ID KCNJ2_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 27-MAR-2024, entry version 181. DE RecName: Full=Inward rectifier potassium channel 2; DE AltName: Full=Cardiac inward rectifier potassium channel; DE AltName: Full=Inward rectifier K(+) channel Kir2.1; DE Short=IRK-1; DE Short=hIRK1; DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 2; GN Name=KCNJ2; Synonyms=IRK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RC TISSUE=Heart; RX PubMed=7696590; DOI=10.1097/00001756-199412000-00024; 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], AND FUNCTION. RC TISSUE=Heart; RX 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 the RT heart inward rectifier K+-channel."; RL Gene 163:313-317(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RC TISSUE=Blood; RX PubMed=9490857; 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 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 subunits."; RL FEBS Lett. 491:305-311(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-143, AND FUNCTION. RC TISSUE=Fetal brain, and Heart; RX PubMed=7840300; DOI=10.1152/ajpheart.1995.268.1.h506; 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 stable RT expression in a human cell line."; RL Am. J. Physiol. 268:H506-H511(1995). RN [7] RP INTERACTION WITH KCNJ4. RX PubMed=12032359; DOI=10.1073/pnas.102609499; RA Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A., RA Rajan S., Derst C., Veh R.W., Daut J.; RT "Heteromerization of Kir2.x potassium channels contributes to the phenotype RT of Andersen's syndrome."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002). RN [8] RP S-NITROSYLATION AT CYS-76. RX PubMed=19608980; DOI=10.1161/circresaha.109.197558; RA Gomez R., Caballero R., Barana A., Amoros I., Calvo E., Lopez J.A., RA Klein H., Vaquero M., Osuna L., Atienza F., Almendral J., Pinto A., RA Tamargo J., Delpon E.; RT "Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of RT Kir2.1 channels."; RL Circ. Res. 105:383-392(2009). RN [9] RP MYRISTOYLATION AT GLY-2, AND SUBCELLULAR LOCATION. RX PubMed=25043870; DOI=10.1016/j.ab.2014.07.006; RA Takamitsu E., Fukunaga K., Iio Y., Moriya K., Utsumi T.; RT "Cell-free identification of novel N-myristoylated proteins from RT complementary DNA resources using bioorthogonal myristic acid analogues."; RL Anal. Biochem. 464:83-93(2014). RN [10] {ECO:0007744|PDB:7ZDZ} RP STRUCTURE BY ELECTRON MICROSCOPY (4.30 ANGSTROMS) OF 42-366, FUNCTION, RP ACTIVITY REGULATION, SUBUNIT, DISULFIDE BOND, AND MUTAGENESIS OF ARG-312. RX PubMed=36149965; DOI=10.1126/sciadv.abq8489; RA Fernandes C.A.H., Zuniga D., Fagnen C., Kugler V., Scala R., RA Pehau-Arnaudet G., Wagner R., Perahia D., Bendahhou S., Venien-Bryan C.; RT "Cryo-electron microscopy unveils unique structural features of the human RT Kir2.1 channel."; RL Sci. Adv. 8:eabq8489-eabq8489(2022). RN [11] RP CHARACTERIZATION OF VARIANTS LQT7 VAL-71 AND TRP-218, AND VARIANTS LQT7 RP VAL-300; 95-SER--PHE-98 DEL AND 314-SER-TYR-315 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., Clark J., RA Deymeer F., George A.L. Jr., Fish F.A., Hahn A., Nitu A., Ozdemir C., RA Serdaroglu P., Subramony S.H., Wolfe G., Fu Y.-H., 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 [12] 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 and RT skeletal muscle phenotypes."; RL Am. J. Hum. Genet. 71:663-668(2002). RN [13] RP VARIANTS LQT7 LEU-186; HIS-216 AND MET-302. RX PubMed=12163457; DOI=10.1172/jci15183; RA Tristani-Firouzi M., Jensen J.L., Donaldson M.R., Sansone V., Meola G., RA Hahn A., Bendahhou S., Kwiecinski H., Fidzianska A., Plaster N., Fu Y.-H., RA Ptacek L.J., Tawil R.; RT "Functional and clinical characterization of KCNJ2 mutations associated RT with LQT7 (Andersen syndrome)."; RL J. Clin. Invest. 110:381-388(2002). RN [14] RP VARIANT ATFB9 ILE-93, AND CHARACTERIZATION OF VARIANT ATFB9 ILE-93. RX PubMed=15922306; DOI=10.1016/j.bbrc.2005.05.054; RA Xia M., Jin Q., Bendahhou S., He Y., Larroque M.M., Chen Y., Zhou Q., RA Yang Y., Liu Y., Liu B., Zhu Q., Zhou Y., Lin J., Liang B., Li L., Dong X., RA Pan Z., Wang R., Wan H., Qiu W., Xu W., Eurlings P., Barhanin J., Chen Y.; RT "A Kir2.1 gain-of-function mutation underlies familial atrial RT fibrillation."; RL Biochem. Biophys. Res. Commun. 332:1012-1019(2005). RN [15] 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., Gudapakkam S., RA Bosi G., Stramba-Badiale M., Jalife J.; RT "A novel form of short QT syndrome (SQT3) is caused by a mutation in the RT KCNJ2 gene."; RL Circ. Res. 96:800-807(2005). RN [16] RP VARIANT LQT7 ARG-75, AND CHARACTERIZATION OF VARIANT LQT7 ARG-75. RX PubMed=16571646; DOI=10.1136/jmg.2006.040816; RA Lu C.W., Lin J.H., Rajawat Y.S., Jerng H., Rami T.G., Sanchez X., RA DeFreitas G., Carabello B., DeMayo F., Kearney D.L., Miller G., Li H., RA Pfaffinger P.J., Bowles N.E., Khoury D.S., Towbin J.A.; RT "Functional and clinical characterization of a mutation in KCNJ2 associated RT with Andersen-Tawil syndrome."; RL J. Med. Genet. 43:653-659(2006). RN [17] RP VARIANTS LQT7 PHE-54 AND PRO-305, AND CHARACTERIZATION OF VARIANTS LQT7 RP PHE-54 AND PRO-305. RX PubMed=17324964; DOI=10.1093/hmg/ddm034; RA Bendahhou S., Fournier E., Gallet S., Menard D., Larroque M.M., RA Barhanin J.; RT "Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred."; RL Hum. Mol. Genet. 16:900-906(2007). CC -!- FUNCTION: Probably participates in establishing action potential CC waveform and excitability of neuronal and muscle tissues CC (PubMed:7590287, PubMed:7696590, PubMed:7840300). Inward rectifier CC potassium channels are characterized by a greater tendency to allow CC potassium to flow into the cell rather than out of it (PubMed:9490857, CC PubMed:7590287, PubMed:36149965). Their voltage dependence is regulated CC by the concentration of extracellular potassium; as external potassium CC is raised, the voltage range of the channel opening shifts to more CC positive voltages (PubMed:7696590, PubMed:7590287). The inward CC rectification is mainly due to the blockage of outward current by CC internal magnesium (PubMed:9490857). Can be blocked by extracellular CC barium or cesium (PubMed:7696590, PubMed:7590287). CC {ECO:0000269|PubMed:36149965, ECO:0000269|PubMed:7590287, CC ECO:0000269|PubMed:7696590, ECO:0000269|PubMed:7840300, CC ECO:0000269|PubMed:9490857}. CC -!- ACTIVITY REGULATION: Channel opening is promoted by binding CC phosphatidylinositol-4,5-bisphosphate (PIP2). CC {ECO:0000269|PubMed:36149965}. CC -!- SUBUNIT: Homotetramer (PubMed:36149965). Homomultimeric and CC heteromultimeric association with KCNJ4/Kir2.3 (PubMed:12032359). CC Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, CC DLG1, CASK and APBA1 plays a key role in its localization and CC trafficking (By similarity). {ECO:0000250|UniProtKB:Q64273, CC ECO:0000269|PubMed:12032359, ECO:0000269|PubMed:36149965}. CC -!- INTERACTION: CC P63252; Q3SXY8: ARL13B; NbExp=4; IntAct=EBI-703457, EBI-11343438; CC P63252; Q99712: KCNJ15; NbExp=3; IntAct=EBI-703457, EBI-7082607; CC P63252; B7U540: KCNJ18; NbExp=4; IntAct=EBI-703457, EBI-19949648; CC P63252; P63252: KCNJ2; NbExp=3; IntAct=EBI-703457, EBI-703457; CC P63252; Q14160: SCRIB; NbExp=2; IntAct=EBI-703457, EBI-357345; CC P63252; A0A0S2Z4U3: SDC3; NbExp=3; IntAct=EBI-703457, EBI-10204280; CC P63252; O00560: SDCBP; NbExp=3; IntAct=EBI-703457, EBI-727004; CC P63252; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-703457, EBI-8652744; CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Membrane; CC Lipid-anchor {ECO:0000269|PubMed:25043870}. CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, skeletal muscle, and CC kidney. Diffusely distributed throughout the brain. CC -!- PTM: S-nitrosylation increases the open probability and inward CC rectifying currents. {ECO:0000269|PubMed:19608980}. CC -!- DISEASE: Long QT syndrome 7 (LQT7) [MIM:170390]: A heart disorder CC characterized by a prolonged QT interval on the ECG and polymorphic CC ventricular arrhythmias. They cause syncope and sudden death in CC response to exercise or emotional stress, and can present with a CC sentinel event of sudden cardiac death in infancy. Long QT syndrome CC type 7 manifests itself as a clinical triad consisting of potassium- CC sensitive periodic paralysis, ventricular ectopy and dysmorphic CC features. {ECO:0000269|PubMed:11371347, ECO:0000269|PubMed:12148092, CC ECO:0000269|PubMed:12163457, ECO:0000269|PubMed:16571646, CC ECO:0000269|PubMed:17324964}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Short QT syndrome 3 (SQT3) [MIM:609622]: A form of short QT CC syndrome, a heart disorder characterized by idiopathic persistently and CC uniformly short QT interval on ECG in the absence of structural heart CC disease in affected individuals. It can cause syncope and sudden death. CC SQT3 has a unique ECG phenotype characterized by asymmetrical T waves. CC {ECO:0000269|PubMed:15761194}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Atrial fibrillation, familial, 9 (ATFB9) [MIM:613980]: A CC familial form of atrial fibrillation, a common sustained cardiac rhythm CC disturbance. Atrial fibrillation is characterized by disorganized CC atrial electrical activity and ineffective atrial contraction promoting CC blood stasis in the atria and reduces ventricular filling. It can CC result in palpitations, syncope, thromboembolic stroke, and congestive CC heart failure. {ECO:0000269|PubMed:15922306}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel CC (TC 1.A.2.1) family. KCNJ2 subfamily. {ECO:0000305}. 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 CCDS; CCDS11688.1; -. DR PIR; I38727; I38727. DR RefSeq; NP_000882.1; NM_000891.2. DR PDB; 6SPZ; X-ray; 2.08 A; P/Q=422-427. DR PDB; 7ZDZ; EM; 4.30 A; A/B/C/D=1-427. DR PDBsum; 6SPZ; -. DR PDBsum; 7ZDZ; -. DR AlphaFoldDB; P63252; -. DR EMDB; EMD-14678; -. DR SMR; P63252; -. DR BioGRID; 109961; 30. DR ComplexPortal; CPX-3071; Inward rectifier potassium channel 2 complex. DR IntAct; P63252; 223. DR STRING; 9606.ENSP00000243457; -. DR BindingDB; P63252; -. DR ChEMBL; CHEMBL1914276; -. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB00243; Ranolazine. DR TCDB; 1.A.2.1.2; the inward rectifier k(+) channel (irk-c) family. DR GlyGen; P63252; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P63252; -. DR PhosphoSitePlus; P63252; -. DR BioMuta; KCNJ2; -. DR DMDM; 54037433; -. DR jPOST; P63252; -. DR MassIVE; P63252; -. DR PaxDb; 9606-ENSP00000243457; -. DR PeptideAtlas; P63252; -. DR ProteomicsDB; 57513; -. DR Antibodypedia; 31891; 397 antibodies from 36 providers. DR DNASU; 3759; -. DR Ensembl; ENST00000243457.4; ENSP00000243457.2; ENSG00000123700.5. DR Ensembl; ENST00000535240.1; ENSP00000441848.1; ENSG00000123700.5. DR GeneID; 3759; -. DR KEGG; hsa:3759; -. DR MANE-Select; ENST00000243457.4; ENSP00000243457.2; NM_000891.3; NP_000882.1. DR UCSC; uc002jir.4; human. DR AGR; HGNC:6263; -. DR CTD; 3759; -. DR DisGeNET; 3759; -. DR GeneCards; KCNJ2; -. DR GeneReviews; KCNJ2; -. DR HGNC; HGNC:6263; KCNJ2. DR HPA; ENSG00000123700; Tissue enhanced (parathyroid). DR MalaCards; KCNJ2; -. DR MIM; 170390; phenotype. DR MIM; 600681; gene. DR MIM; 609622; phenotype. DR MIM; 613980; phenotype. DR neXtProt; NX_P63252; -. DR OpenTargets; ENSG00000123700; -. DR Orphanet; 37553; Andersen-Tawil syndrome. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 51083; Familial short QT syndrome. DR PharmGKB; PA214; -. DR VEuPathDB; HostDB:ENSG00000123700; -. DR eggNOG; KOG3827; Eukaryota. DR GeneTree; ENSGT01030000234586; -. DR HOGENOM; CLU_022738_3_0_1; -. DR InParanoid; P63252; -. DR OMA; STEEHSM; -. DR OrthoDB; 4126787at2759; -. DR PhylomeDB; P63252; -. DR TreeFam; TF313676; -. DR PathwayCommons; P63252; -. DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels. DR Reactome; R-HSA-1296053; Classical Kir channels. DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential. DR Reactome; R-HSA-9729555; Sensory perception of sour taste. DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits. DR SignaLink; P63252; -. DR SIGNOR; P63252; -. DR BioGRID-ORCS; 3759; 12 hits in 1145 CRISPR screens. DR GeneWiki; Kir2.1; -. DR GenomeRNAi; 3759; -. DR Pharos; P63252; Tchem. DR PRO; PR:P63252; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P63252; Protein. DR Bgee; ENSG00000123700; Expressed in inferior vagus X ganglion and 181 other cell types or tissues. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0030315; C:T-tubule; IEA:Ensembl. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:BHF-UCL. DR GO; GO:0086008; F:voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization; IMP:BHF-UCL. DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; TAS:BHF-UCL. DR GO; GO:0015693; P:magnesium ion transport; IEA:Ensembl. DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; TAS:BHF-UCL. DR GO; GO:0086011; P:membrane repolarization during action potential; IMP:BHF-UCL. DR GO; GO:0086013; P:membrane repolarization during cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IEA:Ensembl. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:BHF-UCL. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL. DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL. DR GO; GO:0034765; P:regulation of monoatomic ion transmembrane transport; IBA:GO_Central. DR GO; GO:0060075; P:regulation of resting membrane potential; TAS:BHF-UCL. DR GO; GO:0014861; P:regulation of skeletal muscle contraction via regulation of action potential; IMP:BHF-UCL. DR GO; GO:0055119; P:relaxation of cardiac muscle; IMP:BHF-UCL. DR GO; GO:0090076; P:relaxation of skeletal muscle; IMP:BHF-UCL. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 2.60.40.1400; G protein-activated inward rectifier potassium channel 1; 1. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR041647; IRK_C. DR InterPro; IPR016449; K_chnl_inward-rec_Kir. DR InterPro; IPR003271; K_chnl_inward-rec_Kir2.1. DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto. DR InterPro; IPR013673; K_chnl_inward-rec_Kir_N. DR InterPro; IPR040445; Kir_TM. DR PANTHER; PTHR11767; INWARD RECTIFIER POTASSIUM CHANNEL; 1. DR PANTHER; PTHR11767:SF43; INWARD RECTIFIER POTASSIUM CHANNEL 2; 1. DR Pfam; PF01007; IRK; 1. DR Pfam; PF17655; IRK_C; 1. DR Pfam; PF08466; IRK_N; 1. DR PIRSF; PIRSF005465; GIRK_kir; 1. DR PRINTS; PR01324; KIR21CHANNEL. DR PRINTS; PR01320; KIRCHANNEL. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; P63252; HS. PE 1: Evidence at protein level; KW 3D-structure; Atrial fibrillation; Disease variant; Disulfide bond; KW Ion channel; Ion transport; Lipoprotein; Long QT syndrome; Membrane; KW Myristate; Potassium; Potassium transport; Reference proteome; KW S-nitrosylation; Short QT syndrome; Transmembrane; Transmembrane helix; KW Transport; Voltage-gated channel. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:25043870" FT CHAIN 2..427 FT /note="Inward rectifier potassium channel 2" FT /id="PRO_0000154923" FT TOPO_DOM 2..81 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 82..106 FT /note="Helical; Name=M1" FT /evidence="ECO:0000250" FT TOPO_DOM 107..128 FT /note="Extracellular" FT /evidence="ECO:0000250" FT INTRAMEM 129..140 FT /note="Helical; Pore-forming; Name=H5" FT /evidence="ECO:0000250" FT INTRAMEM 141..147 FT /note="Pore-forming" FT /evidence="ECO:0000250" FT TOPO_DOM 148..156 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 157..178 FT /note="Helical; Name=M2" FT /evidence="ECO:0000250" FT TOPO_DOM 179..427 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 384..427 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 142..147 FT /note="Selectivity filter" FT /evidence="ECO:0000250" FT MOTIF 425..427 FT /note="PDZ-binding" FT /evidence="ECO:0000255" FT BINDING 255 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000269|PubMed:36149965, FT ECO:0007744|PDB:7ZDZ" FT SITE 172 FT /note="Role in the control of polyamine-mediated channel FT gating and in the blocking by intracellular magnesium" FT /evidence="ECO:0000250" FT MOD_RES 76 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:19608980" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:25043870" FT DISULFID 122..154 FT /evidence="ECO:0007744|PDB:7ZDZ" FT VARIANT 54 FT /note="C -> F (in LQT7; there is loss of function when the FT mutant is expressed alone and a dominant-negative effect FT when expressed with wild-type channels; channel trafficking FT and assembly are not affected; dbSNP:rs199473650)" FT /evidence="ECO:0000269|PubMed:17324964" FT /id="VAR_065861" FT VARIANT 67 FT /note="R -> W (in LQT7; dbSNP:rs104894580)" FT /evidence="ECO:0000269|PubMed:12148092" FT /id="VAR_017851" FT VARIANT 71 FT /note="D -> V (in LQT7; loss of function mutation acting in FT a dominant-negative manner; dbSNP:rs104894575)" FT /evidence="ECO:0000269|PubMed:11371347" FT /id="VAR_017852" FT VARIANT 75 FT /note="T -> R (in LQT7; loss of function mutation acting in FT a dominant-negative manner; dbSNP:rs104894585)" FT /evidence="ECO:0000269|PubMed:16571646" FT /id="VAR_065862" FT VARIANT 93 FT /note="V -> I (in ATFB9; has a gain-of-function effect on FT the channels; dbSNP:rs147750704)" FT /evidence="ECO:0000269|PubMed:15922306" FT /id="VAR_065863" FT VARIANT 95..98 FT /note="Missing (in LQT7)" FT /evidence="ECO:0000269|PubMed:11371347" FT /id="VAR_017853" FT VARIANT 172 FT /note="D -> N (in SQT3; gain of function; FT dbSNP:rs104894584)" FT /evidence="ECO:0000269|PubMed:15761194" FT /id="VAR_023842" FT VARIANT 186 FT /note="P -> L (in LQT7; dbSNP:rs104894581)" FT /evidence="ECO:0000269|PubMed:12163457" FT /id="VAR_017854" FT VARIANT 216 FT /note="N -> H (in LQT7; dbSNP:rs104894583)" FT /evidence="ECO:0000269|PubMed:12163457" FT /id="VAR_017855" FT VARIANT 218 FT /note="R -> W (in LQT7; loss of function and FT dominant-negative effect in current; dbSNP:rs104894578)" FT /evidence="ECO:0000269|PubMed:11371347" FT /id="VAR_017856" FT VARIANT 300 FT /note="G -> V (in LQT7; dbSNP:rs104894579)" FT /evidence="ECO:0000269|PubMed:11371347" FT /id="VAR_017857" FT VARIANT 302 FT /note="V -> M (in LQT7; dbSNP:rs104894582)" FT /evidence="ECO:0000269|PubMed:12163457" FT /id="VAR_017858" FT VARIANT 305 FT /note="T -> P (in LQT7; there is loss of function when the FT mutant is expressed alone and a dominant-negative effect FT when expressed with wild-type channels; channel trafficking FT and assembly are not affected; dbSNP:rs199473387)" FT /evidence="ECO:0000269|PubMed:17324964" FT /id="VAR_065864" FT VARIANT 314..315 FT /note="Missing (in LQT7)" FT /id="VAR_017859" FT MUTAGEN 312 FT /note="R->H: Does not significantly alter affinity for FT PIP2, but mutant channels do not open despite binding FT PIP2." FT /evidence="ECO:0000269|PubMed:36149965" FT CONFLICT 330 FT /note="L -> F (in Ref. 4; AAC39555)" FT /evidence="ECO:0000305" FT CONFLICT 340 FT /note="D -> E (in Ref. 4; AAC39555)" FT /evidence="ECO:0000305" FT STRAND 424..427 FT /evidence="ECO:0007829|PDB:6SPZ" 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 //