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Protein

Inward rectifier potassium channel 2

Gene

KCNJ2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei172Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cardiac conduction Source: Reactome
  • cardiac muscle cell action potential involved in contraction Source: BHF-UCL
  • cellular potassium ion homeostasis Source: BHF-UCL
  • cellular response to mechanical stimulus Source: Ensembl
  • magnesium ion transport Source: Ensembl
  • membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
  • membrane repolarization during action potential Source: BHF-UCL
  • membrane repolarization during cardiac muscle cell action potential Source: BHF-UCL
  • positive regulation of potassium ion transmembrane transport Source: Ensembl
  • potassium ion import Source: BHF-UCL
  • potassium ion transmembrane transport Source: BHF-UCL
  • potassium ion transport Source: UniProtKB
  • protein homotetramerization Source: UniProtKB
  • regulation of cardiac muscle cell contraction Source: Ensembl
  • regulation of heart rate by cardiac conduction Source: BHF-UCL
  • regulation of membrane repolarization Source: BHF-UCL
  • regulation of resting membrane potential Source: BHF-UCL
  • regulation of skeletal muscle contraction via regulation of action potential Source: BHF-UCL
  • relaxation of cardiac muscle Source: BHF-UCL
  • relaxation of skeletal muscle Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123700-MONOMER.
ReactomeiR-HSA-1296041. Activation of G protein gated Potassium channels.
R-HSA-1296053. Classical Kir channels.
R-HSA-5576886. Phase 4 - resting membrane potential.
R-HSA-997272. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.

Protein family/group databases

TCDBi1.A.2.1.2. inward rectifier k(+) channel (irk-c) family.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:KCNJ2
Synonyms:IRK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6263. KCNJ2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 81CytoplasmicBy similarityAdd BLAST80
Transmembranei82 – 106Helical; Name=M1By similarityAdd BLAST25
Topological domaini107 – 128ExtracellularBy similarityAdd BLAST22
Intramembranei129 – 140Helical; Pore-forming; Name=H5By similarityAdd BLAST12
Intramembranei141 – 147Pore-formingBy similarity7
Topological domaini148 – 156ExtracellularBy similarity9
Transmembranei157 – 178Helical; Name=M2By similarityAdd BLAST22
Topological domaini179 – 427CytoplasmicBy similarityAdd BLAST249

GO - Cellular componenti

  • dendritic spine Source: Ensembl
  • Golgi apparatus Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • intercalated disc Source: Ensembl
  • intrinsic component of membrane Source: UniProtKB
  • neuronal cell body Source: Ensembl
  • plasma membrane Source: Reactome
  • rough endoplasmic reticulum Source: Ensembl
  • smooth endoplasmic reticulum Source: Ensembl
  • T-tubule Source: Ensembl
  • voltage-gated potassium channel complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Long QT syndrome 7 (LQT7)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:170390
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06586154C → 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. 1 PublicationCorresponds to variant rs199473650dbSNPEnsembl.1
Natural variantiVAR_01785167R → W in LQT7. 1 PublicationCorresponds to variant rs104894580dbSNPEnsembl.1
Natural variantiVAR_01785271D → V in LQT7; loss of function mutation acting in a dominant-negative manner. 1 PublicationCorresponds to variant rs104894575dbSNPEnsembl.1
Natural variantiVAR_06586275T → R in LQT7; loss of function mutation acting in a dominant-negative manner. 1 PublicationCorresponds to variant rs104894585dbSNPEnsembl.1
Natural variantiVAR_01785395 – 98Missing in LQT7. 1 Publication4
Natural variantiVAR_017854186P → L in LQT7. 1 PublicationCorresponds to variant rs104894581dbSNPEnsembl.1
Natural variantiVAR_017855216N → H in LQT7. 1 PublicationCorresponds to variant rs104894583dbSNPEnsembl.1
Natural variantiVAR_017856218R → W in LQT7; loss of function and dominant-negative effect in current. 1 PublicationCorresponds to variant rs104894578dbSNPEnsembl.1
Natural variantiVAR_017857300G → V in LQT7. 1 PublicationCorresponds to variant rs104894579dbSNPEnsembl.1
Natural variantiVAR_017858302V → M in LQT7. 1 PublicationCorresponds to variant rs104894582dbSNPEnsembl.1
Natural variantiVAR_065864305T → 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. 1 PublicationCorresponds to variant rs199473387dbSNPEnsembl.1
Natural variantiVAR_017859314 – 315Missing in LQT7. 2
Short QT syndrome 3 (SQT3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:609622
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023842172D → N in SQT3; gain of function. 1 PublicationCorresponds to variant rs104894584dbSNPEnsembl.1
Atrial fibrillation, familial, 9 (ATFB9)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06586393V → I in ATFB9; has a gain-of-function effect on the channels. 1 PublicationCorresponds to variant rs147750704dbSNPEnsembl.1

Keywords - Diseasei

Atrial fibrillation, Disease mutation, Long QT syndrome, Short QT syndrome

Organism-specific databases

DisGeNETi3759.
MalaCardsiKCNJ2.
MIMi170390. phenotype.
609622. phenotype.
613980. phenotype.
OpenTargetsiENSG00000123700.
Orphaneti37553. Cardiodysrhythmic potassium-sensitive periodic paralysis.
334. Familial atrial fibrillation.
51083. Familial short QT syndrome.
PharmGKBiPA214.

Chemistry databases

ChEMBLiCHEMBL1914276.

Polymorphism and mutation databases

BioMutaiKCNJ2.
DMDMi54037433.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00001549232 – 427Inward rectifier potassium channel 2Add BLAST426

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei76S-nitrosocysteine1 Publication1

Post-translational modificationi

S-nitrosylation increases the open probability and inward rectifying currents.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, S-nitrosylation

Proteomic databases

PaxDbiP63252.
PeptideAtlasiP63252.
PRIDEiP63252.

PTM databases

iPTMnetiP63252.
PhosphoSitePlusiP63252.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000123700.
CleanExiHS_KCNJ2.
GenevisibleiP63252. HS.

Organism-specific databases

HPAiHPA029109.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi109961. 3 interactors.
IntActiP63252. 5 interactors.
STRINGi9606.ENSP00000243457.

Chemistry databases

BindingDBiP63252.

Structurei

3D structure databases

ProteinModelPortaliP63252.
SMRiP63252.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi142 – 147Selectivity filterBy similarity6
Motifi425 – 427PDZ-bindingSequence analysis3

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP63252.
KOiK04996.
OMAiHNATVAM.
OrthoDBiEOG091G08HC.
PhylomeDBiP63252.
TreeFamiTF313676.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PfamiPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01324. KIR21CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P63252-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSVRTNRYS IVSSEEDGMK LATMAVANGF GNGKSKVHTR QQCRSRFVKK
60 70 80 90 100
DGHCNVQFIN VGEKGQRYLA DIFTTCVDIR WRWMLVIFCL AFVLSWLFFG
110 120 130 140 150
CVFWLIALLH GDLDASKEGK ACVSEVNSFT AAFLFSIETQ TTIGYGFRCV
160 170 180 190 200
TDECPIAVFM VVFQSIVGCI IDAFIIGAVM AKMAKPKKRN ETLVFSHNAV
210 220 230 240 250
IAMRDGKLCL MWRVGNLRKS HLVEAHVRAQ LLKSRITSEG EYIPLDQIDI
260 270 280 290 300
NVGFDSGIDR IFLVSPITIV HEIDEDSPLY DLSKQDIDNA DFEIVVILEG
310 320 330 340 350
MVEATAMTTQ CRSSYLANEI LWGHRYEPVL FEEKHYYKVD YSRFHKTYEV
360 370 380 390 400
PNTPLCSARD LAEKKYILSN ANSFCYENEV ALTSKEEDDS ENGVPESTST
410 420
DTPPDIDLHN QASVPLEPRP LRRESEI
Length:427
Mass (Da):48,288
Last modified:October 11, 2004 - v1
Checksum:iAB37CAD4B99B4050
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti330L → F in AAC39555 (PubMed:9490857).Curated1
Sequence conflicti340D → E in AAC39555 (PubMed:9490857).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06586154C → 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. 1 PublicationCorresponds to variant rs199473650dbSNPEnsembl.1
Natural variantiVAR_01785167R → W in LQT7. 1 PublicationCorresponds to variant rs104894580dbSNPEnsembl.1
Natural variantiVAR_01785271D → V in LQT7; loss of function mutation acting in a dominant-negative manner. 1 PublicationCorresponds to variant rs104894575dbSNPEnsembl.1
Natural variantiVAR_06586275T → R in LQT7; loss of function mutation acting in a dominant-negative manner. 1 PublicationCorresponds to variant rs104894585dbSNPEnsembl.1
Natural variantiVAR_06586393V → I in ATFB9; has a gain-of-function effect on the channels. 1 PublicationCorresponds to variant rs147750704dbSNPEnsembl.1
Natural variantiVAR_01785395 – 98Missing in LQT7. 1 Publication4
Natural variantiVAR_023842172D → N in SQT3; gain of function. 1 PublicationCorresponds to variant rs104894584dbSNPEnsembl.1
Natural variantiVAR_017854186P → L in LQT7. 1 PublicationCorresponds to variant rs104894581dbSNPEnsembl.1
Natural variantiVAR_017855216N → H in LQT7. 1 PublicationCorresponds to variant rs104894583dbSNPEnsembl.1
Natural variantiVAR_017856218R → W in LQT7; loss of function and dominant-negative effect in current. 1 PublicationCorresponds to variant rs104894578dbSNPEnsembl.1
Natural variantiVAR_017857300G → V in LQT7. 1 PublicationCorresponds to variant rs104894579dbSNPEnsembl.1
Natural variantiVAR_017858302V → M in LQT7. 1 PublicationCorresponds to variant rs104894582dbSNPEnsembl.1
Natural variantiVAR_065864305T → 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. 1 PublicationCorresponds to variant rs199473387dbSNPEnsembl.1
Natural variantiVAR_017859314 – 315Missing in LQT7. 2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11688.1.
PIRiI38727.
RefSeqiNP_000882.1. NM_000891.2.
UniGeneiHs.1547.

Genome annotation databases

EnsembliENST00000243457; ENSP00000243457; ENSG00000123700.
ENST00000535240; ENSP00000441848; ENSG00000123700.
GeneIDi3759.
KEGGihsa:3759.
UCSCiuc002jir.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11688.1.
PIRiI38727.
RefSeqiNP_000882.1. NM_000891.2.
UniGeneiHs.1547.

3D structure databases

ProteinModelPortaliP63252.
SMRiP63252.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109961. 3 interactors.
IntActiP63252. 5 interactors.
STRINGi9606.ENSP00000243457.

Chemistry databases

BindingDBiP63252.
ChEMBLiCHEMBL1914276.

Protein family/group databases

TCDBi1.A.2.1.2. inward rectifier k(+) channel (irk-c) family.

PTM databases

iPTMnetiP63252.
PhosphoSitePlusiP63252.

Polymorphism and mutation databases

BioMutaiKCNJ2.
DMDMi54037433.

Proteomic databases

PaxDbiP63252.
PeptideAtlasiP63252.
PRIDEiP63252.

Protocols and materials databases

DNASUi3759.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000243457; ENSP00000243457; ENSG00000123700.
ENST00000535240; ENSP00000441848; ENSG00000123700.
GeneIDi3759.
KEGGihsa:3759.
UCSCiuc002jir.4. human.

Organism-specific databases

CTDi3759.
DisGeNETi3759.
GeneCardsiKCNJ2.
GeneReviewsiKCNJ2.
HGNCiHGNC:6263. KCNJ2.
HPAiHPA029109.
MalaCardsiKCNJ2.
MIMi170390. phenotype.
600681. gene.
609622. phenotype.
613980. phenotype.
neXtProtiNX_P63252.
OpenTargetsiENSG00000123700.
Orphaneti37553. Cardiodysrhythmic potassium-sensitive periodic paralysis.
334. Familial atrial fibrillation.
51083. Familial short QT syndrome.
PharmGKBiPA214.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP63252.
KOiK04996.
OMAiHNATVAM.
OrthoDBiEOG091G08HC.
PhylomeDBiP63252.
TreeFamiTF313676.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123700-MONOMER.
ReactomeiR-HSA-1296041. Activation of G protein gated Potassium channels.
R-HSA-1296053. Classical Kir channels.
R-HSA-5576886. Phase 4 - resting membrane potential.
R-HSA-997272. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.

Miscellaneous databases

GeneWikiiKir2.1.
GenomeRNAii3759.
PROiP63252.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123700.
CleanExiHS_KCNJ2.
GenevisibleiP63252. HS.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PfamiPF01007. IRK. 1 hit.
PF08466. IRK_N. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01324. KIR21CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNJ2_HUMAN
AccessioniPrimary (citable) accession number: P63252
Secondary accession number(s): O15110, P48049
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: November 30, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.