Inward rectifier potassium channel 2

Details

Name
Inward rectifier potassium channel 2
Synonyms
  • Cardiac inward rectifier potassium channel
  • hIRK1
  • Inward rectifier K(+) channel Kir2.1
  • IRK-1
  • IRK1
  • Potassium channel, inwardly rectifying subfamily J member 2
Gene Name
KCNJ2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052067|Inward rectifier potassium channel 2
MGSVRTNRYSIVSSEEDGMKLATMAVANGFGNGKSKVHTRQQCRSRFVKKDGHCNVQFIN
VGEKGQRYLADIFTTCVDIRWRWMLVIFCLAFVLSWLFFGCVFWLIALLHGDLDASKEGK
ACVSEVNSFTAAFLFSIETQTTIGYGFRCVTDECPIAVFMVVFQSIVGCIIDAFIIGAVM
AKMAKPKKRNETLVFSHNAVIAMRDGKLCLMWRVGNLRKSHLVEAHVRAQLLKSRITSEG
EYIPLDQIDINVGFDSGIDRIFLVSPITIVHEIDEDSPLYDLSKQDIDNADFEIVVILEG
MVEATAMTTQCRSSYLANEILWGHRYEPVLFEEKHYYKVDYSRFHKTYEVPNTPLCSARD
LAEKKYILSNANSFCYENEVALTSKEEDDSENGVPESTSTDTPPDIDLHNQASVPLEPRP
LRRESEI
Number of residues
427
Molecular Weight
48287.82
Theoretical pI
Not Available
GO Classification
Functions
identical protein binding / inward rectifier potassium channel activity / phosphatidylinositol-4,5-bisphosphate binding / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization
Processes
cardiac conduction / cardiac muscle cell action potential involved in contraction / cellular potassium ion homeostasis / cellular response to mechanical stimulus / magnesium ion transport / membrane depolarization during cardiac muscle cell action potential / membrane repolarization during action potential / membrane repolarization during cardiac muscle cell action potential / positive regulation of potassium ion transmembrane transport / potassium ion import across plasma membrane / potassium ion transmembrane transport / potassium ion transport / protein homotetramerization / regulation of cardiac muscle cell contraction / regulation of heart rate by cardiac conduction / regulation of membrane repolarization / regulation of resting membrane potential / regulation of skeletal muscle contraction via regulation of action potential / relaxation of cardiac muscle / relaxation of skeletal muscle
Components
dendritic spine / Golgi apparatus / integral component of plasma membrane / intercalated disc / intrinsic component of membrane / neuronal cell body / plasma membrane / rough endoplasmic reticulum / smooth endoplasmic reticulum / T-tubule / voltage-gated potassium channel complex
General Function
Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. 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 or cesium.
Specific Function
Identical protein binding
Pfam Domain Function
Transmembrane Regions
82-106 157-178
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0052068|Inward rectifier potassium channel 2 (KCNJ2)
ATGGGCAGTGTGCGAACCAACCGCTACAGCATCGTCTCTTCAGAAGAAGACGGTATGAAG
TTGGCCACCATGGCAGTTGCAAATGGCTTTGGGAACGGGAAGAGTAAAGTCCACACCCGA
CAACAGTGCAGGAGCCGCTTTGTGAAGAAAGATGGCCACTGTAATGTTCAGTTCATCAAT
GTGGGTGAGAAGGGGCAACGGTACCTCGCAGACATCTTCACCACGTGTGTGGACATTCGC
TGGCGGTGGATGCTGGTTATCTTCTGCCTGGCTTTCGTCCTGTCATGGCTGTTTTTTGGC
TGTGTGTTTTGGTTGATAGCTCTGCTCCATGGGGACCTGGATGCATCCAAAGAGGGCAAA
GCTTGTGTGTCCGAGGTCAACAGCTTCACGGCTGCCTTCCTCTTCTCCATTGAGACCCAG
ACAACCATAGGCTATGGTTTCAGATGTGTCACGGATGAATGCCCAATTGCTGTTTTCATG
GTGGTGTTCCAGTCAATCGTGGGCTGCATCATCGATGCTTTCATCATTGGCGCAGTCATG
GCCAAGATGGCAAAGCCAAAGAAGAGAAACGAGACTCTTGTCTTCAGTCACAATGCCGTG
ATTGCCATGAGAGACGGCAAGCTGTGTTTGATGTGGCGAGTGGGCAATCTTCGGAAAAGC
CACTTGGTGGAAGCTCATGTTCGAGCACAGCTCCTCAAATCCAGAATTACTTCTGAAGGG
GAGTATATCCCTCTGGATCAAATAGACATCAATGTTGGGTTTGACAGTGGAATCGATCGT
ATATTTCTGGTGTCCCCAATCACTATAGTCCATGAAATAGATGAAGACAGTCCTTTATAT
GATTTGAGTAAACAGGACATTGACAACGCAGACTTTGAAATCGTGGTCATACTGGAAGGC
ATGGTGGAAGCCACTGCCATGACGACACAGTGCCGTAGCTCTTATCTAGCAAATGAAATC
CTGTGGGGCCACCGCTATGAGCCTGTGCTCTTTGAAGAGAAGCACTACTACAAAGTGGAC
TATTCCAGGTTCCACAAAACTTACGAAGTCCCCAACACTCCCCTTTGTAGTGCCAGAGAC
TTAGCAGAAAAGAAATATATCCTCTCAAATGCAAATTCATTTTGCTATGAAAATGAAGTT
GCCCTCACAAGCAAAGAGGAAGACGACAGTGAAAATGGAGTTCCAGAAAGCACTAGTACG
GACACGCCCCCTGACATAGACCTTCACAACCAGGCAAGTGTACCTCTAGAGCCCAGGCCC
TTACGGCGAGAGTCGGAGATATGA
Chromosome Location
17
Locus
17q24.3
External Identifiers
ResourceLink
UniProtKB IDP63252
UniProtKB Entry NameKCNJ2_HUMAN
HGNC IDHGNC:6263
General References
  1. Raab-Graham KF, Radeke CM, Vandenberg CA: Molecular cloning and expression of a human heart inward rectifier potassium channel. Neuroreport. 1994 Dec 20;5(18):2501-5. [PubMed:7696590]
  2. Wood LS, Tsai TD, Lee KS, Vogeli G: Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel. Gene. 1995 Oct 3;163(2):313-7. [PubMed:7590287]
  3. Tare M, Prestwich SA, Gordienko DV, Parveen S, Carver JE, Robinson C, Bolton TB: Inwardly rectifying whole cell potassium current in human blood eosinophils. J Physiol. 1998 Jan 15;506 ( Pt 2):303-18. [PubMed:9490857]
  4. Derst C, Karschin C, Wischmeyer E, Hirsch JR, Preisig-Muller R, Rajan S, Engel H, Grzeschik K, Daut J, Karschin A: Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits. FEBS Lett. 2001 Mar 2;491(3):305-11. [PubMed:11240146]
  5. Ashen MD, O'Rourke B, Kluge KA, Johns DC, Tomaselli GF: Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line. Am J Physiol. 1995 Jan;268(1 Pt 2):H506-11. [PubMed:7840300]
  6. Preisig-Muller R, Schlichthorl G, Goerge T, Heinen S, Bruggemann A, Rajan S, Derst C, Veh RW, Daut J: Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7774-9. [PubMed:12032359]
  7. Gomez R, Caballero R, Barana A, Amoros I, Calvo E, Lopez JA, Klein H, Vaquero M, Osuna L, Atienza F, Almendral J, Pinto A, Tamargo J, Delpon E: Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels. Circ Res. 2009 Aug 14;105(4):383-92. doi: 10.1161/CIRCRESAHA.109.197558. Epub 2009 Jul 16. [PubMed:19608980]
  8. Takamitsu E, Fukunaga K, Iio Y, Moriya K, Utsumi T: Cell-free identification of novel N-myristoylated proteins from complementary DNA resources using bioorthogonal myristic acid analogues. Anal Biochem. 2014 Nov 1;464:83-93. doi: 10.1016/j.ab.2014.07.006. Epub 2014 Jul 18. [PubMed:25043870]
  9. Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL Jr, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptacek LJ: Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell. 2001 May 18;105(4):511-9. [PubMed:11371347]
  10. Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL Jr, Benson DW: KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet. 2002 Sep;71(3):663-8. Epub 2002 Jul 29. [PubMed:12148092]
  11. Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R: Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002 Aug;110(3):381-8. [PubMed:12163457]
  12. Xia M, Jin Q, Bendahhou S, He Y, Larroque MM, Chen Y, Zhou Q, Yang Y, Liu Y, Liu B, Zhu Q, Zhou Y, Lin J, Liang B, Li L, Dong X, Pan Z, Wang R, Wan H, Qiu W, Xu W, Eurlings P, Barhanin J, Chen Y: A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem Biophys Res Commun. 2005 Jul 15;332(4):1012-9. [PubMed:15922306]
  13. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, di Barletta MR, Gudapakkam S, Bosi G, Stramba-Badiale M, Jalife J: A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005 Apr 15;96(7):800-7. Epub 2005 Mar 10. [PubMed:15761194]
  14. Lu CW, Lin JH, Rajawat YS, Jerng H, Rami TG, Sanchez X, DeFreitas G, Carabello B, DeMayo F, Kearney DL, Miller G, Li H, Pfaffinger PJ, Bowles NE, Khoury DS, Towbin JA: Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome. J Med Genet. 2006 Aug;43(8):653-9. Epub 2006 Mar 29. [PubMed:16571646]
  15. Bendahhou S, Fournier E, Gallet S, Menard D, Larroque MM, Barhanin J: Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred. Hum Mol Genet. 2007 Apr 15;16(8):900-6. Epub 2007 Feb 26. [PubMed:17324964]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00243Ranolazineapproved, investigationalunknowninhibitorDetails
DB04855DronedaroneapprovedyesinhibitorDetails
DB01136Carvedilolapproved, investigationalunknowninhibitorDetails