UniProtKB - Q15842 (KCNJ8_HUMAN)
ATP-sensitive inward rectifier potassium channel 8
KCNJ8
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 similarity1 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 170 | Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity | 1 |
GO - Molecular functioni
- ATP-activated inward rectifier potassium channel activity Source: BHF-UCL
- ATPase-coupled cation transmembrane transporter activity Source: ARUK-UCL
- ATP binding Source: ARUK-UCL
- inward rectifier potassium channel activity Source: GO_Central
- sulfonylurea receptor binding Source: Ensembl
- voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Source: BHF-UCL
GO - Biological processi
- defense response to virus Source: Ensembl
- heart development Source: Ensembl
- inorganic cation transmembrane transport Source: ARUK-UCL
- kidney development Source: Ensembl
- membrane repolarization during ventricular cardiac muscle cell action potential Source: BHF-UCL
- potassium ion import across plasma membrane Source: BHF-UCL
- potassium ion transmembrane transport Source: ARUK-UCL
- potassium ion transport Source: ProtInc
- regulation of ion transmembrane transport Source: GO_Central
- response to exogenous dsRNA Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- transport across blood-brain barrier Source: ARUK-UCL
Keywordsi
Molecular function | Ion channel, Voltage-gated channel |
Biological process | Ion transport, Potassium transport, Transport |
Ligand | Potassium |
Enzyme and pathway databases
PathwayCommonsi | Q15842 |
Reactomei | R-HSA-1296025, ATP sensitive Potassium channels |
SignaLinki | Q15842 |
SIGNORi | Q15842 |
Protein family/group databases
TCDBi | 1.A.2.1.13, the inward rectifier k(+) channel (irk-c) family |
Names & Taxonomyi
Protein namesi | Recommended name: ATP-sensitive inward rectifier potassium channel 8Alternative name(s): Inward rectifier K(+) channel Kir6.1 Potassium channel, inwardly rectifying subfamily J member 8 uKATP-1 |
Gene namesi | Name:KCNJ8 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6269, KCNJ8 |
MIMi | 600935, gene |
neXtProti | NX_Q15842 |
VEuPathDBi | HostDB:ENSG00000121361 |
Subcellular locationi
Other locations
- Membrane ; Multi-pass membrane protein Curated
Mitochondrion
- mitochondrion Source: Ensembl
Plasma Membrane
- inward rectifying potassium channel Source: Ensembl
- plasma membrane Source: GO_Central
- sarcolemma Source: Ensembl
- voltage-gated potassium channel complex Source: ProtInc
Other locations
- myofibril Source: Ensembl
- potassium ion-transporting ATPase complex Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 69 | CytoplasmicBy similarityAdd BLAST | 69 | |
Transmembranei | 70 – 94 | Helical; Name=M1By similarityAdd BLAST | 25 | |
Topological domaini | 95 – 126 | ExtracellularBy similarityAdd BLAST | 32 | |
Intramembranei | 127 – 138 | Helical; Pore-forming; Name=H5By similarityAdd BLAST | 12 | |
Intramembranei | 139 – 145 | Pore-formingBy similarity | 7 | |
Topological domaini | 146 – 154 | ExtracellularBy similarity | 9 | |
Transmembranei | 155 – 176 | Helical; Name=M2By similarityAdd BLAST | 22 | |
Topological domaini | 177 – 424 | CytoplasmicBy similarityAdd BLAST | 248 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Involvement in diseasei
Sudden infant death syndrome (SIDS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065878 | 332 | Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication | 1 | |
Natural variantiVAR_065879 | 346 | V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 PublicationCorresponds to variant dbSNP:rs147316959EnsemblClinVar. | 1 |
Hypertrichotic osteochondrodysplasia (HTOCD)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079518 | 65 | V → M in HTOCD; unknown pathological significance; displays gain of function; increased open state stability, reduced sensitivity to ATP inhibition and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels. 2 PublicationsCorresponds to variant dbSNP:rs606231263EnsemblClinVar. | 1 | |
Natural variantiVAR_075226 | 176 | C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs606231264EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 65 | V → L: No effect on channel activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 3764 |
GeneReviewsi | KCNJ8 |
MalaCardsi | KCNJ8 |
MIMi | 239850, phenotype 272120, phenotype |
OpenTargetsi | ENSG00000121361 |
Orphaneti | 130, Brugada syndrome 1517, Hypertrichotic osteochondrodysplasia, Cantu type |
PharmGKBi | PA30050 |
Miscellaneous databases
Pharosi | Q15842, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4770 |
DrugBanki | DB11148, Butamben DB01251, Gliquidone DB01289, Glisoxepide DB01016, Glyburide DB00922, Levosimendan DB00914, Phenformin DB01154, Thiamylal DB01392, Yohimbine |
DrugCentrali | Q15842 |
Genetic variation databases
BioMutai | KCNJ8 |
DMDMi | 2493600 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154947 | 1 – 424 | ATP-sensitive inward rectifier potassium channel 8Add BLAST | 424 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 6 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q15842 |
MassIVEi | Q15842 |
PaxDbi | Q15842 |
PeptideAtlasi | Q15842 |
PRIDEi | Q15842 |
ProteomicsDBi | 60787 |
PTM databases
iPTMneti | Q15842 |
PhosphoSitePlusi | Q15842 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000121361, Expressed in myocardium and 200 other tissues |
ExpressionAtlasi | Q15842, baseline and differential |
Genevisiblei | Q15842, HS |
Organism-specific databases
HPAi | ENSG00000121361, Tissue enhanced (heart) |
Interactioni
Binary interactionsi
Q15842
With | #Exp. | IntAct |
---|---|---|
EMD [P50402] | 3 | EBI-17440235,EBI-489887 |
TMEM140 [Q9NV12] | 3 | EBI-17440235,EBI-2844246 |
TMEM54 [Q969K7] | 3 | EBI-17440235,EBI-3922833 |
GO - Molecular functioni
- sulfonylurea receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 109966, 42 interactors |
ELMi | Q15842 |
IntActi | Q15842, 15 interactors |
STRINGi | 9606.ENSP00000240662 |
Miscellaneous databases
RNActi | Q15842, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 375 – 424 | DisorderedSequence analysisAdd BLAST | 50 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 140 – 145 | Selectivity filterBy similarity | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 390 – 424 | Polar residuesSequence analysisAdd BLAST | 35 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3827, Eukaryota |
GeneTreei | ENSGT00990000203615 |
HOGENOMi | CLU_022738_4_0_1 |
InParanoidi | Q15842 |
OMAi | ISEEIQW |
OrthoDBi | 956263at2759 |
PhylomeDBi | Q15842 |
TreeFami | TF313676 |
Family and domain databases
Gene3Di | 2.60.40.1400, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR041647, IRK_C IPR016449, K_chnl_inward-rec_Kir IPR003278, K_chnl_inward-rec_Kir6.1 IPR013518, K_chnl_inward-rec_Kir_cyto IPR040445, Kir_TM |
PANTHERi | PTHR11767, PTHR11767, 1 hit PTHR11767:SF11, PTHR11767:SF11, 1 hit |
Pfami | View protein in Pfam PF01007, IRK, 1 hit PF17655, IRK_C, 1 hit |
PIRSFi | PIRSF005465, GIRK_kir, 1 hit |
PRINTSi | PR01331, KIR61CHANNEL PR01320, KIRCHANNEL |
SUPFAMi | SSF81296, SSF81296, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF5GY12 | F5GY12_HUMAN | ATP-sensitive inward rectifier pota... | KCNJ8 | 114 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079518 | 65 | V → M in HTOCD; unknown pathological significance; displays gain of function; increased open state stability, reduced sensitivity to ATP inhibition and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels. 2 PublicationsCorresponds to variant dbSNP:rs606231263EnsemblClinVar. | 1 | |
Natural variantiVAR_075226 | 176 | C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs606231264EnsemblClinVar. | 1 | |
Natural variantiVAR_065878 | 332 | Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 Publication | 1 | |
Natural variantiVAR_049670 | 334 | V → A. Corresponds to variant dbSNP:rs34811413EnsemblClinVar. | 1 | |
Natural variantiVAR_065879 | 346 | V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 PublicationCorresponds to variant dbSNP:rs147316959EnsemblClinVar. | 1 | |
Natural variantiVAR_065225 | 422 | S → L Found in Brugada syndrome and other J-wave syndromes; unknown pathological significance; the mutant channel displays an increase in glibenclamide-sensitive potassium currents compared to wild type. 1 PublicationCorresponds to variant dbSNP:rs72554071EnsemblClinVar. | 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 |
CCDSi | CCDS8692.1 |
RefSeqi | NP_004973.1, NM_004982.3 XP_005253415.1, XM_005253358.4 XP_016874772.1, XM_017019283.1 XP_016874773.1, XM_017019284.1 |
Genome annotation databases
Ensembli | ENST00000240662; ENSP00000240662; ENSG00000121361 ENST00000665145; ENSP00000499300; ENSG00000121361 ENST00000667884; ENSP00000499462; ENSG00000121361 |
GeneIDi | 3764 |
KEGGi | hsa:3764 |
MANE-Selecti | ENST00000240662.3; ENSP00000240662.2; NM_004982.4; NP_004973.1 |
UCSCi | uc001rff.4, human |
Similar proteinsi
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 |
CCDSi | CCDS8692.1 |
RefSeqi | NP_004973.1, NM_004982.3 XP_005253415.1, XM_005253358.4 XP_016874772.1, XM_017019283.1 XP_016874773.1, XM_017019284.1 |
3D structure databases
SMRi | Q15842 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109966, 42 interactors |
ELMi | Q15842 |
IntActi | Q15842, 15 interactors |
STRINGi | 9606.ENSP00000240662 |
Chemistry databases
ChEMBLi | CHEMBL4770 |
DrugBanki | DB11148, Butamben DB01251, Gliquidone DB01289, Glisoxepide DB01016, Glyburide DB00922, Levosimendan DB00914, Phenformin DB01154, Thiamylal DB01392, Yohimbine |
DrugCentrali | Q15842 |
Protein family/group databases
TCDBi | 1.A.2.1.13, the inward rectifier k(+) channel (irk-c) family |
PTM databases
iPTMneti | Q15842 |
PhosphoSitePlusi | Q15842 |
Genetic variation databases
BioMutai | KCNJ8 |
DMDMi | 2493600 |
Proteomic databases
jPOSTi | Q15842 |
MassIVEi | Q15842 |
PaxDbi | Q15842 |
PeptideAtlasi | Q15842 |
PRIDEi | Q15842 |
ProteomicsDBi | 60787 |
Protocols and materials databases
Antibodypediai | 4014, 252 antibodies from 31 providers |
DNASUi | 3764 |
Genome annotation databases
Ensembli | ENST00000240662; ENSP00000240662; ENSG00000121361 ENST00000665145; ENSP00000499300; ENSG00000121361 ENST00000667884; ENSP00000499462; ENSG00000121361 |
GeneIDi | 3764 |
KEGGi | hsa:3764 |
MANE-Selecti | ENST00000240662.3; ENSP00000240662.2; NM_004982.4; NP_004973.1 |
UCSCi | uc001rff.4, human |
Organism-specific databases
CTDi | 3764 |
DisGeNETi | 3764 |
GeneCardsi | KCNJ8 |
GeneReviewsi | KCNJ8 |
HGNCi | HGNC:6269, KCNJ8 |
HPAi | ENSG00000121361, Tissue enhanced (heart) |
MalaCardsi | KCNJ8 |
MIMi | 239850, phenotype 272120, phenotype 600935, gene |
neXtProti | NX_Q15842 |
OpenTargetsi | ENSG00000121361 |
Orphaneti | 130, Brugada syndrome 1517, Hypertrichotic osteochondrodysplasia, Cantu type |
PharmGKBi | PA30050 |
VEuPathDBi | HostDB:ENSG00000121361 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3827, Eukaryota |
GeneTreei | ENSGT00990000203615 |
HOGENOMi | CLU_022738_4_0_1 |
InParanoidi | Q15842 |
OMAi | ISEEIQW |
OrthoDBi | 956263at2759 |
PhylomeDBi | Q15842 |
TreeFami | TF313676 |
Enzyme and pathway databases
PathwayCommonsi | Q15842 |
Reactomei | R-HSA-1296025, ATP sensitive Potassium channels |
SignaLinki | Q15842 |
SIGNORi | Q15842 |
Miscellaneous databases
BioGRID-ORCSi | 3764, 3 hits in 1041 CRISPR screens |
GeneWikii | KCNJ8 |
GenomeRNAii | 3764 |
Pharosi | Q15842, Tbio |
PROi | PR:Q15842 |
RNActi | Q15842, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000121361, Expressed in myocardium and 200 other tissues |
ExpressionAtlasi | Q15842, baseline and differential |
Genevisiblei | Q15842, HS |
Family and domain databases
Gene3Di | 2.60.40.1400, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR041647, IRK_C IPR016449, K_chnl_inward-rec_Kir IPR003278, K_chnl_inward-rec_Kir6.1 IPR013518, K_chnl_inward-rec_Kir_cyto IPR040445, Kir_TM |
PANTHERi | PTHR11767, PTHR11767, 1 hit PTHR11767:SF11, PTHR11767:SF11, 1 hit |
Pfami | View protein in Pfam PF01007, IRK, 1 hit PF17655, IRK_C, 1 hit |
PIRSFi | PIRSF005465, GIRK_kir, 1 hit |
PRINTSi | PR01331, KIR61CHANNEL PR01320, KIRCHANNEL |
SUPFAMi | SSF81296, SSF81296, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KCNJ8_HUMAN | |
Accessioni | Q15842Primary (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: | February 23, 2022 | |
This is version 197 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families