PaeA, YtfL, UPF0053 inner membrane protein, Duf21 domain containing protein, HlyC/CorC family transporter, hemolysin homolog of 447 aas and 4 N-terminal TMSs (residues 1 - 200) followed by a large hydrophilic domain (cystathionine beta-synthase, CBS, residues 201 - 447), possibly with a single TMS at about residue 320. It transports cadaverine and putrescine.  In fact, Salmonella, Klebsiella pneumoniae (TC# 1.A.112.1.12) and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels of polyamines and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Iwadate et al. 2021 demonstrated that PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. PaeA is involved in stationary phase survival when cells are grown in acidic medium in which they produce cadaverine. The paeA mutant is sensitive to putrescine, but not spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH > 8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA mutant phenotype, and overexpression of paeA in exponential phase partially complements a cadB mutant grown in acidic medium. Thus, PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions (Iwadate et al. 2021).

PaeA of E. coli

Uncharacterized protein of 181 aas and 1 N-terminal TMS followed by three peaks of low degrees of hydrophobicity.

UP of Salmonella enterica

Type 10 protein secretion system consisting of proteins encoded within a single gene cluster that includes (1) a LysR-type transcriptional regulator (Stm0014; Q8ZS13; 315 aas), (2) a holin (Stm0015; Q8ZS12; 114 aas; see also TC family # 1.E.5), (3) a peptidoglycan hydrolase (a muramidase; Stm0016; Q8ZS11; 177 aas), (4) a second transcriptional regulator, ToxR-like,  (Stm17; Q8ZS10), and (5) the secreted exo-chitinase (Stm0018; Q8ZS09; 699 aas).

Type 10 secretion system of Salmonella enterica (Typhi)

LysR-type transcriptional regulator, Q8ZS13
Holin, Q8ZS12
Peptidoglycan hydrolyase, Q8ZS11
ToxR-like transcriptional regulator, Q8ZS10
Chitinase (secreted), ChiA, Q8ZS09

Nitrite channel transporter, NirC, of 382 aas. Structure/function studies including the x-ray structure of the Salmonella orthologue have been reported (Rycovska-Blume et al. 2015).

NirC of Thermofilum pendens

The flagellar motor (pmf-dependent) (MotA-MotB). TMSs 3 and 4 of MotA and the single TMS of MotB comprise the proton channel, which is inactive until the complex assembles into a motor. Hosking et al. 2006 identify a periplasmic segment of the MotB protein that acts as a plug to prevent premature proton flow. The plug is in the periplasm just C-terminal to the MotB TMS flanked by Pro52 and Pro65. The Pro residues and Ile58, Tyr61, and Phe62 are essential for plug function (Hosking et al. 2006).

The mechanism of proton passage and coupling to flagellar rotation has been proposed (Nishihara and Kitao 2015).  About a dozen MotA/B complexes are anchored to the peptidoglycan layer around the motor through the C-terminal peptidoglycan-binding domain of MotB (Castillo et al. 2013). Dynamic permeation by hydronium ions, sodium ions, and water molecules has been observed using steered molecular dynamics simulations, and free energy profiles for ion/water permeation were calculated (Kitao and Nishihara 2017). They also examined the possible ratchet motion of the cytoplasmic domain induced by the protonation/deprotonation cycle of the MotB proton binding site, Asp32. The motor (MotAB) consists of a dynamic population of mechanosensitive stators that are embedded in the inner membrane and activate in response to external load. This entails assembly around the rotor, anchoring to the peptidoglycan layer to counteract torque from the rotor and opening of a cation channel to facilitate an influx of cations, which is converted into mechanical rotation. Stator complexes are comprised of four copies of an integral membrane A subunit and two copies of a B subunit. Each B subunit includes a C-terminal OmpA-like peptidoglycan-binding (PGB) domain. This is thought to be linked to a single N-terminal transmembrane helix by a long unstructured peptide, which allows the PGB domain to bind to the peptidoglycan layer during stator anchoring. The high-resolution crystal structures of flagellar motor PGB domains from Salmonella enterica have been solved (Liew et al. 2017). Change in the C ring conformation for switching and rotation involve loose and tight intersubunit interactions (Sakai et al. 2019).

MotA and MotB of E. coli

The motor complex of the bacterial flagellum, MotAB. MotA is 295 aas long with about 5 putative TMSs in a 2 + 1 + 2 TMS arrangement, possibly with a C-terminal additional TMS.  MotB is 309 aas long with a single N-terminal TMS.  They comprise the stator element of the flagellar motor complex and are required for rotation of the flagellar motor. Together they form the transmembrane proton channel. These two proteins are 94 and 91% identical to the E. coli complex (TC# 1.A.30.1.1) (Morimoto and Minamino 2014).

MotAB of Salmonella enterica, subspecies Typhimurium

SiiAB putative energizer of giant adhesin, SiiE (repetitive 5,559 aa protein) export (Wille et al. 2013).

SiiAB of Salmonella enterica 
SiiA (210 aas; 1 TMS) (E1WEU7)
SiiB (462 aas; 3 TMSs) (E1WEU8) 

Divalent cation (Mg²⁺, Co²⁺ and Ni²⁺) transport system, CorA

CorA of Salmonella typhimurium (P0A2R8)

Zn²⁺/Cd²⁺ efflux system, ZntB. Mg²⁺ is not transported. Wan et al. 2011 reported crystal structures in dimeric and physiologically relevant homopentameric forms at 2.3 Å and 3.1 Å resolutions, respectively. The funnel-like structure is similar to that of the homologous Thermotoga maritima CorA Mg²⁺ channel and a Vibrio parahaemolyticus ZntB (VpZntB). However, the central α7 helix forming the inner wall of the StZntB funnel is oriented perpendicular to the membrane instead of the marked angle seen in CorA or VpZntB. Consequently, the StZntB funnel pore is cylindrical, not tapered, which may represent an "open" form of the ZntB soluble domain. There are three Zn²⁺ binding sites in the full-length ZntB, two of which could be involved in Zn²⁺ transport.

ZntB of Salmonella enterica serovar Typhimurium

Outer membrane porin of 383 aas, OmpS2.  Activated by OmpR and LeuO (Fernández-Mora et al. 2004).

OmpS2 of Salmonella typhi

Outer membrane porin, OmpS1 of 394 aas.  mutants defective for OmpS1 are attenuated for virulence in mice (Rodríguez-Morales et al. 2006).

OmpS1 in Salmonella enterica serovar Typhi

Weakly anion-selective NmpC (OmpD) porin (Prilipov et al. 1998).  Transports methyl benzyl viologen, ceftriaxone and hydrogen peroxide in Salmonella species (Hu et al. 2011; Calderón et al. 2010).

NmpC of E. coli

The MisL autotransporter/fibronectin binding protein; expression of misL is regulated by MisT (Tükel et al., 2007)

MisL of Salmonella typhimurium (AAD16954)

Autotransporter-1, ShdA (2035 aas) (Kingsley et al., 2003).

ShdA of Salmonella enterica (Q9XCJ4)

Autotransporter-1, BigA (1953 aas) (Lauri et al. 2011).

BigA of Salmonella typhimurium (P25927)

Ferric enterobactin (also ferricorynebactin) receptor, IroN

IroN of Salmonella typhimurium

TonB-dependent receptor of 700 aas, YncD, a probable iron transporter/receptor in the outer membrane.  Deletion of the orthologous yncD genes in Salmonella strains leads to attenuated strains, potentially useful for vaccine development (Xiong et al. 2012; Xiong et al. 2015). Its synthesis is depressed by inclusion of high glucose concentrations in the medium (Yang et al. 2011). YncD is a receptor for a T1-like Escherichia coli phage named vB_EcoS_IME347 (IME347) (Li et al. 2018).

YncD of E. coli

TolC outer membrane exporter of hemolysin, drugs, siderophores such as enterobactin, etc. (Bleuel et al., 2005). The 3-d structure is available (PDB#1EK9). The three monomers form a continuous channel, and each monomer contributes 4 β-strands to the 12 stranded β-barrel (Koronakis et al. 2000). The Salmonella enterica subspecies Typhi homologue is the ST50 antigen (G4C2H4) used in tests for typhoid fever, and a 2.98 Å resolution structure revealed a trimer that forms an alpha-helical tunnel and a beta-barrel transmembrane channel traversing the periplasmic space and outer membrane, respectively (Guan et al. 2015). K. pneumoniae TolC plays a role in resistance towards most antibiotics, suggesting that it can interact with the AcrB efflux pump (Iyer et al. 2019).

TolC of E. coli

Chitoporin, ChiP or YbfM of 468 aas. Takes up chitosugars such as chitobiose.  It also plays a role in carbapenem (imipenem) resistance.  The orthologue in Proteus mirabilis is ImpR, and that in Salmonella species is YbfM. It is subject to regulation by the small RNA, MicM (Tsai et al. 2015).  Loss of OmpC and OmpF results in poor growth, by expression of chiP restores growth (Knopp and Andersson 2015).

ChiP of E. coli (P75733)

Oligosaccharide porin, ScrY (transports sucrose, raffinose and maltooligo-saccharides) (Kim et al. 2002).  The 3-d structure known (PDB ID 1A0S).  Sucrose translocation through the pore showed two main energy barriers within the constriction region of ScrY. Three asparate residues are key residues, opposing the passage of sucrose, all located within the L3 loop (Sun et al. 2016).

ScrY of Salmonella typhimurium

OmpL porin. Nearly identical to Salmonella typhimurium YshA which appears to be a 10 β-stranded transmembrane β-barrel which forms a pore with a radius of 0.7nm (Freeman et al., 2011). May be an oligogalacturonate-specific porin (Shevchik and Hugouvieux-Cotte-Pattat, 2003).

OmpL of E. coli

Outer membrane porin, OmpW.  Involved in paraquot efflux (Gil et al. 2007). OmpW also participates in the efflux of EmrE-specific substrates across the OM (Beketskaia et al. 2014). The 3-d structure is available (PDB#2F1C).

OmpW of Salmonella typhimurium

The trimeric AT adhesin, essential for virulence, SadA (1461 aas).  The high resolution structure has been solved using the "dictionary" approach (Hartmann et al. 2012).  It's insertion into the outer membrane may be dependent on the BAM complex (TC# 1.B.33) as well as a small inner membrane lipoprotein, SadB (Grin et al. 2013).

SadA of Salmonella enterica

The ZirS/T (ZirS (276 aas)) is the putative exoprotein passenger domain, but it shows no sequence similarity to passenger domains of other Int/Inv family members. ZirT (660 aas) is the outer membrane β-barrel postulated transporter (Gal-Mor et al., 2008).

ZirST of Salmonella enterica
ZirS β-barrel domain protein (Q8ZP79)
ZirT (Q8ZP78)

DUF481 outer membrane protein of 241 aas, an N-terminal signal sequence and 10 putative β-TMSs.

DUF481 OMP of Salmonella enterica

Gasdermin family protein of 252 aas and 1 or 2 central TMSs. The 3-D structure is known (7N52_A-D). Bacterial gasdermins are activated by caspase-like proteases, oligomerize into large membrane pores, and defend against pathogenic bacteriophage (Johnson et al. 2022). They mediate an ancient mechanism of prokaryotic cell death (Johnson et al. 2022).

Gasdermin protein of Salmonella enterica subsp. enterica serovar Typhi (Salmonella typhi)

Co²⁺-resistance protein, CorC, of 292 aas and 0 TMSs (Sponder et al. 2010).  The E. coli orthologue (P6AE78) is 97% identical to the S. enterica protein.

CorC of Salmonella typhimurium (P0A2L3)

Small toxic protein shoB osf 32 aas and 1 TMS.

ShoB of Salmonella enterica subsp. enterica

Spider peptide, Gomesin, of 84 aas and 1 N-terminal TMS.  Gomesin is active against several Gram-positive bacteria such as Bacillus spp, Staphylococcus spp and E.faecalis, several Gram-negative bacteria such as E. coli, K. pneumoniae,   and Salmonella spp, filamentous fungi such as N. crassa, T. viridae and yeasts such as  C. albicans. It is active against the parasite L.amazonensis as well. Tanner et al. 2018 concluded that it is hemolytic, permeabilizing cell membranes, probably a pore former, but Zhang et al. 2019 concluded that it induces membrane protrusion, folding and laceration without forming pores.

Gomesin of Acanthoscurria gomesiana (Tarantula spider) (Phormictopus pheopygus)

IIITCP protein complex, IpaB/IpaC/IpaD. Physical contact with host cells initiates secretion and leads to assembly of a pore, IpaB/IpaC, in the host cell membrane. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and the two pore-forming proteins, IpaB and IpaC. The atomic structures of IpaD and a protease-stable coiled-coil fragment in the N-terminal regions of IpaB from S. flexneri and the homologous SipB from Salmonella enterica have been determined (Barta et al. 2012).  Structural comparisons revealed similarity to the coiled-coil regions of pore-forming proteins such as colicin Ia (TC# 1.C.1.1.1).  Interaction between IpaB and IpaD at the needle tip is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips (Veenendaal et al. 2007). The N-terminus of IpaC is extracellular and the C-terminus is intracellular, and its topology has been studied (Russo et al. 2019). Residures lining the pore channel of the plasma membrane-embedded Shigella flexneri type 3 secretion translocase, IpaB, have been identified (Chen et al. 2021).

IpaB/IpaD of Shigella dysenteriae
IpaB (P18011)
IpaD (P18013)
IpaC (P18012)

IIICP protein complex SseB/SseC/SseD; SseB: translocon sheath protein; SseC and SseD: translocon pore subunits of the Salmonella pathogenicity island 2 (SPI2)

The Subtilase cytotoxin, SubAB. Pentameric SubB, but not SubA, is homologous to ArtB of Salmonella enterica. SubA (AB5 subtilase) cytotoxin inactivates the endoplasmic reticulum chaperone, BiP (Paton et al., 2006; Beddoe et al., 2010).

Subtilase cytotoxin AB (SubAB) of E. coli
Subtilase A (Q3ZTX7)
Subtilase B (Q3ZTX8)

Putative uncharacterized holin of 75 aas and 1 or 2 TMSs.  Shows extensive similarity to members of TC family 1.E.25.

Holin of Salmonella enterica

Enterobacterial phage holin family 2 protein, GpY from phage P2

GpY of phage P2

Putative holin of 107 aas and 1 C-terminal TMS.

Putative holin of Salmonella phage SSU5

Holin, Stm0015, of 114 aas and 3 TMSs. This holin, together with a peptidoglycan hydrolase, Stm0016, comprises a secretion system (type 10) for an exo-chitinase of 699 aas (Stm0018) (partially homologous to the protein listed under TC# 9.B.29.2.7 (Chi1)).

Holin of Salmonella enterica (subsp. Typhimurium)

Small toxic membrane protein, Stm of 71 aas

Stm of Salmonella enterica

Tar ligand binding domain-containing protein, partial. of 72 aas and 1 TM

Tar ligand binding protein of Salmonella enterica

Putative holin of 196 aas and 2 or 3 TMSs.

Putative holin of Salmonella phage ViI

Putative holin (DUF745 protein) of 102 aas and 3 TMSs.

Holin of Salmonella phage SPN1S

Putative holin of 79 aas and 2 TMSs

Holin of Salmonella phage Akira

DNA/protein translocase of phage Salmonella phage P22 consisting of gp7, gp20, gp16 and gp26 (Perez et al., 2009). A homologue of gp20 in the phage Sf6 of S. flexneri, gp12, forms a decameric constricted channel though the outer member of the bacterium (Zhao et al. 2016). The other two recognized constituents of the Sf6 phage injectisome are gp11 (like gp7 of phage P22) and gp13 (like gp16 of phage P22).

DNA/protein translocase of phage P22
gp7 (Q01074) DNA transfer protein of the injectisome
gp16 (Q01146) DNA/protein translocase of the injectisome
gp20 (Q01076) Lytic transglycosylase of the injectisome
gp26 (Q35837) Tail Needle protein

The PduA shell protein of 99 aas which forms a hexameric array with a porein the array for diffusion of 1,2-propanediol but not propionaldehyde (Park et al. 2017).  A serine that protrudes into the poreat the point of construction to form a hydrogen bond with propionaldehyde prevent it's free diffusion. 

PduA of Salmonella typhimurium

PduB shell protein of 270 aas of a propanediol utilization polyhedral body

PduB of Salmonella paratyphi C

Samonella phage P22 portal protein 1 of 725 aas and no TMSs. It forms a dodecameric ring structure and plays an important role in ejection of the phage DNA, through the cell envelope, into the host cell cytoplasm (Lokareddy et al. 2017). See family description for more details.

Portal protein of Salmonella phage P22

Minor myo-inositol transporter, IolT2, of 478 aas (Kröger et al. 2010).

IolT2 of Salmonella enterica

Florfenicol-chloramphenicol resistance drug exporter, FloR of 404 aas and 12 TMSs (Braibant et al. 2005).

FloR of Salmonella enterica subsp. enterica serovar Typhimurium str. DT104

Methylviologen (paraquat):H⁺ antiporter, SmvA (also exports ethidium bromide, acriflavin, malachite green, pyronine B and benzyl viologen) (Villagra et al. 2008).

SmvA of Salmonella typhimurium

P-glycerate:P_i antiporter, Pgt.  Takes up phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for rapid growth (Saier et al. 1975).  Not present in E. coli K12, but is present in many intracellular pathogenic strains of E. coli (Tang and Saier, unpublished observations).

PgtP of Salmonella typhimurium

2-Deoxy-D-ribose porter, DeoP (Christensen et al., 2003).  Plays a role in colonization of the mouse intestine (Martinez-Jéhanne et al. 2009).

DeoP of Salmonella typhimurium LT-2 (gi 16767076)

BtsT (from the German word for pyruvate: """"Brenztraubensäure"""" transporter) or YjiY of 716 aas and 18 TMSs.  It is a high affinity (K_m + 16 μM), inducible, specific pyruvate:proton uptake symporter (Kristoficova et al. 2017). Expression of the btsT (yjiY) gene is regulated by the LytS-like histidine kinase, BtsS, a sensor of extracellular pyruvate, together with the LytTR-like response regulator, BtsR (Kristoficova et al. 2017).It may also mediate uptake of specific peptides, thus initiating their metabolism, but this has not been demonstrated directly. It indirectly influences flagellar biosynthesis and virulence. BtsT (YjiY) is required for successful colonization of Salmonella in the mouse gut (Garai et al. 2015). It also influences expression of the mgtC gene to regulate biofilm formation (Garai et al. 2017).

YjiY of Salmonella enterica; subspecies Typhimurium (strain LT2)

Chlorhexidine-responsive putative chlorhxidine exporter of 160 aas and 4 TMSs, AceI (Hassan et al. 2013). It confers resistance to both proflavine and acriflavine by an active efflux mechanism (Hassan et al. 2015). AceR is an activator of aceI gene expression when challenged with chlorhexidine (Liu et al. 2018). This system also exports polyamines (organic diamines) such as cadaverine and putrescine (and possibly spermidine with low affinity).  It is induced preferentially by cadaverine and putrescine, and to a much lesser extent by spermidine. An AceI-E15Q mutant is inactive (Hassan et al. 2019).

AceI of Salmonella typhi

PbgA (YejM) of 586 aas and 5 N-terminal TMSs with a C-terminal alkaline phosphatase-like domain (Dalebroux et al. 2015). The globular domains of PbgA resemble the structures of the arylsulfatase protein family and contains a novel core hydrophobic pocket that may be responsible for binding and transporting cardiolipin (Dong et al. 2016).  PhoPQ is activated within the intracellular phagosome environment of the host animal, where it promotes remodeling of the outer membrane and resistance to innate immune antimicrobial peptides. Maintenance of the PhoPQ-regulated outer membrane barrier requires PbgA, an inner membrane protein with a transmembrane domain essential for growth, and a periplasmic domain required for PhoPQ-activated increases in outer membrane cardiolipin. Fan et al. 2020 reported the crystal structure of cardiolipin-bound PbgA, adopting a transmembrane fold that features a cardiolipin binding site in close proximity to a long and deep cleft spanning the lipid bilayer. The end of the cleft extends into the periplasmic domain of the protein, which is structurally coupled to the transmembrane domain via a functionally critical C-terminal helix. In conjunction with a conserved putative catalytic dyad situated at the middle of the cleft, structural and mutational analyses suggest that PbgA is a multifunction membrane protein that mediates cardiolipin transport, a function essential for growth, and perhaps catalysis of an unknown enzymatic reaction (Fan et al. 2020).

PbgA of Salmonella enterica

C₄-dicarboxylate transporter, YhiT (probably transports succinate, fumarate, aspartate, asparagine, carbamoyl phosphate and dihydroorotate; Zaharik et al., 2007)

YhiT of Salmonella enterica
(Q8ZLD2)

Uncharacterized protein of 119 aas and 4 TMSs.  May be a fragment.

UP of Salmonella sp.

Melibiose permease. Catalyzes the coupled stoichiometric symport of a galactoside with a cation (either Na⁺, Li⁺, or H⁺). Based on LacY, a 3-d model has been derived (Yousef and Guan, 2009). Asp55 and Asp59 are essential for Na⁺ binding. Asp124 may play a critical role by allowing Na⁺-induced conformational changes and sugar binding. Asp19 may facilitate melibiose binding (Granell et al., 2010).  The alternate access mechanism fits better into a flexible gating mechanism rather than the archetypical helical rigid- body rocker-switch mechanism (Wang et al. 2016).  Crystal structures of Salmonella typhimurium MelB in two conformations, representing an outward partially occluded and an outward inactive state (Ethayathulla et al. 2014). MelB adopts a typical MFS fold and contains a previously unidentified cation-binding motif. Three conserved acidic residues form a pyramidal-shaped cation-binding site for Na⁺, Li⁺ or H⁺, which is in close proximity to the sugar-binding site. Both cosubstrate-binding sites are mainly contributed by the residues from the amino-terminal domain (Ethayathulla et al. 2014). The Glucose Enzyme IIA protein of the PTS binds MelB either in the absence or presence of a galactoside, and binding decreases the affinity for melibiose, giving rise to inducer exclusion (Saier 1989; Hariharan and Guan 2014).

MelB of E. coli (A7ZUZ0)

Na⁺-dependent, smf-driven, sialic acid transporter, STM1128 (NanP) (Severi et al., 2010). Also transports the related sialic acids, N-glycolylneuraminic acid (Neu5Gc) and 3-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN) (Hopkins et al. 2013). 

STM1128 (NanP) of Salmonella enterica (Q8ZQ35)

Lysine:H⁺ symporter. Forms a stable complex with CadC to allow lysine-dependent adaptation to acidic stress (Rauschmeier et al. 2013). The Salmonella orthologue is 95% identical to the E. coli protein and is highly specific for Lysine. Residues involved in lysine binding have been identified (Kaur et al. 2014).

LysP of E. coli

ProY of 457 aas and 12 TMSs.  96% identical to ProY of Salmonella enterica, a cryptic proline transporter in this organism (Liao et al. 1997).

ProY of E. coli

Asparagine transporter of 499 aas and 12 TMSs, 91% identical to the orthologue in Salmonella enterica (2.A.3.1.8) (Jennings et al. 1995).

AnsP of E. coli

Asparagine permease (AnsP) of 497 aas and 12 TMSs (Jennings et al. 1995).

AnsP of Salmonella typhimurium

The Ceftriaxone resistance porter, YjeH (Hu et al. 2007).

YjeH of Salmonella enterica (serovar Typhimurium) (Q8ZKC0)

Broad specificity heavy metal divalent cation uptake transporter, ZupT (Fe²⁺, Co²⁺, Mn²⁺, Cd²⁺ and Zn²⁺ are transported) (Grass et al., 2005). Point mutations change the specificity and kinetics of metal uptake (Taudte and Grass, 2010). Important for virulence in Salmonella (Karlinsey et al., 2010). ZupT has an asymmetric binuclear metal center in the transmembrane domain; one metal-binding site, M1, binds zinc, cadmium, and iron, while the other, M2, binds iron only and with higher affinity than M1. Using site-specific mutagenesis and transport activity measurements in whole cells and proteoliposomes, Roberts et al. 2021 showed that zinc is transported from M1, while iron is transported from M2. The two sites share a common bridging ligand, a conserved glutamate residue. M1 and M2 have ligands from highly conserved motifs in transmembrane domains 4 and 5. Additionally, M2 has a ligand from transmembrane domain 6, a glutamate residue, which is conserved in the gufA subfamily of ZIP transporters, including ZupT and the human ZIP11. Unlike cadmium, iron transport from M2 does not inhibit the zinc transport activity but slightly stimulates it. This stimulated activity is mediated through the bridging carboxylate ligand. The binuclear zinc-iron binding center in ZupT has likely evolved to enable the transport of essential metals from two different sites without competition; a similar mechanism of metal transport is likely to be found in the gufA subfamily of ZIP transporter proteins (Roberts et al. 2021).

ZupT of E. coli (P0A8H3)

Chloride anion exchanger (Down-regulated in adenoma) (Protein DRA) (Solute carrier family 26 member 3).  The intracellular pH regulates ion exchange (Hayashi et al. 2009). Reduced functional expression of NHE3, and DRA contribute to Cl^- and Na⁺ stool loss in microvillus inclusion disease (MVID) diarrhea (Kravtsov et al. 2016). Mutations cause Congenital Chloride Diarrhea (CCD), an autosomal recessive disease in humans.  Upon infection with Salmonella, DRA levels go down, preventing Cl- absorption giving rise to diarrhea (A. Quach, personal communication). NHE-3 (TC# 2.A.53.2.18) was markedly downregulated, while the Na⁺-HCO₃^--cotransporter (NBC-1; TC# 2.A.31.2.12) and Na⁺-glucose transporter type-2 (SGLT2 or SGLT-2; TC#2.A.1.7.26) were upregulated after kidney transplantation (Velic et al. 2004).

SLC26A3 of Homo sapiens

Me²⁺ (Mn²⁺, Fe²⁺, Cd²⁺, Co²⁺, Zn²⁺, Ni²⁺):H⁺ symporter, MntH (Mn²⁺ · MntR and Fe²⁺ · Fur repressible). Specific resides in TMS1 and 6 line the pore and play a role in pH regulation (Courville et al., 2004; Haemig et al. 2010). Important for virulence in Salmonella (Karlinsey et al., 2010).

MntH (YfeP) of E. coli (P0A769)

The putative rhamnogalacturonide transporter (Rodionov et al. 2004)

RhiABC of Salmonella typhimurium
RhiA (R) (P43020)
RhiB (M, 4 TMSs) (Q8ZKR9)
RhiC (M, 12 TMSs) (Q8ZKS0)

The gold (Au²⁺) resistance efflux pump, GesABC (induced by GolS in the presence of Au²⁺; also mediates drug resistance when induced by Au²⁺ (Pontel et al., 2007). Also exports a variety of organic chemicals including chloramphenicol (Conroy et al., 2010).

GesABC of Salmonella enterica
GesA (MFP) (Q8ZRG8)
GesB (RND) (Q8ZRG9)
GesC (OMF) (Q8ZRH0)

O-antigen transmembrane translocase, Wzx (Franklin et al. 2011). In S. enterica groups B, D2 and E, Wzx translocation exhibits specificity for the repeat-unit structure, as variants with single sugar differences are translocated with lower efficiency, and little long-chain O antigen is produced. It appears that Wzx translocases are specific for their O antigen for normal levels of translocation (Hong et al. 2012).

Wzx of Salmonella enterica subsp. enterica

O-antigen transmembrane translocase, Wzx (Franklin et al. 2011).  For S. enterica groups B, D2 and E, Wzx translocation exhibits specificity for the repeat-unit structure, as variants with single sugar differences are translocated with lower efficiency, and little long-chain O antigen is produced. It appears that Wzx translocases are specific for their O antigen for normal levels of translocation (Hong et al. 2012).

Wzx of Salmonella typhimurium subsp. houtenae

The mouse virulence factor, MviN. (May flip the Lipid II peptidoglycan precursor from the cytoplasmic side of the inner membrane to the periplasmic surface) (Vasudevan et al., 2009). MviN, a putative lipid flippase (Fay and Dworkin, 2009).  In E. coli, MviN is an essential protein which when defective results in the accumulation of polyprenyl diphosphate-N-acetylmuramic acid-(pentapeptide)-N-acetyl-glucosamine.  This may be the peptidoglycan intermediated exported via MviN (Inoue et al. 2008).  It is essential for the growth of several bacteria.

MviN of Salmonella typhimurium (P37169)

Aromatic amino acid exporter (exports Phe, Tyr, Trp, and their toxic analogues (Doroshenko et al., 2007)). Also called the paraquat (methyl viologen) exporter, YddG (also exports benzyl viologen and possibly L-alanine; Hori et al., 2011). The topology of YddG has been shown to be 10 TMSs with N- and C- termini on the inside (Airich et al., 2010).

YddG of Salmonella typhimurium

The undecaprenyl phosphate-α-aminoarabinose flippase ArnE/ArnF heterodimer from the cytoplasm to the periplasm (Yan et al., 2007).

ArnEF flippase of Salmonella typhi
ArnE (P81891)
ArnF (125aas; Q8Z537)

Protein PagO

PagO of Salmonella typhimurium

The tricarboxylate transporter, TctABC (Somers and Kay 1983; Winnen et al. 2003).  The high resolution structure of the receptor, TctC, is known (Sweet et al. 1984).

TctABC of Salmonella enterica
TctA (M, 12 TMS)
TctB (M, 4 TMS)
TctC (R)

YdhK of Salmonella typhimurium

MsbA of 582 aas and 6 TMSs in an M-C arrangement.  The X-ray structure at 2.8 Å resolution in an inward-facing conformation after cocrystallization with lipid A and using a stabilizing facial amphiphile has been reported (Padayatti et al. 2019). The structure displays a large amplitude opening in the transmembrane portal, which is likely to be required for lipid A to pass from its site of synthesis into the protein-enclosed transport pathway. Putative lipid A density is observed further inside the transmembrane cavity, consistent with a trap and flip model. Additional electron density attributed to lipid A is observed near an outer surface cleft at the periplasmic ends of the transmembrane helices (Padayatti et al. 2019). This protein is 96% identical to the E. coli ortholog, TC# 3.A.1.106.1.

MsbA of Salmonella enterica

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

IroC of Salmonella enterica (MCMC) (Q8RMB7)

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)

OsmU (OsmVWXY) transporter for glycine betaine and choline-O-sulfate uptake. Induced by osmotic stress (0.3M NaCl) (Frossard et al., 2012). Also called OpuCA/CB1/CB2/CC.

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

Zinc (Zn²⁺) porter of E. coli, ZnuABC.  Required for Zn²⁺ homeostasis and virulence in the close E. coli relative, Salmonella enterica (Ammendola et al., 2007).

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

Cobalt (Co²⁺) porter (Rodionov et al., 2006).  CbiMN is a bipartite S-subunit with 8 TMSs (Siche et al. 2010). Dynamic interactions of CbiN and CbiM trigger activity of the transporter (Finkenwirth et al. 2019). Substrate binding (S) components rotate within the membrane to expose their binding pockets alternately to the exterior and the cytoplasm. In contrast to vitamin transporters, metal-specific systems rely on additional proteins with essential functions. CbiN, with two TMSs tethered by an extracytoplasmic loop of 37 amino-acid residues is the auxiliary component that temporarily interacts with the CbiMQO₂ Co²⁺ transporter. CbiN induces Co²⁺ transport activity in the absence of CbiQO₂ in cells producing the S component CbiM plus CbiN or a Cbi(MN) fusion. Finkenwirth et al. 2019 showed that any deletion in the CbiN loop abolished transport activity. Protein-protein contacts between segments of the CbiN loop and loops in CbiM were demonstrated, and an ordered structure of the CbiN loop was shown. The N-terminal loop of CbiM, containing three of four metal ligands was partially immobilized in wild-type Cbi(MN) but completely immobile in inactive variants with CbiN loop deletions. Thus, CbiM-CbiN loop-loop interactions facilitate metal insertion into the binding pocket (Finkenwirth et al. 2019).

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

The putative queuosine uptake transporter, QrtTUVW (Rodionov et al., 2009).

QrtTUVW of Salmonella enterica su. typh.
QrtT (M) (Q8XGV9)
QrtU (M) (Q8Z3V9)
QrtV (C) (Q8Z3V8)
QrtW (C) (Q8Z3V7)

Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium  ligands only one substrate molecule in between its two transmembrane subunits, HisM and HisQ (Heuveling et al. 2019).

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

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)

Flagellar protein export system.  Infrequent ATP hydrolysis by the FliI₆FliJ ring is sufficient for gate activation, allowing processive translocation of export flagellar protein substrates for efficient flagellar assembly (Minamino et al. 2014). FliO has been identified as a flagellar basal body chaparone protein (Fabiani et al. 2017). The flagellar protein export apparatus switches its substrate specificity when hook length has reached approximately 55 nm, and the hydrophilic C-terminal domain of FlhB is involved in this switching process (Inoue et al. 2019). A positively chargef region of Salmonella FliI is required for ATPase formation and efficient flagellar protein export (Kinoshita et al. 2021).

Flagellar subunit export system of Salmonella typhimurium (10 subunits)

Na⁺-transporting oxalo-acetate decarboxylase. Subunit stoichiometries have been described (Balsera et al., 2011). The crystal structure of the carboxyltransferase at 1.7 A resolution shows a dimer of alpha(8)beta(8) barrels with an active site metal ion, identified spectroscopically as Zn²⁺ (Granjon et al. 2010).

Oxaloacetate decarboxylase of Salmonella typhimurium

Hydrogenase HyaABCDEF, important for H₂ oxidation during fermentation (Zbell and Maier 2009).

HyaABCDEF of Salmonella enterica suspecies enterica serovar Typhimurium
HyaA (367 aas, 4 TMSs)
HyaB (600 aas, 0 TMSs)
HyaC (347 aas, 4 TMSs)
HyaD (198 aas, 0 TMSs)
HyaE (134 aas, 0 TMSs)
HyaF (353 aas, 0 TMSs)

D-glucosaminate group translocating uptake porter, DgaABCD (IIA-141 aas, IIB-161 aas, IIC-249 aas, and IID-285 aas, respectively) (Miller et al. 2013).  Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) uses d-glucosaminate (2-amino-2-deoxy-d-gluconic acid) as a carbon and nitrogen source via DgaABCD (d-glucosaminate PTS permease components EIIA, EIIB, EIIC, and EIID). Two other genes in the dga operon (dgaE and dgaF) are required for wild-type growth with d-glucosaminate. Transcription of dgaABCDEF is dependent on RpoN (σ⁵⁴) and an RpoN-dependent activator gene, dgaR. Introduction of a plasmid bearing dgaABCDEF under the control of the lac promoter into E. coli strains allowed them to grow on minimal medium containing d-glucosaminate. d-Glucosaminate is transported and phosphorylated at the C-6 position by DgaABCD. DgaE converts the resulting d-glucosaminate-6-phosphate to 2-keto-3-deoxygluconate 6-phosphate (KDGP), which is subsequently cleaved by the aldolase DgaF to form glyceraldehyde-3-phosphate and pyruvate. DgaF catalyzes the same reaction as that catalyzed by Eda, a KDGP aldolase in the Entner-Doudoroff pathway, and the two enzymes can substitute for each other in their respective pathways. Orthologs of the dga genes are largely restricted to certain enteric bacteria and a few Firmicutes (Miller et al. 2013).

DgaABCD of Samonella enterica Typhimurium

PTS uptake system for glucoselysine and fructoselysine, GfrABCD (Miller et al. 2015).  Two glycases, GfrE and GfrF, are requred for the utilization of these two compounds for growth, respectively, and GfrF was shown to hydrolyze fructoselysine-6-P to lysine and fructose-6-P.  Expression of the operon, gfrABCDEF, is regulated by a transcriptional activator, GfrR and sigma factor RpoN (Miller et al. 2015).  GfrD affects proteolytic processing, a necessary but insufficient step for CadC activation, rendering CadC able to activate target genes involved in lysine metabolism (Lee et al. 2013).

GfrABCD of Salmonella typhimurium
GfrA, IIA, 140 aas
GfrB, IIB, 153 aas
GfrC, IIC, 259 aas
GfrD, IID, 278 aas

The (putative) ATP-dependent, NMN synthesizing, nicotinamide nucleoside phosphorylating, group translocator, PnuC/NadR

PnuC/NadR of Salmonella typhimurium
PnuC (P24520)
NadR (AAL23395)

Lipopolysaccharide glycosyl transferase, WbbF

WbbF of Salmonella enterica serovar Borreza plasmid pWQ799 (Q52257)

Suppressor of copper-sensitivity B, ScsB (Gupta et al. 1997). Part of a transmembrane peroxide reductase complex (Cho et al. 2012).

ScsB of Salmonella typhimurium

Thiosulfate reductase, PhsABC (Heinzinger et al., 1995) (Clark and Barrett 1987). Menaquinone is the sole electron donor. The endoergonic reduction reaction is driven by the pmf by a reverse loop mechanism (Stoffels et al. 2012). The enzyme can catalyze oxidation of sulfide to sulfite and sulfite to thiosulfate in an exergonic reaction that is pmf-independent (Stoffels et al. 2012). Because the endoergonic reaction is dependent on the pmf, there may be a proton channels in the complex, (possibly subunit C) that allows proton flux into the cell, coupled to the reduction reaction.

PhsABC of Salmonella typhimurium
PhsA (α) (molybdopterin subunit; 758 aas and 1 - 3 TMSs) (P37600)
PhsB (β) (cytochrome b reductase; 192 aas) (P0A1I1)
PhsC (γ) (cytochrome b subunit; 254 aas and 5 TMSs in a 1 + 2 + 2 TMS arrangement) (P37602)

SteD of 111 aas and 2 adjacent C-terminal TMSs. (See family description; Godlee et al. 2022).

SecD of Salmonella type III secretion system

Uncharacterized protein of 111 aas and 2 TMSs.

UP of Salmonella enterica

Tir N-terminal domain-containing protein of 543 aas and 2 TMSs.

Tir of Salmonella enterica

Uncharacterized protein of 117 aas and 4 TMSs

UP of Salmonella enterica subsp. enterica serovar Tallahassee

Uncharacterized protein of 113 aas and 1 TMS.

UP of Salmonella enterica

The ethanolamine facilitator EutH, of 408 aas and 11 or 12 TMSs.  The E. coli orthologue (P76552) is identical to the S. enterica protein. They are probably involved in the diffusion of protonated ethanolamine (EA) into the cell at low pH where most EA is protonated, and this permease becomes necessary. It contributes to bacterial survival and replication in acidified macrophage vacuoles (Anderson et al. 2018). It is associated with a bacterial ethanol metabolizing bacteria microcompartment, Eut1 (Kirst and Kerfeld 2021).

EutH of Salmonella enterica (P41796)

STY0450 or ImpX of 108 aas and 2 TMSs.  Suggested to be a nucleoside exporter, specifically of adenosine and thymidine (see family description) (Bucarey et al. 2006).

ImpX of Salmonella enterica ss. Typhi

Phage shock protein, PspA (induced by extracytoplasmic stress; promotes Salmonella virulence, possibly by maintaining the proton motive force (pmt)).

PspA of Salmonella enterica (E8XKQ3)

Uncharacterized protein, YhjG (675aas; 2 TMSs)

YhjG of Salmonella enterica (G5LV43)

DUF2919 family protein of 159 aas and 4 TMSs

DUF2919 protein of Salmonella enterica

O-antigen polymerase, Rfc. May link the O-antigen tetrasaccharide units into long chains, giving rise to typical smooth LPS This LPS is essential for M1 macrophage polarization (Luo et al. 2016).

O-antigen polymerase of Salmonella typhi (P0A236)

Putative glycosyl transferase, GtrI

GtrI of Salmonella enterica

Putative outer membrane protein of 244 aas

Omp of Salmonella enterica

O-antigen polymerase, Wzy of 374 aas.

Wyz of Salmonella choleraesuis

Uncharacterized protein of 215 aas and 6 TMSs

UP of Salmonella schwarzengrund

Putative Mg²⁺ transporter, MgtC (Retamal et al. 2009). The MgtC virulence protein binds to the F-type ATP synthase and maintains ATP homeostasis required for pathogenesis during phagosome acidification (Lee and Lee 2015). The mgtC gene, which is present in S. enterica but not in E. coli, is responsible for the differences in RpoS accumulation between these two bacterial species. Thus, bacteria possess a mechanism to control RpoS accumulation responding to cytoplasmic Mg²⁺ levels, the difference of which causes distinct RpoS accumulation patterns in closely related bacterial species (Park et al. 2018).

MgtC of Salmonella typhimurium

1-acyl-sn-glycerol-3-phosphate acyltransferase, gamma, AGPAT3, of 376 aas and 2 TMSs, N- and C-terminal.  It converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (Prasad et al. 2011).

AGPAT3 of Homo sapiens

PgtP protease (Kukkonen and Korhonen 2004).

PgtP of Salmonella enterica

Ethanol utilization; acetate kinase, EutQ (COG4766; Pfam06249). It is homologous and similar in sequence to the Salmonella orthologous acetate kinases, EutQ and EutP (Moore and Escalante-Semerena 2016).

EutQ of E. coli (233 aas; gi#15832576)