| Structural highlights
Disease
S12A3_HUMAN Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
S12A3_HUMAN Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158][1] [2] [3] [4] [5]
References
- ↑ Richardson C, Rafiqi FH, Karlsson HK, Moleleki N, Vandewalle A, Campbell DG, Morrice NA, Alessi DR. Activation of the thiazide-sensitive Na+-Cl kinases SPAK and OSR1. J Cell Sci. 2008 Mar 1;121(Pt 5):675-84. PMID:18270262 doi:10.1242/jcs.025312
- ↑ Cruz-Rangel S, Melo Z, Vazquez N, Meade P, Bobadilla NA, Pasantes-Morales H, Gamba G, Mercado A. Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011 Sep;301(3):C601-8. doi:, 10.1152/ajpcell.00070.2011. Epub 2011 May 25. PMID:21613606 doi:https://dx.doi.org/10.1152/ajpcell.00070.2011
- ↑ Glaudemans B, Yntema HG, San-Cristobal P, Schoots J, Pfundt R, Kamsteeg EJ, Bindels RJ, Knoers NV, Hoenderop JG, Hoefsloot LH. Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. Eur J Hum Genet. 2012 Mar;20(3):263-70. doi: 10.1038/ejhg.2011.189. Epub 2011 Oct , 19. PMID:22009145 doi:https://dx.doi.org/10.1038/ejhg.2011.189
- ↑ Nan J, Yuan Y, Yang X, Shan Z, Liu H, Wei F, Zhang W, Zhang Y. Cryo-EM structure of the human sodium-chloride cotransporter NCC. Sci Adv. 2022 Nov 11;8(45):eadd7176. doi: 10.1126/sciadv.add7176. Epub 2022 Nov , 9. PMID:36351028 doi:https://dx.doi.org/10.1126/sciadv.add7176
- ↑ Fan M, Zhang J, Lee CL, Zhang J, Feng L. Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter. Nature. 2023 Feb;614(7949):788-793. PMID:36792826 doi:10.1038/s41586-023-05718-0
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