P48549 (IRK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G protein-activated inward rectifier potassium channel 1
Short name=GIRK-1

Alternative name(s):
Inward rectifier K(+) channel Kir3.1
Potassium channel, inwardly rectifying subfamily J member 3

Gene names

Name:	KCNJ3
Synonyms:	GIRK1

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	501 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. This receptor plays a crucial role in regulating the heartbeat.
Subunit structure	Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ3 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to electrical stimulus Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	T-tubule Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from electronic annotation. Source: Compara voltage-gated potassium channel complex Traceable author statement Ref.2. Source: ProtInc
Molecular_function	G-protein activated inward rectifier potassium channel activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48549-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P48549-2)

The sequence of this isoform differs from the canonical sequence as follows:
     235-235: S → G
     236-501: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 501	501	G protein-activated inward rectifier potassium channel 1		PRO_0000154938
Regions
	Topological domain	1 – 80	80	Cytoplasmic By similarity
	Transmembrane	81 – 105	25	Helical; Name=M1; By similarity
	Topological domain	106 – 129	24	Extracellular By similarity
	Intramembrane	130 – 141	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	142 – 148	7	Pore-forming; By similarity
	Topological domain	149 – 157	9	Extracellular By similarity
	Transmembrane	158 – 179	22	Helical; Name=M2; By similarity
	Topological domain	180 – 501	322	Cytoplasmic By similarity
	Motif	143 – 148	6	Selectivity filter By similarity
Sites
	Site	173	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Natural variations
	Alternative sequence	235	1	S → G in isoform 2.		VSP_045432
	Alternative sequence	236 – 501	266	Missing in isoform 2.		VSP_045433
	Natural variant	40	1	K → R. Corresponds to variant rs16838016 [ dbSNP | Ensembl ].		VAR_049669
Experimental info
	Sequence conflict	271	1	C → R in AAH22495. Ref.6
	Sequence conflict	291	1	E → K in AAH22495. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 825A28ACE2873269	FASTA	501	56,603
	10 20 30 40 50 60 MSALRRKFGD DYQVVTTSSS GSGLQPQGPG QDPQQQLVPK KKRQRFVDKN GRCNVQHGNL 70 80 90 100 110 120 GSETSRYLSD LFTTLVDLKW RWNLFIFILT YTVAWLFMAS MWWVIAYTRG DLNKAHVGNY 130 140 150 160 170 180 TPCVANVYNF PSAFLFFIET EATIGYGYRY ITDKCPEGII LFLFQSILGS IVDAFLIGCM 190 200 210 220 230 240 FIKMSQPKKR AETLMFSEHA VISMRDGKLT LMFRVGNLRN SHMVSAQIRC KLLKSRQTPE 250 260 270 280 290 300 GEFLPLDQLE LDVGFSTGAD QLFLVSPLTI CHVIDAKSPF YDLSQRSMQT EQFEIVVILE 310 320 330 340 350 360 GIVETTGMTC QARTSYTEDE VLWGHRFFPV ISLEEGFFKV DYSQFHATFE VPTPPYSVKE 370 380 390 400 410 420 QEEMLLMSSP LIAPAITNSK ERHNSVECLD GLDDITTKLP SKLQKITGRE DFPKKLLRMS 430 440 450 460 470 480 STTSEKAYSL GDLPMKLQRI SSVPGNSEEK LVSKTTKMLS DPMSQSVADL PPKLQKMAGG 490 500 AARMEGNLPA KLRKMNSDRF T
	Isoform 2 [UniParc]. Checksum: 3F44F6C322DAC98B	FASTA	235	26,829
	10 20 30 40 50 60 MSALRRKFGD DYQVVTTSSS GSGLQPQGPG QDPQQQLVPK KKRQRFVDKN GRCNVQHGNL 70 80 90 100 110 120 GSETSRYLSD LFTTLVDLKW RWNLFIFILT YTVAWLFMAS MWWVIAYTRG DLNKAHVGNY 130 140 150 160 170 180 TPCVANVYNF PSAFLFFIET EATIGYGYRY ITDKCPEGII LFLFQSILGS IVDAFLIGCM 190 200 210 220 230 FIKMSQPKKR AETLMFSEHA VISMRDGKLT LMFRVGNLRN SHMVSAQIRC KLLKG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins." Chan K.W., Langan M.N., Sui J., Kozak A., Pabon A., Ladias J.A.A., Logothetis D.E. J. Gen. Physiol. 107:381-397(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Cloning of a G protein-activated inwardly rectifying potassium channel from human cerebellum." Schoots O., Yue K.T., Macdonald J.F., Hampson D.R., Nobrega J.N., Dixon L.M., van Tol H.H.M. Brain Res. Mol. Brain Res. 39:23-30(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Splice variant hGIRK1d from human breast cancer cells." Wagner V., Gorischek A., Bauernhofer T., Schreibmayer W. Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cerebellum.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U39196 mRNA. Translation: AAB53094.1. U50964 mRNA. Translation: AAB42176.1. GU074515 mRNA. Translation: ADB11081.1. AK293824 mRNA. Translation: BAG57228.1. AC061961 Genomic DNA. No translation available. AC093633 Genomic DNA. No translation available. AC107060 Genomic DNA. No translation available. BC022495 mRNA. Translation: AAH22495.1.
IPI	IPI00010176.
PIR	G02468.
RefSeq	NP_001247437.1. NM_001260508.1. NP_001247438.1. NM_001260509.1. NP_001247439.1. NM_001260510.1. NP_002230.1. NM_002239.3.
UniGene	Hs.591606.
3D structure databases
ProteinModelPortal	P48549.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000295101.
PTM databases
PhosphoSite	P48549.
Polymorphism databases
DMDM	1352482.
Proteomic databases
PaxDb	P48549.
PRIDE	P48549.
Protocols and materials databases
DNASU	3760.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295101; ENSP00000295101; ENSG00000162989. ENST00000544049; ENSP00000438410; ENSG00000162989.
GeneID	3760.
KEGG	hsa:3760.
UCSC	uc002tyv.1. human.
Organism-specific databases
CTD	3760.
GeneCards	GC02P155555.
HGNC	HGNC:6264. KCNJ3.
HPA	HPA024231.
MIM	601534. gene.
neXtProt	NX_P48549.
PharmGKB	PA215.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG280776.
HOGENOM	HOG000237325.
HOVERGEN	HBG006178.
InParanoid	P48549.
KO	K04997.
OMA	SMQSEQF.
OrthoDB	EOG4GXFMM.
PhylomeDB	P48549.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P48549.
Bgee	P48549.
CleanEx	HS_KCNJ3.
Genevestigator	P48549.
GermOnline	ENSG00000162989. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
InterPro	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR003274. K_chnl_inward-rec_Kir3.1. 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	PR01327. KIR31CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL1914277.
DrugBank	DB01159. Halothane.
GenomeRNAi	3760.
NextBio	14741.
SOURCE	Search...

Entry information

Entry name

IRK3_HUMAN

Accession

Primary (citable) accession number: P48549
Secondary accession number(s): B4DEW7, Q8TBI0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 117 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.