9pif: Difference between revisions

Latest revision as of 06:45, 3 June 2026

Cryo-EM structure of human NCC with chlorthalidone

Structural highlights

9pif is a 3 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.24Å
Ligands:	A1CIB, ATP, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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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[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9pif is ON HOLD  until Paper Publication
+==Cryo-EM structure of human NCC with chlorthalidone==
+<StructureSection load='9pif' size='340' side='right'caption='[[9pif]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9pif]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PIF FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.24&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CIB:2-chloranyl-5-[(1~{R})-1-oxidanyl-3-oxidanylidene-2~{H}-isoindol-1-yl]benzenesulfonamide'>A1CIB</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9pif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pif OCA], [https://pdbe.org/9pif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pif RCSB], [https://www.ebi.ac.uk/pdbsum/9pif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pif ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/S12A3_HUMAN S12A3_HUMAN] Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/S12A3_HUMAN 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]<ref>PMID:18270262</ref> <ref>PMID:21613606</ref> <ref>PMID:22009145</ref> <ref>PMID:36351028</ref> <ref>PMID:36792826</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Danio rerio]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Feng L]]
+[[Category: Zhang J]]

9pif: Difference between revisions

Latest revision as of 06:45, 3 June 2026

Cryo-EM structure of human NCC with chlorthalidone

Structural highlights

Disease

Function

References

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