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P63252 (KCNJ2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inward rectifier potassium channel 2
Alternative name(s):
Cardiac inward rectifier potassium channel
Inward rectifier K(+) channel Kir2.1
Short name=IRK-1
Short name=hIRK1
Potassium channel, inwardly rectifying subfamily J member 2
Gene names
Name:KCNJ2
Synonyms:IRK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subunit structure

Homomultimeric and heteromultimeric association with KCNJ4/Kir2.3. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Heart, brain, placenta, lung, skeletal muscle, and kidney. Diffusely distributed throughout the brain.

Post-translational modification

S-nitrosylation increases the open probabilty and inward rectifying currents.

Involvement in disease

Long QT syndrome 7 (LQT7) [MIM:170390]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 7 manifests itself as a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.14 Ref.15

Short QT syndrome 3 (SQT3) [MIM:609622]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. SQT3 has a unique ECG phenotype characterized by asymmetrical T waves.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Atrial fibrillation, familial, 9 (ATFB9) [MIM:613980]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   DiseaseAtrial fibrillation
Disease mutation
Long QT syndrome
Short QT syndrome
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Voltage-gated channel
   PTMS-nitrosylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle cell action potential involved in contraction

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

cellular potassium ion homeostasis

Traceable author statement PubMed 20086079. Source: BHF-UCL

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

magnesium ion transport

Inferred from electronic annotation. Source: Ensembl

membrane depolarization during cardiac muscle cell action potential

Traceable author statement PubMed 20086079. Source: BHF-UCL

membrane repolarization during action potential

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

membrane repolarization during cardiac muscle cell action potential

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

positive regulation of potassium ion transmembrane transport

Inferred from electronic annotation. Source: Ensembl

potassium ion import

Inferred from direct assay Ref.9. Source: BHF-UCL

potassium ion transmembrane transport

Inferred from direct assay PubMed 12086641. Source: BHF-UCL

potassium ion transport

Inferred from direct assay PubMed 20921230. Source: UniProtKB

protein homotetramerization

Inferred from direct assay PubMed 20921230. Source: UniProtKB

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype Ref.13. Source: BHF-UCL

regulation of membrane repolarization

Inferred from direct assay Ref.9. Source: BHF-UCL

regulation of resting membrane potential

Traceable author statement PubMed 20086079. Source: BHF-UCL

regulation of skeletal muscle contraction via regulation of action potential

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

relaxation of cardiac muscle

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

relaxation of skeletal muscle

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

T-tubule

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

intercalated disc

Inferred from electronic annotation. Source: Ensembl

intrinsic component of membrane

Inferred from direct assay PubMed 20921230. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

rough endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

smooth endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

voltage-gated potassium channel complex

Inferred from direct assay PubMed 12086641. Source: BHF-UCL

   Molecular_functioninward rectifier potassium channel activity

Inferred from direct assay PubMed 20921230. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay PubMed 12086641. Source: BHF-UCL

voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427Inward rectifier potassium channel 2
PRO_0000154923

Regions

Topological domain1 – 8181Cytoplasmic By similarity
Transmembrane82 – 10625Helical; Name=M1; By similarity
Topological domain107 – 12822Extracellular By similarity
Intramembrane129 – 14012Helical; Pore-forming; Name=H5; By similarity
Intramembrane141 – 1477Pore-forming; By similarity
Topological domain148 – 1569Extracellular By similarity
Transmembrane157 – 17822Helical; Name=M2; By similarity
Topological domain179 – 427249Cytoplasmic By similarity
Motif142 – 1476Selectivity filter By similarity
Motif425 – 4273PDZ-binding Potential

Sites

Site1721Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Amino acid modifications

Modified residue761S-nitrosocysteine Ref.8

Natural variations

Natural variant541C → F in LQT7; there is loss of function when the mutant is expressed alone and a dominant-negative effect when expressed with wild-type channels; channel trafficking and assembly are not affected. Ref.15
VAR_065861
Natural variant671R → W in LQT7. Ref.10
VAR_017851
Natural variant711D → V in LQT7; loss of function mutation acting in a dominant-negative manner. Ref.9
VAR_017852
Natural variant751T → R in LQT7; loss of function mutation acting in a dominant-negative manner. Ref.14
VAR_065862
Natural variant931V → I in ATFB9; has a gain-of-function effect on the channels. Ref.12
VAR_065863
Natural variant95 – 984Missing in LQT7.
VAR_017853
Natural variant1721D → N in SQT3; gain of function. Ref.13
VAR_023842
Natural variant1861P → L in LQT7. Ref.11
VAR_017854
Natural variant2161N → H in LQT7. Ref.11
VAR_017855
Natural variant2181R → W in LQT7; loss of function and dominant-negative effect in current. Ref.9
VAR_017856
Natural variant3001G → V in LQT7. Ref.9
VAR_017857
Natural variant3021V → M in LQT7. Ref.11
VAR_017858
Natural variant3051T → P in LQT7; there is loss of function when the mutant is expressed alone and a dominant-negative effect when expressed with wild-type channels; channel trafficking and assembly are not affected. Ref.15
VAR_065864
Natural variant314 – 3152Missing in LQT7.
VAR_017859

Experimental info

Sequence conflict3301L → F in AAC39555. Ref.4
Sequence conflict3401D → E in AAC39555. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P63252 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: AB37CAD4B99B4050

FASTA42748,288
        10         20         30         40         50         60 
MGSVRTNRYS IVSSEEDGMK LATMAVANGF GNGKSKVHTR QQCRSRFVKK DGHCNVQFIN 

        70         80         90        100        110        120 
VGEKGQRYLA DIFTTCVDIR WRWMLVIFCL AFVLSWLFFG CVFWLIALLH GDLDASKEGK 

       130        140        150        160        170        180 
ACVSEVNSFT AAFLFSIETQ TTIGYGFRCV TDECPIAVFM VVFQSIVGCI IDAFIIGAVM 

       190        200        210        220        230        240 
AKMAKPKKRN ETLVFSHNAV IAMRDGKLCL MWRVGNLRKS HLVEAHVRAQ LLKSRITSEG 

       250        260        270        280        290        300 
EYIPLDQIDI NVGFDSGIDR IFLVSPITIV HEIDEDSPLY DLSKQDIDNA DFEIVVILEG 

       310        320        330        340        350        360 
MVEATAMTTQ CRSSYLANEI LWGHRYEPVL FEEKHYYKVD YSRFHKTYEV PNTPLCSARD 

       370        380        390        400        410        420 
LAEKKYILSN ANSFCYENEV ALTSKEEDDS ENGVPESTST DTPPDIDLHN QASVPLEPRP 


LRRESEI 

« Hide

References

[1]"Molecular cloning and expression of a human heart inward rectifier potassium channel."
Raab-Graham K.F., Radeke C.M., Vandenberg C.A.
NeuroReport 5:2501-2505(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]Tang W., Qin C.L., Yang X.C.
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel."
Wood L.S., Tsai T.-D., Lee K.S., Vogeli G.
Gene 163:313-317(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[4]"Inwardly rectifying whole cell potassium current in human blood eosinophils."
Tare M., Prestwich S.A., Gordienko D.V., Parveen S., Carver J.E., Robinson C., Bolton T.B.
J. Physiol. (Lond.) 506:303-318(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Blood.
[5]"Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits."
Derst C., Karschin C., Wischmeyer E., Hirsch J.R., Preisig-Muller R., Rajan S., Engel H., Grzeschik K., Daut J., Karschin A.
FEBS Lett. 491:305-311(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[6]"Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line."
Ashen M.D., O'Rourke B., Kluge K.A., Johns D.C., Tomaselli G.F.
Am. J. Physiol. 268:H506-H511(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-143.
Tissue: Fetal brain and Heart.
[7]"Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome."
Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A., Rajan S., Derst C., Veh R.W., Daut J.
Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCNJ4.
[8]"Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels."
Gomez R., Caballero R., Barana A., Amoros I., Calvo E., Lopez J.A., Klein H., Vaquero M., Osuna L., Atienza F., Almendral J., Pinto A., Tamargo J., Delpon E.
Circ. Res. 105:383-392(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-76.
[9]"Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome."
Plaster N.M., Tawil R., Tristani-Firouzi M., Canun S., Bendahhou S., Tsunoda A., Donaldson M.R., Iannaccone S.T., Brunt E., Barohn R., Clark J., Deymeer F., George A.L. Jr., Fish F.A., Hahn A., Nitu A., Ozdemir C., Serdaroglu P. expand/collapse author list , Subramony S.H., Wolfe G., Fu Y.-H., Ptacek L.J.
Cell 105:511-519(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS LQT7 VAL-71 AND TRP-218, VARIANTS LQT7 VAL-300; 95-SER--PHE-98 DEL AND SER-314-315-TYR DEL.
[10]"KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes."
Andelfinger G., Tapper A.R., Welch R.C., Vanoye C.G., George A.L. Jr., Benson D.W.
Am. J. Hum. Genet. 71:663-668(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT7 TRP-67.
[11]"Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)."
Tristani-Firouzi M., Jensen J.L., Donaldson M.R., Sansone V., Meola G., Hahn A., Bendahhou S., Kwiecinski H., Fidzianska A., Plaster N., Fu Y.-H., Ptacek L.J., Tawil R.
J. Clin. Invest. 110:381-388(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT7 LEU-186; HIS-216 AND MET-302.
[12]"A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation."
Xia M., Jin Q., Bendahhou S., He Y., Larroque M.M., 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. expand/collapse author list , Wan H., Qiu W., Xu W., Eurlings P., Barhanin J., Chen Y.
Biochem. Biophys. Res. Commun. 332:1012-1019(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ATFB9 ILE-93, CHARACTERIZATION OF VARIANT ATFB9 ILE-93.
[13]"A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene."
Priori S.G., Pandit S.V., Rivolta I., Berenfeld O., Ronchetti E., Dhamoon A., Napolitano C., Anumonwo J., di Barletta M.R., Gudapakkam S., Bosi G., Stramba-Badiale M., Jalife J.
Circ. Res. 96:800-807(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SQT3 ASN-172, CHARACTERIZATION OF VARIANT SQT3 ASN-172.
[14]"Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome."
Lu C.W., Lin J.H., Rajawat Y.S., Jerng H., Rami T.G., Sanchez X., DeFreitas G., Carabello B., DeMayo F., Kearney D.L., Miller G., Li H., Pfaffinger P.J., Bowles N.E., Khoury D.S., Towbin J.A.
J. Med. Genet. 43:653-659(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT7 ARG-75, CHARACTERIZATION OF VARIANT LQT7 ARG-75.
[15]"Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred."
Bendahhou S., Fournier E., Gallet S., Menard D., Larroque M.M., Barhanin J.
Hum. Mol. Genet. 16:900-906(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT7 PHE-54 AND PRO-305, CHARACTERIZATION OF VARIANTS LQT7 PHE-54 AND PRO-305.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U24055 mRNA. Translation: AAB50277.1.
U12507 mRNA. Translation: AAC50072.1.
U16861 mRNA. Translation: AAA91781.1.
AF153819 Genomic DNA. Translation: AAF73242.1.
AF153820 mRNA. Translation: AAF73241.1.
U22413 mRNA. Translation: AAA64282.1.
AF011904 mRNA. Translation: AAC39555.1.
AF021139 mRNA. Translation: AAB88797.1.
CCDSCCDS11688.1.
PIRI38727.
RefSeqNP_000882.1. NM_000891.2.
UniGeneHs.1547.

3D structure databases

ProteinModelPortalP63252.
SMRP63252. Positions 43-371.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109961. 4 interactions.
IntActP63252. 2 interactions.
STRING9606.ENSP00000243457.

Chemistry

ChEMBLCHEMBL1914276.
GuidetoPHARMACOLOGY430.

Protein family/group databases

TCDB1.A.2.1.2. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteP63252.

Polymorphism databases

DMDM54037433.

Proteomic databases

PaxDbP63252.
PeptideAtlasP63252.
PRIDEP63252.

Protocols and materials databases

DNASU3759.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000243457; ENSP00000243457; ENSG00000123700.
ENST00000535240; ENSP00000441848; ENSG00000123700.
GeneID3759.
KEGGhsa:3759.
UCSCuc002jir.3. human.

Organism-specific databases

CTD3759.
GeneCardsGC17P068165.
GeneReviewsKCNJ2.
HGNCHGNC:6263. KCNJ2.
HPAHPA029109.
MIM170390. phenotype.
600681. gene.
609622. phenotype.
613980. phenotype.
neXtProtNX_P63252.
Orphanet37553. Cardiodysrhythmic potassium-sensitive periodic paralysis.
334. Familial atrial fibrillation.
51083. Familial short QT syndrome.
PharmGKBPA214.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72812.
HOGENOMHOG000237325.
HOVERGENHBG006178.
InParanoidP63252.
KOK04996.
OMAHNATVAM.
OrthoDBEOG7XPZ5K.
PhylomeDBP63252.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeP63252.
CleanExHS_KCNJ2.
GenevestigatorP63252.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003271. K_chnl_inward-rec_Kir2.1.
IPR013518. K_chnl_inward-rec_Kir_cyto.
IPR013673. K_chnl_inward-rec_Kir_N.
[Graphical view]
PANTHERPTHR11767. PTHR11767. 1 hit.
PfamPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01324. KIR21CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

GeneWikiKir2.1.
GenomeRNAi3759.
NextBio14737.
PROP63252.
SOURCESearch...

Entry information

Entry nameKCNJ2_HUMAN
AccessionPrimary (citable) accession number: P63252
Secondary accession number(s): O15110, P48049
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM