Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P48048 (IRK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length391 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processIon transport
Potassium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseBartter syndrome
Disease mutation
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
Potassium
   Molecular functionIon channel
Voltage-gated channel
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiovascular system development

Inferred from electronic annotation. Source: Ensembl

excretion

Traceable author statement PubMed 9015377. Source: ProtInc

kidney development

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

potassium ion transmembrane transport

Traceable author statement PubMed 9015377. Source: GOC

potassium ion transport

Traceable author statement PubMed 9015377. Source: ProtInc

regulation of G-protein activated inward rectifier potassium channel activity

Inferred from electronic annotation. Source: Ensembl

renal sodium ion absorption

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

tissue homeostasis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentplasma membrane

Traceable author statement. Source: Reactome

voltage-gated potassium channel complex

Traceable author statement PubMed 9015377. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

inward rectifier potassium channel activity

Traceable author statement PubMed 9015377. Source: ProtInc

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay PubMed 12086641. Source: BHF-UCL

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 391391ATP-sensitive inward rectifier potassium channel 1
PRO_0000154917

Regions

Topological domain1 – 7777Cytoplasmic By similarity
Transmembrane78 – 10225Helical; Name=M1; By similarity
Topological domain103 – 12725Extracellular By similarity
Intramembrane128 – 13912Helical; Pore-forming; Name=H5; By similarity
Intramembrane140 – 1467Pore-forming; By similarity
Topological domain147 – 1559Extracellular By similarity
Transmembrane156 – 17722Helical; Name=M2; By similarity
Topological domain178 – 391214Cytoplasmic By similarity
Nucleotide binding223 – 2308ATP Potential
Motif141 – 1466Selectivity filter By similarity

Sites

Site1711Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Amino acid modifications

Modified residue441Phosphoserine; by SGK1 Ref.9
Glycosylation1171N-linked (GlcNAc...) Ref.7

Natural variations

Alternative sequence1 – 1919Missing in isoform 2.
VSP_002797
Alternative sequence1 – 1212MNASS…VFDTL → MPTVYLCSEQ in isoform 3.
VSP_002798
Natural variant61R → W.
Corresponds to variant rs34191956 [ dbSNP | Ensembl ].
VAR_049668
Natural variant721V → E in BS2. Ref.12
VAR_001548
Natural variant741D → Y in BS2. Ref.12
VAR_001549
Natural variant991W → C in BS2. Ref.12
VAR_001550
Natural variant1081D → H in BS2. Ref.12
VAR_001551
Natural variant1101P → L in BS2. Ref.12
VAR_001552
Natural variant1151S → F in a breast cancer sample; somatic mutation. Ref.14
VAR_036426
Natural variant1221V → E in BS2. Ref.12
VAR_001553
Natural variant1241N → K in BS2. Ref.13
VAR_019724
Natural variant1671G → E in BS2. Ref.12
VAR_001554
Natural variant1981A → T in BS2. Ref.12
VAR_001555
Natural variant2141A → V in BS2. Ref.11
VAR_019725
Natural variant2191S → R in BS2. Ref.11
VAR_019726
Natural variant3151V → G in BS2. Ref.12
VAR_001556
Natural variant3571M → T in BS2. Ref.11
Corresponds to variant rs59172778 [ dbSNP | Ensembl ].
VAR_019727

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ROM-K1) [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: DF01C89B16BE6205

FASTA39144,795
        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 

« Hide

Isoform 2 (2-4-5) (ROM-K2) (ROM-K4) (ROM-K5) (ROM-K6) [UniParc].

Checksum: 31C776DE544EBC79
Show »

FASTA37242,660
Isoform 3 (ROM-K3) [UniParc].

Checksum: 68BEB24F78327116
Show »

FASTA38944,611

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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

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.
PIRA55119.
RefSeqNP_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.
UniGeneHs.527830.

3D structure databases

ProteinModelPortalP48048.
SMRP48048. Positions 39-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109960. 6 interactions.
MINTMINT-90062.
STRING9606.ENSP00000316136.

Chemistry

BindingDBP48048.
ChEMBLCHEMBL1293292.
DrugBankDB00414. Acetohexamide.
DB00672. Chlorpropamide.
DB01016. Glibenclamide.
DB01120. Gliclazide.
DB00222. Glimepiride.
DB01067. Glipizide.
DB01382. Glycodiazine.
DB00350. Minoxidil.
DB00731. Nateglinide.
DB00912. Repaglinide.
DB00839. Tolazamide.
DB01124. Tolbutamide.
GuidetoPHARMACOLOGY429.

Protein family/group databases

TCDB1.A.2.1.1. inward rectifier k(+) channel (irk-c) family.

PTM databases

PhosphoSiteP48048.

Polymorphism databases

DMDM1352479.

Proteomic databases

PaxDbP48048.
PRIDEP48048.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324003; ENSP00000316136; ENSG00000151704.
ENST00000324036; ENSP00000316233; ENSG00000151704. [P48048-2]
ENST00000392664; ENSP00000376432; ENSG00000151704. [P48048-1]
ENST00000392665; ENSP00000376433; ENSG00000151704. [P48048-2]
ENST00000392666; ENSP00000376434; ENSG00000151704. [P48048-2]
ENST00000440599; ENSP00000406320; ENSG00000151704. [P48048-2]
GeneID3758.
KEGGhsa:3758.
UCSCuc001qeo.2. human. [P48048-1]
uc001qeq.2. human. [P48048-3]

Organism-specific databases

CTD3758.
GeneCardsGC11M128706.
HGNCHGNC:6255. KCNJ1.
HPAHPA026962.
MIM241200. phenotype.
600359. gene.
neXtProtNX_P48048.
Orphanet93604. Antenatal Bartter syndrome.
PharmGKBPA213.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG247934.
HOGENOMHOG000237326.
HOVERGENHBG006178.
InParanoidP48048.
KOK04995.
OMADIWTTVL.
OrthoDBEOG7XPZ5K.
PhylomeDBP48048.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeP48048.
CleanExHS_KCNJ1.
GenevestigatorP48048.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. 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]
PANTHERPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF6. PTHR11767:SF6. 1 hit.
PfamPF01007. IRK. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01321. KIR11CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

GeneWikiROMK.
GenomeRNAi3758.
NextBio14725.
PROP48048.
SOURCESearch...

Entry information

Entry nameIRK1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM