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Anion exchange protein 2

(Redirected from Anion Exchanger 2)

Anion exchange protein 2 (AE2) is a membrane transport protein that in humans is encoded by the SLC4A2 gene.[5][6] AE2 is functionally similar to the Band 3 Cl−/HCO3− exchange protein.

SLC4A2
Identifiers
AliasesSLC4A2, AE2, BND3L, EPB3L1, HKB3, NBND3, solute carrier family 4 member 2
External IDsOMIM: 109280; MGI: 109351; HomoloGene: 128699; GeneCards: SLC4A2; OMA:SLC4A2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6522

20535

Ensembl

ENSG00000164889

ENSMUSG00000028962

UniProt

P04920

P13808

RefSeq (mRNA)

NM_001199692
NM_001199693
NM_001199694
NM_003040

NM_001253892
NM_009207

RefSeq (protein)

NP_001186621
NP_001186622
NP_001186623
NP_003031

NP_001240821
NP_033233

Location (UCSC)Chr 7: 151.06 – 151.08 MbChr 5: 24.63 – 24.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mice have been used to explore the function of AE2. AE2 contributes to basolateral membrane HCO3− transport in the gastrointestinal tract.[7] AE2 is required for spermiogenesis in mice.[8] AE2 is required for normal osteoclast function.[9][10] The activity of AE2 is sensitive to pH.[11]

AE3 has been suggested as a target for prevention of diabetic vasculopathy.[12]

Structure

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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

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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 HCO−3 binding. Further conformational changes then turn the AE2 protein into an outward-facing conformation, releasing HCO−3 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

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164889 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028962 – Ensembl, 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. ^ Tanner MJ (January 1993). "Molecular and cellular biology of the erythrocyte anion exchanger (AE1)". Seminars in Hematology. 30 (1): 34–57. PMID 8434259.
  6. ^ "Entrez Gene: SLC4A2 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1)".
  7. ^ 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. PMC 2853300. PMID 20110461.
  8. ^ 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. PMC 307656. PMID 14673081.
  9. ^ 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. PMC 2579356. PMID 18971331.
  10. ^ 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. PMC 2635809. PMID 19164575.
  11. ^ 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. PMC 2649077. PMID 19103596.
  12. ^ 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. PMID 20180022. S2CID 25917589.
  13. ^ 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. ISSN 2041-1723. PMC 10066210. PMID 37002221. S2CID 257858182.
  14. ^ 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. PMC 2579356. PMID 18971331.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

 

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