6c3p

Structural highlights

Disease

[KCJ11_HUMAN] MODY;Autosomal dominant hyperinsulinism due to Kir6.2 deficiency;Intermediate DEND syndrome;Transient neonatal diabetes mellitus;Permanent neonatal diabetes mellitus;DEND syndrome;Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency;Autosomal recessive hyperinsulinism due to Kir6.2 deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2. The disease is caused by mutations affecting the gene represented in this entry. [ABCC8_HUMAN] Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency;Autosomal dominant hyperinsulinism due to SUR1 deficiency;Transient neonatal diabetes mellitus;DEND syndrome;Autosomal recessive hyperinsulinism due to SUR1 deficiency;MODY;Permanent neonatal diabetes mellitus. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[KCJ11_HUMAN] This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.^{[1] [2] [3]} [ABCC8_HUMAN] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.^{[4] [5]}

See Also

• Potassium channel 3D structures

References

1. ↑ Tammaro P, Ashcroft FM. A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit. J Physiol. 2007 Nov 1;584(Pt 3):743-53. doi: 10.1113/jphysiol.2007.143149. Epub, 2007 Sep 13. PMID:17855752 doi:http://dx.doi.org/10.1113/jphysiol.2007.143149
2. ↑ Cooper PE, McClenaghan C, Chen X, Stary-Weinzinger A, Nichols CG. Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel. J Biol Chem. 2017 Oct 20;292(42):17387-17398. doi: 10.1074/jbc.M117.804971. Epub , 2017 Aug 23. PMID:28842488 doi:http://dx.doi.org/10.1074/jbc.M117.804971
3. ↑ Babenko AP, Gonzalez G, Aguilar-Bryan L, Bryan J. Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells. Circ Res. 1998 Nov 30;83(11):1132-43. PMID:9831708
4. ↑ Saint-Martin C, Zhou Q, Martin GM, Vaury C, Leroy G, Arnoux JB, de Lonlay P, Shyng SL, Bellanne-Chantelot C. Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism. Clin Genet. 2015 May;87(5):448-54. doi: 10.1111/cge.12428. Epub 2014 Jun 6. PMID:24814349 doi:http://dx.doi.org/10.1111/cge.12428
5. ↑ Harel S, Cohen AS, Hussain K, Flanagan SE, Schlade-Bartusiak K, Patel M, Courtade J, Li JB, Van Karnebeek C, Kurata H, Ellard S, Chanoine JP, Gibson WT. Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):345-51. doi: 10.1515/jpem-2014-0265. PMID:25720052 doi:http://dx.doi.org/10.1515/jpem-2014-0265
6. ↑ Lee KPK, Chen J, MacKinnon R. Molecular structure of human KATP in complex with ATP and ADP. Elife. 2017 Dec 29;6. doi: 10.7554/eLife.32481. PMID:29286281 doi:http://dx.doi.org/10.7554/eLife.32481