TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameOrganismal TypeExample
3.A.3.1.1









Na+-, K+-ATPase (Na+ efflux; K+ uptake).  Mutations in the γ-subunit causes renal hypomagnesemia, associated with hypocalciurea (Cairo et al., 2008). The Na/K-ATPase is an important signal transducer that not only interacts and regulates protein kinases, but also functions as a scaffold (Li and Xie, 2009). Capsazepine, a synthetic vanilloid, converts the Na, K-ATPase to a Na-ATPase (Mahmmoud, 2008a). There are alternative α- and β-subunits, α1, α2,... β1, β2,... in muscle which form α1β1, α1β2, α2β1 and α2β2, heterodimers, each with differing Na+ affinities (4-13mM) (Kristensen and Juel, 2010). α3 and β3 isoforms have also been identified. The γ-subunit is the same as TC# 1.A.27.2.1. Poulsen et al. (2010) have proposed a second ion conduction pathway in the C-terminal part of the ATPase. The two C-terminal tyrosines stabilize the occluded Na/K pump conformations containing Na or K ions (Vedovato and Gadsby, 2010). Na+, K+-ATPase mutations causing familial hemiplegic migraines type 2 (FHM2) inhibit phosphorylation (Schack et al., 2012). Salt, the vascular Na+/K+ ATPase and the endogenous glycosides, ouabain and marinobufagenin, play roles in systemic hypertension (Hauck and Frishman, 2012). Protein kinase A (PKA) phosphorylation of (Ser936) opens an intracellular C-terminal water pathway leading to the third Na+-binding site (Poulsen et al., 2012). E960 on the Na+-K+-ATPase and F28 on phospholemman (PLM) are critical for phospholemman (PLM) inhibition, but there is at least one additional site that is important for tethering PLM to the ATPase. Mutations in the Na+/K+-ATPase α3 subunit gene (ATP1A3) cause rapid-onset dystonia-parkinsonism, a rare movement disorder characterized by sudden onset of dystonic spasms and slow movements (Doğanli et al. 2013).  The 3-d strcuture of the Na+-bound Na+,K+-ATPase at 4.3 Å resolution reveals the positions of the three Na+ ions (Nyblom et al. 2013).  Mutations caluse adrenal hypertension (Kopec et al. 2014).

Animals

3 component systems:
Na+-, K+-ATPase from α, β, γ heterotrimer of Homo sapiens
α1 (ATP1A1) (P05023)
α2 (ATP1A2) (P50993)
α3 (ATP1A3) (P13637)
β1 (ATP1B1) (P05026)
β2 (ATP1B2) (Q58I19)
β3 (ATP1B3) (P54709)
γ1 (ATP1G1) (P54710)
3.A.3.1.2









H+-, K+-ATPase (gastric; H+ efflux; K+ uptake) (Two H3O+ are transported per ATP hydrolyzed).  A cryo-electron microscope structure suggests that 1 H+ and 1 K+ are transporter per ATP hydrolyzed, providing the energy needed to generate the one million fold H+ concentration gradient effected by this enzyme (Abe et al. 2012).  The detailed mechanism has been discussed, and the roles of essential residues have been proposed (Shin et al. 2011).  A number of inhibitors of acid secretion have been identified, and these are of pharmacological importance (Shin et al. 2011).

Animals

Gastric H+-, K+-ATPase from Homo sapiens
3.A.3.1.3









Na+-ATPase
Marine algae
Na+-ATPase (HANA) of Heterosigma akashiwo
3.A.3.1.4









Non-gastric H+-, K+- or NH4+-ATPase (Swarts et al., 2005; Worrell et al., 2008)

Animals

H+-, K+ or NH4+-ATPase of Rattus norvegicus (P54708)
3.A.3.1.5









Putative spirochete Na+, K+-ATPase, Lbi6 (1046 aas) (K. Hak & M.H. Saier)
Bacteria
Lbi6 of Leptospira biflexa (B0SMV3)
3.A.3.1.6









Spiny dogfish Na+,K+-ATPase (3-d structure solved at 2.4 Å resolution, Shinoda et al., 2009). The α-subunit is 88% identical to the human Na+,K+ ATPase (TC# 3.A.3.1.1).

Animals

Na+,K+-ATPase α, β, and γ subunits of Squalus acanthias
α (1028aas; Q4H132)
β (305aas; C4IX13)
γ (94aas; Q70Q12)
3.A.3.1.7









H+/K+-ATPase α-subunit (1534aas) (Ramos et al., 2011)

Fungi

H+/K+ ATPase of Aspergillus oryzae (Q2U3D2)
3.A.3.1.8









Putative Na+/K+-ATPase, Mhun_0636 (encoded in an operon with two half sized TrkA homologues, Mhun_0637 and Mhun_0638, that together may regulate the ATPase)

Archaea

Mhun_0636-8 of Methanospirillum hungatei
Mhun_0636 (Q2FLJ9) Mhun_0637 (Q2FLJ8) Mhun_0638 (Q2FLJ6)
3.A.3.1.9









Ouabain-insensitive K+-independent Na+-ATPase ɑ-subunit, AtnA; very similar to the human ɑ-1 chain of the Na+,K+-ATPase (3.A.3.1.1) (Rocafull et al., 2011).

Animals

AtnA of Cavia porcellus (B3SI05)
3.A.3.1.10









Putative archaeal Na+, K+ ATPase, Mac8 (encoded with methylcobalamin: coenzyme M methyltransferase; methanol-specific, a metal chaparone protein and an electron transfer protein) (Chan et al., 2010).

Archaea

Putative Na+/K+ ATPase of Methanosarcina acetivorans (Q8THY0)
3.A.3.1.11









Na+,K+-ATPase α2 subunit, ATP1a2a; ATPA2A deficiency causes brain ventricle dilation and embryonic motility in zebra fish (Do%u011Fanli et al. 2013).

Animals

ATPA2 of Danio rerio (Q90X34)
3.A.3.1.12









Na+,K+-ATPase subunits α (837 aas) and β (302 aas) of the blood fluke ().

Animals (Platyhelminthes)

Na+,K+-ATPase subunits α and β of Schistosoma mansoni
alpha, G4VGA0
beta, G4VTH6
3.A.3.2.1









Plasma membrane Ca2+-ATPase (efflux) (Giacomello et al. 2013).

Eukaryotes

Plasma membrane Ca2+-translocating ATPase of Homo sapiens (P23634)
3.A.3.2.2









Ca2+-ATPase (uptake into vacuoles)
Yeast
Vacuolar membrane Ca2+-translocating ATPase from Saccharomyces cerevisiae Pmc1
3.A.3.2.3









Ca2+-ATPase, Pmr1 (efflux) (also transport Mn2+ and Cd2+) (Lauer et al., 2008)

Eukaryotes

Golgi Ca2+-ATPase Pmr1 of Saccharomyces cerevisiae
3.A.3.2.4









Ca2+-ATPase of 905 aas and 10 TMSs, Pma1

Bacteria

Putative Ca2+-ATPase of Synechocystis sp. pMA1
3.A.3.2.5









The Golgi Ca2+ , Mn2+ -ATPase, hSPCA1 (efflux) (the Hailey-Hailey disease protein). Involved in responses to golgi stress, apoptosis and midgestational death (Okunade et al., 2007). SPCA1 transports Mn2+ from the cytosol into the Golgi. Increasing Golgi Mn2+ transport increased cell viability upon Mn2+ exposure, supporting a role in the management of Mn2+ -induced neurotoxicity (Mukhopadhyay and Linstedt, 2011).

Animals

hSPCA1 of Homo sapiens
3.A.3.2.6









Ca2+, Mn2+- ATPase (efflux)
Fungi
Pmr1 of Neurospora crassa
3.A.3.2.7









The sarco/endoplasmic reticulum Ca2+ -ATPase, SERCA2b or ATP2A2 (encoded by the ATP2A2 gene) (Darier''s disease protein; the spectrum of mutations have been related to patients' phenotypes) (Ahn et al., 2003; Godic et al. 2010).  SERCA1 functions as a heat generator in mitochondria of brown adipose tissue (de Meis et al., 2006). Functions as a Ca2+:H+ antiporter (Karjalainen et al., 2007). Capsaicin converts SERCA to a Ca2+ non-transporting ATPase that generates heat. Capsaicin is the first natural drug that augments uncoupled SERCA, resulting in thermogenesis (Mahmmoud, 2008b). Oligomeric interactions of sarcolipin and the Ca-ATPase have been documented (Autry et al., 2011).  TMS 11, absent in SERCA1a and SERCA2a, functions in regulation (Gorski et al. 2012). The bovine SERCA has also been crystallized (2.9Å resolution; Sacchetto et al., 2012).  These enzymes are regulated differentially by phospholamban (PLN; 1.A.50.1.1) and sarcolipin (SLN; 1.A.50.2.1) (Gorski et al. 2013).  SERCA2 is regulated by TMEM64, a 380 aa 6 TMS membrane protein of the DedA family (TC# 9.B.27)which regulates Ca2+ oscillations by direct interaction with CIRCA2, modulating its activity and influencing osteoblast differentiation (Kim et al. 2013).

Animals

SERCA2b of Homo sapiens (P16615)
3.A.3.2.8









Ca2+-ATPase (efflux) broad Ca2+ dependence (3.2-320 μm)
Protozoa
PfATPase4 of Plasmodium falciparum
3.A.3.2.9









Ca2+,Mn2+-ATPase, hSPCA2 (ATP2C2) (efflux). 64% identical to hSPCA1 (TC #3.A.3.2.5) but lower affinity for Ca2+ and more restricted tissue distribution (brain and testis); present in the trans-Golgi network. May function in Mn2+ detoxification (Xiang et al., 2005).
Animals
hSPCA2 of Homo sapiens (NP_055676)
3.A.3.2.10









The autoinhibited, calmodulin-binding Ca2+-ATPase, isoform 8, ACA8 (Baekgaard et al., 2006)
Plants
ACA8 of Arabidopsis thaliana (Q9LF79)
3.A.3.2.11









Plastid Envelope Ca2+ ATPase, PEA1 (lacks a C-terminal calmodulin domain)
Plants
PEA1 of Arabidopsis thaliana
(Q37145)
3.A.3.2.12









Endomembrane plasma membrane-type Ca2+ ATPase, ACA2 (Arabidopsis Ca2+ ATPase isoform 2) (lacks a C-terminal calmodulin domain, but activity is stimulated 5x by calmodulin which binds to an N-terminal inhibitory domain (Harper et al., 1998; Kamrul Huda et al. 2013).

Plants

ACA2 of Arabidopsis thaliana
(O81108)
3.A.3.2.13









Endoplasmic Reticular (ER)-type ER Ca2+/Mn2+ ATPase, ECA1
Plants
ECA1 of Arabidopsis thaliana
(P92939)
3.A.3.2.14









Autoinhibited Ca2+ ATPase (ACA9) (expressed in pollen plasma membrane and required for male fertility), calmodulin-binding (Schiøtt et al., 2004).

Plants

ACA9 of Arabidopsis thaliana
(Q9LU41)
3.A.3.2.15









Plasma membrane Ca2+ ATPase, Mca1 (Kraev et al., 1999)
Animals
Mca1 of Caenorhabditis elegans
(O45215)
3.A.3.2.16









Golgi Ca2+, Mn2+ ATPase, PMR1 (Van Baelen et al., 2001). (The human orthologue ATP2Cl, TC#3.A.3.2.5, causes Hailey-Hailey disease.)
Animals
PMR1 of Caenorhabditis elegans
(Q9XTG4)
3.A.3.2.17









Intracellular (contractile vacuole) Ca2+ ATPase, PatA (lacks the C-terminal calmodulin domain of most plasma membrane Ca2+ ATPases) (Moniakis et al., 1995)
Slime molds
PatA of Dictyostelium discoideum
(P54678)
3.A.3.2.18









The acidocalcisome (vacuole) Ca2+/H+ ATPase TgA1 (involved in Ca2+ homeostasis, vacuolar polyphosphate storage and virulence) (Luo et al., 2005).
Protozoa
TgA1 of Toxoplasma gondii
(Q9N694)
3.A.3.2.19









Endomembrane (golgi) Ca2+/Mn2+-ATPase, ECA3 (one of 4 close paralogues in A. thaliana (Mills et al., 2008; Kamrul Huda et al. 2013)

Plants

ECA3 of Arabidopsis thaliana (Q0WP80)
3.A.3.2.20









Putative Ca2+ ATPase Cac1 (possible pseudogene?)

Firmicutes

Cac1 of Clostridium acetobutylicum (Q97JK5)
3.A.3.2.21









Putative Ca2+ ATPase, Pmo1

Thermotogales

Pmo1 of Petrotoga mobilis (A9BJX0)
3.A.3.2.22









Putative Ca2+ ATPase, Sth1

Firmicutes

Sth1 of Streptococcus thermophilus (Q5M0A4)
3.A.3.2.23









Putative Ca2+ ATPase most similar to golgi Ca2+ ATPases of eukaryotes

Archaea

Putative Ca2+ ATPase of Methanococcus vannielii (A6URW9)
3.A.3.2.24









Putative Ca2+-ATPase (48% identical to 3.A.3.2.23) (like golgi Ca2+-ATPases of eukaryotes)

Bacteria

Putative Ca2+-ATPase of Aguifex aeolicus (O66938)
3.A.3.2.25









Plasma membrane Ca2+-ATPase, isoform 1a (PMCA1) (78% identical to PMCA4 (TC# 3.A.3.2.1)). Maitotoxin converts it into a Ca2+--permeable nonselective cation channel (Sinkins et al., 2009).

Animals

PMCA1 of Homo sapiens (P20020)
3.A.3.2.26









The M535L virus Ca2+/Mn2+ efflux pump (transcribed during viral infection) (Bonza et al., 2010)

Virus

M535L Ca2+ pump of Paramecium bursaria chlorella virus, MT325 (A7IUR5)
3.A.3.2.27









Plasma Membrane Ca2+-type ATPase, NCA-2 (most like 3.A.3.2.2) (Bowman et al., 2011).

Fungi

NCA-2 of Neurospora crassa (Q9UUY2)
3.A.3.2.28









The probable Mg2+/Ca2+ ATPase antiporter (catalyzes Mg2+ uptake and Ca2+ efflux in a single coupled step; Neef et al. 2011)

Bacteria

Antiporter of Streptococcus pneumoniae (Q04JJ5)
3.A.3.2.29









The putative Ca+ ATPase with an extra C-terminal TMS followed by a lysin (LysM) domain of ~210aas. LysM domains are often found in cell wall degradative enzymes and have peptidoglycan binding sites. Found in Nitrosococcus oceani as well as Nitrosococcus halophilus. The ATPase domain is 46% identical to 3.A.3.2.4.

Bacteria

Putative Ca2+ ATPase of Nitrosococcus  halophilus (D5C355)
3.A.3.2.30









Pleasma membrane Ca2+-ATPase of parenchymal tissue of the liver fluke, PMCA.  Interacts with a calmodulin-like protein, FhCaM1 in a calcium ion dependent fashion (Moore et al. 2012).

Animals

PMCA of Fasciola helpatica
3.A.3.2.31









Sarcoplasmic reticulum Ca2+ ATPase, Atp6.  The inhibitors, artemisinin and its derivatives, bind to a hydrophobic pocket in a transmembrane region near the membrane surface (Naik et al. 2011).

Alveolata
Atp6 of Plasmodium falciparum
3.A.3.2.32









Lobster intracellular SERCA Ca2+ ATPase of 1020 aas.  In related species, expression of the gene is increased under hypersaline conditions, and the enzyme is ivolved in salinity stress adaptation (Wang et al. 2013).

animals (Arthropods)

ATPase of Palinurus argus
3.A.3.2.33









Crustacian plasma membrane calcium ATPase of 1170 aas (Chen et al. 2013).

Animals

Calcium ATPase of Callinectes sapidus (blue crab)
   
3.A.3.2.34









Ca2+/Mn2+-exporting ATPase, Pmr1 of 899 aas (Furune et al. 2008).

Yeast

Pmr1 of Schizosaccharomyces pombe
3.A.3.2.35









Calcium-exporting ATPase, Pmc1 of 1096 aas (Furune et al. 2008)..

Yeast

Pmc1 of Schizosaccharomyces pombe
3.A.3.2.36









SERCA Ca2+-ATPase of 1093 aas (Docampo et al. 2013).

Alveolata

SERCA ATPase of Toxoplasma gondii
3.A.3.2.37









SERCA P-type ATPase of 1036 aas.

Alveolata (Ciliates)

SERCA ATPase of Paramecium tetraurelia
3.A.3.2.38









Plasma membrane Ca2+ ATPase (PMCA) of 1146 aas (Plattner 2014).

Alveolata

PMCA of Paramecium tetraurelia
3.A.3.2.39









Plasma membrae Ca2+ ATPase (PMCA) of 1064 aas (Lescasse et al. 2005).

Alveolata (ciliates)

PMCA of Oxytricha trifallax (Sterkiella histriomuscorum)
3.A.3.2.40









Plasma membrane Ca2+ ATPase, isoform 2, of 1243 aas, ATP2b2.  The mouse orthologue, of 1198 aas (P9R0I7), when mutated (I1023S in TMS 10 and R561S in the catailytic core) gives rise to semi-dominant hearing loss (Carpinelli et al. 2013).

Animals

ATP2b2 of Homo sapiens
3.A.3.3.1









H+-ATPase (efflux)
Plants; fungi; protozoa; slime molds; archaea
H+-ATPase, plasma membrane of Neurospora crassa
3.A.3.3.2









H+ (in)/K+ (out) Mg2+-ATPase (antiporter)
Protozoa
H+/K+ antiport ATPase 1A of Leishmania donovani
3.A.3.3.3









Mn2+/Cd2+-ATPase, MntA (Hao et al. 1999).

Bacteria

MntA of Lactobacillus plantarum
3.A.3.3.4









Putative H+-ATPase
Archaea
Aha1 (MJ1226) of Methanococcus jannaschii
3.A.3.3.5









Plasma membrane H+-ATPase, TbHA1 (912 aas) (3 isoforms are present in T. brucei) (Luo et al., 2006)
Protozoan
TbHA1 of Trypanosoma brucei (AAP30857)
3.A.3.3.6









H+-ATPase, Pma1 (pumps protons out of the cell to generate a membrane potential and regulate cytosolic pH) (Liu et al., 2006; Petrov, 2009). TMSs 4,5,6 and 8 comprise the H+ pathway where essential and important residues have been identified (Miranda et al., 2010).

Yeast

H+-ATPase of Saccharomyces cerevisiae (P05030)
3.A.3.3.7









Plasma membrane H+ ATPase, AHA1 (3 isoforms, AHA1, 2 & 3, exhibit different kinetic properties) (Palmgren and Christensen, 1994). Both the N- and C-termini are directly involved in controlling the pump activity (Ekberg et al., 2010).

Plants

AHA1 of Arabidopsis thaliana
(P20649)
3.A.3.3.8









Plasma membrane H+ ATPase, AHA6 (binds 14-3-3 proteins induced by phosphorylation of Thr948, causing activation; preferentially expressed in pollen; Bock et al., 2006) (82% identical to 3.A.3.3.7).

Plants

AHA6 of Arabidopsis thaliana (Q9SH76)
3.A.3.3.9









proton pumping ATPase, AHA2.  94% identical to AHA1 (3.A.3.3.7).  Cation-binding pockets have been identified (Ekberg et al. 2010).  The pump has been reconstituted into "nanodiscs" in a functionally monomeric form (Justesen et al. 2013).

Plants

Proton pumping ATPase of Arabidopsis thaliana
3.A.3.4.1









Mg2+/Ni2+-ATPase (uptake)
Bacteria
MgtA of Salmonella typhimurium
3.A.3.4.2









Putative spirochete Mg2+-ATPase, Lin3 (843 aas)
Bacteria
Lin3 of Leptospira interrogans (Q72RN5)
3.A.3.4.3









Mg2+ ATPase (1182 aas; 18-20 TMSs) with an N-terminal (residues 1-325) transmembrane domain of 8-10 TMSs; homologous to residues 493-791 in O53781 of Mycobacterium tuberculosis (TC# 2.A.1.3.43). Residues 257-318 hit TMSs 7 and 8 in FmtC (MrpF), TC#2.A.1.3.37 with a score of 8 e-4. The last 3 TMSs of the N-terminal fused domain of 3.A.3.4.3 and 3.A.3.4.4 are homologous (e-10) to the last 3 TMSs in 2.A.1.3.43. The N-terminal domain is homologous to the 8TMS domains of 9.B.3 family members.

Bacteria

Mg2+-ATPase of Pseudomonas stutzeri (F2N2Z6)
3.A.3.4.4









Mg2+ P-type ATPase (1195 aas; 18-20 TMSs) with an extra N-terminal 8-10 TMSs (residues 1-330). Similar to 3.A.3.4.3. The last 3 TMSs of the N-terminal fused domain to 3.A.3.4.3 and 3.A.3.4.4 are homologous (e-10) to the last 3 TMSs in 9.A.30.2.1. The N-terminal domain is homologous to the 8TMS domains of 9.B.3 family members.

Bacteria

Mg2+-ATPase with N-terminal 8-10 TMS domain of ~300 residues of Azotobacter vinelandii (C1DHA2)
3.A.3.5.1









Cu2+-ATPase (uptake)
Bacteria
CopA of Enterococcus hirae
3.A.3.5.2









Cu+-, Ag+-ATPase (efflux)
Bacteria
CopB of Enterococcus hirae
3.A.3.5.3









Cu+-, Ag+-ATPase (efflux from the cytosol into the secretory pathway) (Barnes et al., 2005); ATP7B (Wilson's disease protein, α-chain) (continuously expressed in Purkinje neurons). It delivers Cu+ to the ferroxidase, ceruloplasmin, in liver. May also transport Fe2+ (Takeda et al., 2005). Critical roles for the COOH terminus of ATP7B in protein stability, trans-Golgi network retention, copper sensing, and retrograde trafficking have been reported (Braiterman et al. 2011).  Modeling suggests that Cu+-binding sites HMBDs 5 and 6 are most important for function (Gourdon et al. 2012).

Eukaryotes

Cu+-ATPase, ATP7B, of Homo sapiens
3.A.3.5.4









Ag+-ATPase (efflux)
Bacteria
Ag+-ATPase, SilP of Salmonella typhimurium
3.A.3.5.5









Cu+, Ag+-ATPase (efflux) (Fan and Rosen, 2002)
Bacteria
CopA of E. coli
3.A.3.5.6









Cu+-ATPase, ATP7A (MNK or Mc1) (efflux from the cytosol into the secretory pathway) (Menkes disease protein, α-chain) (Tümer 2013). Expressed in Purkinje cells early in development and later in Bergmann glia. In melanocytes, it delivers Cu2+ to tyrosinase (Barnes et al., 2005). ATP7A has dual functions: 1) it incorporates copper into copper-dependent enzymes; and 2) it maintains intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics between different cellular locations, depending on copper levels (Bertini and Rosato, 2008). The lumenal loop Met672-Pro707 of copper-transporting ATPase ATP7A binds metals and facilitates copper release from the intramembrane sites (Barry et al., 2011).  Modeling suggests that Cu+-binding sites HMBDs 5 and 6 are most important for function (Gourdon et al. 2012).

Animals

ATP7A of Homo sapiens
3.A.3.5.7









Cu+-Ag+-ATPase (efflux), CopA. Exhibits maximal activity at 75˚C (Cattoni et al., 2007). The 3-D structure of the ATP-binding domain has been solved (2HC8_A) (functions with the Cu+ chaperone, CopZ; 130aas) (González-Guerrero and Argüello, 2008). This protein has both N- and C- terminal metal binding domains (MBDs). The N-MBD exhibits a conserved ferredoxin-like fold, binds metals to CXXC, and regulates turnover. The C-MBD interacts with the ATP-binding (ATPB) domain and the actuator (A) domain (Agarwal et al., 2010).

Euryarchaea

CopAZ of Archaeoglobus fulgidus:
CopA (PaeS) (O29777)
CopZ (2HU9_A)
3.A.3.5.8









Cu+ transporting ATPase (intracellular, in the transgolgi membrane), Ccc2
Yeast
Ccc2 of Candida albicans
3.A.3.5.9









Cu+ transporting (copper detoxification) ATPase, Crp1
Yeast
Crp1 of Candida albicans
3.A.3.5.10









Cu+ (Km 0.3 μM), Ag+ transporting ATPase, CopB (Mana-Capelli et al., 2003)

Euryarchaea

CopB of Archaeoglobus fulgidus (AAB91079)
3.A.3.5.11









Chloroplast envelope Cu+-uptake ATPase, PAA1 or HMA1.  Essential for growth under adverse light conditions (Seigneurin-Berny et al. 2006).

Plants

PAA1 of Arabidopsis thaliana (Q9SZC9)
3.A.3.5.12









Chloroplast thylakoid Cu+-ATPase, PAA2 (delivers Cu+ to the thylakoid lumen)
Plants
PAA2 of Arabidopsis thaliana (AAP55720)
3.A.3.5.13









The archaeal Cu+ efflux pump (CopA)

Archaea

CopA of Sulfolobus solfataricus (Q97UU7)
3.A.3.5.14









The yeast Cd2+ efflux pump, PCA1 (Adle et al., 2007)
Yeast
PCA1 of Saccharomyces cerevisiae (P38360)
3.A.3.5.15









The transferable, plasmid-localized Copper sensitivity (uptake) ATPase, TcrA (811aas) (43% identical to 3.A.3.1.1) (Hasman, 2005)
Bacteria
TcrA of Enterococcus faecium (ABA39707)
3.A.3.5.16









The transferable, plasmid-localized Copper resistance efflux) ATPase, TcrB (43% identical to 3.A.3.5.2) (Hasman, 2005)
Bacteria
TcrB of Enterococcus faecium (AAL05407)
3.A.3.5.17









Golgi Cu2+ ATPase, Ccc2, retrieves Cu2+ from the metallochaperone Atx1 and transports it to the lumen of golgi vesicles (Lowe et al., 2004)
Yeast
Ccc2 of Saccharomyces cerevisiae
(P38995)
3.A.3.5.18









The copper resistance ATPase, CopA (Ettema et al., 2006Lübben et al., 2007; Villafane et al., 2009).

Bacteria

CopA of Bacillus subtilis (O32220)
3.A.3.5.19









The Cu2+, Fe3+, Pb2+ resistance efflux pump, CopA (induced by copper and to a lesser extent by Fe3+ and Pb2+) (Sitthisak et al., 2007)
Gram-positive bacterium
CopA of Staphylococcus aureus (Q7A3E6)
3.A.3.5.20









The gold (Au2+) resistance ATPase, GolT (regulated by GolS in response to Au2+; it may function with a cytoplasmic metal binding protein, GolB (AAL19308; Pontel et al., 2007).
Bacteria
GolT of Salmonella enterica (Q8ZRG7)
3.A.3.5.21









The Cu+, Ag+-ATPase, CtrA2 (Chintalapati et al., 2008)
Bacteria
CtrA2 of Aquifex aeolicus (O67432)
3.A.3.5.22









The Cu2+-ATPase, CtrA3 (Chintalapati et al., 2008)
Bacteria
CtrA3 of Aquifex aeolicus (O67203)
3.A.3.5.23









Putative spirochete Cu+ ATPase (6 proteins in spirochetes)
Bacteria
Lin1 of Leptospira interrogans (Q72N56)
3.A.3.5.24









The putative copper ATPase, Sso1 (PacS)

Crenarchaeota

PacS of Sulfolobus solfataricus (Q97VH4)
3.A.3.5.25









The putative copper ATPase, Pae1

Crenarchaeota

Pae1 of Pyrobaculum aerophilum (Q8ZUJ0)
3.A.3.5.26









The putative copper ATPase, Tro1

Euryarchaeota

Tro1 of Thermoplasma volcanium (Q978Z8)
3.A.3.5.27









Putative Copper P-type ATPase (46% identical to 3.A.3.5.10)

Korarchaea

Putative Copper P-type ATPase of Candidatus Korarchaeum cryptofilum (B1L487)
3.A.3.5.28









The putative copper ATPase, Ape2

Crenarchaeota

Ape2 of Aeropyrum pernix (Q9YBZ6)
3.A.3.5.29









The copper (Cu2+) transporting ATPase, Ccc2

Yeast

Ccc2 of Schizosaccharomyces pombe (O59666)
3.A.3.5.30









Copper (Cu+) exporting P-ATPase, CopA (3-D structure known to 3.2 Å; PDB# 3RFU; Gourdon et al. 2011).  The internal surface of the ATPase interacts with the copper chaparone, CopZ (Padilla-Benavides et al. 2012).

Bacteria

CopA of Legionella pneumophila (Q5X2N1)
3.A.3.5.31









Mycobacterial copper transporter, MctB (Wolschendorf et al., 2011).

Bacteria

MctB of Mycobacterium abscessus (B1MHH7)
3.A.3.5.32









Copper-transporting ATPase RAN1 (EC 3.6.3.4) (Protein HEAVY METAL ATPASE 7) (Protein RESPONSIVE TO ANTAGONIST 1)
Plants
RAN1 of Arabidopsis thaliana
3.A.3.5.34









Cu+ export ATPase, CopA1, required to maintain cytoplasmic copper levels (González-Guerrero et al. 2010; Raimunda et al. 2013).

Proteobacteria

CopA1 of Pseudomonas aeruginosa
3.A.3.6.1









Zn2+-, Cd2+-, Pb2+-ATPase (efflux)
Bacteria; plants; fungi; protozoa
CadA of Staphylococcus aureus plasmid
3.A.3.6.2









Zn2+-, Cd2+-, Co2+-, Hg2+-, Ni2+-, Cu2+, Pb2+-ATPase (efflux) (Hou and Mitra, 2003)
Bacteria
ZntA of E. coli
3.A.3.6.3









Cd2+-, Zn2+, Co2+-ATPase (efflux)
Bacteria
CadA (HP0791) of Helicobacter pylori
3.A.3.6.4









Pb2+-ATPase (efflux)
Bacteria
PbrA of Ralstonia metallidurans
3.A.3.6.5









Mono- and divalent heavy metal (Cu+, Ag+, Zn2+, Cd2+) ATPase, Bxa1. bxa1 gene expression is induced by all four heavy metal ions (Tong et al., 2002). The His-rich domain is essential for both monovalent (Ag+ and Cu+) and divalent ( Cd2+ and Zn2+) metal tolerance (Nakakihara et al. 2009).

Bacteria

Bxa1 ATPase of Oscillatoria brevis
3.A.3.6.6









Chloroplast envelope Cu+-ATPase, HMA1 (Seigneurin-Berny et al., 2006). Transports many heavy metals (Zn2+, Cu2+, Cd2+, Co2+), increasing heavy metal tolerance. Also transports Ca2+ (Km=370nM) in a thapsigargin-sensitive fashion (Moreno et al, 2008).
Plants
HMA1 of Arabidopsis thaliana
(Q9M3H5)
3.A.3.6.7









The Zn2+ (and Cd2+)-ATPase, HMA2. HMA2 maintains metal homeostasis and has a long C-terminal sequence rich in Cys and His residues that binds Zn2+, Kd≈16 nM and regulates activity (Eren et al., 2006).
Plants
HMA2 of Arabidopsis thaliana (Q9SZW4)
3.A.3.6.8









The Cd2+ resistance ATPase, CadA (Wu et al., 2006)

Bacteria

CadA of Listeria monocytogenes (Q60048)
3.A.3.6.9









The Zn2+ uptake ATPase, ZosA (YkvW) (Gaballa and Helmann, 2002)
Bacteria
ZosA of Bacillus subtilis (O31688)
3.A.3.6.10









The Cd2+, Zn2+, Co2+ resistance ATPase, CadA (YvgW)
Bacteria
CadA of Bacillus subtilis (O32219)
3.A.3.6.11









The Zn2+ efflux P-type ATPase, CadA1 (Leedjarv et al., 2007)
Proteobacteria
CadA1 of Pseudomonas putida (Q88RT8)
3.A.3.6.12









The Cd2+/Pb2+ resistance P-type ATPase, CadA2; induced by Zn2+, Cd2+, Pb2+, Ni2+, Co2+ and Hg2+ (Leedjarv et al., 2007)
Proteobacteria
CadA2 of Pseudomonas putida (Q88CP1)
3.A.3.6.13









The heavy metal efflux pump, AztA (exports Zn2+, Cd2+, Pb2+; has two adjacent heavy metal binding domains (Liu et al., 2007)

Bacteria

AztA of Anabaena (Nostoc) sp. PCC7120 (Q8ZS90)
3.A.3.6.14









The heavy metal (Zn2+, Cd2+) P-type ATPase, Smc04128 (Rossbach et al., 2008)
Bacteria
Smc04128 of Sinorhizobium meliloti (Q92T56)
3.A.3.6.15









The heavy metal transporter A (HmtA) mediates uptake of copper and zinc but not of silver, mercury, or cadmium (Lewinson et al., 2009).

Proteobacteria

HmtA of Pseudomonas aeruginosa (Q9I147)
3.A.3.6.16









The putative heavy metal ATPase, Mac1

Euryarchaeota

Mac1 of Methanosarcina acetivorans (Q8TJZ4)
3.A.3.6.17









Cd2+-selective export ATPase, HMA3 (expressed in root cell tonoplasts wherein Cd2+ is sequestered (Ueno et al., 2010)).

Plants

HMA3 of Oryza sativa (Q8H384)
3.A.3.6.18









Cd2+/Zn2+ exporting ATPase, HMA4. (very similar to HMA3; TC# 3.A.3.6.7). Important for Zn2+ nutrition. Has a C-terminal domain containing 13 cysteine pairs and a terminal stretch of 11 histidines with a high affinity for Zn2+ and Cd2+ and a capacity to bind 10 Zn2+ ions per C-terminus (Baekgaard et al., 2010).

Plants

HMA4 of Arabidopsis thaliana (O64474)
3.A.3.6.19









Ca2+/Zn2+ ATPase, OsHMA2 (Satoh-Nagasawa et al., 2012).

Plants

HMA2 of Oryza sativa (E7EC32)
3.A.3.6.20









Cadmium/zinc-transporting ATPase 4, HMA3

Plants
HMA3 of Arabidopsis thaliana
3.A.3.6.21









Cobalt ion exporting ATPase, slr0797 (Rutherford et al. 1999).

Cyanobacteria

Co-ATPase of Synechocystis PCC6803
3.A.3.6.22









Co2+-specific P1B-ATPase, CoaT (Zielazinski et al., 2012).

Bacteria

CoaT of Sulfitobacter sp. NAS-14.1 (A3T2G5)
3.A.3.6.23









Heavy metal (Pb2+, Cd2+, Zn2+) export ATPase of 970 aas, PbtA (Hložková et al. 2013; Suman et al. 2014)

Proteobacteria

PbtA of Achromobacter xylosoxidans
3.A.3.7.1









K+-ATPase (uptake), KdpFABC. (KdpA is homologous to other K+ transporters such as KcsA (1.A.1.1.1), KtrB (2.A.38.4.2 and 2.A.38.4.3), and HKT (2.A.38.3.1 and 2.A.38.3.2); KdpB is homologous to P-ATPase α-subunits; KdpC and KdpF may facilitate complex assembly and stabilize the complex (Bramkamp et al., 2007; Haupt et al., 2005; Greie and Altendorf, 2007; Irzik et al., 2011). The KdpFABC acts as a functional and structural dimer with the two KdpB subunits in direct contact, but the enzyme can dissociate to the monomer (Heitkamp et al., 2008). KdpF is part of and stabilizes the KdpABC complex (Gassel et al., 1999).  Transcription of the kdp operon is activated by the KdpDE sensor kinase/response regulator pair, and unphosphorylated IIANtr of the PTS (TC# 4.A) binds KdpD to stimulate its activity, thereby enhancing kdp operon expression (Lüttmann et al. 2009).

Bacteria

KdpABCF of E. coli
KdpA (P03959)
KdpB (P03960)
KdpC (P03961)
KdpF (P36937)
3.A.3.7.2









High affinity potassium uptake ATPase, KdpABC.  Regulated by direct interaction of the IIANtr protein with the sensor kinase/response regulator, KdpDE (Prell et al. 2012).

Proteobacteria

KdpABC of Rhizobium leguminosarum
3.A.3.8.1









Golgi Aminophospholipid (phosphatidyl serine and phosphatidyl ethanolamine) translocase (flipping from the exofacial to the cytosolic leaflet of membranes to generate phospholipid asymmetry), required for vesicle-mediated protein transport from the Golgi and endosomes. The system has been reconstituted after purification in proteoliposomes. It flips phosphatidyl serine but not phosphatidylcholine or sphinogomyelin (Zhou and Graham, 2009).

Animals

ATPase II of Bos taurus
3.A.3.8.2









Golgi aminophospholipid translocase (flipping from the exofacial to the cytosolic leaflet of membranes), required for vesicle-mediated protein transport from the Golgi and endosomes (Pomorski et al., 2003). The system has been reconstituted after purification in proteoliposomes. It flips phosphatidyl serine but not phosphatidylcholine or sphingomyelin (Zhou and Graham, 2009).

Eukaryotes

DRS2 of Saccharomyces cerevisiae
3.A.3.8.3









Miltefosine/glycerophospholipid uptake translocase and phospholipid uptake flippase, MIL (Pérez-Victoria et al., 2003)

Protozoa

MIL of Leishmania donovani (Q6VXY9)
3.A.3.8.4









Inwardly directed phospholipid and lysophospholipid (phosphatidylcholine, phosphatidyl serine and lysophosphoethanolamine) flippase, Dnf1 (functions with the β-subunit, Lem3) (Elvington et al., 2005; Pomorski et al., 2003; Riekhof and Voelker, 2006; Riekhof et al., 2007) Also transports the anti-neoplastic and anti-parasitic ether lipid substrates related to edelfosine (Riekhof and Voelker, 2009) (is not required for phosphotidyl serine inwardly directed flipping (Stevens et al. 2008)). Transports diacyl phospholipids in preference to lyso (monoacyl) phospholipids (Baldridge et al. 2013).

Yeast

Dnf1 of Saccharomyces cerevisiae (P32660)
3.A.3.8.5









Inwardly directed phosphatidylcholine, phosphatidyl serine, and lysophosphoethanolamine flippase, Dnf2 (functions with the β-subunit, Lem3) (Elvington et al., 2005; Pomorski et al., 2003; Riekhof and Voelker, 2006; Riekhof et al., 2007). This plasma membrane P-type ATPase (ACT4) is a phospholipid flippase that contributes to endocytosis, protein transport and all polarity (Hua et al., 2002). Transports monoacyl (lyso) phospholipids much better than diacyl phospholipids, but can be mutated to transport diacyl phospholipids (Baldridge et al. 2013).

Yeast

Dnf2 of Saccharomyces cerevisiae (Q12675)
3.A.3.8.6









Golgi phospholipid transporting (flipping) ATPase3 (1213aas; 10TMSs). Involved in growth of roots and shoots. Uses a β-ATPase3 subunit, ALIS1 (TC#8.A.27.4) (Paulsen et al., 2008).
Plants
ATPase3/ALIS1 of Arabidopsis thaliana (Q9XIE6)
3.A.3.8.7









The aminophospholipid ATPase1 (ALA1) (mediate chilling tolerance; Gomes et al., 2000)

Plants

ALA1 of Arabidopsis thaliana (P98204)
3.A.3.8.8









The phosphatidylserine flippase in photoreceptor disc membranes, ATP8A2 (Coleman et al., 2009). The beta-subunit, CDC50A, allows the stable expression, assembly, subcellular localization, and lipid transport activity of ATP8A2 (Coleman and Molday, 2011).  Missennse mutations in ATP8A2 are associated with cerebellar atrophy and guadrupedal locomotion (Emre Onat et al. 2012).

Animals

ATP8A2 of Mus musculus (P98200)
3.A.3.8.9









The phospholipid flipping ATPase (contributes to vesicle biogenesis in the secretory and endocytic pathways). Forms heteromeric complexes with ALIS Cdc50-like β-subunits (ALIS1 = Q9LTW0; TC#8.A.27.1.4) promoting functionality (López-Marqués et al., 2010). The beta-subunit, CDC50A, allows the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2 (Coleman and Molday, 2011).

Plants

Ala2 of Arabidopsis thaliana (P98205)
3.A.3.8.10









Lipid flippase, Apt1 (involved in stress tolerance and virulence). Deletion of Apt1 causes (1) altered actin distribution, (2) increased sensitivity to stress conditions (oxidative and nitrosative stress) and to trafficking inhibitors, such as brefeldin A and monensin, a reduction in exported acid phosphatase activity, and (3) hypersensitivity to the antifungal drugs amphotericin B, fluconazole, and cinnamycin (Hu and Kronstad, 2010).

Yeast

Apt1 of Cryptococcus neoformans (Q5KP96)
3.A.3.8.11









The golgi P-type ATPase, Drs2p, (ACT3; ATP8A2) required for phospholipid translocation across the golgi membrane: PL (in) + ATP → PL (out) + ADP + Pì (flippase activity). Interacts with CDC50 (Bryde et al., 2010). Activated by ArfGEF when bound to the C-terminus (Natarajan et al. 2009). The beta-subunit, CDC50A, allows the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2 (Coleman and Molday, 2011).

Yeast

Drs2p of Saccharomyces cerevisiae (P39524)
3.A.3.8.12









Probable phospholipid-transporting ATPase IF (EC 3.6.3.1) (ATPase IR) (ATPase class VI type 11B)
Animals
ATP11B of Homo sapiens
3.A.3.8.13









Probable phospholipid-transporting ATPase IA (EC 3.6.3.1) (ATPase class I type 8A member 1) (Chromaffin granule ATPase II)
Animals
ATP8A1 of Homo sapiens
3.A.3.8.14









Phospholipid (e.g., cardiolipin) transporter, Atp8b1. A mutant version is associated with severe
pneumonia in humans and mice. It binds and internalizes cardiolipin from
extracellular fluid via a basic residue-enriched motif. Administration
of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene
transfer in mice lessens bacterium-induced lung injury and improves
survival (Ray et al., 2010).  Mutations have been identified that give rise to progressive familial intrahepatic cholestasis (Stone et al. 2012).

Animals

Atp8b1 of Homo sapiens (O43520)
 
3.A.3.9.1









Na+-ATPase (efflux)
Fungi and protozoa
Pmr2ap (ENa1) of Saccharomyces cerevisiae
3.A.3.9.2









K+-ATPase (efflux)
Fungi and protozoa
Cta3 of Schizosaccharomyces pombe
3.A.3.9.3









Monovalent alkali cation (Na+ and K+) ATPase (efflux of both cations)
Fungi and protozoa
ENA2 of Debaryomyces occidentalis
3.A.3.9.4









Na+ ATPase, ENA1 (Watanabe et al., 2002)
Fungi
ENA1 of Zygosaccharomyces rouxii (BAA11411)
3.A.3.9.5









Plasma membrane K+ or Na+ efflux ATPase (required for growth at pH9, and for Na+ or K+ tolerance above pH8; Benito et al., 2009) (50% identical to 3.A.3.9.3).

Fungi

Ena1 of Ustilago maydis (B5B9V9)
3.A.3.9.6









Endoplasmic reticulum K+ or Na+ efflux ATPase; confers Na+ resistance (Benito et al., 2009) (43% identical to 3.A.3.9.2).

Fungi

Ena2 of Ustilago maydis (Q4PI59)
3.A.3.10.1









P-type ATPase 13a1 of 1193 aas

Plants

ATPase 13a1 of Ricinus communis (Castor bean)
3.A.3.10.2









Zebrafish ATP13A2 (Parkinson''s disease protein) is essential for embryonic survival (Lopes da Fonseca et al. 2013).

Fish

ATP13A2 of Danio rerio (Q7SXR0)
3.A.3.10.3









The endoplasmic reticular ATPase, Spf1 or Cod1. Plays a role in ER Mn2+ homeostasis by pumping Mn2+ into the ER lumen (Cronin et al., 2002; Cohen et al. 2013).  Deletion of the gene results in ER stress and lowered Mn2+ in the ER lumen Cohen et al. 2013).  Deletion of the gene results in ER stress and lowered Mn2+ in the ER lumen Cohen et al. 2013Cohen et al. 2013).

Yeast

Spf1 or Cod1 of Saccharomyces cerevisiae (P39986)
3.A.3.10.4









P-type ATPase of 1308 aas

Alveolata

ATPase of Babesia equi
3.A.3.10.5









P-type ATPase of 1291 aas

Alveolata

ATPase of Cryptosporidium parvum
3.A.3.10.6









Putative Mn2+-exporting P-type ATPase of 1146 aas.

Microsporidia

APase of Encephalitozoon cuniculi (Q8SRH4)
3.A.3.10.7









This protein was orginally designated the functionally uncharacterized P-type ATPase, FUPA13 (Thever and Saier 2009).  It is the Parkinson''s disease (PD) gene product, PARK9, and its defect gives rise to multiple abnormalities (Dehay et al. 2012).  It is similar to the probable manganese exporter in yeast, Ypk1 (TC# 3.A.3.10.8), and may have the same function, but in lysosomes. Toxic levels of manganese cause a syndrome simiilar to PD (Chesi et al. 2012).

Animals

PARK9 of Homo sapiens
3.A.3.10.8









This protein was originally designated the functionally uncharacterized P-type ATPase 14 (FUPA14) (Thever and Saier 2009), but it has been shown to be a vacuolar ATPase, Ypk1, that functions in manganese detoxification and homeostasis (Chesi et al. 2012).  It therefore is likely to catalyze export of manganese ions from the cytoplasm into the vacuole.

Fungi

Ypk1 of Saccharomyces cerevisiae (gi6324865)
3.A.3.10.9









This protein was previously designated the functionally uncharacterized P-type ATPase (FUPA15) (Thever and Saier 2009).  Probable manganese exporter by similarity (see 3.A.3.10.7 and 3.A.3.10.8).

Slime molds

Putative Mn2+-ATPase of Dictyostelium discoideum
3.A.3.10.10









Putative Mn2+-exporting P-type ATPase of 1343 aas.

Stramenopiles

ATPase of Albugo laibachii
3.A.3.10.11









This protein was reviously designated the functionally uncharacterized P-type ATPase 16 (FUPA16)  (Thever and Saier 2009).  Probable manganese exporter by similarity.

Alveolata (ciliates)

Putative Mn2+ ATPase of Tetrahymena thermophila (Q23QW3)
3.A.3.10.12









P-type ATPase of 1982 aas

Ciliates

ATPase of Tetrahymena thermophila
3.A.3.10.13









This protein was previously designated the functionally uncharacterized P-type ATPase 17 (FUPA17) (Thever and Saier 2009), but it has been shown to be a Ca2+/Mn2+-exporting ATPase designated Cation-transporting ATPase 5 (Cta5 or ATP13A2) (Furune et al. 2008).

Yeast

ATPase of Schizosaccharomyces pombe (O14022)
3.A.3.10.14









This protein was previously designated the functionally uncharacterized P-type ATPase 18 (FUPA18 of 1491 aas) (Thever and Saier 2009).  It may be a Mn2+-ATPase (by similarity).

Alveolata

FUPA18a of Cryptosporidium parvum (Q5CW06)
3.A.3.10.15









This protein was previously designated the functionally uncharacterized P-type ATPase 19 (FUPA19 of 1807 aas) (Thever and Saier 2009).  The unusually large size and number of TMSs is unique to this protein.  Whether this is a consequence of an artifact of sequencing is not known.  It may be a Mn2+-ATPase (by similarity).

 

Alveolata

ATPase of Tetrahymena thermophilus
3.A.3.10.16









This protein was previously designated the functionally uncharacterized P-type ATPase 20 (FUPA20) (Thever and Saier 2009).  It may be a Mn2+-exporting ATPase (by similarity).

Alveolata (ciliates)

ATPase of Tetrahymena thermophila (Q22V52)
3.A.3.10.17









This protein was previously designated the functionally uncharacterized P-type ATPase 21 (FUPA21 of 1372 aas) (Thever and Saier 2009).  It may be a Mn2+-ATPase (by similarity).

Protozoan

ATPase of Thalassiosira pseudonana
3.A.3.10.18









This protein was previously designated the functionally uncharacterized P-type ATPase 22 (FUPA22 of 1212-2393 aas) (Thever and Saier 2009).  It may be a Mn2+-exporting ATPase (by similarity).

Alveolata

ATPase of Cryptosporidium parvum (Q5CTJ9)
3.A.3.10.19









Probable Mn2+-exporting ATPase, ATP13A1 of 1204 aas.  Defects cause Mn2+-dependent neurological disorders.  Orthologous to the yeast Mn2+-ATPase, Spf1 (Cohen et al. 2013).

Animals

ATP13A1 of Homo sapiens
3.A.3.23.1









Functionally uncharacterized P-type ATPase family 23 (FUPA23) (8 proteins from Actinomycetes; 650-802 aas) (Chan et al. 2010).

Actinobacteria

FUPA23a of Streptomyces coelicolor (Q9KXM5)
3.A.3.23.2









Functionally uncharacterized P-type ATPase family 23 (FUPA23.2) (5 proteins from Firmicutes (778-1056aas; 10TMSs; type 2)).
Firmicutes
FUPA23b of Enterococcus faecalis (Q835V4)
3.A.3.23.3









Functionally uncharacterized P-type ATPase family 23 (FUPA23) (2 proteins from Cyanobacteria (826-831aas; 10+MSs, type 2))

Cyanobacteria

FUPA23c of Trichodesmium erythraeum (Q10YH7)
3.A.3.24.1









Functionally uncharacterized P-type ATPase family 24 (FUPA24) (6 proteins of Actinomycetes; 760-1625 aas) (Chan et al. 2010).

Actinobacteria

FUPA24a of Mycobacterium bovis (Q7U2U7)
3.A.3.24.2









Functionally uncharacterized P-type ATPase family 24 (FUPA24) (1607aas); The first half is most like type I (Copper) ATPases, while the second half is most like type II ATPases (Ca2+).

Chloroflexi

FUPA24b of Thermomicrobium roseum (B9L3W5)
3.A.3.24.3









Functionally uncharacterized P-type ATPase family 24 (FUPA24) (1430aas)

δ-Proteobacteria

FUPA24c of Haliangium ochraceum (D0LKA4)
3.A.3.24.4









Functionally uncharacterized P-type ATPase family 24 (FUPA24) (1446aas)

γ-Proteobacteria

FUPA24d of Hahella chejuensis (ABC27339)
3.A.3.25.1









Functionally uncharacterized P-type ATPase family 25 (FUPA25.1) (4 proteins from Actinomycetes; 645-776 aas) (Chan et al. 2010).

Actinobacteria

FUPA25a of Streptomyces coelicolor (Q9RJ01)
3.A.3.25.2









Functionally uncharacterized P-type ATPase family 25 (FUPA25.2) (3 proteins from α- and β-proteobacteria; 617-759 aas). These proteins show greatest similarity with established families 5&6. Family 25 members have 6 TMSs and lack TMSs A&B. Some fairly close homologues have 7 TMSs.
Proteobacteria
FUPA25b of Sinorhizobium meliloti (Q92Z60)
3.A.3.25.3









Functionally uncharacterized P-type ATPase family 25 (FUPA25.3) (2 proteins from firmicutes; 601-623 aas; 7TMSs and an extra putative N-terminal TMS).
Firmicutes
FUPA25c of Enterococcus faecalis (Q830Z1)
3.A.3.25.4









P-type ATPase with a C-terminal hemeerythrin (Hr) domain (Traverso et al., 2010). The Hr domain binds two iron ions per monomer (a diiron center) and may provide a regulatory or more direct function in iron transport (Traverso et al., 2010).

Bacteria

P1B-5- ATPase of Acidothermus cellulolyticus (A0LQU2)
3.A.3.26.1









Functionally uncharacterized P-type ATPase family 26 (FUPA26) (3 proteins from Corynebacteria 841-976 aas) (Chan et al. 2010).

Actinobacteria

FUPA26a of Corynebacterium diphtheriae (Q6NJJ6)
3.A.3.27.1









Functionally uncharacterized P-type ATPase family 27 (FUPA27) (multiple proteins from α-, β- and γ- proteobacteria; 817-851aas) (Chan et al. 2010).

Proteobacteria

FUPA27a of Neisseria meningitidis (Q9JZI0)
3.A.3.27.2









Functionally uncharacterized P-type ATPase family 27 (FUPA27), Lbi2 (

Spirochetes

FUPA27b of Leptospira biflexa (B0STR2)
3.A.3.27.3









Functionally uncharacterized ε-proteobacteria P-type ATPase

ε-proteobacteria

FUPA27c of Nitratiruptor sp. SB155-2 (A6Q500)
3.A.3.27.4









The Cu2+ - ATPase, CtpA. Required for assembly of periplasmic and membrane embedded copper-dependent oxidases, but not for copper tolerance (Hassani, et al. 2010). Possibly CtpA delivers Cu2+ directly to the enzymes in the membrane rather than catalyzing transmembrane transport: similar to (3.A.3.27.1).

Bacteria

CtpA of Rubrivivax gelatinosus (Q5GCB0)
3.A.3.27.5









Cu+ export ATPase, CopA2; provides copper for cytochrome oxidase assembly (González-Guerrero et al. 2010; Raimunda et al. 2013).

Proteobacteria

CopA2 of Pseudomonas aeruginosa
3.A.3.28.1









Functionally uncharacterized P-type ATPase family 28 (FUPA28) (2 proteins in γ-proteobacteria, 847-852 aas) (Chan et al. 2010).

Proteobacteria

FUPA28a of Legionella pneumophila (Q5ZYY0)
3.A.3.29.1









Functionally uncharacterized P-type ATPase family 29 (FUPA29) (1 protein from a δ-proteobacterium, 798 aas) (Chan et al. 2010).

Proteobacteria

FUPA29a of Bdellovibrio bacteriovorus (Q6MK07)
3.A.3.29.2









Functionally uncharacterized P-type ATPase family 29(FUPA29)(2 proteins from flavobacteria; 792-795)

Bacteroidetes

FUPA29b of Flavobacterium johnsoniae (A5FGV9)
3.A.3.30.1









Functionally uncharacterized P-type ATPase family 30 (FUPA30) (4 proteins from α-, β- and δ-proteobacteria; 825-896 aas) (Chan et al. 2010).

Proteobacteria

FUPA30a of Bdellovibrio bacteriovorus (Q6MPD9)
3.A.3.30.2









Functionally uncharacterized P-type ATPase family 30 (FUPA30) (1 protein from Flavobacteria 838 aas)
Bacteroidetes
FUPA30b of Flavobacterium johnsoniae (A5FBE4)
3.A.3.30.3









Functionally uncharacterized P-type ATPase family 30 (FUPA30), Lbi5 (1 protein in spirochetes)
Spirochetes
FUPA30c of Leptospira biflexa (B0SLF7)
3.A.3.30.4









Functionally uncharacterized P-type ATPase family 30 (FUPA30) (1 ptotein from cyanobacteria; 867 aas).

Cyanobacteria

FUPA30d of Anabaena variabilis (Q3M5P5)
3.A.3.31.1









Functionally uncharacterized P-type ATPase family 31 (FUPA31) (3 proteins from γ-proteobacteria; 673-1068) (most closely related to FUPA32 homologues) (probably an active enzyme) (Chan et al. 2010).

Proteobacteria

FUPA31a of Methylococcus capsulatus (Q606V3)
3.A.3.31.2









Functionally uncharacterized P-type ATPase family 31 (FUPA31b) (probably a pseudogene). Bears a C-terminal domain of the EcsC family (see 3.A.1.143.1) not found in other P-type ATPases.

Proteobacteria

FUPA31b of Methylococcus capsulatus (Q606U9)
3.A.3.32.1









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (multiple proteins from α-, β-, γ-, δ- and ε-proteobacteria (690-720 aas) (Chan et al. 2010).

Proteobacteria

FUPA32a of Azoarcus sp. EbN1 (Q5P8C0)
3.A.3.32.2









Probable heavy metal cation-transporting P-type ATPase, FUPA32.2 (718aas)
Actinobacteria
FUPA32b of Mycobacterium bovis (P0A503)
3.A.3.32.3









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (many homologues in Firmicutes (704-730 aas))

Firmicutes

FUPA32c of Clostridium bartiettii (A6NST6)
3.A.3.32.4









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (3 proteins from Fusobacteria) (735 aas)
Fusobacteria
FUPA32d of Fusobacterium nucleatum (Q8REB9)
3.A.3.32.5









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (699 aas) (1 protein in Spirochetes)

Spirochetes

FUPA32e of Treponema denticola (Q73QH0)
3.A.3.32.6









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (2 proteins from Euryarchaeota)

Euryarchaeota

FUPA32f of Methanobrevibacter smithii (A5UJX0)
3.A.3.32.7









Functionally uncharacterized P-type ATPase family 32 (FUPA32) (several proteins from Verrucomicrobia)

Verrucomicrobia

FUPA32g of Akkermansia muciniphila (B2UR24)
3.A.3.32.8









Functionally uncharacterized P-type ATP family 32 (FUPA32) (several in cyanobacteria)

Cyanobacteria

FUPA32h of Thermosynechococcus elongatus (Q8DL41)