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Protein

ATP-sensitive inward rectifier potassium channel 8

Gene

KCNJ8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 similarity1 Publication

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

  • ATP-activated inward rectifier potassium channel activity Source: BHF-UCL
  • ATP binding Source: Ensembl
  • inward rectifier potassium channel activity Source: ProtInc
  • voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionIon channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296025 ATP sensitive Potassium channels

Protein family/group databases

TCDBi1.A.2.1.13 the 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

EuPathDBiHostDB:ENSG00000121361.3
HGNCiHGNC:6269 KCNJ8
MIMi600935 gene
neXtProtiNX_Q15842

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 dbSNP:rs147316959EnsemblClinVar.1
Hypertrichotic osteochondrodysplasia (HTOCD)3 Publications
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_07951865V → 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_075226176C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs606231264EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65V → L: No effect on channel activity. 1 Publication1

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, 33 interactors
ELMiQ15842
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, 2 hits
InterProiView protein in InterPro
IPR014756 Ig_E-set
IPR016449 K_chnl_inward-rec_Kir
IPR003278 K_chnl_inward-rec_Kir6.1
IPR013518 K_chnl_inward-rec_Kir_cyto
PANTHERiPTHR11767 PTHR11767, 1 hit
PTHR11767:SF11 PTHR11767:SF11, 1 hit
PfamiView protein in Pfam
PF01007 IRK, 1 hit
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_07951865V → 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_075226176C → S in HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity. 1 PublicationCorresponds to variant dbSNP:rs606231264EnsemblClinVar.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 dbSNP:rs34811413EnsemblClinVar.1
Natural variantiVAR_065879346V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. 1 PublicationCorresponds to variant dbSNP:rs147316959EnsemblClinVar.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 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
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

Similar proteinsi

Entry informationi

Entry nameiKCNJ8_HUMAN
AccessioniPrimary (citable) accession number: Q15842
Secondary accession number(s): O00657
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 172 of the entry and version 1 of the sequence. See 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

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