center of NikM2 and occludes a region corresponding to the substrate-binding sites of the vitamin-specific S component. Nickel binds to NikM2 by coordination to four nitrogen atoms in Met1, His2 and His67. These nitrogens form a square-planar geometry, similar to that of the metal ion-binding sites in the amino-terminal Cu2+- and Ni2+-binding (ATCUN) motif (Yu et al. 2013).  Constituents other than NikN2 and NikM2 are not known but may be required for activity (T. Eitinger, personal communication).

NikM2N2 of Thermoanaerobacter tengcongensis  (Caldanaerobacter subterraneus subsp. tengcongensis)

Putative Ni2+/Co2+ uptake porter, NikMNOQ (Yu et al. 2013).

NikMNOQ of Thermoanaerobacter tengcongensis

Cobalt (Co2+) porter (Rodionov et al., 2006).  CbiMN is a bipartite S-subunit with 8 TMSs (Siche et al. 2010).

CbiMNOQ of Salmonella typhimurium
CbiM (M) (Q05594)
CbiN (Essential auxillary subunit) (Q05595)
CbiO (C) (Q05596)
CbiQ (M) (Q05598)

Ni2+, Co2+ uptake transporter, NikMNOQ (subunit sizes: NikMN, 347 aas, 9 TMSs; NikQ, 284 aas, 4 TMSs; NikO, 254 aas, 0 TMS.  NikMN can take up Ni2+ without NikQ or NikO (Kirsch and Eitinger 2014).

NikMNQO of Rhodobacter capsulatus
NikMN (M; 9 TMSs)
NikQ  (M; 5 TMSs)
NikO (C; 0 TMSs)

Ni2+/Co2+ uptake porter, CbiMNOQ (CbiM, 222 aas, 5 TMSs; CbiN, 103 aas, 2 TMSs; CbiO, 280 aas, 0 TMSs; CbiQ, 244 aas, 5 TMSs).  CbiMN can take up Ni2+ without CbiO or CbiQ (Kirsch and Eitinger 2014).

CbiMNOQ of Rhodobacter capsulatus
CbiM (M)
CbiN (M)
CbiO (C)
CbiQ (M)  
3.A.1.24:  The Methionine Uptake Transporter (MUT) Family (Similar to 3.A.1.3 and 3.A.1.12)

The L- and D-methionine porter (also transports formyl-L-methionine) (Zhang et al., 2003). The 3.7A structure of MetNI has been solved. An allosteric regulatory mechanism operates at the level of transport activity so increased intracellular levels of the transported ligand stabilize an inward-facing, ATPase-inactive state of MetNI to inhibit further ligand translocation into the cell (Kadaba et al., 2008).  The structure of an MetQ homologue in Neisseria meningitidis has been solved at 2.25 Å resolution revealing a bound methionine in the cleft between the two domains (Yang et al. 2009).

MetNIQ (abc-yaeE-yaeC) of E. coli
MetN (C) AAC73310
MetI (M) AAC73309
MetQ (R) AAC73308

The L- and D-methionine porter (also transports methionine sulfoxide (Hullo et al., 2004)
MetNPQ (YusCBA) of Bacillus subtilis
MetN (C) CAB15264
MetP (M) CAB15263
MetQ (R) CAB15262

The methionine porter, AtmBDE (Sperandio et al., 2007)
AtmBDE of Streptococcus mutans
AtmB (R) (Q8K8K9)
AtmD (C) (Q8K8K8)
AtmE (M) (Q8K8K7)

L-Methionine uptake porter, MetQNI
MetQNI of Corynebacterium glutamicum
MetQ (R) (Q8NSN1)
MetN (C) (Q8NSN2)
MetI (M) (Q8NSN3)

L-Histidine uptake porter, MetIQN (Johnson et al. 2008)

MetIQN of Pseudomonas aeruginosa
MetI (M) (Q9HT69)
MetQ (R) (Q9HT68)
MetN (C) (Q9HT70)

Putative peptide transporter, PepABC.  The three components of this system are encoded in an operon with a gene encoding a peptidase (Q04MS7), providing the only tentative evidence for the substrate transported.  However the similarity with the methionine transporter of Streptococcus mutans (TC# 3.A.1.24.3) suggests that this porter may also be a methionine uptake porter.

PepABC of Streptococcus pneumoniae
PepA (R; 284 aas)
PepB (C; 353 aas)
PepC (M; 230 aas)
3.A.1.25:  The Biotin Uptake Transporter (BioMNY) Family

The biotin uptake porter (binding receptor lacking) (see also the VUT or ECF family; BioY; 2.A.88.1.1) (Rodionov et al., 2006; Hebbeln et al., 2007). BioN (the EcfT component of the biotin transporter) appears to be required for intramolecular signaling and subunit assembly (Neubauer et al., 2009). The Ala-Arg-Ser and Ala-Arg-Gly signatures in BioN are coupling sites to the BioM ATPases (Neubauer et al., 2011).  Subunit stoicheometries have been estimated with the prediction that there are oligomeric forms of BioM and BioY in the BioMNY complex (Finkenwirth et al. 2010).

BioMNY of Rhizobium etli
BioM (C) (226 aas; 0 TMSs; Q6GUB2)
BioN (M) (202 aas; 5 TMSs; Q6GUB1)
BioY (M) (189 aas; 6 TMSs; Q6GUB0)

Putative biotin Ecf transporter, EcfSAA'T (function assigned based on genome context analyses). 

Putative Ecf transporter, EcfSAA'T, of Methanospirillum hungatei 
EcfS (M) (Q2FUL6)
EcfA (C) (Q2FUL5)
EcfA' (C) (Q2FUM0)
EcfT (M) (Q2FNH6) 

Putative biotin Ecf transporter, EcfSAA'T (function assigned based on genome context analyses).

The putative EcfSAA'T transporter of Methanocorpusculum labreanum
EcfS (A2SPQ3)
EcfA (A2SPQ4)
EcfA' (A2SPQ5)
EcfT (A2SPQ6) 

The biotin uptake system, BioMNY. The 3-d structure of the EcfS subunit, BioY, at 2.1Å resolution is known (Berntsson et al., 2012). BioY and ThiT from L. lactis show similar N-terminal structures for interaction with the ECF module but divergent C-terminal structures for substrate binding. BioY alone binds biotin but doesn''t transport it (Berntsson et al., 2012).  Ala-Arg-Ser and Ala-Arg-Gly signatures in BioN are probably coupling sites to the two BioM ATPase subunits (Neubauer et al., 2011Neubauer et al., 2011).

BioMNY of Lactococcus lactis 
BioM (A) (A2RI01)
BioN (T) (A2RI03)
BioY (S) (A2RMJ9) 

Biotin/Riboflavin ECF transport system, EcfAA'T/RibU/BioY (Karpowich and Wang 2013). RibU binds riboflavin with high affinity, and the protein-substrate complex is exceptionally stable in solution. The crystal structure of riboflavin-bound RibU reveals an electronegative binding pocket at the extracellular surface in which the substrate is completely buried (Karpowich et al. 2016).

EcfAA''T/RibU/BioY of Thermatoga martima
EcfA (C) (Q9WY65)
EcfA'' (C) (Q9X1Z1)
EcfT (M) (Q9X2I1)
BioY (M) (Q9X1G6)
RibU (M) (Q9WZQ6)

Riboflavin ECF transport system, EcfAA'T/RibU (Karpowich and Wang 2013).

EcfAA'T/RibU of Streptococcus thermophilus 
EcfA (C) (Q5M244)
EcfA' (C) (Q5M243)
EcfT (M) (Q5M245)
RibU (M) (Q5M614)

The riboflavin uptake system, BioMNY.  BioM, EtcA, ATPase, 234 aas;  BioN, EtcT, 190 aas, 5 TMSs; BioY, EtcS, 210 aas, 5 TMSs BioY can also function as a secondary carrier and is therefore listed separately under TC# 2.A.88.1.3.  ATP-dependent conformational changes drive substrate capture and release when BioMNY are together in a complex (Finkenwirth et al. 2015).

RibMNY of Rhodobacter capsulatus
3.A.1.26:  The Putative Thiamine Uptake Transporter (ThiW) Family

The putative thiazole ABC porter (COG4732), ThiW; 718 aas; 5 TMSs; domain order: M-C-C; plus the putative ATPase binding subunit, CbiQ homologue (binding receptor unknown) (Rodionov et al., 2009)

ThiW/CbiQ of Chloroflexus aurantiacus
CbiQ M (T) (A9WGA9)

ThiW homologue/CbiQ homologue (ThiW: 647 aas; M-C-C; 5-6TMSs) (Rodionov et al., 2009)

ThiW/ChiQ of Methanocorpusculum labreanum
CbiQ M (T) (A2SPE9)

ThiW homologue (711 aas; M-C-C) (No known binding receptor) plus a CbiQ homologue (Rodionov et al., 2009)

ThiW/CbiQ homologues of Actinomyces odontolyticus
CbiQ M (T) (A7BAX3)

ThiW/CbiQ homologues (ThiW: 697 aas; M-C-C) (No known binding receptor) (Rodionov et al., 2009)

ThiW/CbiQ homologues of Mycobacterium tuberculosis
ThiW MCC (SAA) (P63399)
CbiQ M (T) (P64997)

ThiW/CbiQ/CbiO homologues (ThiW: 174 aas; 5 putative TMSs).  Possible thiamin uptake porter (Rodionov et al., 2009).

ThiW/CbiQ/CbiO homologues of Roseiflexus castenholzii
ThiW (M) (S) (A7NRF9)
CbiQ (M) (T) (A7NRG1)
CbiO C-C (A-A) (A7NRG0)

The ThiW/CbiQ/CbiO1/CbiO2 homologues (ThiW: 184 aas; 1-6 TMSs) (Rodionov et al., 2009)

ThiW/CbiQ/CbiO1/CbiO2 homologues of Aeropyrum pernix
ThiW M (S) (Q9Y974)
CbiQ M (T) (Q9Y982)
CbiO1 C (A) (Q9Y979)
CbiO2 C (A) (Q9Y977)

The putative hydroxyethyl thiazole (biosynthetic precursor of thiamine) porter, ThiW-EcfA1-A2-EcfT (this is a group II ECF transporter which uses a universal energy-coupling module (EcfA1-EcfA2-EcfT) in many firmicutes; Rodionov et al., 2002).

ThiW-EcfA1-EcfA2-EcfT of Enterococcus faecalis
ThiW (M) (Q830K3)
EcfA1 (C) (Q839D5)
EcfA2 (C) (Q839D4)
EcfT (M) (Q839D3)

Putative biotin Ecf transporter, EcfSAT

Putative Ecf transpoter, EcfSAT, of Archaeoglobus fulgidus 
S-subunit (M) (O29098) 
A-subunit (C) (O29097) 
T-subunit (M) (O29096) 

The folate transporter, FolT/EcfAA''T (The 3-d structure is known to 3.0Å resolution (Xu et al. 2013; 4HUQ).  This transporter uses the same ECF energy coupling complex (AA''T) as 3.A.1.28.2.

FolT/EcfAA'T of Lactobacillus brevis
FolT (M; EcfS subunit) (Q03S56)
EcfA (C) (Q03PY6)
EcfA' (C) (Q03PY7)
EcfT (M) (Q03PY5)

ATP-dependent folic acid uptake porter, FolT/EcfT/EcfA1/EcfA2.  The crystal structure of FolT has been solved to 3.2 Å resolution in substrate-bound and free conformations, revealing a potential gating mechanism (Zhao et al. 2015).

FolT/EcfT/EcfA1/EcfA2 of Enterococcus faecalis
FolT, 182 aas, 5 TMSs
EcfT, 264 aas, 6 TMSs
EcfA1, 279 aas
EcfA2, 289 aas

Putative pantothenate uptake porter, PanT/EcfA/EcfA'/EcfT (Rodionova et al. 2015).

Putative ABC (Ecf) pantothenate transporter of Ktedonobacter racemifer
PanT, (M, substrate binding subunit)
EcfA, (C)
EcfA', (C)
EcfT, (M, transducer subunit)
3.A.1.27:  The γ-Hexachlorocyclohexane (HCH) Family (Similar to 3.A.1.12 and 3.A.1.24)

The γ-hexachlorocyclohexane (γHCH) uptake permease, LinKLMN (most similar to 3.A.1.12.4, the QAT family) (Endo et al., 2007)
LinKLMN of Sphingobium japonicum
LinK (M) (BAF51698)
LinL (C) (BAF51699)
LinM (R) (BAF51700)
LinN (lipoprotein) (BAF51701)

The chloroplast lipid (trigalactosyl diacyl glycerol (TDG)) transporter, Tdg1,2,3 (Lu et al., 2007). Lipids such as mono- and digalactolipids are synthesized in the endoplasmic reticulum (ER) of plant cells and transferred to the thylakoid membranes of chloroplasts. Mutations in an outer chloroplastic envelope protein with 350 aas and 7 putative TMSs in the last 250 residues may catalyze translocation as part of a lipid transfer complex (Xu et al., 2003; Roston et al. 2012).

Tdg 1,2,3 of Arabidopsis thaliana:
Tdg1 (M) (Q8L4R0)
Tdg2 (R) (Q3EB35)
Tdg3 (C) (Q9AT00)

ABC transporter maintaining outer membrane (OM) lipid asymmetry, MlaABCDEF (YrbABCDEF) (Malinverni and Silhavy, 2009). MlaA (VacJ) is a "spreading" protein, essential for Shigella pathogenicity (Suzuki et al., 1994).  The ABC transporter, MlaEFBD, provides energy for maintaining OM lipid asymmetry via the transport of aberrantly localized phospholipids (PLs) from the OM to the inner membrane (IM) (Thong et al. 2016). MlaD forms stable hexamers within the complex, functions in substrate binding with strong affinity for PLs, and modulates ATP hydrolytic activity. MlaB plays critical roles in both the assembly and activity of the transporter.  MlaA forms a complex with OmpC and OmpF in the outer membrane to extract PLs from the outer leaflet of the OM (Chong et al. 2015). MlaA is a monomeric α-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-Å-thick doughnut embedded in the inner leaflet of the OM with a central, amphipathic pore (Abellón-Ruiz et al. 2017). This architecture prevents access of inner leaflet phospholipids to the pore, but allows outer leaflet phospholipids to bind to a pronounced ridge surrounding the channel.

MlaABCDEF of E. coli
MlaA, YrbA, OM lipoprotein component (251aas) (P76506)
MlaB, YrbB cytoplasmic STAS component (97aas) (P64602)
MlaC, YrbC periplasmic binding receptor (R) (211aas) (P0ADV7)
MlaD, YrbD anchored periplasmic binding receptor (R) (183aas) (P64604)
MlaE, YrbE inner membrane permease component (M) (260aas) (P64606)
MlaF, YrbF ATP binding protein (C) (269aas) (P63386)

The cholesterol uptake porter (Mohn et al., 2008). Takes up cholesterol, 5-α-cholestanol, 5-α-cholestanone, β-sitosterol, etc. (It is not established that all of these proteins comprise the system or that other gene products are not involved.)

Cholesterol uptake porter of Rhodococcus jostii
YrbE4A (ro04696; 254aas; 5-6 TMSs) (M) (Q0S7K4)
YrbE4B (ro04697; 283aas; 5 TMSs) (M) (Q0S7K3)
MceE4A (ro04698; 391aas; 1 N-terminal TMS) (R) (Q0S7K2)
MceE4B (ro04699; 338aas; 1 N-terminal TMS) (R) (Q0S7K1)
MlkA (ro01974; 363aas; 0 TMSs) (C) (Q0SFA1)
MlkB (ro01744; 346aas; 0 TMSs) (C) (Q0SD37)  

The Mce/Yrb/Mlk (Mammalian cell entry) ABC-type putative steroid uptake transporter (involved in several aspects of mycobacterial pathogenesis) (Mohn et al., 2008; Joshi et al., 2006).

The Mce transporter of Mycobacterium tuberculosis H37Rv
YrbE4A (M) (254aas; 6 TMSs) (O53546)
YrbE4B (M) (280aas; 5 TMSs) (O53545)
MceA (R) (242aas; 1 TMS) (O06356)
MceB (R) (244aas; 1 TMS) (O07422)
Mlk (C) (Mkl; MceG; 359aas; 0 TMSs) (P63357)
3.A.1.28:  The Queuosine (Queuosine) Family

The putative queuosine uptake transporter, QrtTUVW (Rodionov et al., 2009) (most similar to 2.A.88.2.1)
QrtTUVW of Salmonella enterica su. typh.
QrtT (M) (Q8XGV9)
QrtU (M) (Q8Z3V9)
QrtV (C) (Q8Z3V8)
QrtW (C) (Q8Z3V7)

The folate transporter, FolT/EcfAA''T (The 3-d structure is known to 3.0Å resolution (Xu et al. 2013; 4HUQ)

EcfAA'ST of Lactobacillus brevis
EcfA (C) (Q03PY5)
EcfA' (C) (QO3PY6)
EcfS (M) (QO3NM0)
EcfT (M) (Q03PY7)
3.A.1.29:  The Methionine Precursor (Met-P) Family

The putative methionine precursor/uptake transporter, MtsTUV (T is most similar to 3.A.1.23.2; U is most similar to 2.A.36.7.1 and 3.A.1.14.2; V is most similar to 3.A.1.23.2 and 3.A.1.25.1) (Rodionov et al., 2009)

MtsTUV of Lactobacillus johnsoni
MtsT (M) (Q74I63)
MtsU (C) (Q74I62)
MtsV (M) (Q74I61)
3.A.1.30:  The Thiamin Precursor (Thi-P) Family

The putative thiamin precursor uptake transporter, YkoEDC (Rodionov et al., 2009) (E is most similar to 3.A.1.4.3; D is most similar to 3.A.1.26.2; C is most similar to 3.A.1.23.2).

YkoEDC of Bacillus subtilis
YkoE (M) (O34738)
YkoD (C-C) (O34362)
YkoC (M) (O34572)

Putative thiamin transporter

Potential thiamin transporter of Streptococcus pneumoniae 
Membrane Protein 1 (Q97RJ2) 
ABC ATPase (Q97RS3)
Membrane Protein 2 (Q97RS4) 
3.A.1.31:  The Unknown-ABC1 (U-ABC1) Family

The putative uptake transporter of unknown substrate specificity, HtsTUV (Rodionov et al., 2009)

HtsTUV of Bifidobacterium longum
HtsT (M) (Q8G6E7)
HtsU (M) (Q8G6E8)
HtsV (C-C) (Q8G6E9)

EcfSTAA of unknown function.

EstSTA of Treponema denticola
EstS (Q73JF1)
EstT  (Q73JF2)
EstAA  (Q73JF3)  

RLI1 ATPase of 608 aas and 0 TMSs.  Binds to the ribosome, IF3, IF5 and IF2 to promote preinitiation complex assembly (Dong et al. 2004).

RLI1 of
3.A.1.32:  The Cobalamin Precursor (B12-P) Family

The putative cobalamin precursor uptake transporter, CbrTUV (Rodionov et al., 2009) (CbrT is most similar to 2.A.1.15.1; CbrU is most similar to 3.A.1.26.1 (MFS; e-4); CbrV is most similar to 2.A.53.11.1 and 3.A.1.2.2 (score of 0.035)) (CbrT has 6 putative TMSs; CbrV has 8-10 putative TMSs).
CbrTUV of Streptomyces coelicolor
CbrT (M) (Q9KXJ5)
CbrU (C-C) (Q9KXJ6)
CbrV (M) (Q9KXJ7)

Putative vitamin transporter, EcfSTAA

Putative vitamin transporter of Methanosphaera stadtmanae, EcfSTAA'
EcfT (M) (Q2NFA7)
EcfA-A' (C) (Q2NFA8)
EcfS (M) (Q2NFA9) 

Putative cobalamin (vitamin B12) uptake porter, CbrVUT (Rodionova et al. 2015). The ATPase subunit has not been identified.

CbrVUT of Chloroflexus aurantiacus
CbrV (M, 9 TMSs)
CbrU (R, 1 TMS)
CbrT (M, 6 TMSs)
3.A.1.33:  The Methylthioadenosine (MTA) Family

The putative methylthio adenosine uptake transporter (Rodionov et al., 2009).  MtaTUV (MtaT and MtaU are most similar to 3.A.1.26.1 (ThiW); MtaV is most similar to 3.A.1.25.1 (BioN) and 3.A.1.23.2 (CbiQ)).
MtaTUV of Thermoanaerobacter tengcongensis
MtaT (M) (Q8R9M1)
MtaU (C-C) (Q8R9L8)
MtaV (M) (Q8R9L9)
3.A.1.34:  The Tryptophan (TrpXYZ) Family

The putative tryptophan uptake transporter, TrpXYZ. Regulated by tryptophan-specific T-box (Vitreschak et al. 2008)

TrpXYZ of Streptococcus pyogenes
TrpX (R) (Q99ZY6)
TrpY (M) (Q99ZY4)
TrpZ (C) (Q99ZY3)
3.A.1.101:  The Capsular Polysaccharide Exporter (CPSE) Family

Capsular polysaccharide exporter
KpsMT of E. coli KpsM
KpsM (M) - (P24584)
KpsT (C) - (P24586)

Vi polysaccharide exporter, VexBC (Hashimoto et al, 1993).
VexBC of Salmonella typhi
VexB (M) - (P43109)
VexC (C) - (P43110)

Capsular polysialate exporter, CtrC/D (functions with 1.B.18.2.3 (OMA) and 1.B.4.2.1 (MPA2)) (Larue et al., 2011).

CtrABCD of Neisseria meningitidis
CtrC (M) (B3FHE1)
CtrD (C) (B3FHE0) 
3.A.1.102:  The Lipooligosaccharide Exporter (LOSE) Family

Lipooligosaccharide exporter (nodulation proteins, NodIJ)
NodIJ of Rhizobium galegae
NodJ (M)
NodI (C)
3.A.1.103:  The Lipopolysaccharide Exporter (LPSE) Family

Lipopolysaccharide exporter
RfbAB of Klebsiella pneumoniae
RfbA (M)
RfbB (C)

Heteropolysaccharide O-antigen exporter (Feng et al., 2004). The C-terminal cytoplasmic domain of Wzt (a IgG-like β-sandwich) determines the specificity of the transporter for either O8 or O9a O-PS (Cuthbertson et al., 2007).
Wzm/Wzt of E. coli
Wzm (M) (AAS99164)
Wzt (C) (AAS99165)

ABC transporter required for O-antigen biosynthesis and multicellular development, RfbAB (Guo et al. 1996). Functions with the RfbC glycosyl transferase (TC#4.D.1.3.4). 

RfbAB of Myxococcus xanthus 
RfbA (M) 260aas (Q50862)
RfbB (C) 437aas (Q50863) 

RfbAB lipopolysaccharide exporter (Guo et al. 1996).

RfbAB of Myxococcus xanthus.
RfbA (MXAN_4623) (M)
RfbB (MXAN_4622) (C) 

ABC transporter mediating ethanol tolerance, Slr0977 (M)/Slr0982 (C) (Zhang et al. 2015).  Present in a gene cluster with (lipo)polysaccharide biosynthetic enzymes, so could be a cell surface carbohydrate export system.

Ethanol tolerance transporter of Synechocystis sp. (strain PCC 6803 / Kazusa)

Two component lipopolysaccharide exporter, Wzm/Wzt.  Wzm is the membrane component (265 aas with 6 TMSs) which forms a ring-like large ion conductance channel. The ATPase, Wzt, functions both as the energizer and regulator (Mohammad et al. 2016).

Wzm/Wzt of Pseudomonas aeruginosa

ABC-type polysaccharide/polyol phosphate export systems, permease componentof 262 aas and 6 or 7 TM

Transporter of Acidovorax sp. MR-S7

ABC transporter of 258 aas and 6 TMSs.

Candidatus Moranbacteria
ABC transporter of Moranbacteria bacterium
3.A.1.104:  The Teichoic Acid Exporter (TAE) Family

Teichoic acid exporter, TagGH.  Appears to be present in a large complex with the teichoic acid precursor synthetic enzymes (Formstone et al. 2008).  The substrate may be the diphospholipid-linked disaccharide portion of the teichoic acid precursor (Schirner et al. 2011).  3-d structural studies have been reported (Ko et al. 2016).

TagGH of Bacillus subtilis
TagG (M)
TagH (C)

The teichoic acid precursor exporter, TarGH. May be specific for the diphospholipid linked disaccharide portion of the teichoic acid precursor (Schirner et al. 2011). TarG is the target of a small antimicrobial inhibitor of S. aureus growth (Swoboda et al. 2009). TarGH is a WTA transporter and has been purified and reconstituted in proteoliposomes (Matano et al. 2017). They showed that a new compound series inhibits TarH-catalyzed ATP hydrolysis even though the binding site maps to TarG, near the opposite side of the membrane. These are the first ABC transporter inhibitors to block ATPase activity by binding to the transmembrane domain.

TarGH of Staphylococcus aureus 
TarG (M) (D1GQ18)
TarH (C) (D1GQ17) 
3.A.1.105:  The Drug Exporter-1 (DrugE1) Family

Daunorubicin; doxorubicin (drug resistance) exporter
DrrAB of Streptomyces peucetius
DrrA (C)
DrrB (M)

Oleandomycin (drug resistance) exporter
OleC4-OleC5 of Streptomyces antibioticus
OleC4 (C)
OleC5 (M)

The 4A-4E-O-dideacetyl-chromomycin A3 (biosynthetic precursor of chromomycin) exporter (may also export chromomycin and mithramycin (Menendez et al., 2007).
CmrAB of Streptomyces greseus
CmrA(C) (Q70J75)
CmrB(M) (Q70J76)

The pyoluteorin (a chlorinated polyketide) efflux pump, PltHIJKN (Brodhagen et al. 2005; Huang et al. 2006).

PltHIJKN of Pseudomonas sp. M18:
PltH (336aas; MFP) - (Q4VWD0)
PltI (589aas; C-C) - (Q4VWC9)
PltJ (377aas; M; COG0842; similar to 9.B.74.2 (ABC-2)) - (Q4VWC8)
PltK (372aas; M; The C-terminal hydrophobic half has 5TMSs and is most similar to PltJ, and then to 9.B.74.2, but it is also homologous to 3.A.1.105.2 and 3.A.1.102.1) - (Q4VWC7)
PltN (480aas; OMF) - (Q4VWC6)

AbcG homologue

AbcG homologue of Drosophia melanogaster

The ABC-2-like transporter

ABC-2-like transporter of Dehalococcoides ethenogenes
ABC2 protein (M) (Q3Z8A7)
ATPase (C) (Q3Z8A8)

Putative ABC2 tranport system, SagGHI; may export streptolysin S.

Putative Streptolysin ABC2 tranport system, SagGHI.
SagG (C) (Q9A0K0)
SagH (M) (Q9A0J9)
SagI (M) (Q9A0J8)

ABC-2 transporter.  The two genes encoding this system are adjacent to one encoding an squalene-hopene cyclase that coverts squalene to hopene.  The substrate could therefore be hopene or a hydrocarbon triterpene derivative of it (Racolta et al. 2012).

ABC2 membrane protein (Q7UE57) and ATPase (Q7UE58) of Rhodopirellula baltica

ABC2 membrane proteins (J7ZHK9 and J8A8S6) with ATPase (J8ABC0) transporter

ABC2 transporter of Bacillus cereus

AbcG homologue, ABCH1 of 705 aas and 6 TMSs in a C-M arrangement.  May be involved in steroid or drug efflux (Popovic et al. 2010).  Of the vertbrates, it may be restricted to fish. 

AbcH1 (C-M) of Danio rerio

ABC-2 transporter probably specific for a lantibiotic.  The genes for this system are adjacent to an S2P-M50 peptidase (G0Q3D2), probably involved in pro-lantibiotic processing, as well as a lantibiotic biosynthetic enzyme (G0Q3D1) and a lantibiotic dehydratase (G0Q3D0). 

ABC-2/ATPase of Streptomyces griseus
ABC-2 (M) (G0Q3D4)
ATPase (C) (G0Q3D3)

ABC-2 transporter with ABC ATPase

ABC transporter
ABC2 (M) (F8D412)
ABC ATPase (C) (F8D413) 

SclAB (Sco4359-60) (Gominet et al. 2011).

SclAB of Streptomyces coelicolor.
SclA (C)
SclB (M)

RagAB, involved in both aerial hyphae formation and sporulation (San Paolo et al. 2006).

RagAB of Streptomyces coelicolor.
RagA: Sco4075 (C)
RagB: Sco4074 (M) 

Putative drug exporter, YbhFGRS (Moussatova et al. 2008).

YbhFGRS of E. coli
YbhF, (C) (578 aas)
YbhG, (MFP) (332 aas)
YbhR, (M) (368 aas)
YbhS, (M) ((377 aas)

Putative ABC export system (MDR?), RbbA/YhhJ/YhiI (All three genes are in a single operon; this system may comprise a single ABC exporter with MFP; substrate unknown (Moussatova et al. 2008 and unpublished observations).


RbbA/YhhJ/YhiI of E. coli
RbbA (C-M; 911 aas; C8TJS4)
YhhJ (M; 374 aas; P0AGH1)
YhiI (MFP; 355 aas; P37626)

The putative polyketide drug exporter, YadGH.  May also transport phospholipids, participating in phospholipid trafficking together with the Mla complex. It interacts with MlaABCDEF (TC# 3.A.1.27.3) to preserve outer membrane asymmetry (Malinverni and Silhavy 2009; M. Babu et al., in press).

YadGH of E. coli
YadG (C; 308 aas)
YadH (M, 256 aas)

S2P-M50 protein with C-terminal ABC ATPase domain

M50 peptidase of Catenulispora acidiphila (C7QI22)

Poorly characterized ABC exporter involved in bacterial competitiveness and bioflim morphology, YfiLMN (Stubbendieck and Straight 2017).

YfiLMN of Bacillus subtilis
YfiL (C) 311 aas, 0 TMSs
YfiM (M) 296 aas, 6 TMSs
YfiN (N) 385 aas, 6 TMSs

Putative 5 component ABC exporter with two membrane constituents, two cytoplasmic ATPases, and one membrane fusion protein (truncated at the N-terminus, probably because of an incorrect initiation codon assignment).

5-component ABC exporter of Bdellovibrio bacteriovorus
Q6MLX4 (M)
Q6MLX5 (M)
Q6MLX6 (C)
Q6MLX7 (C)

Uncharacterized ABC transporter with two components, a transmembrane protein with 6 TMSs and an ATPase. The substrate in unknown.

Candidatus Saccharibacteria
ABC system of Candidatus Saccharibacteria bacterium
3.A.1.106:  The Lipid Exporter (LipidE) Family

Phospholipid, LPS, lipid A and drug exporter (flippase from the inner leaflet of the cytoplasmic membrane to the outer leaflet) (Eckford and Sharom, 2010). MsbA also confers drug resistance to azidopine, daunomycin, vinblastine, Hoechst 33342 and ethidium (Reuter et al., 2003). Four x-ray structures, trapped in different conformations, two with and two without nucleotide, have been solved (Ward et al., 2007). They suggest an alternating accessibility mode of transport with major conformational changes.  The mechanism and conformational transitions have been discussed (Moradi and Tajkhorshid 2013).  MsbA is energized both by ATP hydrolysis and the H+ electrochemical gradient (Singh et al. 2016). Mi et al. 2017 used single-particle cryo-electron microscopy to elucidate the structures of lipid-nanodisc- embedded MsbA in three functional states. The 4.2 A-resolution structure of the transmembrane domains of nucleotide-free MsbA revealed that LPS binds deeply inside MsbA at the height of the periplasmic leaflet. Two sub-nanometre-resolution structures of MsbA with ADP-vanadate and ADP revealed a closed and an inward-facing conformation, respectively.

MsbA (M-C) of E. coli

The homodimeric Sav1866 multidrug exporter (transports doxorubicin, verapamil, ethidium, tetraphenylphosphonium, vinblastine and the fluorescent dye, Hoechst 33342; 3-D structure known at 3 Å resolution; Dawson and Locher, 2006; Velamakanni et al., 2008) The empty site opens by rotation of the nucleotide-binding domain whereas the ATP-bound site remains occluded (Jones and George, 2011). Conformational changes induced by ATP-binding and hydrolysis have been proposed (Becker et al. 2010; Becker et al. 2010; Oliveira et al., 2011). 

Sav1866 of Staphylococcus aureus (M-C) 2HYDA/2HYDB (578 aas)

The dimeric multidrug resistance exporter, ABC1/2 (exports the peptide antimicrobials, nisin and polymyxin; (Margolles et al., 2006) (both ABC1 and ABC2 also show striking similarity to family 3.A.1.117).

ABC1/2 of Brevibacterium longum:
ABC-1 (M-C) (ZP_00121338)
ABC-2 (M-C) (ZP_00121339)

The duplicated ABC transporter, CgR_1214 (1247 aas; MC(poorly conserved) MC(well conserved))
CgR_1214 of Corynebacterium glutamicum (MCMC) (A4QD95)

The heterodimeric multidrug efflux pump, SmdAB (exports norfloxacin, tetracycline, 4',6-diamidino-2-phenylindole (DAPI), and Hoechst 33342) (Matsuo et al., 2008).
SmdAB of Serratia marcescens:
SmdA (M-C) (A7VN01)
SmdB (M-C) (A7VN02)

Multidrug efflux pump, Rv0194 (exports & causes resistance to ampicillin, streptomycin and chloramphenicol by 32- to 64-fold and to vancomycin and tetracycline by 4- to 8-fold (Danilchanka et al., 2008)).
Rv0194 of Mycobacterium tuberculosis (MCMC) (O53645)

The Salmochelin/Enterobactin secretory exporter, IroC (Crouch et al., 2008; Müller et al. 2009).

IroC of Salmonella enterica (MCMC) (Q8RMB7)

The heterodimeric BmrC/BmrD (YheHI) MDR transporter.  Transports a wide range of structurally unrelated drugs including doxorubicin, mitoxantrone, ethidium, and hoechst 33342 (Torres et al., 2009). It activates the sensor kinase, KinA, during sporulation initiation (Fukushima et al. 2006). Large scale purification has been achieved (Galián et al. 2011).  It has been reconstituted in giant unilamellar vesicles (Dezi et al. 2013).  It exhibits an asymmetric configuration of catalytically inequivalent nucleotide binding sites. The two-state transition of the TMS domains, from an inward- to an outward-facing conformation, may be driven exclusively by ATP hydrolysis (Mishra et al. 2014).

BmrC/BmrD (YheHI) of Bacillus subtilis
YheH (M-C) (O07549)
YheI (M-C) (O07550)

SoxR regulon single protein ABC exporter, Sco7008, containing an N-terminal membrane domain and a C-terminal ATPase domain (Shin et al. 2011). SoxR responds to extracellular redox-active compounds.  Thus, it is induced in stationary phase during the production of the benzochromanequinone blue-pigmented antibiotic, actinorhodin (Naseer et al. 2014). Possibly an actinorhodin exporter.

Sco7008 (M-C) of Streptomyces coelicolor.

Involved in the export of a molecule required for the autochemotactic process. AbcA integrated permease/ATPase (M-C) protein, MXAN_1286 (Ward et al. 1998). 

MXAN_1286 (M-C) of Myxococcus xanthus.

HlyA/MsbA family transporter of 595 aas.  The gene for this protein is adjacent to and probably in the same operon as that encoding 3.A.1.106.12.  They both have 6 TMSs, so they may together comprise a single heterodimeric system. 

ABC exporter of Gloeobacter violaceus

HlyA/MsbA family transporter of 577 aas.  The gene encoding this protein is adjacent to and in the same operon with that encoding 3.A.1.106.11.  They both have 6 TMSs, so they may together comprise a single heterodimeric system. 

ABC exporter of Gloeobacter violaceus

Multidrug resistance-like ABC exporter, MdlAB; exports peptides of 6 - 21 aas (Moussatova et al. 2008).

MdlAB of E. coli
MdlA (M-C; 590 aas)
MdlB (M-C; 593 aas)

Lipid A exporter homologue of 593 aas and 6 TMSs (N-terminal with a C-terminal ATPase domain.  Essential for acid, salt and thermal tolerance (Matsuhashi et al. 2015).

Exporter of Synechocystis sp. PCC6803

Lipid flippase, PglK or WlaB, of 564 aas and 6 N-terminal TMSs with a C-terminal ATPase domain.  Mediates the ATP-dependent translocation of an undecaprenylpyrophosphate-linked heptasaccharide intermediate across the cell membrane, an essential step during the N-linked protein glycosylation pathway. Transport across the membrane is effected via ATP-driven conformation changes. Most likely, only the polar and charged part of the glycolipid enter the substrate-binding cavity, and the lipid tail remains exposed to the membrane lipids during the transmembrane flipping process (Alaimo et al. 2006; Kelly et al. 2006; Perez et al. 2015).

PglK (M-C) of Campylobacter jejuni

Probable integral membrane protein NMA1777 with 6 TMSs in a 2 + 2 + 2 arrangement, ; function and ATPase unknown.

UP of Klebsiella pneumoniae
3.A.1.107:  The Putative Heme Exporter (HemeE) Family

Putative heme exporter, CcmABC=CycVWZ (Note: CcmC may function independently of CcmAB) (Feissner et al., 2006; Christensen et al., 2007)
CycVWZ of Bradyrhizobium japonicum
CycV (C)
CycW (M)
CycZ (M)

The mitochondrial ABC transporter involved in cytochrome c maturation, CcmA/CcmB. (Note: CcmA is nuclearly encoded while CcmB is mitochondrially encoded) (Rayapuram et al., 2007)
CcmA/CcmB of Arabidopsis thaliana
CcmA (C) (Q9C8T1)
CcmB (M) (P93280)

CcmABCD exporter; CcmD (69aas, 1TMS) is required for the release of CcmE (which binds heme in the periplasm) from CcmABC. CcmC (9.B.14.2.3) is required for the transfer of heme to CcmE in the periplasm (Richard-Fogal et al., 2008) In the presence of heme, CcmC and CcmE form a stable complex (Richard-Fogal & Kranz, 2010) as do CcmE and CcmF (San Francisco and Kranz 2014).

CcmABCD of E. coli
CcmA (C) (Q8XE58)
CcmB (M; 7 TMSs) (P0ABM0)
CcmC (M; 6 TMSs) (P0ABM1)
CcmD (M; 1 TMS) (P0ABM7)

Cytochrome c maturation system (heme exporter?), CcmA/B

CcmAB of Pseudomonas virdiflava
CcmA (C) (K6BJ24)
CcmB (M) (K6BIH6)
3.A.1.108:  The β-Glucan Exporter (GlucanE) Family

β-Glucan exporter
NdvA (M-C) of Rhizobium meliloti
3.A.1.109:  The Protein-1 Exporter (Prot1E) Family

α-Hemolysin exporter. HlyB has an (inactive?) N-terminal C39 peptidase-like domain (Lecher et al., 2011).  It is essential for secretion and interacts with the unfolded HlyA, thereby protecting it from cytoplasmic degradation (Lecher et al. 2012).

HlyB (M-C) of E. coli

Cyclolysin exporter, CyaB (Glaser et al., 1988) (Possesses an N-terminal lysosomal sorting signal within the amino-terminal transmembrane domain; Kamakura et al., 2008).

CyaB (M-C) of Bordetella pertussis

LapA adhesin protein exporter, LapB (Hinsa et al., 2003)
LapB of Pseudomonas putida
LapB (MC) (AAN65800)

The biofilm inducible ABC drug (tobramycin, gentamycin, and ciprofloxacin) resistance pump, PA1875-PA1877 (Zhang and Mah, 2008).  It is specifically induced and is most active when  growing in a biofilm.

PA1875-PA1877 of Pseudomonas aeruginosa
PA1875 (OMF; 425 aas) (Q9I2M2)
PA1876 (ABC; M-C; 723 aas) (Q9I2M1)
PA1877 (MFP; 395 aas) (Q9I2M0)

Probable giant non-fimbrial adhesin, SiiE, exporter, SiiFDC.  SiiF interacts with SiiAB (TC# 1.A.30.4.1) which probably forms a proton channel homologous to that of MotAB (TC# 1.A.30.1.1) and facilitates energization of SiiE export using the pmf (Wille et al. 2013).

SiiFDC of Salmonella enterica
SiiF (M-C; 688 aas; E1WEV2)
SiiD (MFP; 425 aas; E1WEV0)
SiiC (OMF; 439 aas; E1WEU9)

Probable 2646 aa extracellular adhesin (acc# C6BWI7) ABC exporter of 715 aas.  Functions as a type I protein secretion system together with an MFP and an OMF which all are encoded within a single operon together with the adhesin and SiiAB homologues as for TC# 3.A.1.109.5.

ABC/MFP/OMF type I protein secretion system of Desulfovibrio salexigens
ABC protein (M-C; 715 aas; C6BWI0)
MFP protein (430 aas; C6BWj0)
OMF protein (513 aas; C6BWI6)

S2P-M50 peptidase with C-terminal ABC ATPase. In a lantibiotic synthesis gene cluster.

M50 peptidase of Catenulispora acidiphila (C7QBX7)

Leukotoxin export protein of 707 aas, LtxB (has a fused M-C structure with 6 TMSs) (Guthmiller et al. 1995). Functions with the MFP, LtxD (TC# 8.A.1.3.4) and the TolC-like protein, TdeA (TC# 1.B.17.3.11).

Leukotoxin exporter of Aggregatibacter (Actinobacillus; Haemophilus) actinomycetemcomitans
3.A.1.110:  The Protein-2 Exporter (Prot2E) Family

Microcin E492 exporter, MceFGH (MceF has 5 - 7 TMSs and is most likely a CAAX amino terminal protease that might function in the processing of microcin E492; MceG has a short hydrophilic N-terminus, a centra 6 TMS ABC domain, and a C-terminal ABC ATPase domain; MceH has 1 N-terminal TMS) (Bieler et al., 2006; Lagos et al., 1999)

MceGH of Klebsiella pneumoniae
MceG (C-M-C) (Q93GK5)
MceH (MFP) (Q93GK4)

Colicin V exporter. The ATPase is a GTPase (Zhong and Tai 1998; ).

CvaB (M-C) of E. coli

The multiple protein exporter, PrsD/PrsE (exports EPS glycanases, PlyA and PlyB, as well as Rhizobium adhering proteins) (Russo et al., 2006). 12 substrates have been identified; PrsDE provide the major route of protein export in R. leguminosarum (Krehenbrink and Downie, 2008).
PrsD/PrsE of Rhizobium leguminosarum
PrsD(M-C) (O05693)
PrsE(MFP) (O05694)

Alkaline protease exporter
AprD (M-C) of Pseudomonas aeruginosa

S-layer protein exporter
RsaD (M-C) of Caulobacter crescentus

Exporter for lipase LipA, protease PrtA and S-layer protein SlaA, LipBCD (Akatsuka et al. 1997).   LipABC is also called PrtDEF.

LipBCD of Serratia marcescens
LipB (M-C) (Q54456)
LipC (MFP) (Q54457)
LipD (OMF) (O87950)


Exporter for heme-binding protein, HasA and metaloprotease, PrtA.  Functions as a complex spanning the two membranes of the cell envelope: HasDEF (HasD = ABC protein; HasE = the MFP; HasF = the OMF (see 2.A.6.2.31 for HasF) (Akatsuka et al. 1997).

HasDEF of Serratia marcescens
HasD (M-C) (Q53368)
HasE (MFP) (Q57387)
HasF (OMF) (Q54452)   

Surface layer protein exporter
SapD (M-C) of Campylobacter fetus

Exporter of HasA lipase, and alkaline protease
HasD (M-C) of Pseudomonas fluorescens

The AlgE-type Mannuronan C-5-Epimerase exporter, EexD (PrtD) (Gimmestad et al., 2006).
EexD of Azotobacter vinelandii (C1DS84)

Secretion system for metalloprotease, PrtA, PrtDEF (Akatsuka et al. 1997). (PrtF=1.B.17.1.2)

PrtDEF of Erwinia chysanthemi 
PrtD (M-C) (P23596)
PrtE (MFP) (P23597) 

Thermostable lipase, TliA (Q9ZG91; 476 aas with a C-terminal region that shows similarity to members of the RTX toxin family (1.C.11)) exporter, TliDEF.  The wild type transporter has a temperature sensitive defect which can be corrected by a single mutation in TliD (Eom et al. 2016).

TliDEF of Pseudomonas fluorescens
TliD, 578 aas (M-C) and 6 N-terminal TMSs
TliE, 433 aas (MFP)
TliF, 481 aas (OMF)

Protein export system, PrtD of 564 aas and 6 TMSs. The 3.15 Å structure has been solved (Morgan et al. 2017).  The structure suggests a substrate entry window just above the transporter's nucleotide binding domains. Highly kinked transmembrane helices, which frame a narrow channel, not observed in canonical peptide transporters, are likely involved in substrate translocation. The PrtD structure supports a polypeptide transport mechanism distinct from alternating access (Morgan et al. 2017).

PrtD of Aquifex aeolicus
3.A.1.111:  The Peptide-1 Exporter (Pep1E) Family

Hemolysin/bacteriocin (cytolysin) exporter with associated proteolytic activity
other sequences
CylT (M-C) (CylB) of Enterococcus faecalis

Subtilin (toxic peptide) exporter
SpaB (M-C) of Bacillus subtilis

Nisin exporter
NisT (M-C) of Lactococcus lactis

Bacteriocin immunity protein, SmbG (198 aas; 6TMSs in a 2+2+2 arrangement. (Exports bacteriocins and causes resistance to antibiotics such as tetracycline, penicillin and triclosan). Upregulated by exposure to antibiotics (Matsumoto-Nakano and Kuramitsu, 2006)
SmbG (M-C) of Streptococcus mutans (Q5TLL2)

The lacticin Q exporter, LcnDR3 (Yoneyama et al., 2009).
LcnDR3 (M-C) of Lactococcus lactis (P37608)

Salivericin 9 exporter, SivT (692 aas; 6 TMSs) (Wescombe et al., 2011)

SivT of Strepococcus salivarius (F8LI02)

Nukacin ISK-1 bacteriocin exporter, NukT of 694 aas and 6 TMSs.  The protease domain is N-terminal, the membrane domain is central, and the ATPase domain in C-terminal. NukT and its peptidase-inactive mutant have been expressed, purified, and reconstituted into liposomes for analysis of their peptidase and ATPase activities. The ATPase activity of the NBD (C) region is required for the cysteine-type peptidase activity, and leader peptide cleavage enhances the ATPase activity (Zheng et al. 2017).

NukT of Staphylococcus warneri (P-M-C)
3.A.1.112:  The Peptide-2 Exporter (Pep2E) Family

Competence factor (CSF; a heptadecapeptide) exporter of 717 aas.  The transporter is fused to an N-terminal peptidase  domain and functions with an MFP  accessory protein, ComB (TC# 8.A.1.4.2) (Ishii et al. 2006). 

ComA (peptidase-M-C) of Streptococcus pneumoniae (functions with MFP accessory protein, ComB)

Pediocin PA-1 exporter
PedD (M-C) of Pediococcus acidilactici

Bacteriocin (lactococcin) exporter. 

LcnC (M-C) of Lactococcus lactis (functions with putative MFP accessory protein LcnD)

Sublancin exporter, SunT
SunT (M-C) of Bacillus subtilis

Exporter of the BlpC peptide pheromone (B5E242) and several bacteriocins, BlpAB (Kochan and Dawid 2013).

BlpAB of Streptococcus pneumoniae
BlpA (M-C) (B3E244)
BlpB (MFP) (B3E242)

Putative ABC transporter (6 TMSs)

ABC Transporter of Ureaplasma parvum (Q9PPY0)

Possible ABC exporter of the bacteriocin, Circularin A (CirB/CirC/CirD) (Kemperman et al., 2003). CirB (Q7WYU1) resembles 3.A.1.112.6, CirB (Q7WYU0) resembles 9.B.98.1.1, and CirD (Q7WYT9) resembles 3.A.1.147.2.

CirBCD of Clostridium beijerinckii
CirB (M) 12 TMSs (Q7WYU1)
CirC (M) 4 TMSs (Q7WYU0)
CirD (C) (Q7WYT9)

Mesenterici Y105 (bacteriocin) ABC exporter and porcessing protease, MesD(E) of 722 aas and 6 TMSs (MesD) (Fremaux et al. 1995). MesDE can transport and catalyze maturation of the two pre-bacteriocins, mesentericin Y105 and B105 (Aucher et al. 2004).  Hydrophobic conserved amino acyl residues and the C-terminal GG doublet of the leader peptide of pre-mesentericin Y105 are critical for optimal secretion (Aucher et al. 2005).  MesE has TC# 8.A.1.4.1.

MesDE of Leuconostoc mesenteroides

ABC bacteriocin exporter with two peptidase domains, Pcat1.  The pathway for peptide export consists of an large α-helical barrel for small folded peptides.  ATP binding alternates access to the transmembrane pathway and reglates protease activity (Lin et al. 2015).

Pcat1 of Ruminiclostridium thermocellus

Bacteriocin exporter of 721 aas and 7 TMSs. Residues 10 - 134: peptidase with N-terminal TMS; residues 167 - 446: TM domain; residues 480 - 715: ATPase.

Peptide exporter of Bacteroides salanitronis
3.A.1.113:  The Peptide-3 Exporter (Pep3E) Family

Modified cyclic peptide (syringomycin) exporter, SyrD
SyrD (M-C) of Pseudomonas syringae

Pyoverdin (siderophore) exporter
PvdE (M-C) of Pseudomonas aeruginosa

The multidrug/microcin J25 (MccJ25; 21 aa cyclic peptide antibiotic; the precursor peptide is McjA) exporter, YojI (Delgado et al., 2005). TolC is also required for export; Vincent and Morero, 2009). This system exports many phytol derivatives (Upadhyay et al. 2014).  Also exports L-cysteine (Yamada et al., 2006).  This is one of two microcin J25 exporters, the other being McjD (TC# 3.A.1.118.1).

YojI of E. coli (P33941)
3.A.1.114:  The Probable Glycolipid Exporter (DevE) Family

Glycolipid exporter (under nitrogen control in heterocysts), DevABC-HgdD (Moslavac et al., 2007). Heterocyst envelope glycolipids (HGLs) function as an O2 diffusion barrier, being deposited over the heterocyst outer membrane, surrounded by an outermost heterocyst polysaccharide envelope. DevBCA and TolC form an ATP-driven efflux pump required for the export of HGLs across the Gram-negative cell wall (Staron et al., 2011). DevB, the MFP, must be hexameric to create a functional export complex.  This system is under NtcA and nitrogen control and is required for heterocyst development (Fiedler et al. 2001).

DevABC-HgdD of Anabaena variabilis (sp. strain PCC7120)
DevA (C)
DevB (MFP)
DevC (M)
HgdD (TolC like)
3.A.1.115:  The Na+ Exporter (NatE) Family

Na efflux pump NatAB

NatAB of Bacillus subtilis
NatA (M)
NatB (C)

Putative Na extrusion pump, NatAB.  NatB has an N-terminal NatB domain (residues 1 - 375) as well as a C-terminal CAAX protease domain (9.B.2; residues 380 - 650).

NatAB of Rhodopirellula baltica

ABC transporter of unknown function

Candidatus Saccharibacteria
ABC transporter
AKM79972, (M)
AKM79973, (C)
3.A.1.116:  The Microcin B17 Exporter (McbE) Family

Microcin B17 exporter
McbEF of E. coli
McbE (M)
McbF (C)
3.A.1.117:  The Drug Exporter-2 (DrugE2) Family

The multidrug exporter, LmrA (can also substitute for MsbA [TC #3.A.1.106.1] to export lipid A; Reuter et al., 2003).  A structural model has been presented (Federici et al. 2007).

LmrA (M-C) of Lactococcus lactis

Hop resistance protein, HorA. Reconstitution in phosphatidyl ethanolamine bilayers resulted in normal activity, but reconstitution in phosphatidyl choline resulted in uncoupling of ATP hydrolysis from transport and a change in the orientations of the TMSs (Gustot et al. 2010).

HorA (M-C) of Lactobacillus brevis

Multidrug resistance efflux pump, BmrA (YvcC) of 589 aas.  The low resolution cryo-electron microscopy reconstitution suggests large conformational changes occur during it's catalytic cycle (Fribourg et al. 2014).

BmrA of Bacillus subtilis
3.A.1.118:  The Microcin J25 Exporter (McjD) Family

The cyclic peptide antibiotic, microcin J25 (MccJ25; the precursor peptide is JcjA) exporter, the self immunity protein, McjD. TolC is also required for export; Vincent and Morero, 2009.  The 3-d structure has been determined to 2.7Å resolution in an outward occluded state (Choudhury et al. 2014).  Binding and efflux as well as stimulation of the ATPase activity upon binding of MccJ25 have been demonstrated (Choudhury et al. 2014).  This is one of two MCCJ25 exporters, the other being YojI (TC# 3.A.1.113.3).  The large conformational changes in some crystal structures may not be necessary even for a large substrate like MccJ25 (Gu et al. 2015).

McjD (M-C) of E. coli
3.A.1.119:  The Drug/Siderophore Exporter-3 (DrugE3) Family

5-Hydroxystreptomycin and other streptomycin-like aminoglycoside exporter, StrVW
StrVW of Streptomyces glaucescens
StrV (M-C)
StrW (M-C)

Tetracycline/oxytetracycline/oxacillin exporter, TetAB
TetAB (StrAB) of Corynebacterium striatum
TetA (M-C)
TetB (M-C)

Exochelin exporter, ExiT (Zhu et al. 1998).

ExiT of Mycobacterium smegmatis

Putative coelichelin (hydroxamate siderophore) exporter, Sco0493; the gene is in a gene cluster encoding the recognized coelichelin uptake system (TC# 3.A.1.14.12) as well as coelichelin biosynthetic enzymes (Barona-Gómez et al. 2006).  Sco0493 may function together with Sco0540 which is another putative ABC exporter of similar equence (see TC# 3.A.1.119.5).  However, alternatively, these two genes may encode two distinct transport systems.

Putative coelichelin exporter, Sco0493, of Streptomyces coelicolor (M-C)

Putative coelichelin (hydroxamate siderophore) exporter, Sco0493; the gene is in a gene cluster encoding the recognized coelichelin uptake system (TC# 3.A.1.14.12) as well as coelichelin biosynthetic enzymes (Barona-Gómez et al. 2006).  Sco0493  (see TC# 3.A.1.119.4) may function together with Sco0540, both of which are putative ABC exporters of similar sequence. Alternatively, these two genes may encode two distinct transport systems.

Sco0540 of Streptomyces coelicolor (M-C)
3.A.1.120:  The (Putative) Drug Resistance ATPase-1 (Drug RA1) Family

Macrolide ATPase (membrane constituent unknown)
SrmB (C-C) of Streptomyces ambofaciens

Tylosin ATPase (membrane constituent unknown)
TlrC (C-C) of Streptomyces fradiae

Oleandomycin resistance ATPase (membrane constituent unknown)
OleB (C-C) of Streptomyces antibioticus

Carbomycin resistance ATPase (membrane constituent unknown)
Carbomycin, CarA (C-C), protein of Streptomyces thermotolerans

The acetate resistance ABC acetate exporter (Nankano et al., 2006)
AatA (C-C) of Acetobacter aceti (BAE71146)

The Uup protein (required for bacterial competitiveness (Murat et al., 2008); 39% identical to 3.A.1.120.5).

Uup of E. coli (P43672)

ABC transporter, SgvT2 (ATP-hydrolyzing subunit of 551 aas. Functions to export griseoviridin and viridogrisein (etamycin) (Xie et al. 2017). However, it may also function as an ATP-binding cassette domain of elongation factor 3, interacting with the ribosome which stimulates its ATPase activity (Sasikumar and Kinzy 2014).

SgvT2 of Streptomyces griseoviridis
3.A.1.121:  The (Putative) Drug Resistance ATPase-2 (Drug RA2) Family

Erythromycin ATPase (membrane constituent unknown)
MsrA (C-C) of Staphylococcus epidermidis

Pristinamycin resistance protein, VgaG
VgaB (C-C) of Staphylococcus aureus

Antibiotic (virginiamycin and lincomycin) resistance protein, VmlR
VmlR (C-C) of Bacillus subtilis (P39115)

The two component ABC-4-type transporter (Rafii and Park, 2008).  Transports multiple drugs including ethidium and fluoroquinolones.

The ABC-4 M/C-C transporter of Clostridium hathewayi (Q83XH0)

ABC-type streptogammin A resistance exporter, VgaA of 522 aas and 0 TMSs (C-C arrangement).  Inhibited by pristinamycin IIA (Jacquet et al. 2008).

VgaA of Staphylococcus aureus

MsrD of 487 aas and 0 TMSs. Involved in macrolide resistance (Zhang et al. 2016). Two ATPase domains are present in tandem. The membrane constituent is not known.

MsrD of Streptococcus pyogenes (C-C)
3.A.1.122:  The Macrolide Exporter (MacB) Family

Macrolide (14- and 15- but not 16-membered lactone macrolides including erythromycin) exporter, MacAB (formerly YbjYZ). Both MacA and MacB are required for activity (Tikhonova et al., 2007). MacAB functions with TolC to export multiple drugs and heat-stable enterotoxin II (enterotoxin STII) (Yamanaka et al., 2008). The crystal structure of MacA is available (Yum et al., 2009). MacB is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA (Lin et al., 2009). Xu et al. (2009) have reported the crystal structure of the periplasmic region of MacB which they claim resembles the periplasmic domain of RND-type transporters such as AcrB (TC# 2.A.6.2.2). Also exports L-cysteine (Yamada et al., 2006). The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by the MacB transporter (Modali and Zgurskaya, 2011). Fitzpatrick et al. 2017 presented an electron cryo-microscopy structure of the tripartite assembly (MacAB-TolC) at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges a TolC trimer in the outer membrane to a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA may act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism (Fitzpatrick et al. 2017). The structure of ATP-bound MacB has been solved, revealing precise molecular details of its mechanism (Crow et al. 2017).

MacAB of E. coli:
MacA(MFP) (P75830)
MacB(C-M) (P75831)

The SpdC antimicrobial peptide resistance efflux pump, YknWXYZ (Butcher and Helmann, 2006; Yamada et al., 2012). YknW interacts directly with YknXYZ.

YknWXYZ of Bacillus subtilis:
YknW (O31709)
YknX (MFP) (O31710)
YknY (C) (O31711)
YknZ (M) (O31712)

The enterocin AS-48 exporter, As-48FGH
As-48FGH on plasmid pMBL of Enterococcus faecalis:
As-48F (MFP) (Q7AUQ4)
As-48H (M) (Q8RKC0)
As-48G (C) (Q8RKC1)

Probable Heme exporter, HrtAB (Stauff et al., 2008)
HrtAB of Staphylococcus aureus:
HrtA (C) (Q7A3X3)
HrtB (M) (Q7A7X2)

ABC transporter of unknown function (DUF214 protein) (4TMSs)/ABC protein [Msed1528/Msed1530]
Msed1528/Msed1530 of Metallosphaera sedula (M) (A4YGY2)

ABC transporter of unknown function (DUF214 protein) (4TMSs)/ABC protein [MA2839/MA2840]
MA2839/MA2840 of Methanosarcina acetivorans
MA2839 (M) (Q8TM31)
MA2840 (C) (Q8TM30)

ABC transporter of unknown function (Duf214 protein (409aas; 4TMSs:1+3)/ABC protein)
Duf214 protein/ ABC protein of Methanococcus voltae:
Duf214 protein (M) (A8TDX0)
ABC protein (C) (A8TDW7)

Putative ABC3 permease, PC1,2,3.
PC1,2,3 of Treponema denticola:
PC1 (C) - Q73MJ2
PC2 (M) - Q73MJ3
PC3 (M) - Q73MJ4

Duf214 protein (405aas)/ ABC protein
Duf214/ABC system of Caldivirga maquilingensis:
Duf214 protein (M) (A8M8Z1)

Duf214 (423aas)/ ABC system
Duf214/ABC system of Sulfolobus tokodaii:
Duf214 protein (M) (Q973J4)

The hemin resistance transporter, HrtAB. Expression is activated by hemin or hemoglobin via the ChrAS transmembrane sensor kinase/response regulator system (Bibb and Schmitt 2010).

HrtAB of Corynebacterium diphtheriae
HrtA (C) (H2GZC3)
HrtB (M) (H2GZC4) 

Arthrofactin efflux pump, ArfDE (Balibar et al. 2005).

ArfDE of Pseudomonas sp. MIS38
ArfD (MFP) (Q84BQ3)
ArfE (ABC) (A0ZUB1)

Putative ABC3-type antimicrobial peptide transporter, fused ATPase-porter protein, U-ABC3-1b (667aas; 4TMSs:1+3)
U-ABC3-1b of Lactobacillus brevis (CM) (Q03RZ6)

ABC transporter of unknown function, but aspects of its structure and mechanism of action are known (Yuan et al. 2001; Zoghbi and Altenberg 2013).  Nucleotide-binding domain dimerization occurs as a result of binding to the natural nucleotide triphosphates, ATP, GTP, CTP and UTP, as well as the analog ATP-gamma-S. All the natural nucleotide triphosphates are hydrolyzed at similar rates, whereas ATP-gamma-S is not hydrolyzed. The non-hydrolyzable ATP analog AMP-PNP, frequently assumed to produce the nucleotide-bound conformation, failed to elicit nucleotide-binding domain dimerization (Fendley et al. 2016).

ABC transporter of Methanocaldococcus jannaschii (Methanococcus jannaschii)
Membrane protein, MJ0797 (M) (Q58207)
ATPase, MJ0796 (C) (Q58206)

Putative heavy metal ion exporter, YbbAB (Moussatova et al. 2008).

YbbAB of E. coli
YbbA (C; 228 aas)
YbbB (M; 804 aas)

Putative macrolide-specific efflux system, MacAB

MacAB of Bifidobacterium longum

LolC/E family lipoprotein releasing system, transmembrane protein of 639 aas and 4 TMSs

Candidatus Saccharibacteria
LolC/E family lipoprotein releasing system, transmembrane protein of Candidatus Saccharibacteria bacterium

MacAB-TolC MDR effllux porter. Exports macrolide antibiotics, virulence factors, peptides and cell envelope precursors. The 3-d crystal structure of MacB has been solved at 3.4 Å resolution (Okada et al. 2017). MacB forms a dimer in which each protomer contains a nucleotide-binding domain and four TMSs that protrude in the periplasm into a binding domain for interaction with the membrane fusion protein MacA. It has unique structural features (Okada et al. 2017).

MacAB of Acinetobacter baumannii
MacA, Q2FD52, 445 aas and 1 TMS
MacB, N9J6M5, 664 aas and 4 TMSs

ABC3-type efflux porter, YtrEF, encoded within an operon, ytrABCDEF, apparently encoding two ABC exporters, one, YtrBCD, with TC# 3.A.1.153.1, and the other, this one. The operon is induced in early stationary phase under the control of YtrA, a GntR-type HTH transcriptional regulator, probably a repressor (Yoshida et al. 2000). These authors suggest this operon may be involve in acetoin secretion and/or reutilization.

YtrEF of Bacillus subtilis
YtrE, C, 231 aas; O34392
YtrF, M, 436 aas; O35005

MacAB-MFP complex of 3 subunits involved in the resistance of antibiotics and antimicrobial peptides. Yang et al. 2018 reported the crystal structures of Spr0694-0695 (MacAB) at 3.3 Å and Spr0693 (MFP; TC# 8.A.1) at 3.0 Å resolution, revealing a MacAB-like efflux pump. The dimeric MacAB adopts a non-canonical fold, the transmembrane domain of which consists of a dimer with eight tightly packed TMSs (4 per subunit) with an extracellular domain between the first and second helices, whereas Spr0693 (the MFP) forms a nanotube channel docked onto the ABC transporter. Structural analyses, combined with ATPase activity and antimicrobial susceptibility assays, enabled the proposal of a putative substrate-entrance tunnel with lateral access controlled by a guard helix (Yang et al. 2018).

MacAB-MFP of Streptococcus pneumoniae
MacA, Spr0694, 233 aas (C)
MacB, Spr0695, 419 aas (M)
MFP, Spr0693, 399 aas, (MFP)
3.A.1.123:  The Peptide-4 Exporter (Pep4E) Family

Pep5 lantibiotic exporter, PepT

PepT (M-C) of Staphylococcus epidermidis

Aureocin A70 multipeptide bacteriocin (AurA, AurB, AurC, AurD) exporter, AurT
AurT (M-C) of Staphylococcus aureus

The one component lantibiotic exporter, GdmT (Sibbald et al., 2006)
GdmT (M-C) of Staphylococcus gallinarum (A3QNP2)
3.A.1.124:  The 3-component Peptide-5 Exporter (Pep5E) Family

The 3-component nisin immunity exporter, NisFEG. Contains an essential E-loop (Okuda et al., 2010).

NisFEG of Lactococcus lactis
NisF (C)
NisE (M)
NisG (M)

The 3-component subtilin immunity exporter, SpaEFG
SpaEFG of Bacillus subtilis
SpaE (M)
SpaF (C)
SpaG (M)

The lantibiotic Nukacin ISK-1 (TC# 1.C.21.1.5)/NukH (BAD01013; 92aas) exporter, NukEFG (Okuda et al., 2008)
NukEFG of Staphylococcus warneri
NukE (M) (Q75V14)
NukF (C) (Q75V15)
NukG (M) (Q75V13)

The macedocin exporter, McdEFG (Papadelli et al., 2007)
McdEFG of Streptococcus macedonicus
McdE (M; 254 aas) (A6MER6)
McdG (M; 245 aas) (A6MER7)
McdF (C; 304 aas) (A6MER5)

The salivaricin exporter, SboEFG (Hyink et al., 2007)
SboEFG of Streptococcus salivarius
SboE (M; 249 aas) (Q09IH9)
SboF (C; 303 aas) (Q09II0)
SboG (M; 242 aas) (Q09IH8)

CprABC antimicrobial peptide resistance ABC exporter.  Exports both mammalian and bacterial toxic peptides (McBride and Sonenshein 2011).

CprABC of Clostridium difficile
CprA (C, 235 aas)
CprB (M, 238 aas, 6 TMSs)
CprC (M, 252 aas, 6 TMSs)
3.A.1.125:  The Lipoprotein Translocase (LPT) Family

Lipoprotein translocation system (translocates lipoproteins from the inner membrane to periplasmic chaperone, LolA, which transfers the lipoproteins to an outer membrane receptor, LolB, which anchors the lipoprotein to the outer membrane of the Gram-negative bacterial cell envelope) (see 1.B.46; Narita et al., 2003; Ito et al., 2006; Watanabe et al., 2007). The structure of ligand-bound LolCDE has been solved (Ito et al., 2006). LolC and LolE each have 4 TMSs (1+3). Unlike most ATP binding cassette transporters mediating the transmembrane flux of substrates, the LolCDE complex catalyzes the extrusion of lipoproteins anchored to the outer leaflet of the inner membrane. The LolCDE complex is unusual in that it can be purified as a liganded form, which is an intermediate of the lipoprotein release reaction (Taniguchi and Tokuda, 2008). LolCDE has been reconstituted from separated subunits (Kanamaru et al., 2007).  LolE binds the outer membrane lipoprotein, PAL (Mizutani et al. 2013).

LolCDE of E. coli
LolC (M)
LolD (C)
LolE (M)

Putative lipoprotein LolCDE homologue LolCE (10TMSs:1+6+3)/LolD
LolCE/LolD of Mycobacterium tuberculosis
LolCE (M) (Q7D911)
LolD (C) (O53899)

Duf214 protein (843aas; 10TMSs:1+6+3)
Duf214 protein/ ABC protein of Frankia sp. CcI3:
Duf214 protein (M) - Q2J9P4
[LolD/FtsE/SalX]-type ABC protein (C) - Q2J9P5

Uncharacterized protein of 371 aas and 6 TMSs

UP of Halorubrum kocurii

Uncharacterized ABC transporter with two consituents, a 4 TMS (in a 1 + 3 TMS arrangement) membrane (M) protein and an ATPase (C). 

Chlamydiae/Verrucomicrobia group
Uncharacterized ABC transporter of Opitutus terrae
3.A.1.126:  The β-Exotoxin I Exporter (βETE) Family

Exporter of β-exotoxin I, BerAB
β-exotoxin exporter, BerAB, of Bacillus thuringiensis
BerA (C)
BerB (M)
3.A.1.127:  The AmfS Peptide Exporter (AmfS-E) Family

Exporter of AmfS extracellular peptidic morphogen (Chater and Horinouchi, 2003; Ueda et al., 2002)
AmfS exporter, AmfAB of Streptomyces griseus
AmfA (MC) (BAA33537)
AmfB (MC) (BBA33538)
3.A.1.128:  The SkfA Peptide Exporter (SkfA-E) Family

Exporter of SkfA processed peptide (spO31422), SkfEF (González-Pastor et al., 2003)

SkfEF (YbdAB) of Bacillus subtilis
SkfE (C) O31427
SkfF (M-M) O31438

Putative ABC exporter, Teth 514-0346 & 0347
Teth 514-0346 & 0347 of Thermoanaerobacter sp. x514:
Teth514-0346 (C) (B0K2P2)
Teth514-0347 (M-M) (B0K2P3)

Putative ABC exporter, CLK2533/CLK2534
CLK2533/CLK2534 of Clostridium botulinum
CLK2533 (M-M) (B1L0U0)
CLK2534 (C) (B1L0U1)

Putative ABC exporter Tiet1371/1372
Tiet1371/72 of Thermotoga lettingae
Tiet1371 (M-M) (A8F6Z4)
Tiet1372 (C) (A8F6Z5)

Putative ABC transporter.  The genes encoding this system map adjacent to a beta-lactamase (A9BGZ6) gene and one encoding a C4 anaerobic dicarboxylate carrier (A9BGZ7).

Putative ABC transporter of Petrotoga mobilis

Putative ABC exporter

ABC exporter of Pyrococcus horikoshii
Membrane protein (M) (O58947)
ATPase (C) O58948)

Uncharacterized ABC permease, TA0065/Ta0066

UP of Thermoplasma acidophilum
Ta0065 (M-M; permease; 515 aas, 12 TMSs)
Ta0066 (C; ATPase)
3.A.1.129:  The CydDC Cysteine Exporter (CydDC-E) Family

Thiol (Cysteine/Glutathione) exporter, CydDC; CydC is also called MdrH (periplasmic cysteine is required for cytochrome bd assembly) (Cruz-Ramos et al., 2004).  The purified asymmetric heterodimer exhibits low ATPase activity which is activated by both thiols and heme (e.g., heme b) compounds, suggesting that heme binds to and activates thiol transport (Yamashita et al. 2014).  Bacterial redox homoeostasis during nitrosative stress is influenced by CydDC.  Periplasmic low molecular weight thiols restore haem incorporation into a cytochrome complex (Holyoake et al. 2016).

CydDC of E. coli
CydD (M-C) (P29018)
CydC (M-C) (P23886)
3.A.1.130:  The Multidrug/Hemolysin Exporter (MHE) Family

The multidrug/hemolysin exporter, CylA/B (note: CylK (AAF01071) may influence its activity)(Gottschalk et al., 2006)
CylA/B of Streptococcus agalactiae
CylA (C) (Q9X432)
CylB (M) (Q9X433)
3.A.1.131:  The Bacitracin Resistance (Bcr) Family

The 2 or 3 component bacitracin-resistance efflex pump, BcrAB or BcrABC (Podlesek et al., 1995; Bernard et al., 2003) (BcrA is most similar to SpaF (3.A.1.124.2), but BcrB (5-6 TMSs) is only distantly related to other ABC2-type membrane proteins (Wang et al., 2009). BcrC is not sufficiently similar to detect similarity in BLAST searches. BcrC (5TMSs) belongs to the PAP2 phosphatase superfamily and may not be a contituent of the BcrAB transporter.

BcrABC of Bacillus licheniformis
BcrA (C) - (P42332)
BcrB (M) - (P42333)

Lantibiotic immunity system, LanEF. Contains an essential E-loop, a variant of the Q-loop, well conserved in nucleotide binding domains of lantibiotic exporters (Okuda et al., 2010).

LanEF of Bacillus licheniformis
LanE (M) (Q65DD3)
LanF (C) (Q65DD1)

Transporter homologue, Tiet1372

Tiet1372 of Thermotoga lettingae (A8F6Z5)
3.A.1.132:  The Gliding Motility ABC Transporter (Gld) Family

The GldAFG putative ABC transporter required for ratchet-type gliding motility; may function in secretion of a macromolecule such as an exopolysaccharide. (Agarwal et al., 1997; Hunnicutt et al., 2002; McBride and Zhu 2013). Soluble GldG homologues (no TMSs) are found in eukaryotes (e.g. intraflagellar protein transporter, IPT52 of Chlamydomonas reinhardtii; XP_001692161)

Bacteroidetes/Chlorobi group
GldAFG of Flavobacterium johnsoniae:
GldA (C; 298 aas) - (O30489)
GldF (M; 241 aas; 6TMSs (2+2+2) - (Q93LN1)
GldG (M-periplasm; putative auxillary subunit with 2TMSs at the N and C-termini; 561 aas)- (Q93LN0).

The NosDFY Copper ABC transporter (Chan et al., 1997)
NosDFY of Sinorhizobium meliloti
NosD (R; periplasmic copper binding receptor)(Q52899)
NosF (C; like GldA) (Q52900)
NosY (M; like GldF) (O07330)

The uncharacterized ABC transporter with GldF-GldG homologues fused
GldAFG homologues of Magnetococcus sp. MC-1
GldFG (M-Aux; 964 aas) (A0L4K8)
GldA (C; 399 aas) (A0L4L0)

The uncharacterized ABC transporter with GldF-GldG homologues fused
GldAFG homologues of Hahella chejuensis
GldF-G (M-Aux; 978 aas) (Q2SDB0)
GldA (C; 315 aas) (Q2SDB1)

Putative ABC2 transporter: Membrane protein of 274aas and 6 TMSs; Cytoplasmic ATPase of 302aas.

Putative ABC2 transporter of Shewanella pealeana
(M) (A8GZV3)
(C) (A8GZV2) 

Putative ABC2 transporter: Membrane protein of 274aas and 6 TMSs; Cytoplasmic ATPase of 302aas.

Putative ABC-2 transporter of Streptococcus pyogenes 
(M) (Q99ZC7)
(C) (Q99ZC8) 

Putative ABC membrane protein with 12 TMSs. (ATPase subunit unknown, and not encoded by an adjacent gene).

ABC membrane protein of Rhodopirellula baltica

ABC transporter, annotated as involved in multi copper protein maturation

ABC exporter of Methanocella conradii
permease (M) (H8I780)
ATPase (C) (H8I779)

Putative ABC exporter, Odosp_3144/Odosp_3145. Odosp_3144 is a 6 TMS ABC2 membrane protein (N-terminal 250 aas) fused to an auxiliary protein with one N- and one C-terminal TMS, homologous to GldG of Cytophaga johnsonae (3.A.1.132.1).

Bacteroidetes/Chlorobi group
Putative ABC transporter of Odoribacter splanchnicus 
Odosp_3144 (M) (761 aas; 7 TMSs) (F9Z892)
Odosp_3145 (C) (306 aas) (F9Z893) 

Putative ABC exporter of unknown function, Gll1303/Gll1302, with two probable subunits of 477 and 494 aas with 6 TMSs each at their N-termini (M) and ATPase domains (C) in the C-termini.

Gll1303/Gll1304 putative ABC exporter of Gloeobacter violaceus
Gll1303, (M)
Gll1302, (M)

Putative ABC exporter with two membrane proteins of 478 and 417 aas and 6 TMSs respectively, and one ATPase.  The encoding genes are adjacent to a TonB-dependent OMR with possible specificity for a siderophore.  Thus, this ABC exporter could transport a siderophore.

Uncharacterized ABC exporter of Saccharophagus degradans
Sde_3610 (C), 249 aas (Q21EL4)
Sde_3609 (M), 478 aas and 6 TMSs (Q21EL5)
Sde_3608 (M), 417 aas and 6 TMSs (Q21EL6)

ABC exporter necessary for social motility, pilus assembly and pilus subunit (PilA) export, PilGHI. Mutants show elevated sporulation rates and abnormal development (Wu et al. 1998).

PilHI of Myxococcus xanthus
PilH (C) ABC protein (O30385)
PilT (M) 6 TMS membrane protein of 255aas (O30386) 
3.A.1.133:  The Peptide-6 Exporter (Pep6E) Family

The modified YydF* peptide exporter, YydIJ (Butcher et al., 2007)
YydIJ of Bacillus subtilis:
YydI (C) (Q45593)
YydJ (M) (Q45592)

A 6TMS homologue of YydJ (ORF1) of 280aas
Bacteroidetes/Chlorobi group
ORF1 of Flavobacteria bacterium BBFL7 (Q26C21)
3.A.1.134:  The Peptide-7 Exporter (Pep7E) Family

The lantibiotic, salivericin A exporter, SalXY
SalXY of Streptococcus salivarius
SalX (C)
SalY (M)

The bacitracin-resistance (putative bacitracin exporter), MbrAB. Participate with BreSR to control its own gene expression (Bernard et al., 2007).
MbrAB of Streptococcus mutans
MbrA (C)
MbrB (M)

The putative bacitracin exporter, BceAB (BarAB; YtsCD) (Bernard et al., 2003; Ohki et al., 2003).  Functions in both signaling to the two component system, BceRS, and in export of the antimicrobial peptide (Dintner et al. 2014).  BceB interacts directly with BceS, and BceB binds bacitracin (Dintner et al. 2014).  Specific regions and residues are invollved in signalling or transport (Kallenberg et al. 2013).  More recent studies suggest taht BceAB may cause bacitracin resistance by transferring undecaprenyl pyrophosphate from the exteral to the internal leaflet of the inner membrane where it can't bind bacitracin and other lantibiotics that use Lipid II as a receptor (Draper et al. 2015).

BceAB (YtsCD) of Bacillus subtilis
BceA (C) CAB15016
BceB (M) CAB15015

The bacitracin/vancoresmycin (a tetramic acid antibiotic) resistance exporter (Becker et al. 2009) (most like 3.A.1.134.2)

SPR0812/SPR0813 of Streptococcus pnenmoiae
SPR0812 (C) (Q8DQ77)
SPR0813 (M) (Q8DQ76)

The MDR exporter, YvcRS. Possibly linked to regulation by a sensor kinase/response regulator system (YvcQP) (Joseph et al., 2002; Bernard et al., 2007).

YvcRS of Bacillus subtilis
YvcR (C) (O06980)
YvcR (M) (O06981)

The cationic peptide/MDR exporter, YxdLM. Possibly linked to a sensor kinase/reponse regulator system (YxdJK) (Joseph et al., 2002; Bernard et al., 2007).

YxdLM of Bacillus subtilis
YxdL (C) (P42423)
YxdM (M) (P42424)

The VraFG ABC transporter interacts with GraXSR [GraX, Q7A2W7; GraS, A6QEW9; GraR, A6QEW8] to form a five-component system required for cationic antimicrobial peptide sensing and resistance (Falord et al., 2012).  VraX has been termed a two component system connector and may not be a component of the transporter.

VraFG/GraXSR of Staphylococcus aureus 
VraF (A6QEX0)
VraG (A6QEX1)
VraX (Q7A2W7)

Antimicrobial peptide exporter, ABC12 or YvoST (Revilla-Guarinos et al. 2013).

YvoST of Lactobacillus casei

Two component toxic peptide exporter with a membrane subunit of 663 aas and 10 TMSs and an ATPase of 256 aas, ABC09 (Revilla-Guarinos et al. 2013).

ABC09 of Lactobacillus casei

Peptide exporter, YsaB (667 aas and 10 TMSs)/YsaC (257 aas).  Probably exports lantibiotic antibiotics (Draper et al. 2015).

YsaBC of Lactococcus lactis
YsaB (M)
YsaC (C)

Lantibiotic detoxification ABC transporter, VraD (252 aas)/VraE (626 aas; 10 TMSs)/VraH ( (Draper et al. 2015).  Upregulated in response to exposure to beta-defensin 3 (Sass et al. 2008).  Exports antimicrobial peptides such as nisin, bacitracin, daptomycin and gallidermin. Expression of vraH in the absence of vraDE is sufficient to mediate low-level resistance, but VraDEH is required to  confer high-level resistance against daptomycin and gallidermin. (Popella et al. 2016).

VraDE of Staphylococcus aureus VraD (Q9RL74)
VraE (Q9KWJ6)
VraH (T1YED1)

ABC multidrug resistance efflux pump, AnrAB.  Exports nisin, gallidermin, bacitracin and β-lactam antibiotics  (Collins et al. 2010).

AnrAB of Listeria monocytogenes
AnrA (C)
AnrB (M; 642 aas and 10 TMSs)
3.A.1.135:  The Drug Exporter-4 (DrugE4) Family

The heterodimeric multidrug exporter, YdaG/YbdA  (Both proteins are ABC half transporters; only the heterodimer is active; ethidium, daunomycin and BCECF-AM are substrates; Lubelski et al., 2004) These proteins have been renamed LmrC and LmrD (Lubelski et al., 2006)

YdaG/YdbA of Lactococcus lactis YdaG (M-C) (AAK04408)
YdbA (M-C) (AAK04409)

The heterodimeric putative multidrug exporter, RscA/RscB; probably orthologous to YdaG/YbdA (TC #3.A.1.117.4) [Transcription is activated by stress conditions (heat, acid) and repressed by a 2-component system, CovRS (Dalton et al., 2006)]
RscAB of Streptococcus pyogenes RscA (M-C) (568 aas) (Q9A1K5)
RscB (M-C) (594 aas) (Q9A1K4)

Narrow spectrum fluoroquinolone (ciprofloxacin and norfloxacin) efflux pump, SatAB (Escudero et al. 2011).

SatAB of Streptococcus suis
SatA, 568 aas (M-C) (G9CHY8)
SatB, 594 aas, (M-C) (G9CHY9)

Multidrug resistance ABC exporter, PatAB (PatA, 564 aas; PatB, 588 aas) (Bidossi et al. 2012).

PatAB of Streptococcus pneumoniae
PatA (M-C)
PatB (M-C)

The hetrodimeric ABC transporter, TM287/TM288.  The 2.9-Å crystal structure has been solved in the inward-facing state. The two nucleotide binding domains (NBDs) remain in contact through an interface involving conserved motifs that connect the two ATP hydrolysis sites.  AMP-PNP binds to a degenerate catalytic site which deviates from the consensus sequence in the same positions as the eukaryotic homologs, CFTR (TC# 3.A.1.202.1) and TAP1-TAP2 (TC# 3.A.1.209.1) (Hohl et al. 2012).  The structural basis for allosteric crosstalk (positive cooperativity) between the two ATP binding sites has been studied (Hohl et al. 2014).  The two NBDs exhibit unexpected differences and flexibility (Bukowska et al. 2015). It exports daunomycin and the nonfluorescent 2,7-bis(carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethylester (BCECF-AM) (Hohl et al. 2012). Timachi et al. 2017 observed hydrolysis-independent closure of the NBD dimer, further stabilized as the consensus site nucleotide is committed to hydrolysis.

TM287/TM288 of Thermatoga maritima

Two component multidrug efflux pump with the 6 TMS membrane domain preceding the ATPase domain in both proteins.  Confers resistance to erythromycin and tetracycline and catalyzes export of Hoechst 33342 (Moodley et al. 2014).  Expression is induced by the presence of erythromycin.

MDR pump of Bifidobacterium longum

Multidrug exporter, EfrAB.  Confers resistance to many structurally unrelated antimicrobial agents, such as norfloxacin, ciprofloxacin, doxycycline, acriflavine, 4,6-diamidino-2-phenylindole, tetraphenylphosphonium chloride, daunorubicin, and doxorubicin (Lee et al. 2003).  Induced by half minimal inhibitory concentrations (MIC) of gentamicin, streptomycin and chloramphenicol which are also exporter (Lavilla Lerma et al. 2014).  In some strains, this system may not be the primary drug exporter (Hürlimann et al. 2016).

EfrAB of Enterococcus faecalis
EfrA (MC), 567 aas and 6 TMSs
EfrB (MC), 589 aas and 6 TMSs

Multidrug efflux pump, EfrCD.  Exports daunorubicin, doxorubicin, ethidium and Hoechst 33342.  Mediates efflux of fluorescent substrates and confers resistance towards multiple dyes and drugs including fluoroquinolones (Hürlimann et al. 2016).

EfrCD of Enterococcus faecalis
EfrC, MC, 571 aas and 6 TMSs
EfrD, MC, 589 aas and 6 TMSs

Multidrug exporter, EfrEF.  Mediates efflux of fluorescent substrates and confers resistance towards multiple dyes and drugs including fluoroquinolones (Hürlimann et al. 2016).

EfrEF of Enterococcus faecalis
EfrE, MC, 575 aas and 6 TMSs
EfrF, MC, 592 aas and 6 TMSs
3.A.1.136:  The Uncharacterized ABC-3-type (U-ABC3-1) Family

Putative ABC3 permease complex U-ABC3-1a (403aas; 4TMSs:1+3)
U-ABC3-1a of Treponema denticola (M) (Q73MJ0)

ABC-type antimicrobial peptide transporter of 421 aas and 4 TMSs

ABC transporter of Bdellovibrio bacteriovorus
3.A.1.137:  The Uncharacterized ABC-3-type (U-ABC3-2) Family

Putative ABC-3-type permease complex, ABC3-2a
ABC3-2a of Pyrobaculum calidifontis:
ABC3-2a (M) (A3MWP2)
ABC3-2a (C) (A3MWP1)

ABC-type antimicrobial peptide transporter of 786 aas and 8 TMSs

ABC transporter of Bdellovibrio bacteriovorus
3.A.1.138:  The Unknown ABC-2-type (ABC2-1) Family

Unknown ABC-2 transporter complex-1, U-ABC2-TC-1
U-ABC2-TC-1 of Picrophilus torridus:
U-ABC2-TC-1a (M) (Q6KYW9)
U-ABC2-TC-1a (C) (Q6KYW8)
3.A.1.139:  The UDP-Glucose/Iron Exporter (U-GlcE) Family (UPF0014 Family)

UDP-glucose exporter, STAR1/STAR2 (sensitive to aluminum rhizotoxicity) (Probable Type I topology) (Huang et al. 2009).

STAR1/STAR2 of Oryza sativa
STAR1 (C) (Q5Z8H2)
STAR2 (M) (Q5W7C1)

The FetA (YbbL)/FetB (YbbM) iron exporter (SwissProt family UDF0014; 6 or 7 putative TMSs).  Expression enhances resistance to oxidative stress (Nicolaou et al. 2013).

FetA/B of E. coli
FetA (C) (P77279)
FetB (M) (P77307)

The uncharacterized ABC exporter, U-ABC-M/C

U-ABCC/U-ABC-M of Spirochaeta africana
U-ABC-C (C) (H9UM45)
U-ABC-M (M) (H9UM46)

Plasma membrane ABC exporter, sensitive to aluminum rhizotoxicity 1/2, STAR1/STAR2 (Larsen et al., 2005). Induced in response to aluminum exposure. 

STAR1/2 of Arabidopsis thaliana 
STAR1 (C) (Q9C9W0)
STAR2 (M) (Q9ZUT3) 
3.A.1.140:  The FtsX/FtsE Septation (FtsX/FtsE) Family

The FtsX/FtsE ABC transporter (Arends et al., 2009) (FtsX is of the type III topology). FtsEX directly recruits EnvC to the septum via an interaction between EnvC and a periplasmic loop of FtsX. FtsEX variants predicted to be ATPase defective still recruit EnvC to the septum but fail to promote cell separation. Amidase activation via EnvC in the periplasm is regulated by conformational changes in the FtsEX complex mediated by ATP hydrolysis in the cytoplasm. Since FtsE has been reported to interact with FtsZ, amidase activity may be coupled with the contraction of the FtsZ cytoskeletal ring (Yang et al., 2011).

FtsX/FtsE of E. coli
FtsX (M) (P0AC31)
FtsE (C) (P0A9R7)

The cell division ABC system, FtsX/FtsE

FstE/X of Caldanaerobacter subterraneus subsp. tengcongensis (Thermoanaerobacter tengcongensis)

Cell division ABC system, FtsXE.

FtsXE of Nostoc punctiforme
FtsX (M), 300 aas, 4 TMSs
FtsE (C), 248 aas

Cell division ABC system, FtsXE of 300 aas and 4 TMSs, and 229 aas and 0 TMSs, respectively.

FtsXE of Actinokineospora spheciospongiae
FtsX, (M), 300 aas and 4 TMSs
FtsE, (C), 229 aas and 0 TMSs

Cell division ABC system, FtsXE.

FtsXE of Candidatus Nitrosopumilus salaria
FtsX, (M), 301 aas, 4 TMSs
FtsE, (C), 222 aas, 0 TMSs

Cell division system, FtsXE.  The FtsEX:PcsB complex forms a molecular machine that carries out peptidoglycan (PG) hydrolysis during normal cell division. FtsEX transduces signals from the cell division apparatus to stimulate PG hydrolysis by PcsB, an amidase, which interacts with extracellular domains of FtsX (Bajaj et al. 2016).

FtsXE of Streptococcus pneumoniae
FtsX, (M), 308 aas and 4 TMSs
FtsE, (C), 226 aas and 0 TMSs
3.A.1.141:  The Ethyl Viologen Exporter (EVE) Family (DUF990 Family)

The ethyl (methyl; benzyl) viologen export pump, EvrABC (EvrB and EvrC of 6 TMSs are members of the large DUF990 superfamily (Prosecka et al., 2009); They appear to be of the ABC-2 topological type).

EvrABC of Synechocystis sp. PCC6803
P73329 slr1910, ABC protein (EvrA)
P74256 slr1174, membrane protein (EvrB)
P74757 slr0610, membrane protein (EvrC)

ABC transporter of unknown specificity, AbcABC

AbcABC of Thermoanaerobacter tengcongensis
AbcA (M) (Q8R6Q6)
AbcB (M) (Q8R6Q5)
AbcC (C) (Q8R6Q4)
3.A.1.142:  The Glycolipid Flippase (G.L.Flippase) Family

Glycolipid translocase (flippase) Spr1816/Spr1817 (R.Hakenbeck, personal communication)

Glycolipid flippase, Spr1816/Spr1817, of Streptococcus pneumoniae
Spr1816 (M) (Q8DNC0)
Spr1817 (C) (Q8DNB9)

ABC exporter, YvfS/YvfR of 284 and 287 aas, respectively

YvfSR of Bdellovibrio bacteriovorus
YvfS (M)
YvfR (C)
3.A.1.143:  The Exoprotein Secretion System (EcsAB(C))

The exoprotein (including α-amylase) secretion system, EcsAB(C) (Leskelä et al., 1999). Also may play roles in sporulation, competence (Leskelä et al., 1996) and transformation using purified DNA (Takeno et al., 2011). An involvement of EcsC in transport is not established, but it is homologous to the C-terminus of the P-type ATPase, 3.A.3.31.2.

EcsAB(C) of Bacillus subtilis 
EcsA (C) (P55339)
EcsB (M) (P55340)
EcsC (M) (P55341) 

YthQ (386aas; 8-9 TMSs)/YthP (ATPase; 0 TMSs)

YthPQ (EscAB) of Bacillus amyloliquefaciens
EscA (YthP) (G0IP52)
EscB (YthQ) (G0IP51)
3.A.1.144:  Functionally Uncharacterized ABC2-1 (ABC2-1) Family



Functionally uncharacterized ABC2 transporter #1.  This system is encoded by two genes that overlap and are therefore probably translationally coupled; they are in the same operon with the genes for 2.A.1.144.2.

ABC2 transporter #1 of Methanocella arvoryzae 
ABC2-1 (M) (Q0W8T3)
ABC2-1 (C) (Q0W8T4) 

Functionally uncharacterized ABC2 transporter #2.  This system is encoded by two genes that overlap and are therefore probably translationally coupled; they are in the same operon with the genes for 2.A.1.144.1.

ABC2 transporter #2 of Methanocella arvoryzae
ABC2-2 (M) (Q0W8T6)
ABC2-2 (C) (Q0W8T7) 

Functionally uncharacterized ABC2 transporter #3.

ABC2 transporter of Myxococcus xanthus
ABC2-3 (M) (Q1D0V0)
ABC2-3 (C) (Q1D0V1) 

Functionally uncharacterized ABC2 transporter #4 of 751 aas with 18 putative TMSs.  The first 6 TMSs are duplicated to give the N-terminal 12 TMSs.  The last 6 TMSs are non-homologous and are of the DUF95 family (TC #9.B.98).

ABC2 transporter of Oscillochloris trichoides 
ABC2 (M) (E1IBA3)
ABC2 (C) (E1IBA4) 
3.A.1.145:  Peptidase Fused Functionally Uncharacterized ABC2-2 (ABC2-2) Family

ABC2 transporter domain fused to an aminopeptidase N domain (Peptidase M1 family) of 1200 aas with 13 putative N-terminal TMSs.

ABC2 protein of Myxococcus xanthus

Putative ABC2 permease of 529 aas and 12 TMSs, Glr0437.

Glr0437 of Gloeobacter violaceus

ABC2 fusion protein of 1194 aas and 13 putative TMSs.  Annotated as ABC transporter involved in multi-copper enzyme maturation; permease component.

Bacteroidetes/Chlorobi group
ABC2 protein of Cecembia lonarensis

Putative ABC2 protein of 537 aas and 14 putative TMSs

ABC2 permease of Methanocella paludicola

Uncharacterized ABC membrane transport protein of 222 aas and 6 TMSs.

Candidatus Wolfebacteria
UP of Candidatus Wolfebacteria bacterium
3.A.1.146:  The actinorhodin (ACT) and undecylprodigiosin (RED) exporter (ARE) family

The probable actinorhodin (ACT) and undecylprodigiosin (RED) exporter (Lee et al. 2012), AreABCD (Sco3956-9).

AreABCD (Sco3956-9) of Streptomyces coelicolor
AreA (C) (Sco3956)
AreB (M) (Sco3957)
AreC (C) (Sco3958)
AreD (M) (Sco3959)

Putative ABC exporter, Isop2111-Isop2114

Isop2111-Isop2114 of Isophaera pallida
Isop2111 (C) (332 aas) (E8R490)
Isop2112 (M) (359 aas; 6 TMSs) (E8R491)
Isop2113 (C) (340 aas) (E8R492)
Isop2114 (M) (298 aas; 7 TMSs) (E8R493) 
3.A.1.147:  Functionally Uncharacterized ABC2-3 (ABC2-3) Family

Putative two component ABC exporter with a membrane protein of 573 aas and 12 TMSs and an ATPase encoded adjacent to the membrane protein and also adjacent to a gene encoding an adenine glycosylase, probably within a single operon.

ABC exporter of Gemmatimonas aurantiaca
Membrane protein (M) (C1A6K7)
ATPase (C) (C1A6K8)

Putative 2-component sporulation-related ABC exporter.  The genes encoding this system are adjacent to a spore germination receptor (TC# 2.A.3.9.5) and a putative signalling molecule transporter (2.A.86.1.11).

Putative 3-component ABC exporter of Paenibacillus mucilaginosus
Protein of 572 aas and 12 putative TMSs (M) (F8FLY8)
ATPase protein of 243 aas (C) (F8FLY7)

Putative two component ABC exporter with the membrane protein having 623 aas and 12 TMSs.

ABC exporter of Isosphaera pallida
Membrane protein (M) (E8R692)
ATPase (C) (E8R694)

Putative two component ABC exporter with a membrane protein of 537 aas and 12 TMSs.

ABC exporter of Ruminococcus torques
Membrane protein (M) (D4M3V3)
ATPase (C) (D4M3V2)

Putative 2 component ABC exporter with a membrane protein of 569 aas and 12 TMSs.

Putative exporter of Natranaerobius thermophilus
Membrane protein (M) (B2A6N2)
ATPase (C) (B2A6N1)

Putative two component ABC exporter

Putative ABC exporter of Clostridium difficile
Membrane protein (M) (C9XJW9)
ATPase (C) (C9XJX0)

Putative ABC transporter with a membrane protein of 582 aas and 11 TMSs.

ABC transporter of Thermaerobacter marianensis
Membrane protein (M) (E6SIR8)
ATPase (C) (E6SIR7)

Putative ABC exporter with a membrane protein of 544 aas and 12 TMSs

ABC exporter of Streptococcus pneumoniae
Membrane protein (M) (B8ZKM8)
ATPase (C) (B8ZKM9)

Putative ABC exporter

ABC exporter of Methanocella conradii
Membrane protein (M) (H8I7G4)
ATPase (C) (H8I7G5)

Uncharacterized protein of 627 aas and 12 TMSs

UP of Desulfosporosinus meridiei
3.A.1.148:  Functionally Uncharacterized ABC2-4 (ABC2-4) Family

ABC lantibiotic NAI-107 immunity exporter, MlbYZ (Pozzi et al. 2015).

MlbYZ of Microbispora sp. ATCC PTA-5024
MlbY (258 aas, 6 TMSs; M)
MlbZ (300 aas; C)

ABC transport system, PspY (264 aas)/PspZ (301 aas)

PspYZ of Planomonospora alba
PspY (M; 264 aas)
PspZ (C; 301 aas)

Uncharacterized ABC transporter

Uncharacterized ABC transporter of Ktedonobacter racemifer

Uncharacterized ABC transporter, AbcYZ [Y (D2BBE4) = M with 6 TMSs; Z (D2BBE3)= C.]

AbcYZ of Streptosporangium roseum
3.A.1.149:  Functionally Uncharacterized ABC2-5 (ABC2-5) Family

ABC immunity system, TrnFG, protecting the bacteria from the bacteriocin, thuricin CD. TrnF is of 213 aas and 6 TMSs while TrnG is of 285 aas and 0 TMSs.  A 79 aa protein, TrnI with 2 TMSs, also provides immunity against thuricin CD, but the mechanism is unknown (Mathur et al. 2014). These proteins incoded in the thuricin operon.

TrnFG of Bacillus thuringiensis

Uncharacterized two component ABC-2 transporter.

UP of Clostridium intestinale
U2PSG5, M, 216 aas, 6 TMSs in a 2 + 4 arrangement
U2NJR5, C, ATPase of 290 aas

Putative 2 component ABC exporter.

Putative ABC exporter
S7U3S6, M, 215 aas, 6 TMSs in a 2 + 4 arrangement
S7U8X0, C, 285 aas, ATPase, ABC-2
3.A.1.150:  Functionally Uncharacterized ABC2-6 (ABC2-6) Family

Putative ABC transporter consisting of an ATPase and three membrane proteins having 4, 10 and 2 TMSs, respectively.  The structure of the ATPase is similar to those of ABC transorteers, and expression is down regulated in response to cold shock (Gerwe et al. 2007).

Putative ABC transporter of Pyrococcus furiosus

Putative ABC transporter consisting of an ATPase and 3 membrane proteins having 4, 10 and 2 TMSs.

Putative ABC transporter of Pyrococcus furiosus
3.A.1.151:  Functionally Uncharacterized ABC2-7 (ABC2-7) Family

3-component putative ABC transporter with two membrane proteins and an ATPase. These three genes are adjacent to a gene encoding a DegV domain-containing protein, a fatty acid binding domain, also found in PTS mannose EIIA proteins (TC# 4.A.6) and dihydrolyacetone kinases (Schulze-Gahmen et al. 2003; Kinch et al. 2005; Nan et al. 2009).

Putative ABC transporter of Halothermothrix orenii

Putative 3-compenent ABC transporter consisting of two membrane proteins and a cytoplasmic ATPase.  Adjacent to genes coding for a MoaJ/NirJ iron-sulfur nitrite-like oxidoreductase and an antilisterial bacteriocin biosynthetic enzyme, AlbA (B5YBB2 and 3, respectively).  The system could be a bacteriocin exporter.

ABC transporter of Dictyoglomus thermophilum
B5YBA9, M, 186 aas and 6 TMSs (may be N-terminally truncated)
B5YBB0, M, 223 aas and 6 TMSs (both in a 2 + 4 arrangement)
BSYBB1, C, 239 aas, ATPase
3.A.1.152:  The lipopolysaccharide export (LptBFG) Family

LPS export system, LptF (M), LptG (M) and LptB (C).  This system is also listed in TCDB under TC#1.B.42.1.2 as part of a multicomponent system.  The entire system is described in detail there. LptB2FG extracts LPSs from the IM and transports them to the outer membrane. Luo et al. 2017 reported the crystal structure of nucleotide-free LptB2FG from P. aeruginosa. It shows that LPS transport proteins LptF and LptG each contain a TM domain (TMD), a periplasmic beta-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggested that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the beta-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB2FG that is distinct from those of classical ABC transporters that transport substrates across the IM (Luo et al. 2017). LptB2FG extracts LPS from the periplasmic face of the IM through a pair of lateral gates and then powers transperiplasmic transport to the OM through a slide formed by either of the periplasmic domains of LptF or LptG, LptC, LptA and the N-terminal domain of LptD. The structural and functional studies of the seven lipopolysaccharide transport proteins provide a platform to explore the unusual mechanisms of LPS extraction, transport and insertion from the inner membrane to the outer membrane (Dong et al. 2017). LptB2 binds novobiocin which stimulates its export activity and renders the membrane more impermeable to novobiocin (Luo et al. 2017 reported the crystal structure of nucleotide-free LptB2FG from P. aeruginosa. It shows that LPS transport proteins LptF and LptG each contain a TM domain (TMD), a periplasmic beta-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggested that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the beta-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB2FG that is distinct from those of classical ABC transporters that transport substrates across the IM (Luo et al. 2017). LptB2FG extracts LPS from the periplasmic face of the IM through a pair of lateral gates and then powers transperiplasmic transport to the OM through a slide formed by either of the periplasmic domains of LptF or LptG, LptC, LptA and the N-terminal domain of LptD. The structural and functional studies of the seven lipopolysaccharide transport proteins provide a platform to explore the unusual mechanisms of LPS extraction, transport and insertion from the inner membrane to the outer membrane (Dong et al. 2017). LptB2 binds novobiocin which stimulates its export activity and renders the membrane more impermeable to novobiocin (Luo et al. 2017). LptB2FG extracts LPS from the periplasmic face of the IM through a pair of lateral gates and then powers transperiplasmic transport to the OM through a slide formed by either of the periplasmic domains of LptF or LptG, LptC, LptA and the N-terminal domain of LptD. The structural and functional studies of the seven lipopolysaccharide transport proteins provide a platform to explore the unusual mechanisms of LPS extraction, transport and insertion from the inner membrane to the outer membrane (Dong et al. 2017). LptB2 binds novobiocin which stimulates its export activity and renders the membrane more impermeable to novobiocin (May et al. 2017).

LptFGB2 of Pseudomonas aeruginosa
LptF, M, Q9HXH4, 375 aas, 6 TMSs
LptG, M, Q9HXH5, 354 aas, 6 TMSs
LptB, C, Q9HVV6, 241 aas, ATPase

Putative ABC exporter of the YjgP/Q (LptFG) family.  The membrane protein has 772 aas and 12 TMSs in a (3 + 3)2 duplicated topology.  The gene adjacent to this membrane protein gene encodes an ABC1 ATPase of 583 aas and 6 N-terminal TMSs with a C-terminal ATPase domain. Most ATPases of family 3.A.1.152 are of the ABC2-type. It is possible, but not demonstrated, that this protein serves to energized the YjgP/Q-dependent transport process.

Putative ABC transporter of Acidobacterium ailaaui

Uncharacterized ABC system of the YjgP/Q family; the two membrane proteins are encoded by adjacent genes, but the gene for the ATPase was not found.  However, a soluble OstA homologue (Q5SL97) of 824 aas is encoded adjacent to the two membrane protein-encoding genes.

UP of Thermus thermophilus

Uncharacterized YjgP/YjgQ family homologue of 441 aas and 6 TMSs. No other YjgP homologue and no ATPase is encoded adjacent to the gene encoding this protein.

UP of Chlorobium phaeovibrioides (Prosthecochloris vibrioformis)

Uncharacterized YjgP/Q homologue of 266 aas and 6 TMSs. No ATPase or another YjgP homologue is encoded by a gene adjacent to this one.

YjgP homologue of Leptonema illini

YjgP/Q homologue of 584 aas an 8 TMSs in a 2 + 3 +3 arrangement.

YjgP homologue of Bizionia argentinensis

YjgP/Q family protein of 392 aas and 6 TMSs

YjgP homologue of Gimesia maris

Uncharacterized YgjP homologue of 585 aas and 6 TMSs; the central hydrophilic domain is 350 aas long, about twice that of many of the homologues.  It might be duplicated.

YgjP homologue of Niabella soli

Lipopolysaccharide transporter that exports LPS from the external surface of the cytoplasmic membrane to the outer membrane, LptB2FG. The 134-kDa protein complex is unique among ABC transporters because it extracts lipopolysaccharide from the external leaflet of the inner membrane and propels it along a filament that extends across the periplasm to directly deliver lipopolysaccharide into the external leaflet of the outer membrane. Dong et al. 2017 reported the crystal structure of this transporter in which both LptF and LptG are composed of a beta-jellyroll-like periplasmic domain and six TMSs. LptF and LptG together form a central cavity containing highly conserved hydrophobic residues. Structural and functional studies suggest that LptB2FG uses an alternating lateral access mechanism to extract lipopolysaccharide and traffic it along the hydrophobic cavity toward the transporter's periplasmic domains. The structure has been presented by Dong et al. 2017.

LptB2FG of Klebsiella pneumoniae
LptB, 241 aas; 0 TMSs, A6TEM0
LptF, 365 aas, 6 TMSs, A6THI3
LptG, 360 aas, 6 TMSs, A6THI4
3.A.1.153:  The Functionally Uncharacterized ABC-X (ABC-X) Family

ABC transporter complex YtrBCD that may play a role in acetoin utilization during stationary phase and sporulation (Yoshida et al. 2000). Expression is induced early in the stationary phase. The six ytr genes form a single operon, transcribed from a promoter present upstream of ytrA. YtrA, which possesses a helix-turn-helix motif of the GntR family, may be a repressor that regulates its own transcription as well as the whole operon. Inactivation of the operon led to a decrease in the maximal cell yield and less-efficient sporulation. B. subtilis produces acetoin as an external carbon storage compound and then reuses it later during stationary phase and sporulation. Possibly the Ytr porter plays a role (Yoshida et al. 2000). The YtrEF system, believed to be a distinct ABC efflux system (M. Saier, unpublished results), can be found under TC# 3.A.1.122.19.

YtrBCD of Bacillus subtilis
YtrB, 292 aas (C)
YtrC, 328 aas (M)
YtrD, 325 aas (M)

Putative ABC acetoin exporter, ABC-2-like protein (M) plus ATPase (C).

ABC porter of Bacillus thuringiensis
ABC2-2-like protein of 375 aas and 8 TMSs (A0RI83)
BAC-type ATPase of 298 aas (A0RI82)
3.A.1.201:  The Multidrug Resistance Exporter (MDR) Family (ABCB)

Broad specificity multidrug resistance (MDR1; ABCB1; P-glycoprotein) efflux pump (exports organic cations and amphiphilic compounds of unrelated chemical structure) (These include: antibiotics, anti-viral agents, cancer chemotheraputic agents, hypertensives, depressants, histamines, emetics, and the protease inhibitor, lopinavir. Pgp also exports immunosuppressants, detergents, long-chain fatty acids, HIV protease inhibitors, synthetic tetramethylrosamine analogues, calcein M, etc.); peptide efflux pump; phospholipid (e.g., phosphatidyl serine), cholesterol and sterol flippase (also called ABCB1 and p-gp)). Binds and probably transports inhibitors and agonists of SUR (2.A.1.208.4) (Bessadok et al., 2011). The 3-d structure has been determined (Aller et al., 2009). It can pump from the cytoplasmic leaflet to either the outer leaflet or the outer medium (Katzir et al., 2010). The inhibitor, 5''-fluorosulfonylbenzoyl 5''-adenosine, an ATP analogue, interacts with both drug-substrate- and nucleotide-binding sites (Ohnuma et al., 2011). Inhibited by sildenafil (Shi et al., 2011), verapamil, indomethacin, probenecid, cetirizine (He et al. 2010), and lapatinib derivatives (Sodani et al., 2012), several of which are also substrates. HG-829 is a potent non-competitive inhibitor (Caceres et al., 2012).  Berberine, palmatine, jateorhizine, cetirizine and coptisine are all P-gp substrates, and cyclosporin A and verapamil are potent inhibitors (He et al. 2010; Zhang et al., 2011).  Transports clarithromycin (CAM), a macrolide antibiotic used to treat lung infections, more effectively than azithromycin (AZM) or telithromycin (TEL) (Togami et al. 2012).  Nucleotides, lipids and drugs bind synergistically to the pump (Marcoux et al. 2013).  Fluorescent substrates have been identified (Strouse et al. 2013).  The centra cavity undergoes alternating access during ATP hydrolysis (van Wonderen et al. 2014).  Structure data suggest that signals are transduced through intracellular loops of the TMDs that slot into grooves on the NBDs. The Q loops at the base of these grooves are required to couple drug binding to the ATP catalytic cycle of drug export (Zolnerciks et al. 2014). Ocotillol analogues are strong competitive inhibitors (Zhang et al. 2015).  Durmus et al. 2015 have reviewed PGP transport of cancer chemotheraputic agents.  ABCB1 variants modulate therapeutic responses to modafinil and may partly explain pharmacoresistance in Narcolepse type 1 (NT1) patients (Moresco et al. 2016).  Inhibitors have been identified (Hemmer et al. 2015).  The open-and-close motion of the protein alters the surface topology of P-gp within the drug-binding pocket, explaning its polyspecificity (Esser et al. 2016). The ATP- and substrate-coupled conformational cycle of the mouse Pgp transporter have been defined showing that the energy released by ATP hydrolysis is harnessed in the NBDs in a two-stroke cycle (Verhalen et al. 2017).  Rilpivirine inhibits MDR1- and BCRP-mediated efflux of abacavir and increases its transmembrane transport (Reznicek et al. 2017).  It transports Huerzine A in the brain a drug that is used for the treatment of Alzheimer's disease (Li et al. 2017). AbcB1 acts in concert with ABCA1, ABCG2 and ABCG4 to efflux amyloid-β peptide (Aβ) from the brain across the blood-brain barrier (BBB) (Kuai et al. 2018).

MDR1 of Homo sapiens

Bile salt export pump, BSEP, ABCB11 or SPGP in the canalicular membrane of liver cells, is associated with progressive familial intrahepatic cholestasis-2 and benign recurrent intrahepatic cholestasis (Kagawa et al., 2008; Stindt et al. 2013; Park et al. 2016). Unconjugaged bile salts and glycine conjugates > taurine conjugates. BSEP mediates biliary excretion of bile acids from hepatocytes. Compounds based on GW4064 (Q96RI1), a representative farnesoid X receptor (RXR) agonist, enhance E297G BSEP transport activity (Misawa et al., 2012).

BSEP of Homo sapiens

Short chain fatty acid phosphatidylcholine translocase (phospholipid flippase), MDR3; AbcB4; Pgy3 (associated with progressive familial intrahepatic cholestasis type 3 (PFIC3) (Degiorgio et al. 2007) and progressive intrafamilial hepatic disease (Quazi and Molday, 2011)). ABCB4 exhibits narrow drug specificity relative to MDR1. Exports digoxin, paclitaxel, vinblastin and bile acids). ABCB4 regulates phosphatidylcholine secretion into bile and its translocation across the plasma membrane in hepatocytes (Voloshyna and Reiss, 2011; Kluth et al. 2014).

MDR3 of Homo sapiens

The multidrug resistance/chloroquine resistance protein, Pfmdr1.  Pfmdr1 is the central system in P.

falciparum artemisinin therapy regimen resistance (Gil and Krishna 2017).
Pfmdr1 of Plasmodium falciparum (P13568)

Auxin efflux pump Pgp1 (MDR1; ABCB1) (Carraro et al. 2012). Regulated by Twd1, an FK506-binding protein immunophilin prolyl/peptidyl isomerase; 8.A.11.1.1 (Bouchard et al., 2006).  Involved in light-dependent hypocotyl elongation (Sidler et al. 1998).

Pgp1 of Arabidopsis thaliana (Q9ZR72)

Auxin efflux pump Pgp19 (MDR11; ABCB19) (regulated by Twd1, an FK506-binding protein immunophilin prolyl/peptidyl isomerase (TC# 8.A.11.1.1) (Bouchard et al., 2006).

Pgp19 of Arabidopsis thaliana (Q9LJX2)

Auxin efflux pump Pgp4; AbcB4; MDR4; PGP4.  Functions in the basipetal redirection of auxin from the root tip. Strongly expressed in root cap and epidermal cells (Terasaka et al., 2005).  Contributes to the basipetal transport in hypocotyls and root tips by establishing an auxin uptake sink in the root cap. Confers sensitivity to 1-N-naphthylphthalamic acid (NPA). Regulates root elongation, the initiation of lateral roots and the development of root hairs. Can transport IAA, indole-3-propionic acid, NPA syringic acid, vanillic acid and some auxin metabolites, but not 2,4-D and 1-naphthaleneacetic acid (Terasaka et al., 2005). Pgps and PINs (TC# 2.A.69) function in coordinated but independent auxin transport but also function interactively in a tissue-specific manner (Blakeslee et al. 2007). Found in the plasma membranes of root hair cells (Cho et al. 2012).

Pgp4 of Arabidopsis thaliana (MCMC) O80725

The aluminum chelate (aluminum sensitivity (ALS1)) protein; expressed in root vacuoles half-type ABC transporter (not induced by aluminum; Larsen et al., 2007).
ALS1 (M-C) of Arabidopsis thaliana (Q0WML0)

Marine skate liver bile salt exporter, BSEP (1348 aas) (transports taurocholine in an ATP-dependent fashion (Cai et al., 2001)) (Most similar to 3.A.1.201.2)
BSEP of Raja erinacea (MC MC) (Q90Z35)

Mdr1; resistance to Cilofungin and other drugs (Lamping et al., 2010)

Mdr1 (MCMC) of Aspergillus fumigatus (B0Y3B6)

Mdr1 azole resistance efflux pump (Lamping et al., 2010)

Mdr1 (MCMC) of Cryptococcus (Filobasidiella) neoformans (O43140)

California mussel ABCB/MDR multixenobiotic resistance efflux pump (Luckenbach and Epel, 2008).

ABCB/MDR transporter of Mytilus californianus (MCMC) (B2WTH9)

Plasma membrane AbcB5. Mediates resistance of tumor cells to doxorubicin and other drugs including taxanes and anthracyclines (Kawanobe et al. 2012). Catalyzes efflux of rhodamine.

AbcB5 of Homo sapiens (Q2M3G0)

P-glycoprotein-1 MDR exporter.  Transports multiple drugs, cancer chemotherapy agents, cancer unrelated compounds and many xenobiotics including ivermectin (Ardelli 2013).  The crystal structure at 3.4 A resolution is available (Jin et al. 2012).  It has 4,000x higher affinity for actinomycin D in the membrane bilayers than in detergent.  A "ball and socket joint" and salt bridges similar to ABC importers suggested that both types of systems, importers and exporters, use the same mechanism to interconnect ATP hydrolysis with transport and achieve alternating access of the substrate binding site to the two sides of the membrane. 

P-glycoprotein-1 of Caenorhabditis elegans

MDR efflux pump, ABCB1a.  Exports canonical MDR susbtrates such as calcein-AM, bodipy-verapamil, bodipy-vinblastine and mitoxantrone (Gokirmak et al. 2012).

ABCB1a of Stronglycentrotus purpuratus

MDR efflux pump, ABCB4a.  Exports canonical MDR susbtrates such as calcein-AM, bodipy-verapamil, bodipy-vinblastine and mitoxantrone (Gokirmak et al. 2012).

ABCB4a of Stronglycentrotus purpuratus

Mitochondrial ABCB10 transporter.  Essential for erythropoiesis, and for protection of mitochondria against oxidative stress.  The 3-d structures of several conformations are available (3ZDQ; Shintre et al. 2013).

ABCB10 of Homo sapiens

Leptomycin B resistance protein 1, Pmd1 of 1362 aas and 13 predicted TMSs (Nishi et al. 1992).

Pmd1 of Schizosaccharomyces pombe

Mitochondrial iron/sulfur complex transporter, AbcB13 of 663 aas (Xiong et al. 2010).

AbcB13 (M-C) of Tetrahymena thermophila

12 TMS multidrug resistance transprter of 1318 aas, AbcB15 (Xiong et al. 2010) is the probable exporter of dichlorodiphenyltrichloroethane (DDT). Expression is induced by treatment with DDT, and this transporter appears to be responsible for DDT tolerance by pumping it out of the cell (Ning et al. 2014).

AbcB15 (M-C-M-C) of Tetrahymena thermophila

Half sized ABCB1 drug (verapamil; rhodamine 6G) exporter of specificity similar to that of P-glycoprotein (3.A.1.201.1).  The 3-d structures of the unbound (2.6 Å) and the allosteric inhibitor-bound (2.4 Å) forms have been determined (Kodan et al. 2014).  The outward opening motion is required for ATP hydrolysis.

ABCB1 of Cyanidioschyzon merolae

Mitochondrial ATP-binding cassette 1, ABCB8.  Mediates doxorubicin resistance in melanoma cells (Elliott and Al-Hajj 2009).  Regulated by the Sp1 transcription factor and down regulated by mthramycin A which blocks Sp1 binding to the DNA (Sachrajda and Ratajewski 2011).

ABCB8 of Homo sapiens

The cyclic AMP efflux pump of 1432 aas, ABCB3 (Miranda et al. 2015).

ABCB3 of Dictyostelium discoideum

Multidrug exporter, MDR49 or Pgp of 1302 aas and 12 TMSs.  Exports many drugs as well as pollutants such as polycyclic aromatic hydrocarbons (PAHs) which are major sources of air, water and soil pollution.  MDR49 is expressed at all developmental stages of the life cycle and in many tissues (Vache et al. 2007).

MDR49 of Drosophila melanogaster (Fruit fly)

MDR transporter, Crmdr1 of 1266 aas and 12 TMSs.  Crmdr1 is constitutively expressed in the root, stem and leaf with lower expression in leaf. It has two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) arranging in "TMD1-NBD1-TMD2-NBD2" direction (Jin et al. 2007).


Crmdr1 of Catharanthus roseus (Madagascar periwinkle) (Vinca rosea)

ABC multidrug exporter, MDR1 of 1341 aas, 12 TMSs and two ATPase domains in an MCMC arrangement.  Miltefosine (hexadecylphosphocholine), the first orally available drug available to treat leishmaniasis, is pumped out of the parasite by MDR1, a P-glycoprotein-like transporter. Overexpression of LtrMDR1 increases miltefosine efflux, leading to a decrease in drug accumulation in the parasites and resistance (Pérez-Victoria et al. 2006).

MDR1 of Leishmania major

Multidrug resistance exporter of 1331 aas and 12 TMSs, TratrD or MDR2. Almost identical throughout must of its length to F2PRR1 from T equinum of 1235 aas and 12 TMSs (Martins et al. 2016). Displays increased levels of transcription of the TruMDR2 gene when mycelia were exposed to acriflavine, benomyl, ethidium bromide, ketoconazole, chloramphenicol, griseofulvin, fluconazole, imazalil, itraconazole, methotrexate, 4-nitroquinoline N-oxide (4NQO) or tioconazole. Disruption of the TruMDR2 gene rendered the mutant more sensitive to terbinafine, 4NQO and ethidium bromide than the control strain, suggesting that this transporter plays a role in modulating drug susceptibility in T. rubrum (Fachin et al. 2006).

TratrD or MDR2 of Trichophyton rubrum (Athlete's foot fungus) (Epidermophyton rubrum)

MDR1 alkaloid/multiple drug efflux transporter of 1292 aas and 12 TMSs (Shitan et al. 2003). 

CjMDR1 of Coptis japonica (Japanese goldthread)

ABC transporter B family member 11 isoform X1 or ABCB11 of 1303 aas and 12 TMSs. Functions to export shikonin (Zhu et al. 2017). Shikonin is a naphthoquinone secondary metabolite with  medicinal value, found in Lithospermum erythrorhizon.

ABCB11 of Jatropha curcas (Barbados nut) (closely related to Lithospermum erythrorhizon)
3.A.1.202:  The Cystic Fibrosis Transmembrane Conductance Exporter (CFTR) Family (ABCC)

Cystic fibrosis transmembrane conductance regulator (CFTR) (also called ABCC7); cyclic AMP-dependent chloride channel; also catalyzes nucleotide (ATP-ADP)-dependent glutathione and glutathione-conjugate flux (Kogan et al., 2003) (may also activate inward rectifying K+ channels). The underlying mechanism by which ATP hydrolysis controls channel opening is described by Gadsby et al., 2006. The most common cause of cystic fibrosis (CF) is defective folding of a cystic fibrosis transmembrane conductance regulator (CFTR) mutant lacking Phe508 (DeltaF508)(Riordan, 2008). The DeltaF508 protein appears to be trapped in a prefolded state with incomplete packing of the transmembrane segments, a defect that can be repaired by direct interaction with correctors such as corr-4a, VRT-325, and VRT-532 (Wang et al., 2007). CFTR interacts directly with MRP4 (3.A.1.208.7) to control Cl- secretion (Li et al., 2007). It has intrinsic adenylate kinase activity that may be of functional importance (Randak and Welsh, 2007). The intact CFTR protein mediates ATPase rather than adenylate kinase activity (Ramjeesingh et al., 2008). Regulated by Na+/H+ exchange regulatory cofactors (NHERF; O14745; TC #8.A.24.1.1) (Seidler et al., 2009). Regulated by protein kinase A and C phosphorylation (Csanády et al., 2010). It is also activated by membrane stretch induced by negative pressures (Zhang et al., 2010). TMS6 plays roles in gating and permeation (Bai et al., 2010; 2011). The 3-D structure revealed the probable location of the channel gate (Rosenberg et al., 2011). Conformational changes opening the CFTR chloride channel pore, coupled to ATP-dependent gating, have been studied (Wang and Linsdell, 2012). Alternating access to the transmembrane domain of CFTR has been demonstrated (Wang and Linsdell, 2012). MRP4 and CFTR function in the regulation of cAMP and beta-adrenergic contraction in cardiac myocytes (Sellers et al., 2012). An asymmetric hourglass, comprising a shallow outward-facing vestibule that tapers toward a narrow "bottleneck" linking the outer vestibule to a large inner cavity extending toward the cytoplasmic extent of the lipid bilayer has been proposed (Norimatsu et al., 2012).

CFTR of Homo sapiens

CFTR of    Epithelial ion channel that plays a role in the regulation of epithelial ion and water transport and fluid homeostasis (Bagnat et al. 2010; Navis et al. 2013; Navis and Bagnat 2015). It mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO3-; selectivity depends on the extracellular chloride concentration. CFTR exerts its function in part by modulating the activity of other ion channels and transporters, and it contributes to the regulation of the pH and the ion content of the epithelial fluid layer. Required for normal fluid homeostasis in the gut (Bagnat et al. 2010) and for normal volume expansion of Kupffer's vesicle during embryonic development as well as for normal establishment of left-right body patterning (Navis et al. 2013; Roxo-Rosa et al. 2015). It is also required for normal resistance to infection by Pseudomonas aeruginosa  (Phennicie et al. 2010).

CFTR of Danio rerio (Zebrafish) (Brachydanio rerio)
3.A.1.203:  The Peroxysomal Fatty Acyl CoA Transporter (P-FAT) Family (ABCD)

Peroxisomal long chain fatty acyl (LCFA) transporter associated with Zellweger Syndrome, ABCD3, PMP70, PXMP1.  Can form heterodimers with ABCD1/ALD and ABCD2/ALDR, but the transporter is perdominantly a homodimer (Hillebrand et al. 2007). Dimerization is necessary to form an active transporter. Interacts with PEX19.  abcd3-knockout mice accumulate bile acid precursors suggesting that Abcd3 imports these compounds as CoA derivatives into peroxisomes (Visser et al. 2007).  These mutants also accumulate pristanic acid suggesting the Abcd3 also imports branchd chain substrates into peroxisomes.

PMP70 of Homo sapiens

Peroxysomal long chain fatty acyl (LCFA) Coenzyme A import porter
Pat1 (758-870 aas; 5 TMSs)/Pat2 (853 aas; 4 TMSs) of Saccharomyces cerevisiae

The peroxysomal long chain fatty acid (LCFA) half transporter, ABCD1 (ALD, the X-linked adrenoleukodystrophy (X-ALD or ALDP) protein) (functions as a homodimer and accepts acyl-CoA esters (van Roermund et al. 2008)). Transports C24:0 and C26:0 as substrates (van Roermund et al., 2011).  ABCD1 deficiency or mutation is associated with plasma and tissue elevation of C24:0 and C26:0 accompanied by demyelination and inflamation (Baarine et al. 2012).  X-ALD is a recessive neurodegenerative disorder that affects the brain's white matter and is associated with adrenal insufficiency. It is characterized by abnormal function of peroxisomes, which leads to an accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system, causing demyelinating disease and adrenocortical insufficiency (Addison's disease or X-linked adrenoleukodystrophy (X-ALD) (Kallabi et al. 2013; Andreoletti et al. 2017) Forms heterodimers with PMP70 (ABCD3; TC#3.A.1.203.1) (Hillebrand et al. 2007).

LCFA transporter of Homo sapiens

The BacA (Rv1819c) porter (selective for the uptake of bleomycin and antimicrobial peptides) (essential for maintenance of extended chronic infection) (Domenech et al., 2009).

BacA of Mycobacterium tuberculosis (M-C) (Q50614)

Peroxisomal importer, Comatose, of substrates for β-oxidation (transports fatty acids and precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) (Dietrich et al., 2009; Visser et al. 2007). The peroxisomal fatty acyl-CoA transporter, Comatose (CTS, ABCD1, ABCD1, ABCC1, PED3, Pxa1; 1337aas) (Nyathi et al., 2010) determines germination potential and fertility and is essential for acetate metabolism (Linka and Esser 2012).  It associates with long chain fatty acyl-CoA synthetases (LACS6 (Q8LPS1) and LACS7 (Q8LKS5) and has intrinsic acyl CoA thiesterase activity (De Marcos Lousa et al. 2013). It has been proposed that it transports and hydrolyzes acyl-CoA esters, releasing a non-esterified fatty acid into the peroxisomal matrix which then needs to be re-activated by peroxisomal LACS6 or LACS7 (Visser et al. 2007).

Comatose of Arabidopsis thaliana (Q94FB9)

Peroxisomal long-chain fatty acid/oleic acid importer, PXA1/PXA2 (Lamping et al., 2010; van Roermund et al., 2011).  PXA1 and PXA2 are two half-ABC transport subunits that can form a heterodimer.  Oxidation of its substrates requires the peroxysomal fatty acyl CoA ligase, suggesting that the free acids are the transported substrates.   

PXA1/PXA2 of Saccharomyces cerevisiae
PXA1 (MC) (P41909)
PXA2 (MC) (P34230)

Peroxisomal fatty acid transporter, ABCD2, ALD1, ALDL1, ALDR, or ALDRP. Transports C22:0 and different unsaturated very long-chain fatty acyl-CoA derivatives including C24:6 and especially C22:6 (van Roermund et al., 2011). The loss of AbcD2 results in greater oxidative stress in murine adrenal cells than the loss of abcd1 (Lu et al. 2007). Based on the 2.85 Å resolution crystal structure of the mitochondrial ABC transporter, ABCB10, Andreoletti et al. 2017 proposed structural models for all three peroxisomal ABCD proteins. The model specifies the positions of the transmembrane and coupling helices and highlights functional motifs and putatively important amino acyl residues.

ABCD2 (M-C) of Homo sapiens (Q9UBJ2)

Peroxisomal/chloroplast fatty acyl CoA transporter, ABCD2 (Linka and Esser 2012).

ABCD2 of Arabidopsis thaliana

ABCD4, PMP70-related, P70R, PMP69 or PXMP1L of 606 aas.  Forms homo- and heterodimers.  May be involved in intracellular processing of vitamin B12 (cobalamin), possibly by playing a role in the lysosomal release of vitamin B12 into the cytoplasm.  Defects cause Methylmalonic aciduria and homocystinuria type cblJ (MAHCJ), a disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) (Coelho et al. 2012).  The amino treminal region determines the subcellular localization of this and other ABC subfamily D proteins (Kashiwayama et al. 2009).

ABCD4 of Homo sapiens

Long chain fatty acid transporter consisting of a heterodimer of AbcD1 (719 aas) and AbcD2 (694 aas) (Xiong et al. 2010).

AbcD1/AbcD2 of Tetrahymena thermophila

Putative fatty acid exporter; homodimer (Moussatova et al. 2008).

YddA (M-C) of E. coli; 561 aas

ABC transporter, BclA, of 586 aas and 6 TMSs in a 2 + 2 + 2 arrangement in the N-terminus and the ABC domain in the C-terminus.  It is a peptide transprter required for bacteroid differentiation.  It catalyzes import of peptides called nodule-specific cysteine-rich (NCR) peptides in the symbiotic nodule cells which house the bacteroids. NCR peptides are related to antimicrobial peptides of innate immunity, but they induce the endosymbionts into a differentiated, enlarged, and polyploid state (Guefrachi et al. 2015). BclA is required for the formation of differentiated and functional bacteroids in the nodules of the NCR peptide-producing Aeschynomene legumes. BclA catalyzes import of NCR peptides and provides protection against the antimicrobial activity of these peptides. Moreover, BclA can complement the role of the related BacA transporter of Sinorhizobium meliloti, which has a similar symbiotic function in the interaction with Medicago legumes (Guefrachi et al. 2015).

BclA of Bradyrhizobium sp. ORS 285

Glycosomal ABC transporter of 683 aas and 6 N-terminal TMSs followed by the ATPase domain. Insertion into the glycosomal membrane is facilitated by the chaparone/receptor, Pex19 (Yernaux et al. 2006).

Glycosomal ABC half transporter of Trypanosoma brucei

Glycosomal ABC transporter of 641 aas and 6 N-terminal TMSs followed by the ATPase domain. Insertion into the glycosomal membrane is facilitated by the chaparone/receptor, Pex19 (Yernaux et al. 2006).

ABC half transporter of Trypanosoma brucei
3.A.1.204:  The Eye Pigment Precursor Transporter (EPP) Family (ABCG)

Eye pigment precursor transporter, White.  Part of a membrane-spanning permease system necessary for the transport of pigment precursors into pigment cells responsible for eye color. White dimerize with Brown for the transport of guanine. The Scarlet (TC# 3.A.1.204.17) and White complex transports a metabolic intermediate (such as 3-hydroxy kynurenine) from the cytoplasm into the pigment granules (Mackenzie et al. 2000).  The White and Scarlet proteins are located in the membranes of pigment granules within pigment cells and retinula cells of the compound eye.  Somatic knockouts of white in the noctuid moth, Helicoverpa armigera block pigmentation of the egg, first instar larva and adult eye, but germ-line knockouts of white are recessive lethal in the embryo (Khan et al. 2017).

White of Drosophila melanogaster

Drug resistance transporter, ABCG2 (MXR; ABCP) (human breast cancer resistance protein, BCRP) (Moitra et al., 2011). It exports urate and haem in haempoietic cells (Latunde-Dada et al., 2006) as well as cytotoxic agents (mitoxantrone, flavopiridol, methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, topotecan, and resveratrol), fluorescent dyes (Hoechst 33342) and other toxic substances (PhIP and pheophorbide a) (Özvegy-Laczka et al., 2005). It also transports folate and sterols: estradiol, and probably cholesterol, progesterone, testosterone and tamoxifen (Janvilisri et al., 2003; Breedveld et al., 2007). It is a homotetramer (Xu et al., 2004). It forms a homodimer bound via a disulfide bond at Cys-603 which stabilizes the protein against ubiquitin-mediated degradation in proteosomes (Wakabayashi et al., 2007), and can for dodecamers with 12 subunits (Xu et al. 2007). It has 6 established TMSs with the N- and C- termini inside (Wang et al., 2008). The following drugs are exported from human breast cancer cell line MCF-7: miloxantrone, daunorubicin, doxorubicin and rhodamine123). Also transports reduced folates and mono-, di- and tri-glutamate derivatives of folic acid and methotrexate (Assaraf et al., 2006). It is an active glutathione efflux pump (Brechbuhl et al., 2010). Mutations in ABCG2 cause hyperuricemia and gout , which led to the identification of urate as a physiological subsrate for ABCG2; it catalyzes elimination of urate across the renal tubular apical membrane (Prestin et al. 2014). Zafirlukast antagonizes ABCG2 multidrug resistance (Sun et al., 2012). Inhibited by Sildenafil (Shi et al., 2011) and lapatinib derivatives (Sodani et al., 2012).  Mutation of basic residues can increase or decrease drug efflux activities (Cai et al. 2010).  A substrate of ABCG2 is d-luciferin, allowing bioluminescent immaging of drug efflux across the blood-brain barrier.  Inhibitors include Ko143, gefetinib and nilotinib (Bakhsheshian et al. 2013).  Fluorescent substrates have been identified (Strouse et al. 2013).  Telabinib reverses chemotheraputic MDR mediated by ABCG2 (Sodani et al. 2014).  Residues involved in protein trafficking and drug transport activity have been identified (Haider et al. 2015).  The 3-d structure in the inward facing conformation has been solved (Rosenberg et al. 2015). Durmus et al. 2015 and Westover and Li 2015 have reviewed BCRP-mediated transport of cancer chemotheraputic agents.  A role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux has been proposed (Macalou et al. 2015).  Functions at the blood:placenta barrier of the mouse (Kumar et al. 2016). The Q141K variant exhibits decreased functional expression and thus increased drug accumulation and decreased urate secretion, and the R482 position, which plays a role the substrate specificity, is located in one of the substrate binding pockets (László et al. 2016). Naturally occurring single nucleotide polymorphisms in humans giving rise to amino acyl residue substitutions in the transmembrane domains result in impared transport of Lucifer Yellow and estrone sulfate (Sjöstedt et al. 2017). A cryoEM structure revealed two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between TMSs. A multidrug recognition and transport mechanism was proposed, and disease-causing single nucleotide polymorphisms were rationalized. The structural basis of cholesterol recognition by G-subfamily ABC transporters was also revealed (Taylor et al. 2017). Catalyzes efflux of ochratoxin A (OTA) (Qi et al. 2017). Penylheteroaryl-phenylamide scaffold allows ABCG2 inhibition. 4-Methoxy-N-(2-(2-(6-methoxypyridin-3-yl)-2H-tetrazol-5-yl)phenyl)benzamide (43) exhibited a highest potency (IC50=61nM)), selectivity, low intrinsic toxicity, and it reversed the ABCG2-mediated drug resistance at 0.1muM (Köhler et al. 2018). ABCG2 acts in concert with ABCA1, ABCB1 and ABCG4 to efflux amyloid-β peptide (Aβ) from the brain across the blood-brain barrier (BBB) (Kuai et al. 2018).

ABCG2 (ABCP) of Homo sapiens (Q9UNQ0)

Putative ABC Transporter WHT-1

WHT-1 of Caenorhabditis elegans (Q11180)

The plant cuticular wax and/or lipid metabolite exporter, CER5; ABCG12; WBC12 (in the plasma membrane of epidermal cells; secretes wax to the plant surface) (Pighin et al., 2004; Panikashvili and Aharoni 2008Panikashvili and Aharoni 2008).

CER5 (C-M) of Arabidopsis thaliana (Q9C8K2)

The ABCG5 (sterolin-1)/ABCG8 (sterolin-2) heterodimeric neutral sterol (cholesterol and plant sterols) (e.g., sitosterol) (phosphoryl donors ATP > CTP > GTP > UTP) exporter; present in the apical membranes of enterocytes and hepatocytes. Cholesteryl oleate, phosphatidyl choline and enantiomeric cholesterol are poorly transported (mutation of either ABCG5 or ABCG8 cause sitosterolemia and coronary atherosclerosis) (Zhang et al., 2006; Wang et al., 2006; 2011). Involved in cell signalling, creation of membrane asymmetry and apoptosis (Quazi and Molday, 2011). The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Lee et al. 2016 used crystallization in lipid bilayers to determine the X-ray structure in a nucleotide-free state at 3.9 A resolution. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter (Lee et al. 2016).

ABCG5/ABCG8 of Homo sapiens
ABCG5 (Q9H222)
ABCG8 (Q9H221)

The efflux porter for phosphatidylcholine and its analogues as well as toxic alkyl phospholipids, ABCG4 (Castanys-Munoz et al., 2007). Also promotes cholesterol efflux to the mature forms of HDL (HDL2 and HDL3) (Voloshyna and Reiss, 2011).

ABCG4 of Leishmania infantum (A4HWI7)

Multidrug resistance efflux pump, AbcG6, causes camptothecin-resistant parasites (Bosedasgupta et al., 2008)

AbcG6 of Leishmania donovani (A8WEV1)

The epidermal plasma membrane cuticular lipid (wax) exporters, ABCG11/ABCG11 and ABCG11/ABCG12; ABCG11 is also called Wbc11; Desperado (DSO); COF1; PEL1. ABCG12 is also called CER5, WBC12 and D3 (Panikashvili and Aharoni 2008).  Required for the cuticle and pollen coat development by controlling cutin and possibly wax transport to the extracellular matrix. Involved in developmental plasticity and stress responses (Bird et al. 2007).  ABCG11 can traffic to the plasma membrane in the absence of ABCG12 and can form flexible dimers. By contrast, ABCG12 was retained in the endoplasmic reticulum in the absence of ABCG11, indicating that ABCG12 can only form dimers with ABCG11 in the plasm membrane of epidermal cells. Some ABCG proteins may be promiscuous, having multiple partnerships, while others may form obligate heterodimers for specialized functions (McFarlane et al. 2010).

ABCG11 of Arabidopsis thaliana

The putative multidrug/pigment exporter, Adp1 (Lamping et al., 2010)

Adp1 (C-M) of Saccharomyces cerevisiae (P25371)

AbcH homologue

AbcH homologue of Caernorhabditis elegans (Q18900)

AbcG Homologue

AbcG of Physcomitrella patens (A9SCA8) 

The intracellular sterol transporter, ABCG1 (Tarling and Edwards, 2011). Involved in cell signalling, creation of membrane asymmetry and apoptosis (Quazi and Molday, 2011). Promotes cholesterol efflux from macrophages to the mature forms of HDL (HDL2 and HDL3) (Voloshyna and Reiss, 2011).  Plays a role in arteriosclerosis (Münch et al. 2012).  The diverse functions invarious cell types have been reviewed by Tarling (2013).  Many mammals have two isoforms, long and short, but mice have only the short isoform (Burns et al. 2013).  Residues have been identified that play roles in stability, oligomerization and trafficking (Wang et al. 2013).  Both the full-length and the short isoforms of ABCG1 can dimerize with ABCG4 (3.A.1.204.20) (Hegyi and Homolya 2016).

ABCG1 of Homo sapiens (P45844)

The ABCG1 transporter homologue 

ABCG1 of Dictyostelium discoideum (Q55DW4)

ABC transporter-like protein ECU11_1340

ECU11_1340 of Encephalitozoon cuniculi

MDR efflux pump, ABCG2a.  Exports canonical MDR susbtrates such as calcein-AM, bodipy-verapamil, bodipy-vinblastine and mitoxantrone (Gokirmak et al. 2012).

ABCG2a of Stronglycentrotus purpuratus

Half ABC transporter, ABCG10.  Secretes isoflavinoids including precursors of the phytoalexin, medicarpin (Banasiak et al. 2013).

ABCG10 of Medicago truncatula

Scarlet.  Part of a membrane-spanning permease system necessary for the transport of pigment precursors into pigment cells responsible for eye color. The scarlet and white (TC# 3.A.1.204.1) complex probably transports a metabolic intermediate (such as 3-hydroxy kynurenine) from the cytoplasm into the pigment granules (Tearle et al. 1989). These proteins are located in the membranes of pigment granules within pigment cells and retinula cells of the compound eye (Mackenzie et al. 2000). Knockouts of scarlet in the noctuid moth, Helicoverpa armigera, are viable and produce pigmentless first instar larvae and yellow adult eyes lacking xanthommatin (Khan et al. 2017).

Scarlet of Drosophila melanogaster

Brown.  Part of a membrane-spanning permease system necessary for the transport of pigment precursors into pigment cells responsible for eye color. Brown and white (TC# 3.A.1.204.1) dimerize for the transport of guanine (Campbell and Nash 2001).  Knockouts of brown in the noctuid moth, Helicoverpa armigera, show no phenotypic effects on viability or pigmentation (Khan et al. 2017).

Brown of Drosophila melanogaster

ABC transporter G family member 3, ABCG3; ABCG.3. Also called the white-brown complex homologue protein 3, WBC3, of 730 aas. Homologue of animal eye pigment precursor uptake porters.  The white, scarlet (TC# 3.A.1.204.17), and brown (3.A.1.204.18) genes of Drosophila melanogaster encode ABC transporter proteins involved with the uptake and storage of metabolic precursors to the red and brown eye colour pigments (Mackenzie et al. 2000).

ABCG3 of Arabidopsis thaliana

ATP-binding cassette sub-family G member 4, ABCG4, half transporter of 646 aas.  ABCG4 can form homodimers, but also heterodimers with its closest relative, ABCG1. Both the full-length and the short isoforms of ABCG1 can dimerize with ABCG4, whereas the ABCG2 multidrug transporter is unable to form a heterodimer with ABCG4 (Hegyi and Homolya 2016). ABCG4 is predominantly localized to the plasma membrane. AbcG4 acts in concert with ABCA1, ABCB1 and ABCG2 to efflux amyloid-β peptide (Aβ) from the brain across the blood-brain barrier (BBB) (Kuai et al. 2018).

ABCG4 of Homo sapiens

Pigment precursor transporter of 644 aas, Ok. In the noctuid moth, Helicoverpa armigera, Ok transports precursors from the cytoplasm into the pigment granules. Knockouts of Ok are viable and produce translucent larval cuticle and black eyes (Khan et al. 2017).

Ok of Bombyx mori

Root heterodimeric half ABCG subfamily lipid  exporter, STR (817 aas)/STR2 (727 aas). Each protein has an ATPase domain followed by a 6 TMS membrane domain.  Exports lipids made from RAM2 (glycerol-3-phosphate acyltransferase)-catalyzed monoacylglycerols, allowing accumulation of extracellular lipids, possibly 2-monopalmitin (Luginbuehl et al. 2017).  Found in the peri-arbuscular membrane and required for colonization by mutualistic mycorrhizal and parasitic fungi (Jiang et al. 2017). Arbuscular mycorrhizal (AM) fungi facilitate plant uptake of mineral nutrients and obtain organic nutrients such as sugars and fatty acids, from the plant, and this ABCG transporter is required to form the symbiosis. Co-overexpressing STR and STR2 led to higher accumulation of extracelular unstaurated lipid polyesters such as cutin monomers (Jiang et al. 2017).

STR/STR2 of Medicago truncatula (Barrel medic) (Medicago tribuloides)

Homo dimeric plasma membrane AbcG1 half ABC transporter of 633 aas and 6 TMSs.  Actively exports volatile organic compounds (Benzenoids and phenylpropanoids such as methylbenzoate and benzyl alcohol, major VOC constituents emitted by flowers) from the flower cell cytoplasm to the external environment (Adebesin et al. 2017).  May also export alcohol glycosides.  Up regulated 100-fold in petunia flowers within the 24 hour period between bud and flower opening stages. Regulated by the ODORANT1 transcription factor (Adebesin et al. 2017).

AbcG1 of Petunia hybrida

Wax precursor (cuticular lipid) exporter of 678 aas and 6 TMSs, AbcG13 (Adebesin et al. 2017).

AbcG13 of Arabidopsis thaliana

ABCG6 of 546 aas and 4 TMSs involved in phosholipid trafficing and drug export in Leishmania tarentolae (Gonzalez-Lobato et al. 2016).

ABCG6 of Trypanosoma grayi (C-M)
3.A.1.205:  The Pleiotropic Drug Resistance (PDR) Family (ABCG)

Pleiotropic drug resistance (PDR; Pdr5) exporter; steroid exporter; sporidesmin toxicity suppressor (Sts1); MDR; cyclic nucleotide exporter; amphipathic anion exporter. Its ATPase activity is inhibited by its substrate, clotrimazole; can use ATP, GTP and maybe UTP to drive efflux (Golin et al., 2007).  Molecular modeling revealed aspects of the binding pocket and mechanism of action (Rutledge et al. 2011).  Charged residues at the end of TMS2 affect transport (Dou et al. 2016).

Pdr5 (Sts1; Ydr1) (C-M-C-M) of Saccharomyces cerevisiae (P33302)

Drug/Sterol/Mutagen exporter, Snq2p
Snq2p of Saccharomyces cerevisiae (P32568)

Weak acid exporter, Pdr12p (exports preservative anions including propionate, sorbate and benzoate) (Mollapour et al., 2008)
Pdr12p of Saccharomyces cerevisiae (Q02785)

Multidrug resistance protein, Cdr1 (confers resistance to cycloheximide and antifungal agents such as azoles and terbinafine) (Holmes et al., 2006; Schuetzer-Muehlbauer et al., 2003); also, transports phospholipids (Shukla et al., 2007). It is the major fluconazole efflux system in fluconazole-resistant C. albicans (Holmes et al., 2008; Basso et al., 2010). Similar to Cdr2. For additional details of both systems, as well as other MDR pumps in various Candida species, see Cannon et al., 1998. Chimeras between Cdr1 and Cdr2 revealed regions determining substrate specificity (Tanabe et al., 2011).  The protein has a large polyspecific drug-binding pocket formed by many of the TMSs (Rawal et al. 2013).  The macrocyclic polyketide, FK520, an analologue of antifungal FK506, and a potent immunosuppressant that prevents T-cell proliferation, displays fungicidal synergism with azoles in Candida albicans and inhibits drug efflux mediated by ABC multidrug transporters including Cdr (Nim et al. 2014).  TMS 5 residues impart substrate specificity and selectively act as a communication link between ATP hydrolysis and drug transport (Puri et al. 2009).  The 4 domains (2Cs and 2 Ms) are connected by intracellular loops that allow coupling between ATP hydrolysis and transport  (Shah et al. 2015) and faciliitate membrane targetting (Shah et al. 2015). Multiple drug binding sites have been identified (Nim et al. 2016). The system also transports steroid hormones such as β-estradiol and corticosterone as well as rhodamine 6G using specific but overlapping binding sites (Baghel et al. 2017).

Cdr1 (C-M-C-M) of Candida albicans (P43071)

Multidrug resistance protein, Cdr2 (confers resistance to azole and other antifungal agents/terbinafine, amorolfine, aspofungin, etc. as well as a variety of metabolic inhibitors) (Schuetzer-Muehlbauer et al., 2003; Basso et al., 2010). Chimeras between Cdr1 an Cdr2 revealed regions determining substrate specificity (Tanabe et al., 2011). Has an external binding site for an inhibiting octapeptide derivative (Niimi et al., 2012).

Cdr2 of Candida albicans (P78595)

Multidrug resistance protein, Cn Afr1 (confers resistance to azole antifungal drugs including fluconazole) (Posteraro et al., 2003)

CnAFR1 (C-M-C-M) of Cryptococcus neoformans (Q8X0Z3)

The multidrug resistance protein, AtrB (confers resistance to all major classes of fungicides as well as natural toxic compounds substrates include: anilinopyrimidine, benzimidazole, phenylpyrrole, phenylpyridylamine, strobirulin, azoles, dicarboximides, quintozene, acriflavin, and rhodamine 6G as well as natural toxins such as camptothecin (an alkaloid) and the stilbene phytoalexin, resveratrol) (Andrade et al., 2000).
AtrB of Aspergillus nidulans (P78577)

The multidrug resistance protein, Pdr11p, mediates sterol uptake by promoting movement of sterols from the plasma membrane to the endoplasmic reticulum where esterification occurs (Li and Prinz, 2004).
Pdr11p of Saccharomyces cerevisiae (P40550)

The plasma membrane Cd2+/Pb2+ efflux pump (heavy metal resistance pump), PDR8 (ABCG36; PEN30, present in root hair and epidermal cells; it may export a broad range of substrates (Kim et al., 2007).  Also reported to transport flavonoid glycosides (phytoalexins) as well as quercitin, kaempeferol, 4-methoxy-indol-3-ylmethylglucosinolate and salicylate (Badri et al. 2012; Stein et al. 2006).  Key factor that controls the extent of cell death in the defense response (Kobae et al. 2006). Necessary for both callose deposition and glucosinolate activation in response to pathogens. Required for limiting invasion by nonadapted powdery mildews (Consonni et al. 2006).

PDR8 of Arabidopsis thaliana (Q9XIE2)

Pleiotropic drug resistance (PDR) exporter, PDR12 (function as a pump to exclude Pb2+ ions and/or Pb2+- containing toxin compounds) (Lee et al., 2005)
PDR12 of Arabidopsis thaliana (Q9M9E1)

The brefeldin resistance protein, Bfr1, (also exports actinomycin D, cerulenin, and cytochalasin B) (Turi and Rose, 1995; Nagao et al., 1995).
Bfr1 of Schizosaccharomyces pombe (P41820)

The plasma membrane Pdr10, a negative regulator for incorporation of Pdr12 (TC# 3.A.1.205.3) into detergent-resistant membranes, a novel role for members of the ABC transporter superfamily (Rockwell et al., 2009) (most like 3.A.1.205.1; 67% identity).
PDR10 of Saccharomyces cerevisiae (P51533)

The putative sterol uptake transporter, Aus1 (also protects against antifungal azoles such as fluconazole and itraconazole; (Nakayama et al., 2007).

Aus1 of Candida glabrata (Q6FUR1)

Anaerobically-induced AusI. Specifically stimulated by phosphatidylserine in proteoliposomes. May translocate cholestrol and derivatives (Marek et al., 2011).

AusI of Saccharomyces cerevisiae (Q08409)

ABCG32/PEC1 transporter.  Required for plant cuticle production (Bessire et al. 2011).

ABCG32/PEC1 of Arabidopsis thaliana

ABC transporter, PDR1.  Secretes phytohormones such as strigolactones that regulate plant shoot architecture and stimulate germination (Kretzschmar et al. 2012).

PDR1 of Petunia hybrida

The monolignol (p-coumaryl alcohol) transporter, ABCG29 or PDR1. In addition to this precursor of lignin biosynthesis, this transporter may transport various phenolic compounds and glucosinolates (Alejandro et al. 2012).  Reported to be required for normal meiotic double strand DNA break formation resulting from interaction with SPO11-1 (De Muyt et al. 2007).

ABCG29 of Arabidopsis thaliana

Small molecule transporter, ABCG10.  Poorly expressed in an lrrB mutant (Sugden et al. 2010).

ABCG10 of Dictyostelium discoideum

TUR2 transporter.  May be a general defense protein. Involved in turion (dormant buds) formation. Confers resistance to the diterpenoid antifungal agent sclareol (van den Brûle et al. 2002).  Induced by abiotic stresses such as cold-stress, cycloheximide and sodium chloride (NaCl). Induction by abscisic acid (ABA) is repressed by cytokinin such as kinetin (Crouzet et al. 2006).

TUR2 of Spirodela polyrrhiza

ABC1 transporter.  Excretes secondary metabolites such as terpenes. Involved in both constitutive and jasmonic acid-dependent induced defense. Secretes the terpenes, sclareol and sclareolide and thereby confers resistance to the fungus, B.cinerea (Stukkens et al. 2005).  Induced by sclareolide and sclareol, and by some phytohormones such as jasmonic acid (JA) and ethylene. Strongly induced by compatible pathogens such as B. cinerea and the bacterium, Pseudomonas syringae pv tabaci, as well as by non pathogenic bacteria such as P. fluorescens, and P. marginalis pv marginalis (Grec et al. 2003).

ABC1 of Nicotiana plumbaginifolia

Plasma membrane ABC family G member 39 (ABCG39) paraquot uptake transporter of 1454 aas.  Also called pleiotropic drug resistance protein, PDR11 or PDR13 (Fujita and Shinozaki 2014).

PDR11 of Arabidopsis thaliana

AbcG34 of 1453 aas and 12 TMSs.  Secretes a major phytoalexin, camalexin, which on the leaf surface protects the plant against necrotophic pathogens (Khare et al. 2017). Also protects against the antifungal agent, sclareol. AtABCG34 expression was induced by Abrassicicola inoculation as well as by methyl-jasmonate, a defense-related phytohormone, and AtABCG34 was polarly localized at the external face of the plasma membrane of epidermal cells of leaves and roots (Khare et al. 2017).

AbcG34 of Arabidopsis thaliana (Mouse-ear cress)

Multidrug resistance (MDR) exporter, (Np)AbcG5/PDR5 of 1498 aas and 12 TMSs.  NpABCG5/NpPDR5 is barely expressed in leaf tissues under normal conditions, but its expression is induced by the biotic stress hormone methyl jasmonate, or when tissues are wounded or chewed by an insect. NpABCG5/NpPDR5 confers resistance to the herbivore Manduca sexta (Toussaint et al. 2017).

PDR5 of Nicotiana plumbaginifolia (Leadwort-leaved tobacco) (Tex-Mex tobacco)

Plasma membrane ABCG1 or PDR1a of 1434 aas and 12 TMSs.  85% identical to TC# 3.A.1.205.21. PDR1 secretes plastid-produced diterpene(s) that are the antimicrobial compounds active in preinvasion defense, as well as the sesquiterpenoid, capsidiol, the major phytoalexin produced by Nicotiana and Capsicum species. Capsidiol is produced in plant tissues attacked by pathogens and plays a major role in postinvasion defense by inhibiting pathogen growth (Shibata et al. 2016).   This protein and ABCG2/PDR2, a close paralogue, export the same compounds and are essential for resistance to the potato late blight pathogen Phytophthora infestans. Thus, ABCG1/2 are involved in the export of both antimicrobial diterpene(s) for preinvasion defense and capsidiol for postinvasion defense against P. infestans.

PDR1 of Nicotiana benthamiana (wild tobacco)

ABC transporter, AtrB or BcatrB, that catalyzes efflux of fungitoxic compounds including the phytoalexin, camalexin.  Camalexin also induces its synthesis (Stefanato et al. 2009).

AtrB of Botryotinia fuckeliana (Noble rot fungus) (Botrytis cinerea)

Multidrug resistance efflux pump of 1567 aas and 12 TMSs. Probably exports many drugs including griseofulvin, itraconazole, terbinafine and amphotericin B (Martins et al. 2016).

MDR of Trichophyton rubrum (Athlete's foot fungus)
3.A.1.206:  The a-Factor Sex Pheromone Exporter (STE) Family (ABCB)

a-Factor sex pheromone (a hydrophobic isoprenylated (farnesylated) carboxymethylated peptide) exporter, Ste6 (Michaelis and Barrowman 2012).

Ste6 of Saccharomyces cerevisiae

Mating factor M secretion protein, Mam1 of 1336 aas and 13 predicted TMSs.  Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size being capable of exporting a mating factor M- GFP fusion protein (Kjaerulff et al. 2005).

Mam1 of Schizosaccharomyces pombe
3.A.1.207:  The Eukaryotic ABC3 (E-ABC3) Family
(functions unknown; ABC-type ATPases have not been identified.)

The hypothetical protein, HP (1209aas; 10TMSs:1+6+3; 2-4 are homologous to 8-10; the FtsX domain) (P. tetraurelia has at least 5 paralogues.)
HP of Paramecium tetraurelia (M) (A0ECD9)

Putative permeases; Duf214 protein (1234aas; 10TMSs: 1+6+3; 2-4 are homologous to 8-10 (the FtsX domain))
Putative permease of Tetrahymena thermophila (M) (Q22NS1)

Hypothetical protein, HP (1465aas; 8TMSs:1+6+1) (D. discoideum has several paralogues)
HP of Dictyostelium discoideum (M) - Q8ST07

Hypothetical protein, HP, 1129aas (homologous are found in many unicellular eukaryotes)

HP of Entamoeba histolytica (M) (C4LT38)
3.A.1.208:  The Drug Conjugate Transporter (DCT) Family (ABCC) (Dębska et al., 2011)

Dębska et al., 2011


Multi-drug resistance-associated protein, MRP1-like protein (MLP1 or MRP1) (Exporter of leukotrienes, glutathione and cysteinyl conjugates of organic anions, drugs, unmodified hydrophobic xenobiotics and hydrophilic conjugated endobiotics). Vincristine and glutathione are co-transported. MRP1 catalyzes export of glutathione during apoptosis (Hammond et al., 2007). Also transports reduced folates as well as mono-, di- and tri-glutamate derivatives of folic acid and methotrexate (Assaraf et al., 2006).
MRP1 of Rattus norvegicus (O88269)

Hepatic canalicular conjugate exporter (the Dubin-Johnson Syndrome protein) (transports bilirubin glucuronides; E2 17 β glucuronide, dianionic bile salts such as taurocholate, taurochenodeoxycholate sulfate and taurolithocholate sulfate; reduced glutathione; glutathione conjugates; glucuronides; cysteinyl leukotrienes; arsenic-glutathione complexes and glutathione disulfide; also exports anthracyclines, epipodophyllotosine, Vinca alkaloids, cisplatin, methotrexate, and the protease inhibitor, lopinavir) (also called ABCC2) (Chen and Tiwari, 2011; Krumpochova et al., 2012).  MK-571 is an inhibitor (Zhang et al., 2011).  Sterol sensing residues have been identified (Gál et al. 2015). Catalyzes efflux of ochratoxin A (OTA) (Qi et al. 2017).

cMRP (MRP2; cMOAT) of Homo sapiens (Q92887)

Oligomycin-resistance protein YOR1 in plasma membrane (confers resistance to oligomycin, rhodamine B, tetracycline, verapamil, eosin Y and ethidium bromide; Grigoras et al., 2007)).

YOR1 (M-C-M-C) of Saccharomyces cerevisiae (P53049)

SUR1 sulfonylurea receptor; subunit and regulator of α-cell ATP-sensitive K+ channel (TC #1.A.2); determines ATP sensitivity; no inherent transport function known; associated with persistent hyperinsulinemic hypoglycemia of infancy due to focal adenomatous hyperplasia (also called ABCC8). Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) cause neonatal diabetes mellitus. Because mutant channels are inhibited less strongly by MgATP, this increases K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes (de Wet et al., 2007). Binds ligands (blockers): glibenclamide, tolbutamide, and meglitinide as well as agonists, SR47063 (a cromakalim analog), P1075 (a pinacidil analog), and diazoxide (Bessadok et al., 2011). ATP activates ATP-sensitive potassium channels composed of mutant sulfonylurea receptor 1 and Kir6.2 with diminished PIP2 sensitivity (Pratt and Shyng, 2011). Dominant missense mutations in ABCC9, promoting open channel formation, cause Cantú syndrome (Harakalova et al., 2012; van Bon et al., 2012). The N-terminal transmembrane domain of SUR1 controls gating of Kir6.2 by modulating channel sensitivity to PIP2 (Pratt et al., 2011). Familial mild hyperglycemia is due to the ABCC8-V84I mutation (Gonsorcikova et al., 2011). ATP regulates KATP channels by promoting dimerization and conformational switching (Ortiz et al. 2013).  Mutations causing neonatal diabetes are attributed to alterations in the affinites for ATP and ADP (Ortiz and Bryan 2015).  Two groups of mutations with different cellular mechanisms have been identified. 1) Channel complexes with mutations in NBD2 of SUR1 traffic normally but are unable to be activated by MgADP. 2) Channel mutations in the TMS domains of SUR1 are retained in the ER and have variable functional impairment (Nessa et al. 2015). KATP channels (Kir6.2/SUR1) in the brain and endocrine pancreas  couple metabolic status to the membrane potential. In beta-cells, increases in cytosolic [ATP/ADP] inhibit KATP channel activity, leading to membrane depolarization and exocytosis of insulin granules. Mutations in ABCC8 (SUR1) or KCNJ11 (Kir6.2) can result in gain or loss of channel activity and cause neonatal diabetes (ND) or congenital hyperinsulinism (CHI), respectively.  Nucleotide binding without hydrolysis switches SUR1 to stimulatory conformations.  Increased affinity for ATP gives rise to ND while decreased affinty gives rise to CHI (Ortiz and Bryan 2015). SUR1 mutations constitute a genetic aetiology for neonatal diabetes, and they act by reducing the KATP channel's ATP sensitivity (Proks et al. 2006).

SUR1 of Homo sapiens (Q09428)

Vacuolar multidrug resistance efflux pump, AtMRP2 (catalyzes vacuolar uptake of glutathione conjugates (i.e., 2,4-dinitrophenyl-GS), glucuronide conjugates (i.e., 17 β-estradiol 17(β-D-glucuronide), and reduced glutathione). Also exports the herbicide, 1-chloro-2, 4-dinitrobenzene, and chlorophyll degradation catabolites (Frelet-Barrand et al., 2008).
AtMRP2 of Arabidopsis thaliana (O64590)

Metal-thiol conjugate exporter, PgpA; glutathione and trypanothione conjugates are exported; confers arsenite and antimonite resistance (trypanothione is glutathione-spermidine).
PgpA of Leishmania tarentolae (P21441)

MRP4 (ABCC4); exporter of cyclic nucleotides (cAMP, cGMP and other nucleotide analogues, particularly purine analogues, methotrexate, bile acids, prostaglandins E1 and E2, reduced folates, 9-(2-phosphonylmethyoxyethyl)adenine, leukotrienes, estradiol 17-β-D-glucuronide) and drug sulfate conjugates (inhibited by nonsteroidal antiinflammatory drugs Reid et al., 2003; Rius et al., 2008)). When overexpressed, it can lower the intracellular concentration of nucleoside/nucleotide analogs, such as the antiviral compounds PMEA (9-(2-phosphonylmethoxyethyl)adenine) or ganciclovir, and of anticancer nucleobase analogs, such as 6-mercaptopurine, after their conversion into the respective nucleotides. MRP4 interacts directly with CFTR (3.A.1.202.1) to control Cl- secretion (Li et al., 2007). It also functions in urate elimination across the renal tubule apical membrane (Prestin et al. 2014). Thus, MRP4 is a broad specificity organic anion exporter (Ritter et al., 2005). MRP4 and CFTR together function in the regulation of cAMP and beta-adrenergic contraction in cardiac myocytes (Sellers et al., 2012). Amino acid changes can alter the uptake of drugs such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA) (Janke et al. 2008).

MRP4 (MOAT-B; ABCC4) of Homo sapiens (O15439)

Drug resistance pump; ABCC1 (MRP1), exports chemotherapeutic agents, organic anions such as leukotriene C4 (LTC4), 17-β-estradiol 17-β-D-glucuronide, glucuronide-X (E217βG, etoposide-glucuronide), estrone-3-sulfate, folic acid and methotrexate, arsenic triglutathione, arsenic and antimonial oxyanions, glutathione (GSH), GSSG, glutathione conjugates (GSH-X; LTC4, DNP-SG, EA-SG, NEH-SG), sulfate-X (E1S, DHEAS), HIV protease inhibitors, anthracyclines, epipodophyllotoxins, and Vinca alkaloids. Changing charged residues in TMS6 (K332, H335 and D336) gave rise to specific changes in specificity (Chen et al., 2006; Haimeur et al., 2002; Leslie et al., 2004). Also exports cobalamine (Vitamin B12) (Beedholm-Ebsen et al., 2010). Also exports cytotoxic metals including antimony, mercuric ions, arsenate and arsenite, but not copper, chromium, cobalt and aluminum, often as glutathione conjugates (Aleo et al., 2005; Vernhet et al., 2000). Notch1 regulates the expression in cultured cancer cells (Cho et al., 2011).  Structural and functional properties of MRP1 have been reviewed comprehensively (He et al. 2011).  Fluorescent substrates have been identified (Strouse et al. 2013).  Pumps out sulfur mustards and nitrogen mustards (mechlorethamine, HN2), potent vesicants developed as chemical warfare agents (Udasin et al. 2015).

MRP1 of Homo sapiens (P33527)

Canicular multispecific organic anion MDR transporter, MRP3 (also called ABCC3) (most similar in sequence to MRP2). MRP3 exports epipodophyllotoxins, etoposide and teniposide, estradiol 17-β-D-glucuronide, leukotriene C4, dinitrophenyl S-glutathione, epoposide glucuronide, methotrexate, bilirubin-glucuronides, bile acids, GSH-X (LTC4, DNP-SG) and sulfate-X (taurolithocholate-3-sulfate).  Substrate translocation and stimulated ATP hydrolysis show positive cooperativity (Hill coefficient = 2) and are half-coupled (Seelheim et al. 2012).  ABCC3 is overexpressed in various types of cancer including carcinogenic stem cells, and plays a role in liver cancer progression (Carrasco-Torres et al. 2015).

MRP3 of Homo sapiens (O15438)

Multidrug (anthracycline) resistance organic anion efflux pump (ABC-C6; MRP6; MOAT-E - the ectopic mineralization disorder, pseudoxanthoma elasticum disease (PXE), protein (Vanakker et al. 2013)) exports glutathione conjugates including leukotriene C4, DNP, and N-ethylmaleimide S-glutathione; also exports anthracyclines, epipodophyllotoxins, cisplatin, and probably exports probenecid, benzbromarone and indomethacin (Chen and Tiwari, 2011).  The system participates in networds of complex diseases (De Vilder et al. 2015). This transporter has an extra N-terminal domain (TMD0) and a loop, L0.  TMD0 is not required for transport function, but L0 maintains ABCC6 in a targeting-competent state for the basolateral membrane and might be involved in regulating the NBDs (Miglionico et al. 2016).  Mutations in the ABCC6 transporter are associated with PseudoXanthoma Elasticum (PXE), a disease of altered elastic properties in multiple tissues. Many of these mutations influence various steps in the biosynthetic pathway, minimally altering local domain structure but adversely impacting ABCC6 assembly and trafficking (Ran and Thibodeau 2016). Loss of function causes pseudoxanthoma elasticum (PXE), an ectopic, metabolic mineralization disorder that affects the skin, eye, and vessels. ABCC6 is assumed to mediate efflux of one or several small molecule compounds from the liver cytosol to the circulation. In mice, abrogating ABCC6 function causes alterations in the liver metabolic profile, suggesting that PXE is a metabolic disease originating from liver disturbance (Rasmussen et al. 2016).

ABCC6 (MRP6) of Homo sapiens (O95255)

Vacuolar metal resistance and drug detoxification protein, yeast cadmium factor (YCF1); transports cadmium-glutathione conjugates, glutathione S-conjugated leukotriene C4, organic glutathione S-conjugates, selenodigluthatione, unconjugated bilirubin, reduced glutathione, and diazaborine (Lazard et al., 2011). Mediates arsenite expulsion, possibly as a glutathione conjugate. Activity is dependent on Tus1p, a guanine nucleotide exchange factor (GEF) for the small GTPase Rho1p and a Rho1p-dependent-positive regulator of Ycf1p (Paumi et al. 2007).


YCF1 of Saccharomyces cerevisiae (P39109)

Bile acid transporter, BAT1 (in vacuoles)
BAT1 of Saccharomyces cerevisiae (P32386)

Cyclic nucleotide (cAMP and cGMP) efflux pump, MRP8 (ABCC11); also exports other nucleoside and nucleotide analogues, and confers resistance to fluoropyrimidines and the anti-AIDS drug, 2',3'-dideoxycytidine (Guo et al., 2003). Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. A SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. Cells with allele A show a lower excretory activity for cGMP than those with allele G. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait (Yoshiura et al., 2006).  Binding sites in ABCC11 for cGMP (cyclic guanosine monophosphate) and 5FdUMP (5-fluoro-2'-deoxyuridine-5'-monophosphate), the active metabolite of the anticancer drug 5-fluoro-uracil, have been identified (Honorat et al. 2013).  MRP8 generally exports a variety of anionic lipophilic compounds including antiviral and anticancer agents (Arlanov et al. 2015).

MRP8 (ABCC11) of Homo sapiens (Q9BX80)

The vacuole (tonoplast) ZmMrp3 anthocyanin pigment transporter (ABCF) (Goodman et al., 2004)
ZmMrp3 of Zea mays
ZmMrp3 (MC-MC) (Q6J0P5)

The general organic anion exporter, MRP5 (MOATC). It exports cyclic AMP, cyclic GMP, 5'-FUMP, glutathione and glutathione conjugates and antimonial tartrate). Also transports reduced folates as well as mono-, di- and tri-glutamate derivatives of folic acid and methotrexate (Assaraf et al., 2006). When overexpressed, it can lower the intracellular concentration of nucleoside/nucleotide analogs, such as the antiviral compounds PMEA (9-(2-phosphonylmethoxyethyl)adenine) or ganciclovir, and of anticancer nucleobase analogues, such as 6-mercaptopurine, after their conversion into the respective nucleotides (Ritter et al., 2005).

MRP5 of Homo sapiens (O15440)

The vacuolar Abc2p (SPAC3F10.11c) transporter for xenobiotics, glutathione S-conjugates and monochlorobimane (Iwaki et al., 2006)
Abc2p of Schizosaccharomyces pombe (MCMC; 1478 aas) (Q10185)

The vacuolar glutathione-conjugate and chlorophyll catabolite transporter, MRP3 (Tommasini et al., 1998).  This protein appears to have an M-M-C-M-C domain order, possibly a characteristic of this ABC subfamily.

MRP3 of Arabidopsis thaliana (Q9LK64)

Vacuolar glutathione conjugate, glutathione exporter; mediates cadmium detoxification and ade2 pigmentation in vivo (Sharma et al., 2002). (Most similar to Ycf1 of S. cerevisiae (TC# 3.A.1.208.11; 41% identity))
Bpt1 of Saccharomyces cerevisiae (P14772)

The possible HCO3- transporter, HLA3 (Duanmu et al., 2009).  Activation of HLA3 expression in high CO2 acclimated cells, where HLA3 is not expressed, resulted in increased Ci accumulation and Ci-dependent photosynthetic O2 evolution specifically in very low CO2 concentrations, which confirms that HLA3 is indeed involved in Ci uptake.  It also suggests that HLA3 is mainly associated with HCO3- transport in very low CO2 concentrations, conditions in which active CO2 uptake is limited (Gao et al. 2015).

HLA3 of Chlamydomonas reinhardtii (A8I268)

The vacuolar MRP1 of 1622 aas. Also called ABCC1 and EST1.  It sequesters in the vacuole glutathione conjugates, folate mono-glutamates (pteroyl-1-glutamate) and antifolates (methotrexate); (Raichaudhuri et al. 2009) (86% identical to MRP2 (3.A.1.208.5). MRP1 of Lithospermum erythrorhizon may play a direct or indirect role in transmembrane transport  of shikonin (Zhu et al. 2017).

MRP1 of Arabidopsis thaliana (Q9C8G9)

The thale cress protein ATMRP5 (ATABCC5), a high-affinity inositol hexakisphosphate transporter; involved in guard cell signaling and phytate storage (Nagy et al., 2009).

MRP5/ABCC5 of Arabidopsis thaliana (Q7GB25)

California mussel ABCC/MRP-type multixenobiotic resistance efflux pump (Luckenbach and Epel, 2008).

ABCC/MRP-type exporter of Mytilus californianus (B2WTI0)

The Sur2B (ABCC9) sulfonylurea receptor. The amino-terminal transmembrane domain of Sur2B binds Kir6.2 (Winkler et al., 2011). Dominant missense mutations in ABCC9, promoting open channel formation, cause Cantú syndrome (Harakalova et al., 2012; van Bon et al., 2012). This protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity.  Associated with early repolarization (ERS) and Brugada (BrS) syndromes (Hu et al. 2014).  This ATP-sensitive potassium (K(ATP)) channel couples glucose metabolism to insulin secretion in pancreatic beta-cells (de Wet et al. 2007).

Sur2B of Homo sapiens (O60706)

Similar to MRP4 of man (TC#3.A.1.208.7). A single amino acid mutation causes resistance to Bt toxin Cry1Ab in the silkworm, Bombyx mori (Atsumi et al., 2012). 83% identical to 3.A.1.208.6.

MRP4-like ABC transporter of Bombyx mori (G1UHW7)

The ABC-thiol (cysteine; glutathione) exporter, MrpA (Mukherjee et al., 2007). 83% identical to 3.A.1.208.6.

MrpA of Leishmania donovani

Mrp2 of 2133 aas.  Confers resistance to quinolone drugs including chloroquine, mefloquine and quinine (Mok et al. 2013).

Mrp2 of Plasmodium falciparum

Multidrug (e.g., ivermectin) exporter, MRP-1 isoform a (Ardelli 2013).

MRP-1 of Ceanorhabditis elegans

Vacuolar iron transporter, Abc3(+) of 1465 aas.  Induced by low iron and repressed by high iron.  Required for growth in a low iron medium.  Probably mobilizes stored vacuolar iron (Pouliot et al. 2010).

Abc3 of Schizosaccharomyces pombe

Multidrug resistance-associated protein 9, MRP9 of 1359 aas. Also called ABCC12. Expressed in testis, but widely expressed in other tissues at low levels. Isoform 5 is specifically expressed in brain, testis and breast cancer cells.

MRP9 or ABCC12 of Homo sapiens

ABCC13 of Macaca mulatta (Rhesus macaque)

Multidrug resistance-associated protein 7, MRP7 or ABCC10 of 1492 aas. Probably involved in cellular detoxification through lipophilic anion extrusion. Isoform 1 is specifically expressed in spleen; isoform 2 is more widely expressed.
MRP7 of Homo sapiens

MRP-like ABC transporter of 1513 aas.  Induced by copper, cadmium and oxidative stress (González-Guerrero et al. 2010).

ABC1 of Rhizophagus irregularis (Arbuscular mycorrhizal fungus) (Glomus intraradices)

Multidrug resistance export pump, ABCC or MRP1 of 1822 aas (González-Pons et al. 2009).

Mrp1 of Plasmodium falciparum

ABCC13 of 1505 aas.  Required for phytic acid accumulation in developing seeds. Phytic acid is the primary storage form of phosphorus in cereal grains and other plant seeds (Xu et al. 2009).

ABCC13 of Oryza sativa

MDR1 (ABCC1) of 1514 aas; 96% identical to the characterized protein of the same length from Rhopalosiphum padi (Bird cherry-oat aphid) (Aphis padi), which exports the insecticides, imidacloprid and chlorpyrifos (Kang et al. 2016).

ABCC1 of Acyrthosiphon pisum (Pea aphid)

ABC transporter with two components, one of 551 aas and 6 TMSs and the other of 585 aas and 6 TMSs; both have the M-C domain order.

ABC transporter of Bdellovibrio exovorus

ABC-type multidrug transporter with two fused ATPases and two fused permease domains; of 1228 aas and 12 TMSs.

Possible MDR pump of Bdellovibrio bacteriovorus

ABC transporter, a 2 component system, both proteins with the M-C domain order.

ABC transporter of Bdellovibrio bacteriovorus

dMDR of 1548 aas; exports daunorubicin (Chahine et al. 2012).

MDR of Drosophila melanogaster (Fruit fly)

Putative fumonisin (mycotoxin) exporter of 1489 aas and about 16 TMSs, Fum19.  Present in an operon with fumonisin biosynthetic enzymes (Proctor et al. 2003).

Fum19 of Gibberella moniliformis (Maize ear and stalk rot fungus) (Fusarium verticillioides)

The antifungal agent, EchonocandinB, exporter, EcdL of 1479 aas and 16 TMSs (Bera et al. 2017).

EcdL of Aspergillus rugulosus

MRP4 ABC anthocyanin/phytic acid efflux porter of 1510 aas and 12 TMSs.  It exports anthocyanin in aleurone tissues ().  ABC transporter that may affect phytic acid transport and compartmentalization. It function directly or indirectly in removing phytic acid from the cytosol. and is required for phytic acid accumulation in developing seeds. It is expressed most highly in embryos, but also in immature endosperm, germinating seed and vegetative tissues. Silencing expression of this transporter in an embryo-specific manner produced low-phytic-acid, high-Pi transgenic maize seeds that germinate normally (Shi et al. 2007). Phytic acid is the primary storage form of phosphorus in cereal grains and other plant seeds.

MRP4 of Zea mays

Arsenate/thioarsentate exporter, MRP12 or ABCC12

AbcC12 of Arabidopsis thaliana (Mouse-ear cress)
3.A.1.209:  The MHC Peptide Transporter (TAP) Family (ABCB)

MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002). TAP1 has 10 TMSs, 4 unique N-terminal TMSs and 6 TMSs that form the translocation pore with N- and C-termini in the cytosol (Schrodt et al., 2006). The TAP2 nucleotide binding site appears to be the main catalytic active site driving transport suggesting asymmetry in the transporter (Perria et al., 2006). The TAP complex shows strict coupling between peptide binding and ATP hydrolysis, revealing no basal ATPase activity in the absence of peptides (Herget et al., 2009).  There are three binding sites on TAP1 for tapasis which interconnects TAP and MHC class I, promotes TAP stability and facilitates heterodimerization (Leonhardt et al. 2014).  TAP is the target of GN1 (TC#8.B.25.1.1), a virally encoded protein inhibitor of viral peptide exposure on the cell surface (Verweij et al. 2008; Rufer et al. 2015). Tapasin (448 aas; O15533) stabilizes TAP2 (Papadopoulos and Momburg 2007). Tapasin is involved in the association of MHC class I with the transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading). TAP plays a key role in the adaptive immune defense against infected or malignantly transformed cells by translocating proteasomal degradation products into the lumen of the endoplasmic reticulum for loading onto MHC class I molecules. TAP transports peptides from 8 to 40 residues, including even branched or modified molecules, suggestive of structural flexibility of the substrate-binding pocket. The bound peptides in side-chains' mobility was strongly restricted at the ends of the peptide, whereas the central region was flexible. Peptides bind to TAP in an extended kinked structure, analogous to those bound to MHC class I proteins (Herget et al., 2011). TAP translocates proteasomal degradation products from the cytosol into the lumen of the endoplasmic reticulum, where these peptides are loaded onto MHC class I molecules by a macromolecular peptide-loading complex (PLC) and subsequently shuttled to the cell surface for inspection by cytotoxic T lymphocytes. As a central adapter protein, tapasin (O15533) (Li et al. 2000) recruits other components of the PLC at the N-terminal domains of TAP. Koch et al. 2006 found that the N-terminal domains of human TAP1 and TAP2 independently bind to tapasin, thus providing two separate loading platforms for PLC assembly. Tapasin binding is dependent on the first N-terminal TMS of TAP1 and TAP2, demonstrating that these two helices contribute independently to the recruitment of tapasin and associated factors (Koch et al. 2006).

TAP1/TAP2 of Homo sapiens

Homodimeric transporter ABCB9 or TAPL. Transports a broad spectrum of peptides (low affinity) from the cytosol to the lysosomal lumen. It exists in two forms (812 aas and 1257 aas). The latter full length protein confers resistance to taxanes and anthracyclines (Kawanobe et al., 2012). Resistance and transport were demonstrated for paclitaxel and docetaxel. Transports a broad range of peptides of 6-60aas (23aas optimal). Has also been detected in the ER. It is stabilized by interaction with LAMP-1 and LAMP-2 (see 9.A.16). (Demirel et al., 2012).  The protein consists of a care transporter plus an N-terminal transmembrane domain (TMD0) required to tageting to the lysosome and for interactions with LAMP-1 and -2 (Tumulka et al. 2013)

TAPL or ABCB9 of Homo sapiens (Q9NP78)

Haf-4/Haf-9 heterodimeric half transporter of 787 aas and 815 aas, respectively.  Probably tranports antigenic peptides. Both proteins localize to the membrane of nonacidic, lysosome-associated, membrane protein homologue (LMP-1)-positive intestinal granules from larval to adult stages. Mutants of haf-4 and haf-9 exhibited granular defects in late larval and young adult intestinal cells, associated with decreased brood size, prolonged defecation cycle, and slow growth (Kawai et al. 2009). Thus they may mediate intestinal granular formation. HAF-4-HAF-9 heterodimer formation is required for their stabilization (Tanji et al. 2013). The HAF-4- and HAF-9-localizing organelles are distinct intestinal organelles associated with the endocytic pathway (Tanji et al. 2016; Tanji et al. 2017).

Haf-4/Haf-9 of Caenorhabditis elegans
3.A.1.210:  The Heavy Metal Transporter (HMT) Family (ABCB)

The mitochondrial iron transporter, ATM1.  The crystal structures of the nucleotide-free and glutathione-bound inward facing, open conformations have been solved at 3.1 and 3.4 Å resolution respectively (Srinivasan et al. 2014).  The glutathione binding site is near the inner membrane surface in a large cavity.  An unknown sulfur compound appears to be exported by Atm1 and used for the synthesis of iron/sulfur centers in the cytoplasm.  This compound also signals iron sufficiency/deficiency to the nucleus (Philpott et al. 2012).

ATM1 of Saccharomyces cerevisiae

The vacuolar heavy metal tolerance protein precursor, HMT1 (transports phytochelins and Cd2+·phytochelin complexes) (Prévéral et al., 2009).
HMT1 of Schizosaccharomyces pombe

The ABC transporter homologue
ABC transporter homologue in Rickettsia prowazekii

ABC7 or ABCB7 iron transporter (X-linked sideroblastis anemia protein, XLSA/A (Fujiwara and Harigae 2013)).  Glutathione-complexed [2Fe-2S] stimulates the ATPase activity in both solution and proteoliposome-bound forms (Kd ∼ 68 μM). This cluster is a likely natural substrate for this transporter, which has been implicated in cytosolic Fe-S cluster protein maturation (Qi et al. 2014).

ABC7 iron transporter of Homo sapiens

Multidrug resistance homologues, Pfmdr2, protein
Pfmdr2 protein of Plasmodium falciparum

Mitochondrial outer membrane/lysosome anionic porphyrin uptake half ABC transporter, ABCB6. Expressed in many mammalian tissues (including fetal liver) in response to intracellular porphyrin. Porphyrin uptake activates de novo porphyrin (haem) biosynthesis (Krishnamurthy et al., 2006).  The first TMS contains a lysosomal targetting signal (Kiss et al. 2015).

ABCB6 of Homo sapiens (Q9NP58; 842 aas)

The homodimeric heavy metal tolerance protein 1, CeHMT-1 (exports phytochelatin ((γ-Glu-Cys)n)-Cd2+ complexes) (Vatamaniuk et al., 2005).  The N-terminal hydrophobic extension domain is required (but not sufficient) for dimerization and therefore is essential for normal function (Kim et al. 2010).

CeHMT-1 of Caenorhabditis elegans (AAM33380)

Mitochondrial ABC transporter, ATM3, involved in iron homeostasis (Chen et al. 2007) and heavy metal resistance (Kim et al. 2006). There are three isoforms: ATM1, ATM2 and ATM3 (Chen et al., 2007). ATM3 can replace the yeast iron/sulfur cluster exporter better than ATM1 or ATM2. Atm3 is most similar to the human and yeast homologues, TC# 3.A.1.210.4 and 3.A.1.210.1, 51% and 47% identical, respectively.  It may function in cytosolic iron-sulfur cluster biogenesis (Bernard et al. 2009) as well as molybdenum cofactor biosynthesis (Teschner et al. 2010).  It performs an essential function in the generation of cytoplasmic iron-sulfur proteins by mediating export of Fe/S cluster precursors. Not required for mitochondrial and plastid Fe-S enzymes. Probably involved in the export of cyclic pyranopterin monophosphate (cPMP) from mitochondria into the cytosol. Mediates glutathione-dependent resistance to heavy metals such as cadmium and lead, as well as their transport from roots to leaves. Regulates nonprotein thiols (NPSH) and the cellular level of glutathione (GSH).

ATM3 of Arabidopsis thaliana (Q9LVM1)

The Ni2+/Co2+ exporter AtmA.  Repressed by Zn2+, but not induced by Ni2+ or Co2+ (Mikolay and Nies, 2009).

AtmA of Cuperiavidus metallidurans (Q1LRE9).

Mitochondrial ABC iron/sulfur complex transporter, AbcB12 of 542 aas.

AbcB12 (M-C) of Tetrahymena thermophila

Inner membrane miltochondrial homodimeric Atm1 of 608 aas and 6 TMSs per subunit.  The structure has been solved to 2.4 Å resolution (Lee et al. 2014).  Required for the formation of cytosolic iron-sulfur cluster-containing proteins (Lill et al. 2012).

Atm1 of Novosphingobium aromaticivorans

ABCB3 of 704 aas and 6 TMSs.  Essential for the biosynthesis of heme in mitochondria, and of iron-sulfur centers (ISC) in the cytoplasm. The protein is an ABC half-transporter that has an N-terminal extension required to target LmABCB3 to the mitochondrion.  Martínez-García et al. 2016 showed that LmABCB3 interacts with porphyrins and is required for the mitochondrial synthesis of heme from a host precursor. It complements the severe growth defect in yeast lacking ATM1, an orthologue of human ABCB7, involved in exporting from mitochondria a gluthatione-containing compound required for the generation of cytosolic ISC. Docking analyzes using trypanothione, the main thiol in the parasite, showed how both, LmABCB3 and yeast ATM1, contain a similar thiol-binding pocket. LmABCB3 is an essential gene as dominant negative inhibition of LmABCB3 is lethal for the parasite. The abrogation of only one allele of the gene did not impede promastigote growth in axenic culture but prevented the replication of intracellular amastigotes and the virulence of the parasites in a mouse model of cutaneous leishmaniasis.

ABCB3 of Leishmania major
3.A.1.211:  The Cholesterol/Phospholipid/Retinal (CPR) Flippase Family (ABCA)

The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009). Mediates efflux of cellular cholesterol and phospholipids to apoA-I (Voloshyna and Reiss, 2011).  Hyperglycemia accelerates ABCA1 degradation (Chang et al. 2013).  Human ABCA1 is down regulated upon infection with Chlamydia pneumoniae which inhibits bacterial growth (Korhonen et al. 2013).  Curcumin induces expression of ABCA1 (Tian et al. 2013).

ABC1 of Mus musculus

The retinal-specific ABC transporter (RIM protein, ABCR or ABCA4) (Stargardt's disease protein, involved in retinal/macular degeneration) in the rod outer segment. ABCA4 is an unusual uptake porter that flips N-retinylidene-phosphatidylethanolamine, a product generated from the photobleaching of rhodopsin, from the lumen to the cytoplasmic side of disc membranes following the photobleaching of rhodopsin, insuring that retinoids do not accumulate in disc membranes Molday, 2007; Molday et al. 2009; Tsybovsky et al. 2013). Also transports several vitamin A derivatives (Sun, 2011).   ABCA4 also actively transports phosphatidylethanolamine in the same direction. Mutations known to cause Stargardt disease decrease N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine transport activity of ABCA4 (Quazi et al. 2012).

RIM protein (ABCR) of Homo sapiens

Multidrug resistance pump, ABCA2 (ABC2). Mediates trafficking of LDL-derived free cholesterol (Voloshyna and Reiss, 2011). Transports endogenous lipids such as myelin (Soichi et al. 2007).

ABCA2 of Homo sapiens

The aced cell death 7 (ced-7) protein (translocates molecules that mediate adhesion between dying and engulfing embryonic cells during programmed death).
Ced-7 of Caenorhabditis elegans (P34358)

The surfactant-secreting porter, ABCA3 (exports lipids and proteins into lamellar bodies). Fatal surfactant deficiency (FSD) can result from mutations in ABCA3, causing abnormal intracellular localization (type I) or decreased ATP hydrolysis (type II). Other mutations cause pediatric interstitial lung disease (pILD) (Matsumura et al. 2008).  ABCA3 is found in lamellar bodies of lung alveolar type II cells where it probably secretes surfactants (mixture of lipids; e.g., PC) and proteins (e.g., surfactant proteins A, B, C and D) stored in lamellar bodies and exocytosed (Matsumura et al., 2006). ABCA3 plays an essential role in pulmonary surfactant lipid metabolism and lamellar body biogenesis, probably by transporting these lipids as substrates (Ban et al., 2007). Cheong et al., 2007 have shown that ABCA3 is critical for lamellar body biogenesis in mice. They suggest it functions in surfactant-protein B processing and lung development late in gestation. Lymphoma exosomes shield target cells from antibody attack, and exosome biogenesis is modulated by lysosome-associated ABCA3 which mediates resistance to chemotherapy. Silencing ABCA3 enhances susceptability of target cells to antibody-mediated lysis. Mechanisms of cancer cell resistance to drugs and antibodies are linked in an ABCA3-dependent pathway of exosome secretion (Aung et al., 2011). 

ABCA3 of Homo sapiens (Q99758)

Xenobiotic transporter, ABCA8 (transports estradiol-β-glucuronide, taurocholate, LTC4, para-amino-hippurate and ochratoxin-A (Tsuruoka et al., 2002)
ABCA8 of Homo sapiens (O94911)

Half sized ABCA exporter, AbcA
AbcA of Dictyostelium discoideum
M-C 655 aas; (Q94479)

AbcA12 Keratinocyte lipid transporter.  Transports lipids in lamellar granules to the apical surface of granular layer keratinocytes. Extracellular lipids, including ceramide, are thought to be essential for skin barrier function. ABCA12 mutations underlie the three main types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations lead to defective lipid transport via lamellar granules in the keratinocytes, resulting in malformation of the epidermal lipid barrier and ichthyosis phenotypes. Lipid transport by ABCA12 is indispensable for intact differentiation of keratinocytes (Akiyama, 2011). 

AbcA12 of Mus musculus (B9EKF0)

ABCA5. Mediates cholesterol efflux to HDL3 (Voloshyna and Reiss, 2011).

ABCA5 of Homo sapiens (Q8WWZ7)

ABCA7. Regulates cellular efflux of phospholipids but not cholesterol, to apo A-1 (Voloshyna and Reiss, 2011).  Associated with late-onset Alzheimer's disease, possibly by influencing amyloid-β (Abeta) accumulation (Zhao et al. 2014).  Known functions of ABCA7 are summarized in Zhao et al. 2014

ABCA7 of Homo sapiens (Q8IZY2)

AOH1; ABCA1 transporter.  Substrates unknown.

ABCA1 of Arabidopsis thaliana

ABCA12 transporter of 917 aas. 

ABCA12 of Arabidopsis thaliana

ABCA12 keratinocyte lipid transporter of 2595 aas (Shimizu et al. 2014).  Functions in epidermal lipid barrier formation and keratinocyte differentiation (Akiyama 2013).  Defects cause a form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE) (Akiyama 2013). ABCA12 plays a role in lipid transport from the Golgi apparatus to lamellar granule in human granular layer keratinocytes (Sakai et al. 2007).

ABCA12 of Homo sapiens

cAMP-dependent and sulfonylurea-sensitive anion transporter, ABCA1 of 2261 aas. Key gatekeeper influencing and possibly catalyzing intracellular phospholipid and cholesterol transport (Orlowski et al. 2007).  Interacts with the MEGF10 protein.  95% identical to the mouse orthologue, 3.A.1.211.1.  Cholesterol efflux from THP-1 macrophages decreases in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression (Wang et al. 2017). The cryoEM struction (4.1 Å) revealed that the two transmembrane domains contact each other through a narrow interface in the intracellular leaflet of the membrane, and two extracellular domains of ABCA1 enclose an elongated hydrophobic tunnel. Structural mapping of dozens of disease-related mutations allowed potential interpretation of their diverse pathogenic mechanisms. Structural-based analyses suggested a plausible ""lateral access"" mechanism for ABCA1-mediated lipid export that may be distinct from the conventional alternating-access paradigm. AbcA1 acts in concert with ABCB1, ABCG2 and ABCG4 to efflux amyloid-β peptide (Aβ) from the brain across the blood-brain barrier (BBB) (Kuai et al. 2018).

ABCA1 of Homo sapiens

ATP-binding cassette sub-family A member 6, ABCA6 of 1617 aas. Ttransporter which may play a role in macrophage lipid homeostasis. Up-regulated during monocyte differentiation into macrophages. Down-regulated by cholesterol loading of macrophages.
ABCA6 of Homo sapiens

ATP-binding cassette sub-family A member 9, ABCA9 of 1624 aas. May play a role in monocyte differentiation and lipid homeostasis. Expressed in fetal tissues with highest expression in fetal heart and kidney. Up-regulated during monocyte differentiation into macrophages. Down-regulated by cholesterol loading of macrophages.

ABCA9 of Homo sapiens

ATP-binding cassette sub-family A member 10, ABCA10 of 1543 aas. May play a role in macrophage lipid homeostasis. Highly expressed in skeletal muscle, heart, brain and gastrointestinal tract. Down-regulated by cholesterol loading of macrophages.

ABCA10 of Homo sapiens

ATP-binding cassette sub-family A member 13, ABCA13, of 5058 aas. Expressed in testis, bone marrow and trachea.

ABCA13 of Homo sapiens

ABC transporter A family member 2, ABCA2 or ABCA.2 of 1621 aas.
ABCA2 of Dictyostelium discoideum
3.A.1.212:  The Mitochondrial Peptide Exporter (MPE) Family (ABCB)

The mitochondrial peptide exporter, Mdl1p (exports peptides of 6-21 amino acyl residues from the mitochondrial matrix as well as degradation products of misassembled respiratory chain complexes) (Janas et al., 2003; van der Does et al., 2006; Gompf et al., 2007). A leaderless Mdl1p targets to the ER membrane instead of to the mitochondria (Gompf et al., 2007).
Mdl1p of Saccharomyces cerevisiae (P33310)

ABC mitochondrial peptide/MDR half transporter, MdlB. High copy number suppressor of ATM1 [iron-sulfur cluster transporter (3.A.1.210.1)]
Md1B of Saccharomyces cerevisiae (M-C) (P33311)

ABC-type MDR2 of 802 aas and 6 TMSs.  Exports many drugs including antifungal agents (Martins et al. 2016).

MDR of Trichophyton tonsurans (Scalp ringworm fungus)