TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*2.A.31.1.1









Anion exchanger (HCO3-:Cl- antiporter; also called Band 3, transports a variety of inorganic and organic anions. Anionic phospholipids are ''flipped'' from one monolayer to the other in erythrocytes and the nephron). Mutations cause Southeast Asian ovalocytosis (SAO) hereditary spherocytosis and distal renal tubular acidosis (dRTA) with impaired acid secretion in humans (Chu et al., 2010; Kittanakom et al., 2008; Toye et al., 2008). Activated by glycophorin A (Stewart et al., 2011). Kanadaptin (SLC4a1; Q9BWU0) has been reported to interact with kidney AE1 (Chen et al. 1998), but Kittanakom et al. 2005 could not detect this interaction. Hübner et al. 2002, 2003 reported nuclear and mitochondrial targetting of kanadaptin.  Some point mutations allow the normally electroneutral anion exchanger to catalyze Na+ and K+ conductance or induce a cation leak in the still functional anion exchanger. A structural model of the AE1 membrane spanning domain, based on the structure of Uracil-proton symporter, suggests that there is a unique transport site comprising TMSs 3-5 and 8 that may function in anion exchange and cation leak (Barneaud-Rocca et al. 2013). The spectrin-actin-based cytoskeletal network is attached to the plasma membrane through interactions with ankyrin, which binds to both spectrin and a beta-hairpin loop in the cytoplasmic domain of band 3 (Stefanovic et al. 2007).

Eukaryota
Metazoa
SLC4A1 of Homo sapiens
*2.A.31.1.2









Anion exchanger-2 (AE2; 1241 aas); catalyzes solium-independent Cl-:HCO3- exchange; forms a metabolon with the carbonic anhydrase, Car2 (AAH11949) (Gonzalez-Begne et al., 2007) and with another carbonic anhydrase, CAIX (Q16790) which also forms complexes with AE1 and AE3, activating all of these  transporters about 30% (Morgan et al. 2007).  Cys residues play a role in pH sensitivity, but are not essential for activity (Reimold et al. 2013).

Eukaryota
Metazoa
SLC4A2 of Homo sapiens
*2.A.31.1.3









Anion exchange protein 3 (AE 3) (Anion exchanger 3) (CAE3/BAE3) (Cardiac/brain band 3-like protein) (Neuronal band 3-like protein) (Solute carrier family 4 member 3).  The motif LDADD is a binding site for the N-terminal basic region of carbonic ahnydride II (not I), facilitating bicarbonate transport (Moraes and Reithmeier 2012). 

Eukaryota
Metazoa
SLC4A3 of Homo sapiens
*2.A.31.1.4









Anion exchanger 1 (AE1, Band 3 anion exchanger, Slc4a1) of 918 aas and 13 TMSs in a 1 + 12 TMS arrangement that looks like a 1 + 6 + 6 arrangement.  The protein functions both as a transporter that mediates electroneutral inorganic anion exchange (e.g., Cl- against HCO3-) across the cell membrane and as a structural protein. It is a major integral membrane glycoprotein of the erythrocyte membrane required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its N-terminal cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. It mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine. A mutant containing the sole C462 can drive a marginal Cl- current, but the minimal configuration necessary to get optimal functional expression includes residues C462, C583 and C588 (Martial et al. 2007).

Eukaryota
Metazoa
AE1 of Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri)
*2.A.31.2.1









Electroneutral Na+:HCO3- cotransporter (NBC)
Eukaryota
Metazoa
NBCn1-D of Rattus norvegicus
*2.A.31.2.2









Electrogenic Na+:HCO3- cotransporter, rkNBC (NBCI, NBCe1, SLC4A4). The human orthologue, NBCe1/SLC4A4;Q9Y6R1, is stimulated by carbonic anhydrase II and IX which together form a transport metabolon (Becker and Deitmer, 2007; Orlowski et al., 2012). The bicarbonate channel in the C-terminal two-thirds of the protein is regulated by the N-terminal hydrophilic domain (Chang et al., 2008) which may actually form part of the channel (Zhu et al. 2013). The topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis have been identified (Zhu et al., 2010). Defective membrane expression of the Na+/HCO3- cotransporter NBCe1 is associated with familial migraines (Suzuki et al., 2010). This transporter plays a role in pH regulation and bicarbonate transport in the kideny proximal tubule (Yamazaki et al., 2011; Zhu et al. 2013). The three lysyl residues in the KKMIK motif in TMS5 plays a role in DIDS inhibition (Lu and Boron 2007). Electrogenicity of NBCe1 probably depends on interactions between TM1-5 and TM6-13 (Choi et al. 2007).

Eukaryota
Metazoa
rkNBC (NBCl) of Rattus norvegicus
*2.A.31.2.3









Electrogenic Na+:HCO3- symporter/Cl- antiporter, NCBE (regulates intracellular pH) (Wang et al., 2000; Damkier et al., 2010). Expressed in specific brain cell types; glycosylation required for functional expression (Chen et al., 2008). Loss reduces brain ventricle volume, impairs visual function and protects against fatal epileptic seizures in mice (Hilgen et al. 2012).  NCBE is involved in the control of neuronal pH and excitability; may contribute to the secretion of cerebrospinal fluid (Jacobs et al., 2008). The human orthologue (Q6U841) is an electroneutral Na+/HCO3- cotransporter (NBCn2 or NCBE) with Cl- self exchange activity (Parker et al., 2008).  NCBE/NBCn2 is predominantly expressed in the central nervous system (CNS) with highest concentrations in the choroid plexus. Its primary function is to regulate intracellular neuronal pH and to maintain the pH homeostasis across the blood-cerebrospinal fluid barrier. NCBE is predicted to contain at least 10 transmembrane helices. The N- and C- termini are both cytoplasmic, with a large N-terminal domain (Nt-NCBE) and a relatively small C-terminal domain (Ct-NCBE). The Nt-NCBE is likely to be involved in bicarbonate recognition and transport and contains key areas of regulation involving pH sensing and protein-protein interactions.  It has an intrinsic disordered structure (Bjerregaard-Andersen et al. 2013).

Eukaryota
Metazoa
NCBE of Mus musculus
*2.A.31.2.4









Electroneutral Na+-driven HCO3-/Cl- (+ H+) exchanger, NDCBE1; SLC4A8; NBCn1 (Boron et al. 2009).

Eukaryota
Metazoa
SLC4A8 of Homo sapiens
*2.A.31.2.5









Kidney apical membrane anion exchanger of β-intercalated cells, AE4a
Eukaryota
Metazoa
AE4a of Oryctolagus cuniculus
*2.A.31.2.6









The Na+-dependent Cl-/HCO3- exchanger, NDAE1 (Romero et al., 2000)
Eukaryota
Metazoa
NDAE1 of Drosophila melanogaster (Q9VM32)
*2.A.31.2.7









Squid Na+-dependent Cl-/HCO3- symporter, NDCBE (1198 aas) (Piermarini et al., 2007b)

Eukaryota
Metazoa
NDCBE of Loligo pealei (Q8I8G6)
*2.A.31.2.8









Electrogenic HCO3-:Na+ symporter, NBCe2 (3:1 stoichiometry) (Millar and Brown, 2008)

Eukaryota
Metazoa
SLC4A5 of Homo sapiens
*2.A.31.2.9









The electrogenic Na+ bicarbonate cotransporter (NBCe1) (Sussman et al., 2009).

Eukaryota
Metazoa
NBCe1 of Danio rerio (Q3ZMH2)
*2.A.31.2.10









The Na+-driven Cl--HCO3- exchanger, ABTS-1 (extrudes Cl- from the cell) (Bellemer et al., 2011).

Eukaryota
Metazoa
ABTS-1 of Caenorhabditis elegans (B3WFV9)
*2.A.31.2.11









Sodium bicarbonate cotransporter 3 (Sodium bicarbonate cotransporter 2) (Sodium bicarbonate cotransporter 2b) (Bicarbonate transporter) (Solute carrier family 4 member 7)
Eukaryota
Metazoa
SLC4A7 of Homo sapiens
*2.A.31.2.12









Electrogenic sodium bicarbonate cotransporter 1, NBCe1 (Sodium bicarbonate cotransporter, NBC) (Na+/HCO3- cotransporter) (Solute carrier family 4 member 4) (kNBC1) of 1079 aas (Boron et al. 2009). NBCe1, together with carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes (Theparambil et al. 2017).

Eukaryota
Metazoa
SLC4A4 of Homo sapiens
*2.A.31.2.13









Anion exchange protein 4 (AE 4) (Anion exchanger 4) (Sodium bicarbonate cotransporter 5) (Solute carrier family 4 member 9)
Eukaryota
Metazoa
SLC4A9 of Homo sapiens
*2.A.31.2.14









Sodium-driven chloride bicarbonate exchanger (Solute carrier family 4 member 10)
Eukaryota
Metazoa
SLC4A10 of Homo sapiens
*2.A.31.2.15









Sodium bicarbonate cotransporter, NBC, of 1194 aas and 12 TMSs. It can transport HCO3- (or a related species, such as CO32-).  It functions in adaptation to pH stress, both acid- and base-stress (Cai et al. 2017).

Eukaryota
Metazoa
NBC of Litopenaeus vannamei (Pacific white shrimp)
*2.A.31.3.1









Boron efflux transporter for xylem loading (Takano et al., 2002; Miwa et al., 2010)

Eukaryota
Viridiplantae
BOR1 of Arabidopsis thaliana
*2.A.31.3.2









Boron efflux transporter, Ynl275w (Jennings et al., 2007)
Eukaryota
Fungi
Ynl275 of Saccharomyces cerevisiae
*2.A.31.3.3









Probable boron transporter 3
Eukaryota
Viridiplantae
BOR3 of Arabidopsis thaliana
*2.A.31.3.4









Borate/boric acid (boron) efflux transporter, Bor1.  Involved in boron deficiency tolerance (Cañon et al. 2013).

Eukaryota
Viridiplantae
Bor1 of Citrus macrophylla
*2.A.31.3.5









Borate exporter of 666 aas and 13 TMSs with 5 cytooplasmic α-helices, Bot1.  Also known as the barley root anion-permeable transporter.  Confers tolerance to boron. It is believed to be trimeric.  Transport is dependent on Na+ (Nagarajan et al. 2016).

Eukaryota
Viridiplantae
Bot1 of Hordeum vulgare
*2.A.31.4.1









Boron transporter, NcBC1 or SLC4a11. In the absence of borate, it functions as a Na+ and OH- (H+) channel; in the presence of borate, it functions as an electrogenic Na+-coupled borate cotransporter (Park et al., 2004).  Three genetic corneal dystrophies (congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndrome and Fuchs endothelial corneal dystrophy) arise from mutations of the SLC4a11 gene, which cause blindness from fluid accumulation in the corneal stroma.  It can mediate water flux at a rate comparable to aquaporin in a process that is independent of solute transport (Vilas et al. 2013).  Reviewed by Patel and Parker 2015.  A 3-d homology model rationalizes vaious pathology-causing mutations (Badior et al. 2016).

Eukaryota
Metazoa
SLC4A11 of Homo sapiens