Reviewed, UniProtKB/Swiss-Prot P63252 (IRK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Inward rectifier potassium channel 2
Alternative name(s):
    Potassium channel, inwardly rectifying subfamily J member 2
    Inward rectifier K(+) channel Kir2.1
    Cardiac inward rectifier potassium channel
    IRK1

Gene names

Name:	KCNJ2
Synonyms:	HIRK1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. 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 extracellular barium or cesium.
Subunit structure	Homomultimeric and heteromultimeric association with Kir2.3, resulting in an enhanced G-protein-induced current. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Heart, brain, placenta, lung, skeletal muscle, and kidney. Diffusely distributed throughout the brain.
Involvement in disease	Defects in KCNJ2 are the cause of long QT syndrome type 7 (LQT7) [MIM:170390]; also called Andersen syndrome or Andersen cardiodysrhythmic periodic paralysis. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to excercise or emotional stress. LQT7 manifests itself as a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features. Ref.8 Ref.9 Ref.10 Defects in KCNJ2 are the cause of short QT syndrome type 3 (SQT3) [MIM:609622]. Short QT syndromes are heart disorders characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. They cause syncope and sudden death. SQT3 has a unique ECG phenotype characterized by asymmetrical T waves. Ref.11
Sequence similarities	Belongs to the inward rectifier-type potassium channel family.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Disease	Disease mutation Long QT syndrome Short QT syndrome
Domain	Transmembrane
Ligand	Potassium
Molecular function	Ionic channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	potassium ion transport Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKAP5	P24588	1	EBI-703457,EBI-703640
FLNA	P21333	1	EBI-703457,EBI-350432

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 427	427	Inward rectifier potassium channel 2		PRO_0000154923
Regions
	Topological domain	1 – 81	81	Cytoplasmic By similarity
	Transmembrane	82 – 106	25	M1 By similarity
	Topological domain	107 – 128	22	Extracellular By similarity
	Topological domain	148 – 156	9	Extracellular By similarity
	Transmembrane	157 – 178	22	M2 By similarity
	Topological domain	179 – 427	249	Cytoplasmic By similarity
	Region	129 – 140	12	H5 (pore-forming helix) By similarity
	Motif	142 – 147	6	Selectivity filter By similarity
	Motif	425 – 427	3	PDZ-binding Potential
Sites
	Site	172	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Amino acid modifications
	Modified residue	337	1	Phosphotyrosine Ref.7
Natural variations
	Natural variant	67	1	R → W in LQT7. Ref.9		VAR_017851
	Natural variant	71	1	D → V in LQT7; loss of function and dominant-negative effect in current. Ref.8		VAR_017852
	Natural variant	95 – 98	4	Missing in LQT7.		VAR_017853
	Natural variant	172	1	D → N in SQT3; gain of function. Ref.11		VAR_023842
	Natural variant	186	1	P → L in LQT7. Ref.10		VAR_017854
	Natural variant	216	1	N → H in LQT7. Ref.10		VAR_017855
	Natural variant	218	1	R → W in LQT7; loss of function and dominant-negative effect in current. Ref.8		VAR_017856
	Natural variant	300	1	G → V in LQT7. Ref.8		VAR_017857
	Natural variant	302	1	V → M in LQT7. Ref.10		VAR_017858
	Natural variant	314 – 315	2	Missing in LQT7.		VAR_017859
Experimental info
	Sequence conflict	330	1	L → F in AAC39555. Ref.4
	Sequence conflict	340	1	D → E in AAC39555. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P63252-1 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: AB37CAD4B99B4050	FASTA	427	48,288
	10 20 30 40 50 60 MGSVRTNRYS IVSSEEDGMK LATMAVANGF GNGKSKVHTR QQCRSRFVKK DGHCNVQFIN 70 80 90 100 110 120 VGEKGQRYLA DIFTTCVDIR WRWMLVIFCL AFVLSWLFFG CVFWLIALLH GDLDASKEGK 130 140 150 160 170 180 ACVSEVNSFT AAFLFSIETQ TTIGYGFRCV TDECPIAVFM VVFQSIVGCI IDAFIIGAVM 190 200 210 220 230 240 AKMAKPKKRN ETLVFSHNAV IAMRDGKLCL MWRVGNLRKS HLVEAHVRAQ LLKSRITSEG 250 260 270 280 290 300 EYIPLDQIDI NVGFDSGIDR IFLVSPITIV HEIDEDSPLY DLSKQDIDNA DFEIVVILEG 310 320 330 340 350 360 MVEATAMTTQ CRSSYLANEI LWGHRYEPVL FEEKHYYKVD YSRFHKTYEV PNTPLCSARD 370 380 390 400 410 420 LAEKKYILSN ANSFCYENEV ALTSKEEDDS ENGVPESTST DTPPDIDLHN QASVPLEPRP LRRESEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a human heart inward rectifier potassium channel." Raab-Graham K.F., Radeke C.M., Vandenberg C.A. NeuroReport 5:2501-2505(1994) [PubMed: 7696590] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	Tang W., Qin C.L., Yang X.C. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel." Wood L.S., Tsai T.-D., Lee K.S., Vogeli G. Gene 163:313-317(1995) [PubMed: 7590287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[4]	"Inwardly rectifying whole cell potassium current in human blood eosinophils." Tare M., Prestwich S.A., Gordienko D.V., Parveen S., Carver J.E., Robinson C., Bolton T.B. J. Physiol. (Lond.) 506:303-318(1998) [PubMed: 9490857] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[5]	"Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits." Derst C., Karschin C., Wischmeyer E., Hirsch J.R., Preisig-Muller R., Rajan S., Engel H., Grzeschik K., Daut J., Karschin A. FEBS Lett. 491:305-311(2001) [PubMed: 11240146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[6]	"Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line." Ashen M.D., O'Rourke B., Kluge K.A., Johns D.C., Tomaselli G.F. Am. J. Physiol. 268:H506-H511(1995) [PubMed: 7840300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-143. Tissue: Fetal brain and Heart.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-337, MASS SPECTROMETRY.
[8]	"Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome." Plaster N.M., Tawil R., Tristani-Firouzi M., Canun S., Bendahhou S., Tsunoda A., Donaldson M.R., Iannaccone S.T., Brunt E., Barohn R., Clark J., Deymeer F., George A.L. Jr., Fish F.A., Hahn A., Nitu A., Ozdemir C., Serdaroglu P. , Subramony S.H., Wolfe G., Fu Y.-H., Ptacek L.J. Cell 105:511-519(2001) [PubMed: 11371347] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS LQT7 VAL-71 AND TRP-218, VARIANTS LQT7 VAL-300; 95-SER--PHE-98 DEL AND SER-314-315-TYR DEL.
[9]	"KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes." Andelfinger G., Tapper A.R., Welch R.C., Vanoye C.G., George A.L. Jr., Benson D.W. Am. J. Hum. Genet. 71:663-668(2002) [PubMed: 12148092] [Abstract] Cited for: VARIANT LQT7 TRP-67.
[10]	"Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)." Tristani-Firouzi M., Jensen J.L., Donaldson M.R., Sansone V., Meola G., Hahn A., Bendahhou S., Kwiecinski H., Fidzianska A., Plaster N., Fu Y.-H., Ptacek L.J., Tawil R. J. Clin. Invest. 110:381-388(2002) [PubMed: 12163457] [Abstract] Cited for: VARIANTS LQT7 LEU-186; HIS-216 AND MET-302.
[11]	"A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene." Priori S.G., Pandit S.V., Rivolta I., Berenfeld O., Ronchetti E., Dhamoon A., Napolitano C., Anumonwo J., di Barletta M.R., Gudapakkam S., Bosi G., Stramba-Badiale M., Jalife J. Circ. Res. 96:800-807(2005) [PubMed: 15761194] [Abstract] Cited for: VARIANT SQT3 ASN-172, CHARACTERIZATION OF VARIANT SQT3 ASN-172.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U24055 mRNA. Translation: AAB50277.1. U12507 mRNA. Translation: AAC50072.1. U16861 mRNA. Translation: AAA91781.1. AF153819 Genomic DNA. Translation: AAF73242.1. AF153820 mRNA. Translation: AAF73241.1. U22413 mRNA. Translation: AAA64282.1. AF011904 mRNA. Translation: AAC39555.1. AF021139 mRNA. Translation: AAB88797.1.
IPI	IPI00007614.
PIR	I38727.
RefSeq	NP_000882.1.
UniGene	Hs.1547
3D structure databases
HSSP	HSSP built from PDB template 1N9P based on UniProtKB P35562.
SMR	P63252. Positions 187-370.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63252. 2 interactions.
STRING	P63252.
Protein family/group databases
TCDB	1.A.2.1.2. inward rectifier K+ channel (IRK-C) family.
PTM databases
PhosphoSite	P63252.
Proteomic databases
PeptideAtlas	P63252.
PRIDE	P63252.
Genome annotation databases
Ensembl	ENST00000243457; ENSP00000243457; ENSG00000123700; Homo sapiens. [Genome view]
GeneID	3759.
KEGG	hsa:3759.
UCSC	uc002jir.1. human.
Organism-specific databases
CTD	3759.
GeneCards	GC17P065677.
H-InvDB	HIX0039037.
HGNC	HGNC:6263. KCNJ2.
MIM	170390. phenotype. 600681. gene. 609622. phenotype.
Orphanet	334. Atrial fibrillation, familial. 37553. Cardiodysrythmic potassium-sensitive periodic paralysis. 768. Long QT syndrome, familial. 51083. Short QT syndrome, familial.
PharmGKB	PA214.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P63252.
HOVERGEN	P63252.
OMA	MDNADFE.
Gene expression databases
ArrayExpress	P63252.
Bgee	P63252.
CleanEx	HS_KCNJ2.
Genevestigator	P63252.
GermOnline	ENSG00000123700. Homo sapiens.
Family and domain databases
InterPro	IPR016449. K_chnl_inward-rec_Kir. IPR001838. K_chnl_inward-rec_Kir-like. IPR003271. K_chnl_inward-rec_Kir2.1. IPR013521. K_chnl_inward-rec_Kir_Cr2. IPR013518. K_chnl_inward-rec_Kir_cyto. IPR013673. K_chnl_inward-rec_Kir_N. [Graphical view]
Gene3D	G3DSA:2.60.40.1400. IR_K+channel_cytopl. 1 hit.
PANTHER	PTHR11767. K+channel_IR. 1 hit. PTHR11767:SF15. KIR21_channel. 1 hit.
Pfam	PF01007. IRK. 1 hit. PF08466. IRK_N. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01324. KIR21CHANNEL. PR01320. KIRCHANNEL.
ProDom	PD001103. K+channel_IR. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other Resources
NextBio	14737.
SOURCE	Search...

Entry information

Entry name

IRK2_HUMAN

Accession

Primary (citable) accession number: P63252
Secondary accession number(s): O15110, P48049

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	November 3, 2009
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.