P48048 (IRK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-sensitive inward rectifier potassium channel 1

Alternative name(s):
ATP-regulated potassium channel ROM-K
Inward rectifier K(+) channel Kir1.1
Potassium channel, inwardly rectifying subfamily J member 1

Gene names

Name:	KCNJ1
Synonyms:	ROMK1

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	391 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In the kidney, probably plays a major role in potassium homeostasis. 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 channel is activated by internal ATP and can be blocked by external barium.
Enzyme regulation	Inhibited by WNK3. Ref.10
Subunit structure	Interacts with SGK1 and SLC9A3R2/NHERF2. Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Phosphorylation at Ser-44 by SGK1 is necessary for its expression at the cell membrane. Ref.9
Tissue specificity	In the kidney and pancreatic islets. Lower levels in skeletal muscle, pancreas, spleen, brain, heart and liver. Ref.6
Post-translational modification	Phosphorylation at Ser-44 by SGK1 is necessary for its expression at the cell membrane.
Involvement in disease	Bartter syndrome 2 (BS2) [MIM:241200]: An autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. Bartter syndrome type 2 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ1 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Bartter syndrome Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding Potassium
Molecular function	Ion channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiovascular system development Inferred from electronic annotation. Source: Compara excretion Traceable author statement PubMed 9015377. Source: ProtInc kidney development Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara regulation of G-protein activated inward rectifier potassium channel activity Inferred from electronic annotation. Source: Compara renal sodium ion absorption Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome tissue homeostasis Inferred from electronic annotation. Source: Compara
Cellular_component	voltage-gated potassium channel complex Traceable author statement PubMed 9015377. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW inward rectifier potassium channel activity Traceable author statement PubMed 9015377. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48048-1)

Also known as: ROM-K1;

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: P48048-2)

Also known as: 2-4-5; ROM-K2; ROM-K4; ROM-K5; ROM-K6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: Missing.

Isoform 3 (identifier: P48048-3)

Also known as: ROM-K3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNASSRNVFDTL → MPTVYLCSEQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 391	391	ATP-sensitive inward rectifier potassium channel 1		PRO_0000154917
Regions
	Topological domain	1 – 77	77	Cytoplasmic By similarity
	Transmembrane	78 – 102	25	Helical; Name=M1; By similarity
	Topological domain	103 – 127	25	Extracellular By similarity
	Intramembrane	128 – 139	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	140 – 146	7	Pore-forming; By similarity
	Topological domain	147 – 155	9	Extracellular By similarity
	Transmembrane	156 – 177	22	Helical; Name=M2; By similarity
	Topological domain	178 – 391	214	Cytoplasmic By similarity
	Nucleotide binding	223 – 230	8	ATP Potential
	Motif	141 – 146	6	Selectivity filter By similarity
Sites
	Site	171	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Amino acid modifications
	Modified residue	44	1	Phosphoserine; by SGK1 Ref.9
	Glycosylation	117	1	N-linked (GlcNAc...) Ref.7
Natural variations
	Alternative sequence	1 – 19	19	Missing in isoform 2.		VSP_002797
	Alternative sequence	1 – 12	12	MNASS…VFDTL → MPTVYLCSEQ in isoform 3.		VSP_002798
	Natural variant	6	1	R → W. Corresponds to variant rs34191956 [ dbSNP | Ensembl ].		VAR_049668
	Natural variant	72	1	V → E in BS2. Ref.12		VAR_001548
	Natural variant	74	1	D → Y in BS2. Ref.12		VAR_001549
	Natural variant	99	1	W → C in BS2. Ref.12		VAR_001550
	Natural variant	108	1	D → H in BS2. Ref.12		VAR_001551
	Natural variant	110	1	P → L in BS2. Ref.12		VAR_001552
	Natural variant	115	1	S → F in a breast cancer sample; somatic mutation. Ref.14		VAR_036426
	Natural variant	122	1	V → E in BS2. Ref.12		VAR_001553
	Natural variant	124	1	N → K in BS2. Ref.13		VAR_019724
	Natural variant	167	1	G → E in BS2. Ref.12		VAR_001554
	Natural variant	198	1	A → T in BS2. Ref.12		VAR_001555
	Natural variant	214	1	A → V in BS2. Ref.11		VAR_019725
	Natural variant	219	1	S → R in BS2. Ref.11		VAR_019726
	Natural variant	315	1	V → G in BS2. Ref.12		VAR_001556
	Natural variant	357	1	M → T in BS2. Ref.11 Corresponds to variant rs59172778 [ dbSNP | Ensembl ].		VAR_019727

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ROM-K1) [UniParc]. Last modified February 1, 1996. Version 1. Checksum: DF01C89B16BE6205	FASTA	391	44,795
	10 20 30 40 50 60 MNASSRNVFD TLIRVLTESM FKHLRKWVVT RFFGHSRQRA RLVSKDGRCN IEFGNVEAQS 70 80 90 100 110 120 RFIFFVDIWT TVLDLKWRYK MTIFITAFLG SWFFFGLLWY AVAYIHKDLP EFHPSANHTP 130 140 150 160 170 180 CVENINGLTS AFLFSLETQV TIGYGFRCVT EQCATAIFLL IFQSILGVII NSFMCGAILA 190 200 210 220 230 240 KISRPKKRAK TITFSKNAVI SKRGGKLCLL IRVANLRKSL LIGSHIYGKL LKTTVTPEGE 250 260 270 280 290 300 TIILDQININ FVVDAGNENL FFISPLTIYH VIDHNSPFFH MAAETLLQQD FELVVFLDGT 310 320 330 340 350 360 VESTSATCQV RTSYVPEEVL WGYRFAPIVS KTKEGKYRVD FHNFSKTVEV ETPHCAMCLY 370 380 390 NEKDVRARMK RGYDNPNFIL SEVNETDDTK M
	Isoform 2 (2-4-5) (ROM-K2) (ROM-K4) (ROM-K5) (ROM-K6) [UniParc]. Checksum: 31C776DE544EBC79	FASTA	372	42,660
	10 20 30 40 50 60 MFKHLRKWVV TRFFGHSRQR ARLVSKDGRC NIEFGNVEAQ SRFIFFVDIW TTVLDLKWRY 70 80 90 100 110 120 KMTIFITAFL GSWFFFGLLW YAVAYIHKDL PEFHPSANHT PCVENINGLT SAFLFSLETQ 130 140 150 160 170 180 VTIGYGFRCV TEQCATAIFL LIFQSILGVI INSFMCGAIL AKISRPKKRA KTITFSKNAV 190 200 210 220 230 240 ISKRGGKLCL LIRVANLRKS LLIGSHIYGK LLKTTVTPEG ETIILDQINI NFVVDAGNEN 250 260 270 280 290 300 LFFISPLTIY HVIDHNSPFF HMAAETLLQQ DFELVVFLDG TVESTSATCQ VRTSYVPEEV 310 320 330 340 350 360 LWGYRFAPIV SKTKEGKYRV DFHNFSKTVE VETPHCAMCL YNEKDVRARM KRGYDNPNFI 370 LSEVNETDDT KM
	Isoform 3 (ROM-K3) [UniParc]. Checksum: 68BEB24F78327116	FASTA	389	44,611
	10 20 30 40 50 60 MPTVYLCSEQ IRVLTESMFK HLRKWVVTRF FGHSRQRARL VSKDGRCNIE FGNVEAQSRF 70 80 90 100 110 120 IFFVDIWTTV LDLKWRYKMT IFITAFLGSW FFFGLLWYAV AYIHKDLPEF HPSANHTPCV 130 140 150 160 170 180 ENINGLTSAF LFSLETQVTI GYGFRCVTEQ CATAIFLLIF QSILGVIINS FMCGAILAKI 190 200 210 220 230 240 SRPKKRAKTI TFSKNAVISK RGGKLCLLIR VANLRKSLLI GSHIYGKLLK TTVTPEGETI 250 260 270 280 290 300 ILDQININFV VDAGNENLFF ISPLTIYHVI DHNSPFFHMA AETLLQQDFE LVVFLDGTVE 310 320 330 340 350 360 STSATCQVRT SYVPEEVLWG YRFAPIVSKT KEGKYRVDFH NFSKTVEVET PHCAMCLYNE 370 380 KDVRARMKRG YDNPNFILSE VNETDDTKM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of multiple forms of the human kidney ROM-K potassium channel." Shuck M.E., Bock J.H., Benjamin C.W., Tsai T.-D., Lee K.S., Slightom J.L., Bienkowski M.J. J. Biol. Chem. 269:24261-24270(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Kidney.
[2]	"Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA." Yano H., Philipson L.H., Kugler J.L., Tokuyama Y., Davis E.M., le Beau M.M., Nelson D.J., Bell G.I., Takeda J. Mol. Pharmacol. 45:854-860(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Kidney.
[3]	"Nucleotide sequence analysis of the human KCNJ1 potassium channel locus." Bock J.H., Shuck M.E., Benjamin C.W., Chee M., Bienkowski M.J., Slightom J.L. Gene 188:9-16(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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).
[6]	"Isolation and chromosomal localization of a human ATP-regulated potassium channel." Krishnan S.N., Desai T., Ward D.C., Haddad G.G. Hum. Genet. 96:155-160(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-177, TISSUE SPECIFICITY. Tissue: Brain cortex.
[7]	"Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function." Pabon A., Chan K.W., Sui J.L., Wu X., Logothetis D.E., Thornhill W.B. J. Biol. Chem. 275:30677-30682(2000) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-117.
[8]	"Molecular requirements for the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase SGK1." Palmada M., Embark H.M., Yun C., Bohmer C., Lang F. Biochem. Biophys. Res. Commun. 311:629-634(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SGK1 AND SLC9A3R2/NHERF2.
[9]	"Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A." Yoo D., Kim B.Y., Campo C., Nance L., King A., Maouyo D., Welling P.A. J. Biol. Chem. 278:23066-23075(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-44 BY SGK1, SUBCELLULAR LOCATION.
[10]	"WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)." Leng Q., Kahle K.T., Rinehart J., MacGregor G.G., Wilson F.H., Canessa C.M., Lifton R.P., Hebert S.C. J. Physiol. (Lond.) 571:275-286(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[11]	"Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK." Simon D.B., Karet F.E., Rodriguez-Soriano J., Hamdan J.H., DiPietro A., Trachtman H., Sanjad S.A., Lifton R.P. Nat. Genet. 14:152-156(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BS2 VAL-214; ARG-219 AND THR-357.
[12]	"Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity." Karolyi L., Konrad M., Koeckerling A., Ziegler A., Zimmermann D.K., Roth B., Wieg C., Grzeschik K.-H., Koch M.C., Seyberth H.W., Vargas R., Forestier L., Jean G., Deschaux M., Rizzoni G.F., Niaudet P., Antignac C., Feldmann D. , Lorridon F., Cougoureux E., Laroze F., Alessandri J.-L., David L., Saunier P., Deschenes G., Hildebrandt F., Vollmer M., Proesmans W., Brandis M., van den Heuvel L.P.W.J., Lemmink H.H., Nillesen W., Monnens L.A.H., Knoers N.V.A.M., Guay-Woodford L.M., Wright C.J., Madrigal G., Hebert S.C. Hum. Mol. Genet. 6:17-26(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BS2 GLU-72; TYR-74; CYS-99; HIS-108; LEU-110; GLU-122; GLU-167; THR-198 AND GLY-315.
[13]	"A hyperprostaglandin E syndrome mutation in Kir1.1 (renal outer medullary potassium) channels reveals a crucial residue for channel function in Kir1.3 channels." Derst C., Wischmeyer E., Preisig-Mueller R., Spauschus A., Konrad M., Hensen P., Jeck N., Seyberth H.W., Daut J., Karschin A. J. Biol. Chem. 273:23884-23891(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BS2 LYS-124.
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-115.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U12541 mRNA. Translation: AAA61712.1. U12542 mRNA. Translation: AAA61713.1. U12543 mRNA. Translation: AAA61714.1. U12544 mRNA. Translation: AAA61715.1. U12545 mRNA. Translation: AAA61716.1. U03884 mRNA. Translation: AAA20594.1. U65406 Genomic DNA. Translation: AAC51220.1. U65406 Genomic DNA. Translation: AAC51221.1. U65406 Genomic DNA. Translation: AAC51222.1. CH471065 Genomic DNA. Translation: EAW67724.1. BC074752 mRNA. Translation: AAH74752.1. BC136360 mRNA. Translation: AAI36361.1. BC136361 mRNA. Translation: AAI36362.1. S78737 mRNA. Translation: AAB35012.1.
IPI	IPI00007612. IPI00216258. IPI00216259.
PIR	A55119.
RefSeq	NP_000211.1. NM_000220.4. NP_722448.1. NM_153764.2. NP_722449.3. NM_153765.2. NP_722450.1. NM_153766.2. NP_722451.1. NM_153767.3.
UniGene	Hs.527830.
3D structure databases
ProteinModelPortal	P48048.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-90062.
STRING	9606.ENSP00000316136.
Protein family/group databases
TCDB	1.A.2.1.1. inward rectifier K+ channel (IRK-C) family.
PTM databases
PhosphoSite	P48048.
Polymorphism databases
DMDM	1352479.
Proteomic databases
PaxDb	P48048.
PRIDE	P48048.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324003; ENSP00000316136; ENSG00000151704. ENST00000324036; ENSP00000316233; ENSG00000151704. ENST00000392664; ENSP00000376432; ENSG00000151704. ENST00000392665; ENSP00000376433; ENSG00000151704. ENST00000392666; ENSP00000376434; ENSG00000151704. ENST00000440599; ENSP00000406320; ENSG00000151704.
GeneID	3758.
KEGG	hsa:3758.
UCSC	uc001qeo.1. human.
Organism-specific databases
CTD	3758.
GeneCards	GC11M128706.
HGNC	HGNC:6255. KCNJ1.
HPA	HPA026962.
MIM	241200. phenotype. 600359. gene.
neXtProt	NX_P48048.
Orphanet	93604. Antenatal Bartter syndrome.
PharmGKB	PA213.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG247934.
HOGENOM	HOG000237326.
HOVERGEN	HBG006178.
InParanoid	P48048.
KO	K04995.
OMA	SPFFHMA.
PhylomeDB	P48048.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	P48048.
CleanEx	HS_KCNJ1.
Genevestigator	P48048.
GermOnline	ENSG00000151704. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.1400. 1 hit.
InterPro	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR003268. K_chnl_inward-rec_Kir1.1. IPR013518. K_chnl_inward-rec_Kir_cyto. [Graphical view]
PANTHER	PTHR11767. PTHR11767. 1 hit. PTHR11767:SF6. PTHR11767:SF6. 1 hit.
Pfam	PF01007. IRK. 1 hit. [Graphical view]
PIRSF	PIRSF005465. GIRK_kir. 1 hit.
PRINTS	PR01321. KIR11CHANNEL. PR01320. KIRCHANNEL.
SUPFAM	SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
BindingDB	P48048.
ChEMBL	CHEMBL1293292.
DrugBank	DB00414. Acetohexamide. DB00672. Chlorpropamide. DB01016. Glibenclamide. DB01120. Gliclazide. DB00222. Glimepiride. DB01067. Glipizide. DB01382. Glycodiazine. DB00350. Minoxidil. DB00731. Nateglinide. DB00912. Repaglinide. DB00839. Tolazamide. DB01124. Tolbutamide.
GenomeRNAi	3758.
NextBio	14725.
SOURCE	Search...

Entry information

Entry name

IRK1_HUMAN

Accession

Primary (citable) accession number: P48048
Secondary accession number(s): B2RMR4, Q6LD67

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 29, 2013
This is version 134 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.