KCNJ2_HUMAN
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 03-AUG-2022, entry version 172.
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].
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].
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].
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.
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]
RP CHARACTERIZATION OF VARIANTS LQT7 VAL-71 AND TRP-218, AND VARIANTS LQT7
RP 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., 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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. Inward
CC rectifier potassium channels are characterized by a greater tendency to
CC allow potassium to flow into the cell rather than out of it. Their
CC voltage dependence is regulated by the concentration of extracellular
CC potassium; as external potassium is raised, the voltage range of the
CC channel opening shifts to more positive voltages. The inward
CC rectification is mainly due to the blockage of outward current by
CC internal magnesium. Can be blocked by extracellular barium or cesium.
CC -!- SUBUNIT: Homomultimeric and heteromultimeric association with
CC KCNJ4/Kir2.3. Association, via its PDZ-recognition domain, with LIN7A,
CC LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization
CC and trafficking (By similarity). {ECO:0000250}.
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 heart disorder
CC characterized by idiopathic persistently and uniformly short QT
CC interval on ECG in the absence of structural heart disease in affected
CC individuals. It causes syncope and sudden death. SQT3 has a unique ECG
CC 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 (TC
CC 1.A.2.1) family. KCNJ2 subfamily. {ECO:0000305}.
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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 PDBsum; 6SPZ; -.
DR AlphaFoldDB; P63252; -.
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; P63252; -.
DR PeptideAtlas; P63252; -.
DR PRIDE; P63252; -.
DR ProteomicsDB; 57513; -.
DR Antibodypedia; 31891; 327 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 CTD; 3759; -.
DR DisGeNET; 3759; -.
DR GeneCards; KCNJ2; -.
DR GeneReviews; KCNJ2; -.
DR HGNC; HGNC:6263; KCNJ2.
DR HPA; ENSG00000123700; Tissue enhanced (brain, parathyroid gland).
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; SEHHQAT; -.
DR OrthoDB; 956263at2759; -.
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 BioGRID-ORCS; 3759; 10 hits in 1065 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 180 other tissues.
DR Genevisible; P63252; HS.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR GO; GO:0031224; C:intrinsic component of 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:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; 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:0030007; P:cellular potassium ion homeostasis; TAS:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
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:0034765; P:regulation of ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
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; 2.60.40.1400; -; 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; PTHR11767; 1.
DR PANTHER; PTHR11767:SF43; PTHR11767:SF43; 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; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Atrial fibrillation; Disease variant; Ion channel;
KW Ion transport; Lipoprotein; Long QT syndrome; Membrane; Myristate;
KW Potassium; Potassium transport; Reference proteome; S-nitrosylation;
KW Short QT syndrome; Transmembrane; Transmembrane helix; Transport;
KW 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 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 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 dominant-
FT 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 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
