Anion exchange protein 2
(Redirected fromSLC4A2)
| SLC4A2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SLC4A2,AE2, BND3L, EPB3L1, HKB3, NBND3, solute carrier family 4 member 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM:109280;MGI:109351;HomoloGene:128699;GeneCards:SLC4A2;OMA:SLC4A2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Anion exchange protein 2(AE2) is amembrane transport proteinthat in humans is encoded by theSLC4A2gene.[5][6]AE2 is functionally similar to theBand 3Cl−/HCO3−exchangeprotein.
Micehave been used to explore the function of AE2. AE2 contributes tobasolateral membraneHCO3−transport in thegastrointestinal tract.[7]AE2 is required forspermiogenesisin mice.[8]AE2 is required for normalosteoclastfunction.[9][10]The activity of AE2 is sensitive topH.[11]
AE3 has been suggested as a target for prevention ofdiabetic vasculopathy.[12]
Structure
[edit]The cryo electron microscopic studies revealed that human AE2 protein forms a homodimer and stays in resting state of inward-facing conformation at physiological pH.[13]A loop between transmembrane (TM) helices 10 and 11 extends from TM domain into its cytoplamic domain, forming a "trigger" locking the TM helices in the resting state. In addition, the C-terminal loop (CTD loop) inserts into the anion binding pocket to further block its activities.
Mechanism of ion exchange
[edit]During the process of acid secretion, the cellular pH increases, triggering the release of the "trigger" loop from the cytoplasmic domain.[14]This allows for the re-arrangement of the TM helices, while the CTD loop is forced out, enabling HCO3- binding. Further conformational changes then turn the AE2 protein into an outward-facing conformation, releasing HCO3- into the extracellular environment and capturing Cl- into the binding pocket. Finally, the AE2 protein returns to its inward-facing conformation and releases Cl- into the cytosol. This working cycle of the AE2 protein replaces a weak acid anion with a strong acid anion, thereby lowering the cellular pH and re-balancing pH homeostasis.
See also
[edit]References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000164889–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000028962–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^Tanner MJ (January 1993). "Molecular and cellular biology of the erythrocyte anion exchanger (AE1)".Seminars in Hematology.30(1): 34–57.PMID8434259.
- ^"Entrez Gene: SLC4A2 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1)".
- ^Gawenis LR, Bradford EM, Alper SL, Prasad V, Shull GE (April 2010)."AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon".American Journal of Physiology. Gastrointestinal and Liver Physiology.298(4): G493–G503.doi:10.1152/ajpgi.00178.2009.PMC2853300.PMID20110461.
- ^Medina JF, Recalde S, Prieto J, Lecanda J, Saez E, Funk CD, et al. (December 2003)."Anion exchanger 2 is essential for spermiogenesis in mice".Proceedings of the National Academy of Sciences of the United States of America.100(26): 15847–15852.Bibcode:2003PNAS..10015847M.doi:10.1073/pnas.2536127100.PMC307656.PMID14673081.
- ^Wu J, Glimcher LH, Aliprantis AO (November 2008)."HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function".Proceedings of the National Academy of Sciences of the United States of America.105(44): 16934–16939.Bibcode:2008PNAS..10516934W.doi:10.1073/pnas.0808763105.PMC2579356.PMID18971331.
- ^Josephsen K, Praetorius J, Frische S, Gawenis LR, Kwon TH, Agre P, et al. (February 2009)."Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice".Proceedings of the National Academy of Sciences of the United States of America.106(5): 1638–1641.doi:10.1073/pnas.0811682106.PMC2635809.PMID19164575.
- ^Stewart AK, Kurschat CE, Vaughan-Jones RD, Alper SL (March 2009)."Putative re-entrant loop 1 of AE2 transmembrane domain has a major role in acute regulation of anion exchange by pH".The Journal of Biological Chemistry.284(10): 6126–6139.doi:10.1074/jbc.M802051200.PMC2649077.PMID19103596.
- ^Huang QR, Li Q, Chen YH, Li L, Liu LL, Lei SH, et al. (June 2010). "Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway".Apoptosis.15(6): 693–704.doi:10.1007/s10495-010-0477-9.PMID20180022.S2CID25917589.
- ^Zhang Q, Jian L, Yao D, Rao B, Xia Y, Hu K, et al. (2023-03-31)."The structural basis of the pH-homeostasis mediated by the Cl−/HCO3− exchanger, AE2".Nature Communications.14(1): 1812.doi:10.1038/s41467-023-37557-y.ISSN2041-1723.PMC10066210.PMID37002221.S2CID257858182.
- ^Wu J, Glimcher LH, Aliprantis AO (November 2008)."HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function".Proceedings of the National Academy of Sciences of the United States of America.105(44): 16934–16939.Bibcode:2008PNAS..10516934W.doi:10.1073/pnas.0808763105.PMC2579356.PMID18971331.
Further reading
[edit]- Gehrig H, Müller W, Appelhans H (April 1992). "Complete nucleotide sequence of band 3 related anion transport protein AE2 from human kidney".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1130(3): 326–328.doi:10.1016/0167-4781(92)90446-7.PMID1562608.
- Korsgren C, Cohen CM (July 1988)."Associations of human erythrocyte band 4.2. Binding to ankyrin and to the cytoplasmic domain of band 3".The Journal of Biological Chemistry.263(21): 10212–10218.doi:10.1016/S0021-9258(19)81500-4.PMID2968981.
- Demuth DR, Showe LC, Ballantine M, Palumbo A, Fraser PJ, Cioe L, et al. (June 1986)."Cloning and structural characterization of a human non-erythroid band 3-like protein".The EMBO Journal.5(6): 1205–1214.doi:10.1002/j.1460-2075.1986.tb04348.x.PMC1166929.PMID3015590.
- Palumbo AP, Isobe M, Huebner K, Shane S, Rovera G, Demuth D, et al. (September 1986)."Chromosomal localization of a human band 3-like gene to region 7q35----7q36".American Journal of Human Genetics.39(3): 307–316.PMC1683956.PMID3020980.
- Rybicki AC, Musto S, Schwartz RS (July 1995)."Identification of a band-3 binding site near the N-terminus of erythrocyte membrane protein 4.2".The Biochemical Journal.309. 309 ( Pt 2) (Pt 2): 677–681.doi:10.1042/bj3090677.PMC1135783.PMID7626035.
- Havenga MJ, Bosman GJ, Appelhans H, De Grip WJ (August 1994). "Expression of the anion exchanger (AE) gene family in human brain. Identification of a new AE protein: AE0".Brain Research. Molecular Brain Research.25(1–2): 97–104.doi:10.1016/0169-328X(94)90283-6.PMID7984058.
- Bonaldo MF, Lennon G, Soares MB (September 1996)."Normalization and subtraction: two approaches to facilitate gene discovery".Genome Research.6(9): 791–806.doi:10.1101/gr.6.9.791.PMID8889548.
- Medina JF, Acín A, Prieto J (January 1997). "Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene".Genomics.39(1): 74–85.doi:10.1006/geno.1996.4467.PMID9027488.S2CID223493.
- García C, Montuenga LM, Medina JF, Prieto J (March 1998). "In situ detection of AE2 anion-exchanger mRNA in the human liver".Cell and Tissue Research.291(3): 481–488.doi:10.1007/s004410051017.hdl:10171/20151.PMID9477304.S2CID22738717.
- Jöns T, Drenckhahn D (March 1998). "Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with ankyrin along the basolateral plasma membrane of human gastric parietal cells".European Journal of Cell Biology.75(3): 232–236.doi:10.1016/s0171-9335(98)80117-9.PMID9587054.
- Mobasheri A, Golding S, Pagakis SN, Corkey K, Pocock AE, Fermor B, et al. (1999). "Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts".Cell Biology International.22(7–8): 551–562.doi:10.1006/cbir.1998.0299.PMID10452823.S2CID12201584.
- Hyde K, Harrison D, Hollingsworth MA, Harris A (September 1999). "Chloride-bicarbonate exchangers in the human fetal pancreas".Biochemical and Biophysical Research Communications.263(2): 315–321.doi:10.1006/bbrc.1999.1367.PMID10491290.
- Holappa K, Mustonen M, Parvinen M, Vihko P, Rajaniemi H, Kellokumpu S (October 1999)."Primary structure of a sperm cell anion exchanger and its messenger ribonucleic acid expression during spermatogenesis".Biology of Reproduction.61(4): 981–986.doi:10.1095/biolreprod61.4.981.PMID10491633.
- Karet FE, Finberg KE, Nayir A, Bakkaloglu A, Ozen S, Hulton SA, et al. (December 1999)."Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34".American Journal of Human Genetics.65(6): 1656–1665.doi:10.1086/302679.PMC1288376.PMID10577919.
- Medina JF, Lecanda J, Acín A, Ciesielczyk P, Prieto J (January 2000). "Tissue-specific N-terminal isoforms from overlapping alternate promoters of the human AE2 anion exchanger gene".Biochemical and Biophysical Research Communications.267(1): 228–235.doi:10.1006/bbrc.1999.1951.PMID10623603.S2CID26957969.
- Vince JW, Reithmeier RA (May 2000). "Identification of the carbonic anhydrase II binding site in the Cl(-)/HCO(3)(-) anion exchanger AE1".Biochemistry.39(18): 5527–5533.doi:10.1021/bi992564p.PMID10820026.
- Holappa K, Suokas M, Soininen P, Kellokumpu S (February 2001)."Identification of the full-length AE2 (AE2a) isoform as the Golgi-associated anion exchanger in fibroblasts".The Journal of Histochemistry and Cytochemistry.49(2): 259–269.doi:10.1177/002215540104900213.PMID11156694.
- Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, Burnham CE (February 2001). "Pendrin: an apical Cl−/OH−/HCO3−exchanger in the kidney cortex ".American Journal of Physiology. Renal Physiology.280(2): F356–F364.doi:10.1152/ajprenal.2001.280.2.f356.PMID11208611.
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.
 | Thismembrane protein–related article is astub.You can help Wikipedia byexpanding it. |