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Protein

G protein-activated inward rectifier potassium channel 4

Gene

KCNJ5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Can be blocked by external barium.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei179Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity1

GO - Molecular functioni

  • G-protein activated inward rectifier potassium channel activity Source: UniProtKB
  • inward rectifier potassium channel activity Source: GO_Central
  • voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization Source: BHF-UCL
  • voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionIon channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296041 Activation of G protein gated Potassium channels
R-HSA-997272 Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
SIGNORiP48544

Protein family/group databases

TCDBi1.A.2.1.3 the inward rectifier k(+) channel (irk-c) family

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-activated inward rectifier potassium channel 4
Short name:
GIRK-4
Alternative name(s):
Cardiac inward rectifier
Short name:
CIR
Heart KATP channel
Inward rectifier K(+) channel Kir3.4
Short name:
IRK-4
KATP-1
Potassium channel, inwardly rectifying subfamily J member 5
Gene namesi
Name:KCNJ5
Synonyms:GIRK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000120457.11
HGNCiHGNC:6266 KCNJ5
MIMi600734 gene
neXtProtiNX_P48544

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 86CytoplasmicBy similarityAdd BLAST86
Transmembranei87 – 111Helical; Name=M1By similarityAdd BLAST25
Topological domaini112 – 135ExtracellularBy similarityAdd BLAST24
Intramembranei136 – 147Helical; Pore-forming; Name=H5By similarityAdd BLAST12
Intramembranei148 – 154Pore-formingBy similarity7
Topological domaini155 – 163ExtracellularBy similarity9
Transmembranei164 – 185Helical; Name=M2By similarityAdd BLAST22
Topological domaini186 – 419CytoplasmicBy similarityAdd BLAST234

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Long QT syndrome 13 (LQT13)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613485
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063766387G → R in LQT13. 1 PublicationCorresponds to variant dbSNP:rs199830292EnsemblClinVar.1
Hyperaldosteronism, familial, 3 (HALD3)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. HALD3 patients present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. Hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension.
See also OMIM:613677
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067090151G → E in HALD3; results in a profound alteration of channel function with loss of channel selectivity and membrane depolarization. 3 PublicationsCorresponds to variant dbSNP:rs587777437EnsemblClinVar.1
Natural variantiVAR_065930151G → R in HALD3; detected as germline mutation in a kindred with severe primary aldosteronism and adrenocortical hyperplasia; also found as somatic mutation in aldosterone-producing adrenal adenoma samples; results in loss of channel selectivity and membrane depolarization. 6 PublicationsCorresponds to variant dbSNP:rs386352319EnsemblClinVar.1
Natural variantiVAR_077577152Y → C in HALD3; results in alteration of channel function with reduced channel selectivity and membrane depolarization; increases expression of CYP11B2 and its transcriptional regulator NR4A2. 1 Publication1
Natural variantiVAR_077578157I → S in HALD3; loss of channel selectivity. 1 PublicationCorresponds to variant dbSNP:rs587777438EnsemblClinVar.1
Natural variantiVAR_065931158T → A in HALD3; also found in aldosterone-producing adrenal adenoma samples; results in loss of channel selectivity and membrane depolarization; increases expression of CYP11B2 and its transcriptional regulators NR4A2 and ATF2; increases aldosterone and hybrid steroids 18-oxocortisol and 18-hydroxycortisol synthesis; increases STAR expression and phosphorylation. 5 PublicationsCorresponds to variant dbSNP:rs387906778EnsemblClinVar.1
Somatic mutations in KCNJ5 have been found in aldosterone-producing adrenal adenomas and can be responsible for aldosteronism associated with cell autonomous proliferation. APAs are typically solitary, well circumscribed tumors diagnosed between ages 30 and 70. They come to medical attention due to new or worsening hypertension, often with hypokalemia. The precise role of KCNJ5 mutations in APA is under debate. They produce increased sodium conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium entry, the signal for aldosterone production and cell proliferation. However, they may not be causative of APA development but may be a consequence of tumorigenesis, playing only a contributory role toward aldosterone overproduction and tumor growth (PubMed:22275527). Somatic mutations in KCNJ5 have not been found in non-aldosterone secreting adrenal adenomas suggesting that they are specifically associated with APA (PubMed:22275527 and PubMed:22848660).4 Publications
Mutations in KCNJ5 are involved in the pathogenesis of hypertension without primary aldosteronism but with increased aldosterone response to ACTH stimulation.1 Publication

Keywords - Diseasei

Disease mutation, Long QT syndrome

Organism-specific databases

DisGeNETi3762
GeneReviewsiKCNJ5
MalaCardsiKCNJ5
MIMi613485 phenotype
613677 phenotype
OpenTargetsiENSG00000120457
Orphaneti37553 Cardiodysrhythmic potassium-sensitive periodic paralysis
251274 Familial hyperaldosteronism type III
85142 NON RARE IN EUROPE: Aldosterone-producing adenoma
101016 Romano-Ward syndrome
PharmGKBiPA216

Chemistry databases

ChEMBLiCHEMBL3038488
DrugBankiDB00898 Ethanol
DB01016 Glyburide
GuidetoPHARMACOLOGYi437

Polymorphism and mutation databases

BioMutaiKCNJ5
DMDMi296434543

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001549341 – 419G protein-activated inward rectifier potassium channel 4Add BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP48544
PeptideAtlasiP48544
PRIDEiP48544
ProteomicsDBi55900

PTM databases

iPTMnetiP48544
PhosphoSitePlusiP48544

Expressioni

Tissue specificityi

Islets, exocrine pancreas and heart. Expressed in the adrenal cortex, particularly the zona glomerulosa.1 Publication

Gene expression databases

BgeeiENSG00000120457 Expressed in 154 organ(s), highest expression level in adrenal gland
CleanExiHS_KCNJ5
GenevisibleiP48544 HS

Organism-specific databases

HPAiCAB022569
HPA014722
HPA017353

Interactioni

Subunit structurei

May associate with GIRK1 and GIRK2 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger.By similarity

Protein-protein interaction databases

BioGridi109964, 17 interactors
ComplexPortaliCPX-3278 I(KACh) inward rectifier potassium channel complex
IntActiP48544, 1 interactor
STRINGi9606.ENSP00000339960

Chemistry databases

BindingDBiP48544

Structurei

3D structure databases

ProteinModelPortaliP48544
SMRiP48544
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi149 – 154Selectivity filterBy similarity6

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3827 Eukaryota
ENOG410XQ62 LUCA
GeneTreeiENSGT00760000118842
HOGENOMiHOG000237325
HOVERGENiHBG006178
InParanoidiP48544
KOiK04999
OMAiQARDYIP
OrthoDBiEOG091G08HC
PhylomeDBiP48544
TreeFamiTF313676

Family and domain databases

Gene3Di2.60.40.1400, 1 hit
InterProiView protein in InterPro
IPR014756 Ig_E-set
IPR016449 K_chnl_inward-rec_Kir
IPR003277 K_chnl_inward-rec_Kir3.4
IPR013518 K_chnl_inward-rec_Kir_cyto
PANTHERiPTHR11767 PTHR11767, 1 hit
PfamiView protein in Pfam
PF01007 IRK, 1 hit
PIRSFiPIRSF005465 GIRK_kir, 1 hit
PRINTSiPR01330 KIR34CHANNEL
PR01320 KIRCHANNEL
SUPFAMiSSF81296 SSF81296, 1 hit

Sequencei

Sequence statusi: Complete.

P48544-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGDSRNAMN QDMEIGVTPW DPKKIPKQAR DYVPIATDRT RLLAEGKKPR
60 70 80 90 100
QRYMEKSGKC NVHHGNVQET YRYLSDLFTT LVDLKWRFNL LVFTMVYTVT
110 120 130 140 150
WLFFGFIWWL IAYIRGDLDH VGDQEWIPCV ENLSGFVSAF LFSIETETTI
160 170 180 190 200
GYGFRVITEK CPEGIILLLV QAILGSIVNA FMVGCMFVKI SQPKKRAETL
210 220 230 240 250
MFSNNAVISM RDEKLCLMFR VGDLRNSHIV EASIRAKLIK SRQTKEGEFI
260 270 280 290 300
PLNQTDINVG FDTGDDRLFL VSPLIISHEI NQKSPFWEMS QAQLHQEEFE
310 320 330 340 350
VVVILEGMVE ATGMTCQARS SYMDTEVLWG HRFTPVLTLE KGFYEVDYNT
360 370 380 390 400
FHDTYETNTP SCCAKELAEM KREGRLLQYL PSPPLLGGCA EAGLDAEAEQ
410
NEEDEPKGLG GSREARGSV
Length:419
Mass (Da):47,668
Last modified:May 18, 2010 - v2
Checksum:i7C14A6B0B7EA0FD4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35I → T in AAB07045 (PubMed:10659995).Curated1
Sequence conflicti388G → R in CAA58565 (PubMed:8047164).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06592939R → H1 PublicationCorresponds to variant dbSNP:rs560269341Ensembl.1
Natural variantiVAR_069182145E → Q Found in aldosterone-producing adrenal adenoma samples; somatic mutation. 1 Publication1
Natural variantiVAR_067090151G → E in HALD3; results in a profound alteration of channel function with loss of channel selectivity and membrane depolarization. 3 PublicationsCorresponds to variant dbSNP:rs587777437EnsemblClinVar.1
Natural variantiVAR_065930151G → R in HALD3; detected as germline mutation in a kindred with severe primary aldosteronism and adrenocortical hyperplasia; also found as somatic mutation in aldosterone-producing adrenal adenoma samples; results in loss of channel selectivity and membrane depolarization. 6 PublicationsCorresponds to variant dbSNP:rs386352319EnsemblClinVar.1
Natural variantiVAR_077577152Y → C in HALD3; results in alteration of channel function with reduced channel selectivity and membrane depolarization; increases expression of CYP11B2 and its transcriptional regulator NR4A2. 1 Publication1
Natural variantiVAR_077578157I → S in HALD3; loss of channel selectivity. 1 PublicationCorresponds to variant dbSNP:rs587777438EnsemblClinVar.1
Natural variantiVAR_065931158T → A in HALD3; also found in aldosterone-producing adrenal adenoma samples; results in loss of channel selectivity and membrane depolarization; increases expression of CYP11B2 and its transcriptional regulators NR4A2 and ATF2; increases aldosterone and hybrid steroids 18-oxocortisol and 18-hydroxycortisol synthesis; increases STAR expression and phosphorylation. 5 PublicationsCorresponds to variant dbSNP:rs387906778EnsemblClinVar.1
Natural variantiVAR_065932168L → R Found in aldosterone-producing adrenal adenoma samples; somatic mutation; results in loss of channel selectivity and membrane depolarization. 5 PublicationsCorresponds to variant dbSNP:rs386352318EnsemblClinVar.1
Natural variantiVAR_065933210M → I1 PublicationCorresponds to variant dbSNP:rs138295501EnsemblClinVar.1
Natural variantiVAR_077579259V → M Found in patients with hypertension with ACTH-dependent aldosterone hypersecretion; unknown pathological significance; no effect on channel function. 1 PublicationCorresponds to variant dbSNP:rs759363415Ensembl.1
Natural variantiVAR_063107282Q → E6 PublicationsCorresponds to variant dbSNP:rs7102584EnsemblClinVar.1
Natural variantiVAR_077580348Y → N Probable disease-associated mutation found in patients with hypertension with ACTH-dependent aldosterone hypersecretion; loss of channel selectivity. 1 Publication1
Natural variantiVAR_063766387G → R in LQT13. 1 PublicationCorresponds to variant dbSNP:rs199830292EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39195 mRNA Translation: AAB53093.1
X83582 mRNA Translation: CAA58565.1
L47208 mRNA Translation: AAB07269.1
U52154 mRNA Translation: AAB07045.1
D50134 mRNA Translation: BAA08814.1
AP000920 Genomic DNA No translation available.
AK312837 mRNA Translation: BAG35691.1
BC069571 mRNA Translation: AAH69571.1
BC074838 mRNA Translation: AAH74838.2
BC069386 mRNA Translation: AAH69386.1
BC069482 mRNA Translation: AAH69482.1
BC069499 mRNA Translation: AAH69499.1
BC074839 mRNA Translation: AAH74839.2
CCDSiCCDS8479.1
PIRiG02232
RefSeqiNP_000881.3, NM_000890.3
XP_011541111.1, XM_011542809.2
XP_011541112.1, XM_011542810.2
UniGeneiHs.444595
Hs.632109

Genome annotation databases

EnsembliENST00000338350; ENSP00000339960; ENSG00000120457
ENST00000529694; ENSP00000433295; ENSG00000120457
ENST00000533599; ENSP00000434266; ENSG00000120457
GeneIDi3762
KEGGihsa:3762
UCSCiuc001qet.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39195 mRNA Translation: AAB53093.1
X83582 mRNA Translation: CAA58565.1
L47208 mRNA Translation: AAB07269.1
U52154 mRNA Translation: AAB07045.1
D50134 mRNA Translation: BAA08814.1
AP000920 Genomic DNA No translation available.
AK312837 mRNA Translation: BAG35691.1
BC069571 mRNA Translation: AAH69571.1
BC074838 mRNA Translation: AAH74838.2
BC069386 mRNA Translation: AAH69386.1
BC069482 mRNA Translation: AAH69482.1
BC069499 mRNA Translation: AAH69499.1
BC074839 mRNA Translation: AAH74839.2
CCDSiCCDS8479.1
PIRiG02232
RefSeqiNP_000881.3, NM_000890.3
XP_011541111.1, XM_011542809.2
XP_011541112.1, XM_011542810.2
UniGeneiHs.444595
Hs.632109

3D structure databases

ProteinModelPortaliP48544
SMRiP48544
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109964, 17 interactors
ComplexPortaliCPX-3278 I(KACh) inward rectifier potassium channel complex
IntActiP48544, 1 interactor
STRINGi9606.ENSP00000339960

Chemistry databases

BindingDBiP48544
ChEMBLiCHEMBL3038488
DrugBankiDB00898 Ethanol
DB01016 Glyburide
GuidetoPHARMACOLOGYi437

Protein family/group databases

TCDBi1.A.2.1.3 the inward rectifier k(+) channel (irk-c) family

PTM databases

iPTMnetiP48544
PhosphoSitePlusiP48544

Polymorphism and mutation databases

BioMutaiKCNJ5
DMDMi296434543

Proteomic databases

PaxDbiP48544
PeptideAtlasiP48544
PRIDEiP48544
ProteomicsDBi55900

Protocols and materials databases

DNASUi3762
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338350; ENSP00000339960; ENSG00000120457
ENST00000529694; ENSP00000433295; ENSG00000120457
ENST00000533599; ENSP00000434266; ENSG00000120457
GeneIDi3762
KEGGihsa:3762
UCSCiuc001qet.4 human

Organism-specific databases

CTDi3762
DisGeNETi3762
EuPathDBiHostDB:ENSG00000120457.11
GeneCardsiKCNJ5
GeneReviewsiKCNJ5
HGNCiHGNC:6266 KCNJ5
HPAiCAB022569
HPA014722
HPA017353
MalaCardsiKCNJ5
MIMi600734 gene
613485 phenotype
613677 phenotype
neXtProtiNX_P48544
OpenTargetsiENSG00000120457
Orphaneti37553 Cardiodysrhythmic potassium-sensitive periodic paralysis
251274 Familial hyperaldosteronism type III
85142 NON RARE IN EUROPE: Aldosterone-producing adenoma
101016 Romano-Ward syndrome
PharmGKBiPA216
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3827 Eukaryota
ENOG410XQ62 LUCA
GeneTreeiENSGT00760000118842
HOGENOMiHOG000237325
HOVERGENiHBG006178
InParanoidiP48544
KOiK04999
OMAiQARDYIP
OrthoDBiEOG091G08HC
PhylomeDBiP48544
TreeFamiTF313676

Enzyme and pathway databases

ReactomeiR-HSA-1296041 Activation of G protein gated Potassium channels
R-HSA-997272 Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
SIGNORiP48544

Miscellaneous databases

ChiTaRSiKCNJ5 human
GeneWikiiKCNJ5
GenomeRNAii3762
PROiPR:P48544
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120457 Expressed in 154 organ(s), highest expression level in adrenal gland
CleanExiHS_KCNJ5
GenevisibleiP48544 HS

Family and domain databases

Gene3Di2.60.40.1400, 1 hit
InterProiView protein in InterPro
IPR014756 Ig_E-set
IPR016449 K_chnl_inward-rec_Kir
IPR003277 K_chnl_inward-rec_Kir3.4
IPR013518 K_chnl_inward-rec_Kir_cyto
PANTHERiPTHR11767 PTHR11767, 1 hit
PfamiView protein in Pfam
PF01007 IRK, 1 hit
PIRSFiPIRSF005465 GIRK_kir, 1 hit
PRINTSiPR01330 KIR34CHANNEL
PR01320 KIRCHANNEL
SUPFAMiSSF81296 SSF81296, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKCNJ5_HUMAN
AccessioniPrimary (citable) accession number: P48544
Secondary accession number(s): B2R744
, Q6DK13, Q6DK14, Q92807
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 180 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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