Q15842 (IRK8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

KCNJ8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara kidney development Inferred from electronic annotation. Source: Compara potassium ion import Inferred from electronic annotation. Source: Compara response to exogenous dsRNA Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to pH Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome vasodilation Inferred from electronic annotation. Source: Compara
Cellular_component	ATP-sensitive potassium channel complex Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara myofibril Inferred from electronic annotation. Source: Compara sarcolemma Inferred from electronic annotation. Source: Compara voltage-gated potassium channel complex Traceable author statement PubMed 7890693. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: Compara ATP-activated inward rectifier potassium channel activity Inferred from electronic annotation. Source: Compara inward rectifier potassium channel activity Traceable author statement PubMed 7890693. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 424	424	ATP-sensitive inward rectifier potassium channel 8		PRO_0000154947
Regions
	Topological domain	1 – 69	69	Cytoplasmic By similarity
	Transmembrane	70 – 94	25	Helical; Name=M1; By similarity
	Topological domain	95 – 126	32	Extracellular By similarity
	Intramembrane	127 – 138	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	139 – 145	7	Pore-forming; By similarity
	Topological domain	146 – 154	9	Extracellular By similarity
	Transmembrane	155 – 176	22	Helical; Name=M2; By similarity
	Topological domain	177 – 424	248	Cytoplasmic By similarity
	Motif	140 – 145	6	Selectivity filter By similarity
Sites
	Site	170	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Natural variations
	Natural variant	332	1	Missing in SIDS; the mutant channel displays reduced potassium currents compared to wild type. Ref.6		VAR_065878
	Natural variant	334	1	V → A. Corresponds to variant rs34811413 [ dbSNP | Ensembl ].		VAR_049670
	Natural variant	346	1	V → I in SIDS; the mutant channel displays reduced potassium currents compared to wild type. Ref.6		VAR_065879
	Natural variant	422	1	S → 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		Length	Mass (Da)
	Q15842 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 973EAA5900C6447C	FASTA	424	47,968
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00020003.
RefSeq	NP_004973.1. NM_004982.3.
UniGene	Hs.102308. Hs.619408. Hs.741642.
3D structure databases
ProteinModelPortal	Q15842.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000240662.
PTM databases
PhosphoSite	Q15842.
Polymorphism databases
DMDM	2493600.
Proteomic databases
PaxDb	Q15842.
PRIDE	Q15842.
Protocols and materials databases
DNASU	3764.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000240662; ENSP00000240662; ENSG00000121361. ENST00000539350; ENSP00000443381; ENSG00000121361.
GeneID	3764.
KEGG	hsa:3764.
UCSC	uc001rff.3. human.
Organism-specific databases
CTD	3764.
GeneCards	GC12M021818.
HGNC	HGNC:6269. KCNJ8.
HPA	HPA031066.
MIM	272120. phenotype. 600935. gene.
neXtProt	NX_Q15842.
Orphanet	130. Brugada syndrome.
PharmGKB	PA30050.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG72812.
HOGENOM	HOG000237325.
HOVERGEN	HBG006178.
InParanoid	Q15842.
KO	K05001.
OMA	VIAVRNN.
OrthoDB	EOG4DFPNM.
PhylomeDB	Q15842.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q15842.
Bgee	Q15842.
CleanEx	HS_KCNJ8.
Genevestigator	Q15842.
GermOnline	ENSG00000121361. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
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. [Graphical view]
PANTHER	PTHR11767. PTHR11767. 1 hit.
Pfam	PF01007. IRK. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01331. KIR61CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q15842.
ChEMBL	CHEMBL4770.
DrugBank	DB00922. Levosimendan.
GenomeRNAi	3764.
NextBio	14759.
SOURCE	Search...

Entry information

Entry name

IRK8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.