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Q15842 (IRK8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. 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:
ATP-sensitive inward rectifier potassium channel 8
Alternative name(s):
Inward rectifier K(+) channel Kir6.1
Potassium channel, inwardly rectifying subfamily J member 8
uKATP-1
Gene names
Name:KCNJ8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length424 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This potassium channel is controlled by G proteins. 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 external barium By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Predominantly detected in fetal and adult heart. Ref.3

Involvement in disease

Defects in KCNJ8 may be associated with susceptibility to J-wave syndromes, a group of heart disorders characterized by early repolarization events as indicated by abnormal J-wave manifestation on electrocardiogram (ECG). The J point denotes the junction of the QRS complex and the ST segment on the ECG, marking the end of depolarization and the beginning of repolarization. An abnormal J wave is a deflection with a dome or hump morphology immediately following the QRS complex of the surface ECG. Examples of J-wave disorders are arrhythmias associated with an early repolarization pattern in the inferior or mid to lateral precordial leads, Brugada syndrome, some cases of idiopathic ventricular fibrillation (VF) with an early repolarization pattern in the inferior, inferolateral or global leads, as well as arrhythmias associated with hypothermia.

Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ8 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Voltage-gated channel
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to virus

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from electronic annotation. Source: Ensembl

kidney development

Inferred from electronic annotation. Source: Ensembl

potassium ion import

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Traceable author statement PubMed 7890693. Source: ProtInc

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to pH

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

vasodilation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentATP-sensitive potassium channel complex

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

myofibril

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

sarcolemma

Inferred from electronic annotation. Source: Ensembl

voltage-gated potassium channel complex

Traceable author statement PubMed 7890693. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: Ensembl

ATP-activated inward rectifier potassium channel activity

Inferred from electronic annotation. Source: Ensembl

inward rectifier potassium channel activity

Traceable author statement PubMed 7890693. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 424424ATP-sensitive inward rectifier potassium channel 8
PRO_0000154947

Regions

Topological domain1 – 6969Cytoplasmic By similarity
Transmembrane70 – 9425Helical; Name=M1; By similarity
Topological domain95 – 12632Extracellular By similarity
Intramembrane127 – 13812Helical; Pore-forming; Name=H5; By similarity
Intramembrane139 – 1457Pore-forming; By similarity
Topological domain146 – 1549Extracellular By similarity
Transmembrane155 – 17622Helical; Name=M2; By similarity
Topological domain177 – 424248Cytoplasmic By similarity
Motif140 – 1456Selectivity filter By similarity

Sites

Site1701Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Natural variations

Natural variant3321Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. Ref.6
VAR_065878
Natural variant3341V → A.
Corresponds to variant rs34811413 [ dbSNP | Ensembl ].
VAR_049670
Natural variant3461V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. Ref.6
VAR_065879
Natural variant4221S → L Associated with susceptibility to J-wave syndromes; the mutant channel displays an increase in glibenclamide-sensitive potassium currents compared to wild type. Ref.5
Corresponds to variant rs72554071 [ dbSNP | Ensembl ].
VAR_065225

Sequences

Sequence LengthMass (Da)Tools
Q15842 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 973EAA5900C6447C

FASTA42447,968
        10         20         30         40         50         60 
MLARKSIIPE EYVLARIAAE NLRKPRIRDR LPKARFIAKS GACNLAHKNI REQGRFLQDI 

        70         80         90        100        110        120 
FTTLVDLKWR HTLVIFTMSF LCSWLLFAIM WWLVAFAHGD IYAYMEKSGM EKSGLESTVC 

       130        140        150        160        170        180 
VTNVRSFTSA FLFSIEVQVT IGFGGRMMTE ECPLAITVLI LQNIVGLIIN AVMLGCIFMK 

       190        200        210        220        230        240 
TAQAHRRAET LIFSRHAVIA VRNGKLCFMF RVGDLRKSMI ISASVRIQVV KKTTTPEGEV 

       250        260        270        280        290        300 
VPIHQLDIPV DNPIESNNIF LVAPLIICHV IDKRSPLYDI SATDLANQDL EVIVILEGVV 

       310        320        330        340        350        360 
ETTGITTQAR TSYIAEEIQW GHRFVSIVTE EEGVYSVDYS KFGNTVKVAA PRCSARELDE 

       370        380        390        400        410        420 
KPSILIQTLQ KSELSHQNSL RKRNSMRRNN SMRRNNSIRR NNSSLMVPKV QFMTPEGNQN 


TSES 

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8)."
Inagaki N., Inazawa J., Seino S.
Genomics 30:102-104(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Lung and Placenta.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Genomic organization and expression of KCNJ8/Kir6.1, a gene encoding a subunit of an ATP-sensitive potassium channel."
Erginel-Unaltuna N., Yang W.P., Blanar M.A.
Gene 211:71-78(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[4]"J wave syndromes."
Antzelevitch C., Yan G.X.
Heart Rhythm 7:549-558(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON J-WAVE SYNDROMES.
[5]"Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes."
Medeiros-Domingo A., Tan B.H., Crotti L., Tester D.J., Eckhardt L., Cuoretti A., Kroboth S.L., Song C., Zhou Q., Kopp D., Schwartz P.J., Makielski J.C., Ackerman M.J.
Heart Rhythm 7:1466-1471(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO J-WAVE SYNDROMES, VARIANT LEU-422, CHARACTERIZATION OF VARIANT LEU-422.
[6]"Loss-of-function mutations in the KCNJ8-encoded Kir6.1 KATP channel and sudden infant death syndrome."
Tester D.J., Tan B.H., Medeiros-Domingo A., Song C., Makielski J.C., Ackerman M.J.
Circ. Cardiovasc. Genet. 4:510-515(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SIDS GLU-332 DEL AND ILE-346, CHARACTERIZATION OF VARIANTS SIDS GLU-332 DEL AND ILE-346.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D50312 mRNA. Translation: BAA08851.1.
D50315 Genomic DNA. Translation: BAA08852.1.
BC000544 mRNA. Translation: AAH00544.1.
RefSeqNP_004973.1. NM_004982.3.
XP_005253415.1. XM_005253358.2.
UniGeneHs.102308.
Hs.619408.
Hs.741642.

3D structure databases

ProteinModelPortalQ15842.
SMRQ15842. Positions 35-361.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109966. 1 interaction.
STRING9606.ENSP00000240662.

Chemistry

BindingDBQ15842.
ChEMBLCHEMBL2095152.
DrugBankDB00922. Levosimendan.
GuidetoPHARMACOLOGY441.

Protein family/group databases

TCDB1.A.2.1.13. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteQ15842.

Polymorphism databases

DMDM2493600.

Proteomic databases

PaxDbQ15842.
PRIDEQ15842.

Protocols and materials databases

DNASU3764.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000240662; ENSP00000240662; ENSG00000121361.
GeneID3764.
KEGGhsa:3764.
UCSCuc001rff.4. human.

Organism-specific databases

CTD3764.
GeneCardsGC12M021818.
HGNCHGNC:6269. KCNJ8.
HPAHPA031066.
MIM272120. phenotype.
600935. gene.
neXtProtNX_Q15842.
Orphanet130. Brugada syndrome.
PharmGKBPA30050.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72812.
HOGENOMHOG000237325.
HOVERGENHBG006178.
InParanoidQ15842.
KOK05001.
OMAVIAVRNN.
OrthoDBEOG7XPZ5K.
PhylomeDBQ15842.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ15842.
BgeeQ15842.
CleanExHS_KCNJ8.
GenevestigatorQ15842.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003278. K_chnl_inward-rec_Kir6.1.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]
PANTHERPTHR11767. PTHR11767. 1 hit.
PfamPF01007. IRK. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01331. KIR61CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

GeneWikiKCNJ8.
GenomeRNAi3764.
NextBio14759.
PROQ15842.
SOURCESearch...

Entry information

Entry nameIRK8_HUMAN
AccessionPrimary (citable) accession number: Q15842
Secondary accession number(s): O00657
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 134 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 12

Human chromosome 12: entries, gene names and cross-references to MIM