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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)DescriptionActionsGraphical viewLength
Sitei170Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity1

GO - Molecular functioni

GO - Biological processi

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:ENSG00000121361-MONOMER.
ReactomeiR-HSA-1296025. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6269. KCNJ8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 69CytoplasmicBy similarityAdd BLAST69
Transmembranei70 – 94Helical; Name=M1By similarityAdd BLAST25
Topological domaini95 – 126ExtracellularBy similarityAdd BLAST32
Intramembranei127 – 138Helical; Pore-forming; Name=H5By similarityAdd BLAST12
Intramembranei139 – 145Pore-formingBy similarity7
Topological domaini146 – 154ExtracellularBy similarity9
Transmembranei155 – 176Helical; Name=M2By similarityAdd BLAST22
Topological domaini177 – 424CytoplasmicBy similarityAdd BLAST248

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_065878332Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication1
Natural variantiVAR_065879346V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 PublicationCorresponds to variant rs147316959dbSNPEnsembl.1
Hypertrichotic osteochondrodysplasia (HTOCD)1 Publication
The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
Disease descriptionA rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability.
See also OMIM:239850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075226176C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant rs606231264dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3764.
MalaCardsiKCNJ8.
MIMi239850. phenotype.
272120. phenotype.
OpenTargetsiENSG00000121361.
Orphaneti130. Brugada syndrome.
1517. Hypertrichotic osteochondrodysplasia, Cantu type.
PharmGKBiPA30050.

Chemistry databases

ChEMBLiCHEMBL4770.
DrugBankiDB01251. Gliquidone.
DB01289. Glisoxepide.
DB01016. Glyburide.
DB00922. Levosimendan.
DB00914. Phenformin.
DB01154. Thiamylal.
DB01392. Yohimbine.

Polymorphism and mutation databases

BioMutaiKCNJ8.
DMDMi2493600.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001549471 – 424ATP-sensitive inward rectifier potassium channel 8Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ15842.
PeptideAtlasiQ15842.
PRIDEiQ15842.

PTM databases

iPTMnetiQ15842.
PhosphoSitePlusiQ15842.

Expressioni

Tissue specificityi

Predominantly detected in fetal and adult heart.1 Publication

Gene expression databases

BgeeiENSG00000121361.
CleanExiHS_KCNJ8.
ExpressionAtlasiQ15842. baseline and differential.
GenevisibleiQ15842. HS.

Organism-specific databases

HPAiHPA031066.

Interactioni

Protein-protein interaction databases

BioGridi109966. 19 interactors.
STRINGi9606.ENSP00000240662.

Structurei

3D structure databases

ProteinModelPortaliQ15842.
SMRiQ15842.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi140 – 145Selectivity filterBy similarity6

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ15842.
KOiK05001.
OMAiAMELQCS.
OrthoDBiEOG091G08HC.
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:November 1, 1996 - v1
Checksum:i973EAA5900C6447C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075226176C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant rs606231264dbSNPEnsembl.1
Natural variantiVAR_065878332Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication1
Natural variantiVAR_049670334V → A.Corresponds to variant rs34811413dbSNPEnsembl.1
Natural variantiVAR_065879346V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 PublicationCorresponds to variant rs147316959dbSNPEnsembl.1
Natural variantiVAR_065225422S → L Associated with susceptibility to J-wave syndromes; the mutant channel displays an increase in glibenclamide-sensitive potassium currents compared to wild type. 1 PublicationCorresponds to variant rs72554071dbSNPEnsembl.1

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_005253358.4.
XP_016874772.1. XM_017019283.1.
XP_016874773.1. XM_017019284.1.
UniGeneiHs.102308.
Hs.619408.
Hs.741642.

Genome annotation databases

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

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_005253358.4.
XP_016874772.1. XM_017019283.1.
XP_016874773.1. XM_017019284.1.
UniGeneiHs.102308.
Hs.619408.
Hs.741642.

3D structure databases

ProteinModelPortaliQ15842.
SMRiQ15842.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109966. 19 interactors.
STRINGi9606.ENSP00000240662.

Chemistry databases

ChEMBLiCHEMBL4770.
DrugBankiDB01251. Gliquidone.
DB01289. Glisoxepide.
DB01016. Glyburide.
DB00922. Levosimendan.
DB00914. Phenformin.
DB01154. Thiamylal.
DB01392. Yohimbine.

Protein family/group databases

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

PTM databases

iPTMnetiQ15842.
PhosphoSitePlusiQ15842.

Polymorphism and mutation databases

BioMutaiKCNJ8.
DMDMi2493600.

Proteomic databases

PaxDbiQ15842.
PeptideAtlasiQ15842.
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.
DisGeNETi3764.
GeneCardsiKCNJ8.
HGNCiHGNC:6269. KCNJ8.
HPAiHPA031066.
MalaCardsiKCNJ8.
MIMi239850. phenotype.
272120. phenotype.
600935. gene.
neXtProtiNX_Q15842.
OpenTargetsiENSG00000121361.
Orphaneti130. Brugada syndrome.
1517. Hypertrichotic osteochondrodysplasia, Cantu type.
PharmGKBiPA30050.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiQ15842.
KOiK05001.
OMAiAMELQCS.
OrthoDBiEOG091G08HC.
PhylomeDBiQ15842.
TreeFamiTF313676.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121361-MONOMER.
ReactomeiR-HSA-1296025. ATP sensitive Potassium channels.

Miscellaneous databases

GeneWikiiKCNJ8.
GenomeRNAii3764.
PROiQ15842.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121361.
CleanExiHS_KCNJ8.
ExpressionAtlasiQ15842. baseline and differential.
GenevisibleiQ15842. HS.

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...

Entry informationi

Entry nameiKCNJ8_HUMAN
AccessioniPrimary (citable) accession number: Q15842
Secondary accession number(s): O00657
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 158 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

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.