Gene Symbol: Slc4a2
Description: solute carrier family 4 (anion exchanger), member 2
Alias: Ae2, B3RP, anion exchange protein 2, AE 2, anion exchanger 2 type b1, anion exchanger 2 type b2, anion exchanger 2 type c1, anion exchanger 2 type c2, band 3-related protein, non-erythroid band 3-like protein, solute carrier family 4 member 2
Species: mouse
Products:     Slc4a2

Top Publications

  1. Zhao Y, Chauvet P, Alper S, Baltz J. Expression and function of bicarbonate/chloride exchangers in the preimplantation mouse embryo. J Biol Chem. 1995;270:24428-34 pubmed
    ..Finally, mRNA encoding two members of the band 3-related AE anion exchanger gene family are expressed in preimplantation embryos. ..
  2. Jensen L, Stuart Tilley A, Peters L, Lux S, Alper S, Breton S. Immunolocalization of AE2 anion exchanger in rat and mouse epididymis. Biol Reprod. 1999;61:973-80 pubmed
    ..In this report, we used a recently described SDS antigen unmasking treatment to localize the Cl/HCO(3) exchanger AE2 in rat and mouse epididymis...
  3. Kao L, Kurtz L, Shao X, Papadopoulos M, Liu L, Bok D, et al. Severe neurologic impairment in mice with targeted disruption of the electrogenic sodium bicarbonate cotransporter NBCe2 (Slc4a5 gene). J Biol Chem. 2011;286:32563-74 pubmed publisher
    ..Our findings are the first demonstration of the fundamental importance of NBCe2 in the biology of the nervous system. ..
  4. Alper S, Kopito R, Libresco S, Lodish H. Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. J Biol Chem. 1988;263:17092-9 pubmed
    ..The cDNA encodes a band 3-related protein (B3RP) of 1237 amino acids, with a predicted mass of 137 kDa...
  5. Paine M, Snead M, Wang H, Abuladze N, Pushkin A, Liu W, et al. Role of NBCe1 and AE2 in secretory ameloblasts. J Dent Res. 2008;87:391-5 pubmed
    ..Mice null for the AE2 anion exchanger have abnormal enamel...
  6. Concepcion A, Salas J, Sáez E, Sarvide S, Ferrer A, Portu A, et al. CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b-/- mice favoring autoimmune cholangitis. Oncotarget. 2015;6:28588-606 pubmed publisher
    ..In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl-/HCO3- anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation...
  7. Taylor Burds C, Cheng P, Wray S. Chloride Accumulators NKCC1 and AE2 in Mouse GnRH Neurons: Implications for GABAA Mediated Excitation. PLoS ONE. 2015;10:e0131076 pubmed publisher
    ..At all ages, GnRH neurons were immunopositive for NKCC1 and AE2 but not KCC2 or AE3...
  8. Stewart A, Kurschat C, Vaughan Jones R, Alper S. Putative re-entrant loop 1 of AE2 transmembrane domain has a major role in acute regulation of anion exchange by pH. J Biol Chem. 2009;284:6126-39 pubmed publisher
    Normal pH sensitivity of the SLC4A2/AE2 anion exchanger requires transmembrane domain (TMD) amino acid (aa) residues not conserved in the homologous but relatively pH-insensitive SLC4A1/AE1 polypeptide...
  9. Wu J, Glimcher L, Aliprantis A. HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function. Proc Natl Acad Sci U S A. 2008;105:16934-9 pubmed publisher
    ..Here, we report that the bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2 (SLC4A2), is up-regulated during osteoclast differentiation...

More Information


  1. Stewart A, Kurschat C, Alper S. Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH. Pflugers Arch. 2007;454:373-84 pubmed
    The ubiquitous AE2/SLC4A2 anion exchanger is acutely and independently regulated by intracellular (pH(i)) and extracellular pH (pH(o)), whereas the closely related AE1/SLC4A1 of the red cell and renal intercalated cell is relatively pH-..
  2. Gawenis L, Ledoussal C, Judd L, Prasad V, Alper S, Stuart Tilley A, et al. Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. J Biol Chem. 2004;279:30531-9 pubmed other tissues, homozygous null mutant (AE2(-/-)) mice were prepared by targeted disruption of the AE2 (Slc4a2) gene...
  3. Mardones P, Medina J, Elferink R. Activation of cyclic AMP Signaling in Ae2-deficient mouse fibroblasts. J Biol Chem. 2008;283:12146-53 pubmed publisher
    Anion exchanger 2 (AE2, SLC4A2) is a ubiquitously expressed membrane solute carrier that regulates intracellular pH (pH(i)) by exchanging cytosolic bicarbonate for extracellular chloride...
  4. Mardones P, Chang J, Oude Elferink R. Cyclic AMP and alkaline pH downregulate carbonic anhydrase 2 in mouse fibroblasts. Biochim Biophys Acta. 2014;1840:1765-70 pubmed publisher
    ..Regulation occurs in opposite directions which may be explained by an incoherent feedforward loop consisting of activation by pCREB and repression by ICER. ..
  5. Nguyen H, Stuart Tilley A, Alper S, Melvin J. Cl(-)/HCO(3)(-) exchange is acetazolamide sensitive and activated by a muscarinic receptor-induced [Ca(2+)](i) increase in salivary acinar cells. Am J Physiol Gastrointest Liver Physiol. 2004;286:G312-20 pubmed
    ..Localization studies using a specific antibody to the ubiquitously expressed AE2 isoform labeled acini in both parotid and sublingual glands...
  6. Lecanda J, Urtasun R, Medina J. Molecular cloning and genomic organization of the mouse AE2 anion exchanger gene. Biochem Biophys Res Commun. 2000;276:117-24 pubmed
    The molecular organization of the AE2 (SLC4A2) gene, a member of the multigene family encoding sodium-independent chloride/bicarbonate anion exchangers, has previously been described in both humans and rats...
  7. Urso K, Charles J, Shull G, Aliprantis A, Balestrieri B. Anion Exchanger 2 Regulates Dectin-1-Dependent Phagocytosis and Killing of Candida albicans. PLoS ONE. 2016;11:e0158893 pubmed publisher
    Anion exchanger 2 (Ae2; gene symbol, Slc4a2) is a plasma membrane Cl-/HCO3- exchanger expressed in the gastrointestinal tract, kidney and bone...
  8. Gawenis L, Greeb J, Prasad V, Grisham C, Sanford L, Doetschman T, et al. Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. J Biol Chem. 2005;280:12781-9 pubmed
    ..We conclude that NHE4, which may normally be coupled with the AE2 Cl-/HCO3- exchanger, is important for normal levels of gastric acid secretion, gastric epithelial cell ..
  9. Coury F, Zenger S, Stewart A, Stephens S, Neff L, Tsang K, et al. SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts. Proc Natl Acad Sci U S A. 2013;110:2163-8 pubmed publisher
    ..Here we show that osteoclast-targeted deletion in mice of solute carrier family 4 anion exchanger member 2 (Slc4a2) results in osteopetrosis...
  10. Stewart A, Kurschat C, Vaughan Jones R, Shmukler B, Alper S. Acute regulation of mouse AE2 anion exchanger requires isoform-specific amino acid residues from most of the transmembrane domain. J Physiol. 2007;584:59-73 pubmed
    The widely expressed anion exchanger polypeptide AE2/SLC4A2 is acutely inhibited by acidic intracellular (pH(i)), by acidic extracellular pH (pH(o)), and by the calmodulin inhibitor, calmidazolium, whereas it is acutely activated by NH(4)(..
  11. Gawenis L, Bradford E, Alper S, Prasad V, Shull G. AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon. Am J Physiol Gastrointest Liver Physiol. 2010;298:G493-503 pubmed publisher
    ..However, additional evidence suggests that the AE2 Cl(-)/HCO(3)(-) exchanger, when coupled with the NHE1 Na(+)/H(+) exchanger or a Na(+)-HCO(3)(-) cotransporter (NBC),..
  12. Stewart A, Kerr N, Chernova M, Alper S, Vaughan Jones R. Acute pH-dependent regulation of AE2-mediated anion exchange involves discrete local surfaces of the NH2-terminal cytoplasmic domain. J Biol Chem. 2004;279:52664-76 pubmed
    We have previously defined in the NH2-terminal cytoplasmic domain of the mouse AE2/SLC4A2 anion exchanger a critical role for the highly conserved amino acids (aa) 336-347 in determining wild-type pH sensitivity of anion transport...
  13. Toivola D, Krishnan S, Binder H, Singh S, Omary M. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol. 2004;164:911-21 pubmed
    ..Therefore, colonic keratins have a novel function in regulating electrolyte transport, likely by targeting ion transporters to their cellular compartments. ..
  14. Bronckers A, Lyaruu D. Magnesium, pH regulation and modulation by mouse ameloblasts exposed to fluoride. Bone. 2017;94:56-64 pubmed publisher
    ..The sensitivity of forming enamel to F likely is due to the sensitivity of pH cycling to acidification of enamel associated with F-induced release of protons. ..
  15. Gonzalez Begne M, Nakamoto T, Nguyen H, Stewart A, Alper S, Melvin J. Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice. J Biol Chem. 2007;282:35125-32 pubmed
    ..4-fold in Nhe1-deficient mice, despite only minimal or any change in mRNA and protein levels of the anion exchanger Ae2. Acetazolamide completely blocked the increase in Cl(-)/HCO(3)(-) exchanger activity in Nhe1-null mice suggesting ..
  16. Josephsen K, Praetorius J, Frische S, Gawenis L, Kwon T, Agre P, et al. Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice. Proc Natl Acad Sci U S A. 2009;106:1638-41 pubmed publisher
    ..Immunohistochemistry revealed that Ae2 is exclusively expressed at the contra-lacunar plasma membrane domain of mouse osteoclast...
  17. Alvarez B, Kieller D, Quon A, Robertson M, Casey J. Cardiac hypertrophy in anion exchanger 1-null mutant mice with severe hemolytic anemia. Am J Physiol Heart Circ Physiol. 2007;292:H1301-12 pubmed
    ..No essential role for AE1 in heart function was found. ..
  18. Walker N, Flagella M, Gawenis L, Shull G, Clarke L. An alternate pathway of cAMP-stimulated Cl secretion across the NKCC1-null murine duodenum. Gastroenterology. 2002;123:531-41 pubmed a basolateral membrane anion exchange process with characteristics consistent with the anion exchanger isoform AE2. Chloride uptake by basolateral anion exchanger activity (AE2) supports intracellular cAMP-stimulated chloride ..
  19. Medina J, Acín A, Prieto J. Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene. Genomics. 1997;39:74-85 pubmed
    The human AE2 gene (HGMW-approved symbol SLC4A2) encompasses over 17 kb and contains 23 exons intervened by 22 introns. The size range for the exons is 90-255 bp, whereas that for the introns is 80 bp to 2.2 kb...
  20. Zhou C, Tiberi M, Liang B, Alper S, Baltz J. HCO3(-)/Cl(-) exchange inactivation and reactivation during mouse oocyte meiosis correlates with MEK/MAPK-regulated Ae2 plasma membrane localization. PLoS ONE. 2009;4:e7417 pubmed publisher
    ..A GFP-tagged form of the HCO(3)(-)/Cl(-) exchanger isoform Ae2 (Slc4a2) was strongly expressed at the GV oocyte plasma membrane, but membrane localization decreased markedly during ..
  21. Hisamoto S, Shimoda S, Harada K, Iwasaka S, Onohara S, Chong Y, et al. Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis. J Autoimmun. 2016;75:150-160 pubmed publisher
    ..Earlier work has demonstrated that patients with PBC have reduced expression of the anion exchanger 2 (AE2) on biliary epithelial cells (BEC) and deletion of AE2 gene has led to a PBC-like disorder in mice...
  22. Zolotarev A, Chernova M, Yannoukakos D, Alper S. Proteolytic cleavage sites of native AE2 anion exchanger in gastric mucosal membranes. Biochemistry. 1996;35:10367-76 pubmed
    The AE2 anion exchanger in pig and rabbit gastric mucosal membranes was subjected to limited proteolysis with trypsin, chymotrypsin, and papain, and to enzymatic N-deglycosylation...
  23. Salas J, Banales J, Sarvide S, Recalde S, Ferrer A, Uriarte I, et al. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology. 2008;134:1482-93 pubmed publisher
    Cl(-)/HCO(3)(-) anion exchanger 2 (AE2) is involved in intracellular pH (pH(i)) regulation and transepithelial acid-base transport, including secretin-stimulated biliary bicarbonate excretion...
  24. Kurschat C, Shmukler B, Jiang L, Wilhelm S, Kim E, Chernova M, et al. Alkaline-shifted pHo sensitivity of AE2c1-mediated anion exchange reveals novel regulatory determinants in the AE2 N-terminal cytoplasmic domain. J Biol Chem. 2006;281:1885-96 pubmed
    The mouse anion exchanger AE2/SLC4A2 Cl(-)/HCO(-)(3) exchanger is essential to post-weaning life. AE2 polypeptides regulate pH(i), chloride concentration, cell volume, and transepithelial ion transport in many tissues...
  25. Bronckers A, Lyaruu D, Bervoets T, Medina J, DenBesten P, Richter J, et al. Murine ameloblasts are immunonegative for Tcirg1, the v-H-ATPase subunit essential for the osteoclast plasma proton pump. Bone. 2012;50:901-8 pubmed publisher
  26. Praetorius J, Nejsum L, Nielsen S. A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells. Am J Physiol Cell Physiol. 2004;286:C601-10 pubmed
  27. Tye C, Sharma R, Smith C, Bartlett J. Altered ion-responsive gene expression in Mmp20 null mice. J Dent Res. 2010;89:1421-6 pubmed publisher
    ..These pH changes were greatly attenuated in Mmp20(-/-) mice. Expression of 4 ion-regulatory genes (Atp2b4, Slc4a2, Car6, Cftr) was significantly decreased in enamel organs from Mmp20(-/-) mice...
  28. Lyaruu D, Bronckers A, Mulder L, Mardones P, Medina J, Kellokumpu S, et al. The anion exchanger Ae2 is required for enamel maturation in mouse teeth. Matrix Biol. 2008;27:119-27 pubmed
    ..We tested the hypothesis that in ameloblasts the anion exchanger-2 (Ae2) is involved in pH regulation during maturation stage amelogenesis...
  29. Kudrycki K, Newman P, Shull G. cDNA cloning and tissue distribution of mRNAs for two proteins that are related to the band 3 Cl-/HCO3- exchanger. J Biol Chem. 1990;265:462-71 pubmed
    ..Band 3 mRNAs were observed in many tissues but high levels of expression occurred only in spleen and kidney. Five Band 3 transcripts, ranging in size from 3.6 to 4.9 kilobases, were detected, including three that are expressed in heart. ..
  30. Recalde S, Muruzabal F, Looije N, Kunne C, Burrell M, Saez E, et al. Inefficient chronic activation of parietal cells in Ae2a,b(-/-) mice. Am J Pathol. 2006;169:165-76 pubmed
    In parietal cells, basolateral Ae2 Cl(-)/HCO(3)(-) exchanger (Slc4a2) appears to compensate for luminal H(+) pumping while providing Cl(-) for apical secretion...
  31. White R, Geissler E, Adkison L, Dowler L, Alper S, Lux S. Chromosomal location of the murine anion exchanger genes encoding AE2 and AE3. Mamm Genome. 1994;5:827-9 pubmed
  32. Palumbo A, Isobe M, Huebner K, Shane S, Rovera G, Demuth D, et al. Chromosomal localization of a human band 3-like gene to region 7q35----7q36. Am J Hum Genet. 1986;39:307-16 pubmed
    ..In situ hybridization analysis using the c-DNA for this nonerythroid Band 3 gene further localized the gene to region 7q35----7q36 of human metaphase chromosomes. ..
  33. Schinke T, Schilling A, Baranowsky A, Seitz S, Marshall R, Linn T, et al. Impaired gastric acidification negatively affects calcium homeostasis and bone mass. Nat Med. 2009;15:674-81 pubmed publisher
    ..Thus, we find that osteopetrosis and osteopetrorickets are distinct phenotypes, depending on the site or sites of defective acidification. ..
  34. Kurschat C, Shmukler B, Jiang L, Hevi S, Kim E, Stewart A, et al. Mouse strain-specific coding polymorphism in the Slc4a2/Ae2 gene encodes Ae2c2 variants differing in isoform-specific dominant negative activity. Exp Physiol. 2008;93:458-67 pubmed publisher
    The Slc4a2/Ae2 gene encodes multiple polypeptides arising from alternate promoter usage...
  35. Concepcion A, Salas J, Sarvide S, Saez E, Ferrer A, Lopez M, et al. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses. Eur J Immunol. 2014;44:1341-51 pubmed publisher
    ..could result in immune dysfunctions, as suggested by the CD8(+) T-cell expansion encountered in mice lacking Ae2 (a widely expressed acid loader with electroneutral and Na(+) -independent Cl(-) /HCO3 (-) anion-exchange activity)...
  36. Peña Münzenmayer G, Catalán M, Kondo Y, Jaramillo Y, Liu F, Shull G, et al. Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells. J Biol Chem. 2015;290:10677-88 pubmed publisher
    ..To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl(-)/HCO3 (-) exchangers...
  37. Medina J, Recalde S, Prieto J, Lecanda J, Saez E, Funk C, et al. Anion exchanger 2 is essential for spermiogenesis in mice. Proc Natl Acad Sci U S A. 2003;100:15847-52 pubmed
    ..Among the four AE genes identified in mammals thus far, only Ae2 (Slc4a2) has been determined to be expressed in the male reproductive system, especially in developing spermatozoa and in ..
  38. Walker N, Liu J, Stein S, Stefanski C, Strubberg A, Clarke L. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium. Am J Physiol Gastrointest Liver Physiol. 2016;310:G70-80 pubmed publisher
    ..base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2)...
  39. Jansen I, Mardones P, Lecanda F, de Vries T, Recalde S, Hoeben K, et al. Ae2(a,b)-deficient mice exhibit osteopetrosis of long bones but not of calvaria. FASEB J. 2009;23:3470-81 pubmed publisher
    ..Here we show that the Na(+)-independent chloride/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the long bones of Ae2(a,b)(-/-) mice (deficient in the main ..
  40. Stuart Tilley A, Shmukler B, Brown D, Alper S. Immunolocalization and tissue-specific splicing of AE2 anion exchanger in mouse kidney. J Am Soc Nephrol. 1998;9:946-59 pubmed
    In this study, an epitope-unmasking technique was used to immunolocalize AE2 anion exchanger polypeptide to basolateral plasma membranes of tubular epithelial cells in mouse kidney...
  41. Sun A. Expression of Cl-/HCO3- exchanger in the basolateral membrane of mouse medullary thick ascending limb. Am J Physiol. 1998;274:F358-64 pubmed
    ..Furthermore, mRNA encoding two members (AE2 and AE3) of the AE gene family were demonstrated in microdissected mouse MTAL tubules by reverse transcription-..