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Gene Review

SLC4A2  -  solute carrier family 4 (anion exchanger),...

Homo sapiens

Synonyms: AE 2, AE2, Anion exchange protein 2, Anion exchanger 2, BND3L, ...
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Disease relevance of SLC4A2

  • In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1 [1].
  • Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2 [1].
  • Thus, EBV transformed lymphocytes express the erythroid band 3 (AE1) in addition to AE2 [2].
  • RESULTS: AE3 lesions were more prevalent than AE1 or AE2 lesions in patients with active colitis [3].
  • The degree of aphthae was defined as follows: AE0 = no lesions; AE1 = small nodules without barium flecks (lymphoid hyperplasia); AE2 = minute barium flecks < or = 1 mm in size with a translucent halo (umbilical or eroded lymphoid hyperplasia); AE3 = barium flecks varying from 2 mm to 5 mm in size (typical aphthoid ulcerations) [3].

High impact information on SLC4A2


Chemical compound and disease context of SLC4A2


Biological context of SLC4A2

  • The human AE2 gene (HGMW-approved symbol SLC4A2) encompasses over 17 kb and contains 23 exons intervened by 22 introns [8].
  • The putative promoter region of the human AE2 gene contains no obvious TATA or CCAAT elements in the expected positions but has GC boxes, proposed sites for binding Sp1 transcription factor [8].
  • Na(+)-independent Cl(-)/HCO(3)(-) exchangers (AE1, AE2, AE3) are generally known as ubiquitous, multispanning plasma membrane proteins that regulate intracellular pH and transepithelial acid-base balance in animal tissues [9].
  • The widely expressed AE2 anion exchanger participates in recovery from alkaline load and in regulatory cell volume increase following shrinkage [10].
  • Structure-function studies of recombinant proteins involving chimeras, deletions, and point mutations have delineated regions of AE2, which are important in the exhibition of the regulatory properties absent from AE1 [10].

Anatomical context of SLC4A2


Associations of SLC4A2 with chemical compounds

  • Golgi localization of this AE2 antigen was evident also in cycloheximide-treated cells, indicating that it is a true Golgi-resident protein [9].
  • AE2-mediated anion exchange is also stimulated by ammonium and by hypertonicity by a mechanism sensitive to inhibition by chelation of intracellular Ca2+ and by calmidazolium [12].
  • We speculate that, in the human intestine, AE2 and bAE3 may be the 'housekeeping' isoforms, and the apical AE, the potential candidate for chloride absorption, remains to be identified [13].
  • These results suggest that the full-length AE2 isoform regulates HCO(3)- transport in mature sperm cells and thus their motility in vivo [14].
  • AE2 mRNA and protein expression was measured by RT-PCR and Western blot analysis, respectively, in differentiated human bronchial epithelial cells exposed to H(2)O(2) (100 microM) [15].

Regulatory relationships of SLC4A2

  • AE2 is a widely expressed anion exchanger and has a homologous Ct region with 60% sequence identity to AE1 [16].

Other interactions of SLC4A2

  • AE2 and NHE3 are the first transcripts reported to be upregulated by pVHL [17].
  • These techniques demonstrated the abundant presence of epitopes of the cation exchangers NHE1 and NHE3 and the anion exchanger AE2 in these cells [18].
  • Differential display-PCR identified the AE2 anion exchanger as a candidate VHL target gene [17].
  • Since AE2 has been shown to act as a sulfate transporter at low pH, it is possible that it performs this function in the osteoblast Golgi complex where sulfation reactions occur post-translationally on numerous extracellular matrix macromolecules prior to secretion and mineralization [18].
  • A similar effect of V143Y CAII was found for AE2 and AE3cardiac anion exchanger isoforms [19].

Analytical, diagnostic and therapeutic context of SLC4A2

  • Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene [8].
  • Second, our Northern blotting and RT-PCR analyses demonstrated the presence of only the full-length AE2a mRNA in cells that show prominent Golgi staining with antibodies to AE2 [9].
  • Our Western blotting studies demonstrated that AE2 and bAE3 are localized to the basolateral but not the apical membranes of the intestinal epithelial cells from the human ileum and colon [13].
  • Second, our in situ hybridization analyses showed that AE2 mRNA is expressed in developing sperm cells, indicating that the cloned sequence corresponds to the sperm cell AE [14].
  • The role of transcription factor activator protein (AP)-1 in oxidant regulation of AE2 was evaluated by EMSA and by immunoblotting of nuclear phospho-c-jun [15].


  1. Differential staining of cytoid bodies and skin-limited amyloids with monoclonal anti-keratin antibodies. Eto, H., Hashimoto, K., Kobayashi, H., Fukaya, T., Matsumoto, M., Sun, T.T. Am. J. Pathol. (1984) [Pubmed]
  2. Human erythroid band 3 "anion exchanger 1" is expressed in transformed lymphocytes. Kay, M.M., Vollard, C.H., Vollaard, C.H. Cell. Mol. Biol. (Noisy-le-grand) (1996) [Pubmed]
  3. The significance of colonic mucosal lymphoid hyperplasia and aphthoid ulcers in Crohn's disease. Hizawa, K., Iida, M., Aoyagi, K., Fujishima, M. Clinical radiology. (1996) [Pubmed]
  4. A cluster of cytoplasmic histidine residues specifies pH dependence of the AE2 plasma membrane anion exchanger. Kobayashi, S., Kopito, R.R. Cell (1997) [Pubmed]
  5. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Prieto, J., Qian, C., García, N., Díez, J., Medina, J.F. Gastroenterology (1993) [Pubmed]
  6. Cloning and structural characterization of a human non-erythroid band 3-like protein. Demuth, D.R., Showe, L.C., Ballantine, M., Palumbo, A., Fraser, P.J., Cioe, L., Rovera, G., Curtis, P.J. EMBO J. (1986) [Pubmed]
  7. Staining patterns of human pre-malignant oral epithelium and squamous cell carcinomas by monoclonal anti-keratin antibodies. Reibel, J., Clausen, H., Dabelsteen, E. Acta pathologica, microbiologica, et immunologica Scandinavica. Section A, Pathology. (1985) [Pubmed]
  8. Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene. Medina, J.F., Acín, A., Prieto, J. Genomics (1997) [Pubmed]
  9. Identification of the full-length AE2 (AE2a) isoform as the Golgi-associated anion exchanger in fibroblasts. Holappa, K., Suokas, M., Soininen, P., Kellokumpu, S. J. Histochem. Cytochem. (2001) [Pubmed]
  10. How pH regulates a pH regulator: a regulatory hot spot in the N-terminal cytoplasmic domain of the AE2 anion exchanger. Alper, S.L., Chernova, M.N., Stewart, A.K. Cell Biochem. Biophys. (2002) [Pubmed]
  11. Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with ankyrin along the basolateral plasma membrane of human gastric parietal cells. Jöns, T., Drenckhahn, D. Eur. J. Cell Biol. (1998) [Pubmed]
  12. Molecular physiology of SLC4 anion exchangers. Alper, S.L. Exp. Physiol. (2006) [Pubmed]
  13. Human intestinal anion exchanger isoforms: expression, distribution, and membrane localization. Alrefai, W.A., Tyagi, S., Nazir, T.M., Barakat, J., Anwar, S.S., Hadjiagapiou, C., Bavishi, D., Sahi, J., Malik, P., Goldstein, J., Layden, T.J., Ramaswamy, K., Dudeja, P.K. Biochim. Biophys. Acta (2001) [Pubmed]
  14. Primary structure of a sperm cell anion exchanger and its messenger ribonucleic acid expression during spermatogenesis. Holappa, K., Mustonen, M., Parvinen, M., Vihko, P., Rajaniemi, H., Kellokumpu, S. Biol. Reprod. (1999) [Pubmed]
  15. Oxidative stress activates anion exchange protein 2 and AP-1 in airway epithelial cells. Turi, J.L., Jaspers, I., Dailey, L.A., Madden, M.C., Brighton, L.E., Carter, J.D., Nozik-Grayck, E., Piantadosi, C.A., Ghio, A.J. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  16. Identification of the carbonic anhydrase II binding site in the Cl(-)/HCO(3)(-) anion exchanger AE1. Vince, J.W., Reithmeier, R.A. Biochemistry (2000) [Pubmed]
  17. VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities in renal carcinoma cells. Karumanchi, S.A., Jiang, L., Knebelmann, B., Stuart-Tilley, A.K., Alper, S.L., Sukhatme, V.P. Physiol. Genomics (2001) [Pubmed]
  18. Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts. Mobasheri, A., Golding, S., Pagakis, S.N., Corkey, K., Pocock, A.E., Fermor, B., O'BRIEN, M.J., Wilkins, R.J., Ellory, J.C., Francis, M.J. Cell Biol. Int. (1998) [Pubmed]
  19. A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers. Sterling, D., Reithmeier, R.A., Casey, J.R. J. Biol. Chem. (2001) [Pubmed]
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