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Protein

ATP-sensitive inward rectifier potassium channel 8

Gene

KCNJ8

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

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei170 – 1701Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

GO - Molecular functioni

  1. ATP-activated inward rectifier potassium channel activity Source: GO_Central
  2. ATP binding Source: Ensembl
  3. inward rectifier potassium channel activity Source: ProtInc

GO - Biological processi

  1. defense response to virus Source: Ensembl
  2. heart development Source: Ensembl
  3. kidney development Source: Ensembl
  4. potassium ion import Source: GO_Central
  5. potassium ion transport Source: ProtInc
  6. regulation of ion transmembrane transport Source: GO_Central
  7. response to exogenous dsRNA Source: Ensembl
  8. response to lipopolysaccharide Source: Ensembl
  9. response to pH Source: Ensembl
  10. synaptic transmission Source: Reactome
  11. vasodilation Source: Ensembl
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

ReactomeiREACT_75775. ATP sensitive Potassium channels.

Protein family/group databases

TCDBi1.A.2.1.13. inward rectifier k(+) channel (irk-c) family.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:KCNJ8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6269. KCNJ8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6969CytoplasmicBy similarityAdd
BLAST
Transmembranei70 – 9425Helical; Name=M1By similarityAdd
BLAST
Topological domaini95 – 12632ExtracellularBy similarityAdd
BLAST
Intramembranei127 – 13812Helical; Pore-forming; Name=H5By similarityAdd
BLAST
Intramembranei139 – 1457Pore-formingBy similarity
Topological domaini146 – 1549ExtracellularBy similarity
Transmembranei155 – 17622Helical; Name=M2By similarityAdd
BLAST
Topological domaini177 – 424248CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. ATP-sensitive potassium channel complex Source: Ensembl
  2. mitochondrion Source: Ensembl
  3. myofibril Source: Ensembl
  4. plasma membrane Source: Reactome
  5. sarcolemma Source: Ensembl
  6. voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionSIDS 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.

See also OMIM:272120
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti332 – 3321Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication
VAR_065878
Natural varianti346 – 3461V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication
VAR_065879

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi272120. phenotype.
Orphaneti130. Brugada syndrome.
1517. Hypertrichotic osteochondrodysplasia, Cantu type.
PharmGKBiPA30050.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 424424ATP-sensitive inward rectifier potassium channel 8PRO_0000154947Add
BLAST

Proteomic databases

PaxDbiQ15842.
PRIDEiQ15842.

PTM databases

PhosphoSiteiQ15842.

Expressioni

Tissue specificityi

Predominantly detected in fetal and adult heart.1 Publication

Gene expression databases

BgeeiQ15842.
CleanExiHS_KCNJ8.
ExpressionAtlasiQ15842. baseline and differential.
GenevestigatoriQ15842.

Organism-specific databases

HPAiHPA031066.

Interactioni

Protein-protein interaction databases

BioGridi109966. 12 interactions.
STRINGi9606.ENSP00000240662.

Structurei

3D structure databases

ProteinModelPortaliQ15842.
SMRiQ15842. Positions 35-361.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi140 – 1456Selectivity filterBy similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ15842.
KOiK05001.
OMAiYAYMEKG.
OrthoDBiEOG7XPZ5K.
PhylomeDBiQ15842.
TreeFamiTF313676.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01331. KIR61CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

Q15842-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLARKSIIPE EYVLARIAAE NLRKPRIRDR LPKARFIAKS GACNLAHKNI
60 70 80 90 100
REQGRFLQDI FTTLVDLKWR HTLVIFTMSF LCSWLLFAIM WWLVAFAHGD
110 120 130 140 150
IYAYMEKSGM EKSGLESTVC VTNVRSFTSA FLFSIEVQVT IGFGGRMMTE
160 170 180 190 200
ECPLAITVLI LQNIVGLIIN AVMLGCIFMK TAQAHRRAET LIFSRHAVIA
210 220 230 240 250
VRNGKLCFMF RVGDLRKSMI ISASVRIQVV KKTTTPEGEV VPIHQLDIPV
260 270 280 290 300
DNPIESNNIF LVAPLIICHV IDKRSPLYDI SATDLANQDL EVIVILEGVV
310 320 330 340 350
ETTGITTQAR TSYIAEEIQW GHRFVSIVTE EEGVYSVDYS KFGNTVKVAA
360 370 380 390 400
PRCSARELDE KPSILIQTLQ KSELSHQNSL RKRNSMRRNN SMRRNNSIRR
410 420
NNSSLMVPKV QFMTPEGNQN TSES
Length:424
Mass (Da):47,968
Last modified:October 31, 1996 - v1
Checksum:i973EAA5900C6447C
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti332 – 3321Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication
VAR_065878
Natural varianti334 – 3341V → A.
Corresponds to variant rs34811413 [ dbSNP | Ensembl ].
VAR_049670
Natural varianti346 – 3461V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication
VAR_065879
Natural varianti422 – 4221S → L Associated with susceptibility to J-wave syndromes; the mutant channel displays an increase in glibenclamide-sensitive potassium currents compared to wild type. 1 Publication
Corresponds to variant rs72554071 [ dbSNP | Ensembl ].
VAR_065225

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50312 mRNA. Translation: BAA08851.1.
D50315 Genomic DNA. Translation: BAA08852.1.
BC000544 mRNA. Translation: AAH00544.1.
CCDSiCCDS8692.1.
RefSeqiNP_004973.1. NM_004982.3.
XP_005253415.1. XM_005253358.2.
UniGeneiHs.102308.
Hs.619408.
Hs.741642.

Genome annotation databases

EnsembliENST00000240662; ENSP00000240662; ENSG00000121361.
GeneIDi3764.
KEGGihsa:3764.
UCSCiuc001rff.4. human.

Polymorphism databases

DMDMi2493600.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50312 mRNA. Translation: BAA08851.1.
D50315 Genomic DNA. Translation: BAA08852.1.
BC000544 mRNA. Translation: AAH00544.1.
CCDSiCCDS8692.1.
RefSeqiNP_004973.1. NM_004982.3.
XP_005253415.1. XM_005253358.2.
UniGeneiHs.102308.
Hs.619408.
Hs.741642.

3D structure databases

ProteinModelPortaliQ15842.
SMRiQ15842. Positions 35-361.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109966. 12 interactions.
STRINGi9606.ENSP00000240662.

Chemistry

ChEMBLiCHEMBL2095152.
DrugBankiDB01251. Gliquidone.
DB01289. Glisoxepide.
DB01016. Glyburide.
DB00922. Levosimendan.
DB00914. Phenformin.
DB01154. Thiamylal.
DB01392. Yohimbine.
GuidetoPHARMACOLOGYi441.

Protein family/group databases

TCDBi1.A.2.1.13. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteiQ15842.

Polymorphism databases

DMDMi2493600.

Proteomic databases

PaxDbiQ15842.
PRIDEiQ15842.

Protocols and materials databases

DNASUi3764.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000240662; ENSP00000240662; ENSG00000121361.
GeneIDi3764.
KEGGihsa:3764.
UCSCiuc001rff.4. human.

Organism-specific databases

CTDi3764.
GeneCardsiGC12M021917.
HGNCiHGNC:6269. KCNJ8.
HPAiHPA031066.
MIMi272120. phenotype.
600935. gene.
neXtProtiNX_Q15842.
Orphaneti130. Brugada syndrome.
1517. Hypertrichotic osteochondrodysplasia, Cantu type.
PharmGKBiPA30050.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ15842.
KOiK05001.
OMAiYAYMEKG.
OrthoDBiEOG7XPZ5K.
PhylomeDBiQ15842.
TreeFamiTF313676.

Enzyme and pathway databases

ReactomeiREACT_75775. ATP sensitive Potassium channels.

Miscellaneous databases

GeneWikiiKCNJ8.
GenomeRNAii3764.
NextBioi14759.
PROiQ15842.
SOURCEiSearch...

Gene expression databases

BgeeiQ15842.
CleanExiHS_KCNJ8.
ExpressionAtlasiQ15842. baseline and differential.
GenevestigatoriQ15842.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. 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]
PANTHERiPTHR11767. PTHR11767. 1 hit.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01331. KIR61CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1994) [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(2003) [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(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. 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(2009) [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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SIDS GLU-332 DEL AND ILE-346, CHARACTERIZATION OF VARIANTS SIDS GLU-332 DEL AND ILE-346.

Entry informationi

Entry nameiKCNJ8_HUMAN
AccessioniPrimary (citable) accession number: Q15842
Secondary accession number(s): O00657
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 1997
Last sequence update: October 31, 1996
Last modified: February 3, 2015
This is version 143 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 12
    Human chromosome 12: 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

External Data

Dasty 3

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 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.