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Anion exchange protein 3

From Wikipedia, the free encyclopedia
(Redirected from SLC4A3)
SLC4A3
Identifiers
AliasesSLC4A3, AE3, SLC2C, CAE3/BAE3, solute carrier family 4 member 3
External IDsOMIM: 106195; MGI: 109350; HomoloGene: 129474; GeneCards: SLC4A3; OMA:SLC4A3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005070
NM_201574
NM_001326559

NM_009208
NM_001357149
NM_001357150

RefSeq (protein)

NP_001313488
NP_005061
NP_963868

NP_033234
NP_001344078
NP_001344079

Location (UCSC)Chr 2: 219.63 – 219.64 MbChr 1: 75.52 – 75.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Biological Functions

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Anion exchange protein 3 (AE3) is a membrane transport protein that in humans is encoded by the SLC4A3 gene.[5][6] AE3 is functionally similar to the Band 3 Cl/HCO3 exchange protein but it is expressed primarily in brain neurons and in the heart. Like AE2 its activity is sensitive to pH.[7][8] AE3 mutations have been linked to seizures.[9][10]

SLC4A3 gene mutations have been associated with of Short QT syndrome (SQTS) [11] and recent observations suggest that they are probably the most frequent cause of this disease [12]

Structural features

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The cryo-EM studies on the structures of human AE3 revealed that it forms a homodimer, similar to AE1 and AE2.[13] AE3 is stabilized in an outward-facing conformation as its resting state, in contrast to AE2, which rests in an inward-facing conformation.[14] This outward-facing conformation makes AE3 more vulnerable to the pan-inhibitor of anion transporters, DIDS (4,4-diisothiocyanatostilbene-2,2'-disulfonic acid). In addition to the transmembrane domain (TMD) resolved by cryo-EM, the soluble N-terminal domain (NTD) of AE3 has also been solved in a chimera consisting of the AE3 NTD and AE2 TMD.

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000114923Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006576Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Su YR, Klanke CA, Houseal TW, Linn SC, Burk SE, Varvil TS, Otterud BE, Shull GE, Leppert MF, Menon AG (Jan 1995). "Molecular cloning and physical and genetic mapping of the human anion exchanger isoform 3 (SLC2C) gene to chromosome 2q36". Genomics. 22 (3): 605–9. doi:10.1006/geno.1994.1433. PMID 8001971.
  6. ^ "Entrez Gene: SLC4A3 solute carrier family 4, anion exchanger, member 3".
  7. ^ Casey JR, Sly WS, Shah GN, Alvarez BV (November 2009). "Bicarbonate homeostasis in excitable tissues: role of AE3 Cl-/HCO3- exchanger and carbonic anhydrase XIV interaction". Am. J. Physiol., Cell Physiol. 297 (5): C1091–102. doi:10.1152/ajpcell.00177.2009. PMC 2777400. PMID 19692653.
  8. ^ Hayashi H, Suruga K, Yamashita Y (June 2009). "Regulation of intestinal Cl-/HCO3- exchanger SLC26A3 by intracellular pH". Am. J. Physiol., Cell Physiol. 296 (6): C1279–90. doi:10.1152/ajpcell.00638.2008. PMID 19321737.
  9. ^ Hentschke M, Wiemann M, Hentschke S, Kurth I, Hermans-Borgmeyer I, Seidenbecher T, Jentsch TJ, Gal A, Hübner CA (January 2006). "Mice with a targeted disruption of the Cl-/HCO3- exchanger AE3 display a reduced seizure threshold". Mol. Cell. Biol. 26 (1): 182–91. doi:10.1128/MCB.26.1.182-191.2006. PMC 1317631. PMID 16354689.
  10. ^ Vilas GL, Johnson DE, Freund P, Casey JR (September 2009). "Characterization of an epilepsy-associated variant of the human Cl-/HCO3(-) exchanger AE3". Am. J. Physiol., Cell Physiol. 297 (3): C526–36. doi:10.1152/ajpcell.00572.2008. PMID 19605733. S2CID 29802528.
  11. ^ Thorsen, Kasper; Dam, Vibeke S.; Kjaer-Sorensen, Kasper; Pedersen, Lisbeth N.; Skeberdis, V. Arvydas; Jurevičius, Jonas; Treinys, Rimantas; Petersen, Ida M. B. S.; Nielsen, Morten S.; Oxvig, Claus; Morth, J. Preben; Matchkov, Vladimir V.; Aalkjær, Christian; Bundgaard, Henning; Jensen, Henrik K. (2017-11-22). "Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome". Nature Communications. 8 (1): 1696. doi:10.1038/s41467-017-01630-0. ISSN 2041-1723. PMC 5700076. PMID 29167417.
  12. ^ Christiansen, Morten Krogh; Kjær-Sørensen, Kasper; Clavsen, Natacha C.; Dittmann, Sven; Jensen, Maja Fuhlendorff; Guldbrandsen, Halvor Østerby; Pedersen, Lisbeth Nørum; Sørensen, Rikke Hasle; Lildballe, Dorte Launholt; Müller, Klara; Müller, Patrick; Vogel, Kira; Rudic, Boris; Borggrefe, Martin; Oxvig, Claus (August 2023). "Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome". Heart Rhythm. 20 (8): 1136–1143. doi:10.1016/j.hrthm.2023.02.010. ISSN 1556-3871. PMID 36806574.
  13. ^ Jian, Liyan; Zhang, Qing; Yao, Deqiang; Wang, Qian; Chen, Moxin; Xia, Ying; Li, Shaobai; Shen, Yafeng; Cao, Mi; Qin, An; Li, Lin; Cao, Yu (2024-07-20). "The structural insight into the functional modulation of human anion exchanger 3". Nature Communications. 15 (1): 6134. doi:10.1038/s41467-024-50572-x. ISSN 2041-1723. PMC 11271275. PMID 39033175.
  14. ^ Zhang, Qing; Jian, Liyan; Yao, Deqiang; Rao, Bing; Xia, Ying; Hu, Kexin; Li, Shaobai; Shen, Yafeng; Cao, Mi; Qin, An; Zhao, Jie; Cao, Yu (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. ISSN 2041-1723. PMC 10066210. PMID 37002221.

Further reading

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