ID IRK2_HUMAN Reviewed; 427 AA. AC P63252; O15110; P48049; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 28-JUL-2009, entry version 63. DE RecName: Full=Inward rectifier potassium channel 2; DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 2; DE AltName: Full=Inward rectifier K(+) channel Kir2.1; DE AltName: Full=Cardiac inward rectifier potassium channel; DE AltName: Full=IRK1; GN Name=KCNJ2; Synonyms=HIRK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX MEDLINE=95210614; PubMed=7696590; RA Raab-Graham K.F., Radeke C.M., Vandenberg C.A.; RT "Molecular cloning and expression of a human heart inward rectifier RT potassium channel."; RL NeuroReport 5:2501-2505(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RA Tang W., Qin C.L., Yang X.C.; RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX MEDLINE=96011654; PubMed=7590287; DOI=10.1016/0378-1119(95)00244-Z; RA Wood L.S., Tsai T.-D., Lee K.S., Vogeli G.; RT "Cloning and functional expression of a human gene, hIRK1, encoding RT the heart inward rectifier K+-channel."; RL Gene 163:313-317(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Blood; RX MEDLINE=98154156; PubMed=9490857; RX DOI=10.1111/j.1469-7793.1998.303bw.x; RA Tare M., Prestwich S.A., Gordienko D.V., Parveen S., Carver J.E., RA Robinson C., Bolton T.B.; RT "Inwardly rectifying whole cell potassium current in human blood RT eosinophils."; RL J. Physiol. (Lond.) 506:303-318(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX MEDLINE=21135569; PubMed=11240146; DOI=10.1016/S0014-5793(01)02202-5; RA Derst C., Karschin C., Wischmeyer E., Hirsch J.R., Preisig-Muller R., RA Rajan S., Engel H., Grzeschik K., Daut J., Karschin A.; RT "Genetic and functional linkage of Kir5.1 and Kir2.1 channel RT subunits."; RL FEBS Lett. 491:305-311(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-143. RC TISSUE=Fetal brain, and Heart; RX MEDLINE=95142296; PubMed=7840300; RA Ashen M.D., O'Rourke B., Kluge K.A., Johns D.C., Tomaselli G.F.; RT "Inward rectifier K+ channel from human heart and brain: cloning and RT stable expression in a human cell line."; RL Am. J. Physiol. 268:H506-H511(1995). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-337, AND MASS RP SPECTROMETRY. RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [8] RP CHARACTERIZATION OF VARIANTS LQT7 VAL-71 AND TRP-218, AND VARIANTS RP LQT7 VAL-300; 95-SER--PHE-98 DEL AND SER-314-315-TYR DEL. RX PubMed=11371347; DOI=10.1016/S0092-8674(01)00342-7; RA Plaster N.M., Tawil R., Tristani-Firouzi M., Canun S., Bendahhou S., RA Tsunoda A., Donaldson M.R., Iannaccone S.T., Brunt E., Barohn R., RA Clark J., Deymeer F., George A.L. Jr., Fish F.A., Hahn A., Nitu A., RA Ozdemir C., Serdaroglu P., Subramony S.H., Wolfe G., Fu Y.-H., RA Ptacek L.J.; RT "Mutations in Kir2.1 cause the developmental and episodic electrical RT phenotypes of Andersen's syndrome."; RL Cell 105:511-519(2001). RN [9] RP VARIANT LQT7 TRP-67. RX PubMed=12148092; DOI=10.1086/342360; RA Andelfinger G., Tapper A.R., Welch R.C., Vanoye C.G., George A.L. Jr., RA Benson D.W.; RT "KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac RT and skeletal muscle phenotypes."; RL Am. J. Hum. Genet. 71:663-668(2002). RN [10] RP VARIANTS LQT7 LEU-186; HIS-216 AND MET-302. RX PubMed=12163457; RA Tristani-Firouzi M., Jensen J.L., Donaldson M.R., Sansone V., RA Meola G., Hahn A., Bendahhou S., Kwiecinski H., Fidzianska A., RA Plaster N., Fu Y.-H., Ptacek L.J., Tawil R.; RT "Functional and clinical characterization of KCNJ2 mutations RT associated with LQT7 (Andersen syndrome)."; RL J. Clin. Invest. 110:381-388(2002). RN [11] RP VARIANT SQT3 ASN-172, AND CHARACTERIZATION OF VARIANT SQT3 ASN-172. RX PubMed=15761194; DOI=10.1161/01.RES.0000162101.76263.8c; RA Priori S.G., Pandit S.V., Rivolta I., Berenfeld O., Ronchetti E., RA Dhamoon A., Napolitano C., Anumonwo J., di Barletta M.R., RA Gudapakkam S., Bosi G., Stramba-Badiale M., Jalife J.; RT "A novel form of short QT syndrome (SQT3) is caused by a mutation in RT the KCNJ2 gene."; RL Circ. Res. 96:800-807(2005). CC -!- FUNCTION: Probably participates in establishing action potential CC waveform and excitability of neuronal and muscle tissues. Inward CC rectifier potassium channels are characterized by a greater CC tendency to allow potassium to flow into the cell rather than out CC of it. Their voltage dependence is regulated by the concentration CC of extracellular potassium; as external potassium is raised, the CC voltage range of the channel opening shifts to more positive CC voltages. The inward rectification is mainly due to the blockage CC of outward current by internal magnesium. Can be blocked by CC extracellular barium or cesium. CC -!- SUBUNIT: Homomultimeric and heteromultimeric association with CC Kir2.3, resulting in an enhanced G-protein-induced current. CC Association, via its PDZ-recognition domain, with LIN7A, LIN7B, CC LIN7C, DLG1, CASK and APBA1 plays a key role in its localization CC and trafficking (By similarity). CC -!- INTERACTION: CC P24588:AKAP5; NbExp=1; IntAct=EBI-703457, EBI-703640; CC P21333:FLNA; NbExp=1; IntAct=EBI-703457, EBI-350432; CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, skeletal muscle, CC and kidney. Diffusely distributed throughout the brain. CC -!- DISEASE: Defects in KCNJ2 are the cause of long QT syndrome type 7 CC (LQT7) [MIM:170390]; also called Andersen syndrome or Andersen CC cardiodysrhythmic periodic paralysis. Long QT syndromes are heart CC disorders characterized by a prolonged QT interval on the ECG and CC polymorphic ventricular arrhythmias. They cause syncope and sudden CC death in response to excercise or emotional stress. LQT7 manifests CC itself as a clinical triad consisting of potassium-sensitive CC periodic paralysis, ventricular ectopy and dysmorphic features. CC -!- DISEASE: Defects in KCNJ2 are the cause of short QT syndrome type CC 3 (SQT3) [MIM:609622]. Short QT syndromes are heart disorders CC characterized by idiopathic persistently and uniformly short QT CC interval on ECG in the absence of structural heart disease in CC affected individuals. They cause syncope and sudden death. SQT3 CC has a unique ECG phenotype characterized by asymmetrical T waves. CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel CC family. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=KCNJ2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U24055; AAB50277.1; -; mRNA. DR EMBL; U12507; AAC50072.1; -; mRNA. DR EMBL; U16861; AAA91781.1; -; mRNA. DR EMBL; AF153819; AAF73242.1; -; Genomic_DNA. DR EMBL; AF153820; AAF73241.1; -; mRNA. DR EMBL; U22413; AAA64282.1; -; mRNA. DR EMBL; AF011904; AAC39555.1; -; mRNA. DR EMBL; AF021139; AAB88797.1; -; mRNA. DR IPI; IPI00007614; -. DR PIR; I38727; I38727. DR RefSeq; NP_000882.1; -. DR UniGene; Hs.1547; -. DR HSSP; P35562; 1N9P. DR SMR; P63252; 187-370. DR IntAct; P63252; 2. DR TCDB; 1.A.2.1.2; inward rectifier K+ channel (IRK-C) family. DR PhosphoSite; P63252; -. DR PeptideAtlas; P63252; -. DR PRIDE; P63252; -. DR Ensembl; ENST00000243457; ENSP00000243457; ENSG00000123700; Homo sapiens. DR GeneID; 3759; -. DR KEGG; hsa:3759; -. DR UCSC; uc002jir.1; human. DR GeneCards; GC17P065677; -. DR H-InvDB; HIX0039037; -. DR HGNC; HGNC:6263; KCNJ2. DR MIM; 170390; phenotype. DR MIM; 600681; gene. DR MIM; 609622; phenotype. DR Orphanet; 334; Atrial fibrillation, familial. DR Orphanet; 37553; Cardiodysrythmic potassium-sensitive periodic paralysis. DR Orphanet; 768; Long QT syndrome, familial. DR Orphanet; 51083; Short QT syndrome, familial. DR PharmGKB; PA214; -. DR HOGENOM; P63252; -. DR HOVERGEN; P63252; -. DR OMA; P63252; MDNADFE. DR NextBio; 14737; -. DR ArrayExpress; P63252; -. DR Bgee; P63252; -. DR CleanEx; HS_KCNJ2; -. DR GermOnline; ENSG00000123700; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0030955; F:potassium ion binding; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc. DR InterPro; IPR016449; K_chnl_inward-rec_Kir. DR InterPro; IPR001838; K_chnl_inward-rec_Kir-like. DR InterPro; IPR003271; K_chnl_inward-rec_Kir2.1. DR InterPro; IPR013521; K_chnl_inward-rec_Kir_Cr2. DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto. DR InterPro; IPR013673; K_chnl_inward-rec_Kir_N. DR Gene3D; G3DSA:2.60.40.1400; IR_K+channel_cytopl; 1. DR PANTHER; PTHR11767; K+channel_IR; 1. DR PANTHER; PTHR11767:SF15; KIR21_channel; 1. DR Pfam; PF01007; IRK; 1. DR Pfam; PF08466; IRK_N; 1. DR PIRSF; PIRSF005465; GIRK_kir; 1. DR PRINTS; PR01324; KIR21CHANNEL. DR PRINTS; PR01320; KIRCHANNEL. DR ProDom; PD001103; K+channel_IR; 1. PE 1: Evidence at protein level; KW Complete proteome; Disease mutation; Ion transport; Ionic channel; KW Long QT syndrome; Membrane; Phosphoprotein; Potassium; KW Potassium transport; Short QT syndrome; Transmembrane; Transport; KW Voltage-gated channel. FT CHAIN 1 427 Inward rectifier potassium channel 2. FT /FTId=PRO_0000154923. FT TOPO_DOM 1 81 Cytoplasmic (By similarity). FT TRANSMEM 82 106 M1 (By similarity). FT TOPO_DOM 107 128 Extracellular (By similarity). FT TOPO_DOM 148 156 Extracellular (By similarity). FT TRANSMEM 157 178 M2 (By similarity). FT TOPO_DOM 179 427 Cytoplasmic (By similarity). FT REGION 129 140 H5 (pore-forming helix) (By similarity). FT MOTIF 142 147 Selectivity filter (By similarity). FT MOTIF 425 427 PDZ-binding (Potential). FT SITE 172 172 Role in the control of polyamine-mediated FT channel gating and in the blocking by FT intracellular magnesium (By similarity). FT MOD_RES 337 337 Phosphotyrosine. FT VARIANT 67 67 R -> W (in LQT7). FT /FTId=VAR_017851. FT VARIANT 71 71 D -> V (in LQT7; loss of function and FT dominant-negative effect in current). FT /FTId=VAR_017852. FT VARIANT 95 98 Missing (in LQT7). FT /FTId=VAR_017853. FT VARIANT 172 172 D -> N (in SQT3; gain of function). FT /FTId=VAR_023842. FT VARIANT 186 186 P -> L (in LQT7). FT /FTId=VAR_017854. FT VARIANT 216 216 N -> H (in LQT7). FT /FTId=VAR_017855. FT VARIANT 218 218 R -> W (in LQT7; loss of function and FT dominant-negative effect in current). FT /FTId=VAR_017856. FT VARIANT 300 300 G -> V (in LQT7). FT /FTId=VAR_017857. FT VARIANT 302 302 V -> M (in LQT7). FT /FTId=VAR_017858. FT VARIANT 314 315 Missing (in LQT7). FT /FTId=VAR_017859. FT CONFLICT 330 330 L -> F (in Ref. 4; AAC39555). FT CONFLICT 340 340 D -> E (in Ref. 4; AAC39555). SQ SEQUENCE 427 AA; 48288 MW; AB37CAD4B99B4050 CRC64; MGSVRTNRYS IVSSEEDGMK LATMAVANGF GNGKSKVHTR QQCRSRFVKK DGHCNVQFIN VGEKGQRYLA DIFTTCVDIR WRWMLVIFCL AFVLSWLFFG CVFWLIALLH GDLDASKEGK ACVSEVNSFT AAFLFSIETQ TTIGYGFRCV TDECPIAVFM VVFQSIVGCI IDAFIIGAVM AKMAKPKKRN ETLVFSHNAV IAMRDGKLCL MWRVGNLRKS HLVEAHVRAQ LLKSRITSEG EYIPLDQIDI NVGFDSGIDR IFLVSPITIV HEIDEDSPLY DLSKQDIDNA DFEIVVILEG MVEATAMTTQ CRSSYLANEI LWGHRYEPVL FEEKHYYKVD YSRFHKTYEV PNTPLCSARD LAEKKYILSN ANSFCYENEV ALTSKEEDDS ENGVPESTST DTPPDIDLHN QASVPLEPRP LRRESEI //