Kir6.2
Kir6.2is a major subunit of theATP-sensitive K+channel,alipid-gatedinward-rectifier potassium ion channel.[5]Thegeneencoding the channel is calledKCNJ11and mutations in this gene are associated withcongenital hyperinsulinism.[6]
Structure[edit]
It is an integral membrane protein. The protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled byG-proteinsand is found associated with thesulfonylurea receptor(SUR) to constitute the ATP-sensitive K+channel.
Pathology[edit]
Mutations in this gene are a cause ofcongenital hyperinsulinism(CHI), an autosomal recessive disorder characterized by unregulated insulin secretion.[7]Defects in this gene may also contribute toautosomal dominantnon-insulin-dependent diabetes mellitus type II(NIDDM).[5][8]
See also[edit]
References[edit]
- ^abcGRCh38: Ensembl release 89: ENSG00000187486–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000096146–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ab"Entrez Gene: KCNJ11 potassium inwardly-rectifying channel, subfamily J, member 11".
- ^Smith AJ, Taneja TK, Mankouri J, Sivaprasadarao A (August 2007). "Molecular cell biology of KATP channels: implications for neonatal diabetes".Expert Reviews in Molecular Medicine.9(21): 1–17.doi:10.1017/S1462399407000403.PMID17666135.S2CID24280714.
- ^Kapoor RR, Flanagan SE, Arya VB, Shield JP, Ellard S, Hussain K (April 2013)."Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism".European Journal of Endocrinology.168(4): 557–564.doi:10.1530/EJE-12-0673.PMC3599069.PMID23345197.
- ^Koo BK, Cho YM, Park BL, Cheong HS, Shin HD, Jang HC, et al. (February 2007). "Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population".Diabetic Medicine.24(2): 178–186.doi:10.1111/j.1464-5491.2006.02050.x.PMID17257281.S2CID22127350.
Further reading[edit]
- Aguilar-Bryan L, Bryan J (April 1999)."Molecular biology of adenosine triphosphate-sensitive potassium channels".Endocrine Reviews.20(2): 101–135.doi:10.1210/edrv.20.2.0361.PMID10204114.
- Meissner T, Beinbrech B, Mayatepek E (1999)."Congenital hyperinsulinism: molecular basis of a heterogeneous disease".Human Mutation.13(5): 351–361.doi:10.1002/(SICI)1098-1004(1999)13:5<351::AID-HUMU3>3.0.CO;2-R.PMID10338089.S2CID30125046.
- Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, et al. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels".Pharmacological Reviews.57(4): 509–526.doi:10.1124/pr.57.4.11.PMID16382105.S2CID11588492.
- Gloyn AL, Siddiqui J, Ellard S (March 2006)."Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism".Human Mutation.27(3): 220–231.doi:10.1002/humu.20292.PMID16416420.S2CID38053792.
- Flechtner I, de Lonlay P, Polak M (December 2006). "Diabetes and hypoglycaemia in young children and mutations in the Kir6.2 subunit of the potassium channel: therapeutic consequences".Diabetes & Metabolism.32(6): 569–580.doi:10.1016/S1262-3636(07)70311-7.PMID17296510.
- Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, et al. (November 1995). "Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor".Science.270(5239): 1166–1170.Bibcode:1995Sci...270.1166I.doi:10.1126/science.270.5239.1166.PMID7502040.S2CID26409797.
- Thomas PM, Cote GJ, Hallman DM, Mathew PM (February 1995)."Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy".American Journal of Human Genetics.56(2): 416–421.PMC1801118.PMID7847376.
- Iwasaki N, Kawamura M, Yamagata K, Cox NJ, Karibe S, Ohgawara H, et al. (February 1996). "Identification of microsatellite markers near the human genes encoding the beta-cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese".Diabetes.45(2): 267–269.doi:10.2337/diabetes.45.2.267.PMID8549873.
- Sakura H, Wat N, Horton V, Millns H, Turner RC, Ashcroft FM (October 1996). "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro".Diabetologia.39(10): 1233–1236.doi:10.1007/BF02658512.PMID8897013.S2CID9490874.
- Thomas P, Ye Y, Lightner E (November 1996)."Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy".Human Molecular Genetics.5(11): 1809–1812.doi:10.1093/hmg/5.11.1809.PMID8923010.
- Inoue H, Ferrer J, Warren-Perry M, Zhang Y, Millns H, Turner RC, et al. (March 1997). "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM".Diabetes.46(3): 502–507.doi:10.2337/diabetes.46.3.502.PMID9032109.
- Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM (May 1997). "Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor".Nature.387(6629): 179–183.Bibcode:1997Natur.387..179T.doi:10.1038/387179a0.PMID9144288.S2CID21570773.
- Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, et al. (July 1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis".Nature Genetics.22(3): 239–247.doi:10.1038/10297.PMID10391210.S2CID4636523.
- Tucker SJ, Ashcroft FM (November 1999)."Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2".The Journal of Biological Chemistry.274(47): 33393–33397.doi:10.1074/jbc.274.47.33393.PMID10559219.
- Cui Y, Giblin JP, Clapp LH, Tinker A (January 2001)."A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits".Proceedings of the National Academy of Sciences of the United States of America.98(2): 729–734.doi:10.1073/pnas.011370498.PMC14656.PMID11136227.
- Giblin JP, Cui Y, Clapp LH, Tinker A (April 2002)."Assembly limits the pharmacological complexity of ATP-sensitive potassium channels".The Journal of Biological Chemistry.277(16): 13717–13723.doi:10.1074/jbc.M112209200.PMID11825905.
- Crawford RM, Budas GR, Jovanović S, Ranki HJ, Wilson TJ, Davies AM, Jovanović A (August 2002)."M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia".The EMBO Journal.21(15): 3936–3948.doi:10.1093/emboj/cdf388.PMC126135.PMID12145195.
- Tschritter O, Stumvoll M, Machicao F, Holzwarth M, Weisser M, Maerker E, et al. (September 2002)."The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia".Diabetes.51(9): 2854–2860.doi:10.2337/diabetes.51.9.2854.PMID12196481.
External links[edit]
- GeneReviews/NCBI/NIH/UW entry on Familial Hyperinsulinism
- GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus
- KCNJ11+protein,+humanat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- SUR1+protein,+humanat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.