P63252 (IRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inward rectifier potassium channel 2

Alternative name(s):
Cardiac inward rectifier potassium channel
Inward rectifier K(+) channel Kir2.1
Short name=IRK-1
Short name=hIRK1
Potassium channel, inwardly rectifying subfamily J member 2

Gene names

Name:	KCNJ2
Synonyms:	IRK1

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	427 AA.
Sequence status	Complete.
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	Long QT syndrome 7 (LQT7) [MIM:170390]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 7 manifests itself as a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 Short QT syndrome 3 (SQT3) [MIM:609622]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. SQT3 has a unique ECG phenotype characterized by asymmetrical T waves. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Familial atrial fibrillation 9 (ATFB9) [MIM:613980]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Disease	Atrial fibrillation Disease mutation Long QT syndrome Short QT syndrome
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	magnesium ion transport Inferred from electronic annotation. Source: Compara regulation of cardiac muscle cell action potential Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	dendrite Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	inward rectifier potassium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

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	Helical; Name=M1; By similarity
	Topological domain	107 – 128	22	Extracellular By similarity
	Intramembrane	129 – 140	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	141 – 147	7	Pore-forming; By similarity
	Topological domain	148 – 156	9	Extracellular By similarity
	Transmembrane	157 – 178	22	Helical; Name=M2; By similarity
	Topological domain	179 – 427	249	Cytoplasmic 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
Natural variations
	Natural variant	54	1	C → F in LQT7; there is loss of function when the mutant is expressed alone and a dominant-negative effect when expressed with wild-type channels; channel trafficking and assembly are not affected. Ref.13		VAR_065861
	Natural variant	67	1	R → W in LQT7. Ref.8		VAR_017851
	Natural variant	71	1	D → V in LQT7; loss of function mutation acting in a dominant-negative manner. Ref.7		VAR_017852
	Natural variant	75	1	T → R in LQT7; loss of function mutation acting in a dominant-negative manner. Ref.12		VAR_065862
	Natural variant	93	1	V → I in ATFB9; has a gain-of-function effect on the channels. Ref.10		VAR_065863
	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.9		VAR_017854
	Natural variant	216	1	N → H in LQT7. Ref.9		VAR_017855
	Natural variant	218	1	R → W in LQT7; loss of function and dominant-negative effect in current. Ref.7		VAR_017856
	Natural variant	300	1	G → V in LQT7. Ref.7		VAR_017857
	Natural variant	302	1	V → M in LQT7. Ref.9		VAR_017858
	Natural variant	305	1	T → P in LQT7; there is loss of function when the mutant is expressed alone and a dominant-negative effect when expressed with wild-type channels; channel trafficking and assembly are not affected. Ref.13		VAR_065864
	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 [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

[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-143. Tissue: Fetal brain and Heart.
[7]	"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] [Europe PMC] [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.
[8]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LQT7 TRP-67.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS LQT7 LEU-186; HIS-216 AND MET-302.
[10]	"A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation." Xia M., Jin Q., Bendahhou S., He Y., Larroque M.M., Chen Y., Zhou Q., Yang Y., Liu Y., Liu B., Zhu Q., Zhou Y., Lin J., Liang B., Li L., Dong X., Pan Z., Wang R. , Wan H., Qiu W., Xu W., Eurlings P., Barhanin J., Chen Y. Biochem. Biophys. Res. Commun. 332:1012-1019(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ATFB9 ILE-93, CHARACTERIZATION OF VARIANT ATFB9 ILE-93.
[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] [Europe PMC] [Abstract] Cited for: VARIANT SQT3 ASN-172, CHARACTERIZATION OF VARIANT SQT3 ASN-172.
[12]	"Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome." Lu C.W., Lin J.H., Rajawat Y.S., Jerng H., Rami T.G., Sanchez X., DeFreitas G., Carabello B., DeMayo F., Kearney D.L., Miller G., Li H., Pfaffinger P.J., Bowles N.E., Khoury D.S., Towbin J.A. J. Med. Genet. 43:653-659(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT7 ARG-75, CHARACTERIZATION OF VARIANT LQT7 ARG-75.
[13]	"Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred." Bendahhou S., Fournier E., Gallet S., Menard D., Larroque M.M., Barhanin J. Hum. Mol. Genet. 16:900-906(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT7 PHE-54 AND PRO-305, CHARACTERIZATION OF VARIANTS LQT7 PHE-54 AND PRO-305.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_000891.2.
UniGene	Hs.1547.
3D structure databases
ProteinModelPortal	P63252.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63252. 2 interactions.
STRING	9606.ENSP00000243457.
Protein family/group databases
TCDB	1.A.2.1.2. inward rectifier K+ channel (IRK-C) family.
PTM databases
PhosphoSite	P63252.
Polymorphism databases
DMDM	54037433.
Proteomic databases
PaxDb	P63252.
PeptideAtlas	P63252.
PRIDE	P63252.
Protocols and materials databases
DNASU	3759.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000243457; ENSP00000243457; ENSG00000123700. ENST00000535240; ENSP00000441848; ENSG00000123700.
GeneID	3759.
KEGG	hsa:3759.
UCSC	uc002jir.3. human.
Organism-specific databases
CTD	3759.
GeneCards	GC17P068165.
HGNC	HGNC:6263. KCNJ2.
HPA	HPA029109.
MIM	170390. phenotype. 600681. gene. 609622. phenotype. 613980. phenotype.
neXtProt	NX_P63252.
Orphanet	37553. Cardiodysrythmic potassium-sensitive periodic paralysis. 334. Familial atrial fibrillation. 51083. Familial short QT syndrome.
PharmGKB	PA214.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG72812.
HOGENOM	HOG000237325.
HOVERGEN	HBG006178.
InParanoid	P63252.
KO	K04996.
OMA	HNATVAM.
OrthoDB	EOG4N04DV.
PhylomeDB	P63252.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	P63252.
CleanEx	HS_KCNJ2.
Genevestigator	P63252.
GermOnline	ENSG00000123700. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
InterPro	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR003271. K_chnl_inward-rec_Kir2.1. IPR013518. K_chnl_inward-rec_Kir_cyto. IPR013673. K_chnl_inward-rec_Kir_N. [Graphical view]
PANTHER	PTHR11767. PTHR11767. 1 hit. PTHR11767:SF15. PTHR11767:SF15. 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.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL1914276.
GenomeRNAi	3759.
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:	May 1, 2013
This is version 100 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.