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Protein

Inward rectifier potassium channel 4

Gene

KCNJ4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 and cesium (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei164Role 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: Reactome
  • inward rectifier potassium channel activity Source: ProtInc
  • PDZ domain binding Source: UniProtKB

GO - Biological processi

  • cardiac conduction Source: Reactome
  • potassium ion import Source: GO_Central
  • potassium ion transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168135-MONOMER.
ReactomeiR-HSA-1296041. Activation of G protein gated Potassium channels.
R-HSA-1296053. Classical Kir channels.
R-HSA-5576886. Phase 4 - resting membrane potential.
R-HSA-997272. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.

Names & Taxonomyi

Protein namesi
Recommended name:
Inward rectifier potassium channel 4
Alternative name(s):
HIRK2
HRK1
Hippocampal inward rectifier
Short name:
HIR
Inward rectifier K(+) channel Kir2.3
Short name:
IRK-3
Potassium channel, inwardly rectifying subfamily J member 4
Gene namesi
Name:KCNJ4
Synonyms:IRK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:6265. KCNJ4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 55CytoplasmicBy similarityAdd BLAST55
Transmembranei56 – 80Helical; Name=M1By similarityAdd BLAST25
Topological domaini81 – 120ExtracellularBy similarityAdd BLAST40
Intramembranei121 – 132Helical; Pore-forming; Name=H5By similarityAdd BLAST12
Intramembranei133 – 139Pore-formingBy similarity7
Topological domaini140 – 148ExtracellularBy similarity9
Transmembranei149 – 170Helical; Name=M2By similarityAdd BLAST22
Topological domaini171 – 445CytoplasmicBy similarityAdd BLAST275

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
  • postsynaptic membrane Source: UniProtKB-SubCell
  • voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi117H → E: Loss of pH-sensitivity. 1 Publication1

Organism-specific databases

DisGeNETi3761.
OpenTargetsiENSG00000168135.
PharmGKBiPA30048.

Chemistry databases

ChEMBLiCHEMBL2146347.
GuidetoPHARMACOLOGYi432.

Polymorphism and mutation databases

BioMutaiKCNJ4.
DMDMi1352483.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001549301 – 445Inward rectifier potassium channel 4Add BLAST445

Proteomic databases

PaxDbiP48050.
PRIDEiP48050.

PTM databases

iPTMnetiP48050.
PhosphoSitePlusiP48050.

Expressioni

Tissue specificityi

Heart, skeletal muscle, and several different brain regions including the hippocampus.

Gene expression databases

BgeeiENSG00000168135.
CleanExiHS_KCNJ4.
ExpressionAtlasiP48050. baseline and differential.
GenevisibleiP48050. HS.

Interactioni

Subunit structurei

Homomultimeric and heteromultimeric association with KCNJ2 and KCNJ12. 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). Interacts with TAX1BP3. TAX1BP3 competes with LIN7 family members for KCNJ4 binding.By similarity2 Publications

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109963. 10 interactors.
IntActiP48050. 3 interactors.
MINTiMINT-159020.
STRINGi9606.ENSP00000306497.

Chemistry databases

BindingDBiP48050.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GJ9X-ray2.80C/D436-445[»]
ProteinModelPortaliP48050.
SMRiP48050.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP48050.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni91 – 111Val/Gly/Ala/Pro stretchAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi134 – 139Selectivity filterBy similarity6
Motifi443 – 445PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi102 – 105Poly-Gly4
Compositional biasi362 – 368Poly-Pro7
Compositional biasi383 – 390Poly-Glu8
Compositional biasi391 – 399Poly-Ala9

Domaini

The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48050.
KOiK04998.
OMAiHAPRRKH.
OrthoDBiEOG091G08HC.
PhylomeDBiP48050.
TreeFamiTF313676.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003273. K_chnl_inward-rec_Kir2.3.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]
PANTHERiPTHR11767. PTHR11767. 3 hits.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01326. KIR23CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

P48050-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHGHSRNGQA HVPRRKRRNR FVKKNGQCNV YFANLSNKSQ RYMADIFTTC
60 70 80 90 100
VDTRWRYMLM IFSAAFLVSW LFFGLLFWCI AFFHGDLEAS PGVPAAGGPA
110 120 130 140 150
AGGGGAAPVA PKPCIMHVNG FLGAFLFSVE TQTTIGYGFR CVTEECPLAV
160 170 180 190 200
IAVVVQSIVG CVIDSFMIGT IMAKMARPKK RAQTLLFSHH AVISVRDGKL
210 220 230 240 250
CLMWRVGNLR KSHIVEAHVR AQLIKPYMTQ EGEYLPLDQR DLNVGYDIGL
260 270 280 290 300
DRIFLVSPII IVHEIDEDSP LYGMGKEELE SEDFEIVVIL EGMVEATAMT
310 320 330 340 350
TQARSSYLAS EILWGHRFEP VVFEEKSHYK VDYSRFHKTY EVAGTPCCSA
360 370 380 390 400
RELQESKITV LPAPPPPPSA FCYENELALM SQEEEEMEEE AAAAAAVAAG
410 420 430 440
LGLEAGSKEE AGIIRMLEFG SHLDLERMQA SLPLDNISYR RESAI
Length:445
Mass (Da):49,500
Last modified:February 1, 1996 - v1
Checksum:i893F03365273E8BE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16 – 17KR → NG in AAC60632 (PubMed:8051145).Curated2
Sequence conflicti107A → D in AAA66076 (PubMed:8034048).Curated1
Sequence conflicti350A → G in AAC60632 (PubMed:8051145).Curated1
Sequence conflicti392A → S in AAA66076 (PubMed:8034048).Curated1
Sequence conflicti395A → S in AAA66076 (PubMed:8034048).Curated1
Sequence conflicti396A → R (PubMed:8051145).Curated1
Sequence conflicti398A → G (PubMed:8051145).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07364 mRNA. Translation: AAA19962.1.
U24056 mRNA. Translation: AAA66076.1.
S72503 mRNA. Translation: AAC60632.1.
CR456507 mRNA. Translation: CAG30393.1.
Z97056 Genomic DNA. Translation: CAB09790.1.
BC113506 mRNA. Translation: AAI13507.1.
BC113508 mRNA. Translation: AAI13509.1.
CCDSiCCDS13971.1.
PIRiA54852.
I38521.
RefSeqiNP_004972.1. NM_004981.1.
NP_690607.1. NM_152868.2.
UniGeneiHs.32505.

Genome annotation databases

EnsembliENST00000303592; ENSP00000306497; ENSG00000168135.
GeneIDi3761.
KEGGihsa:3761.
UCSCiuc003avt.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07364 mRNA. Translation: AAA19962.1.
U24056 mRNA. Translation: AAA66076.1.
S72503 mRNA. Translation: AAC60632.1.
CR456507 mRNA. Translation: CAG30393.1.
Z97056 Genomic DNA. Translation: CAB09790.1.
BC113506 mRNA. Translation: AAI13507.1.
BC113508 mRNA. Translation: AAI13509.1.
CCDSiCCDS13971.1.
PIRiA54852.
I38521.
RefSeqiNP_004972.1. NM_004981.1.
NP_690607.1. NM_152868.2.
UniGeneiHs.32505.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GJ9X-ray2.80C/D436-445[»]
ProteinModelPortaliP48050.
SMRiP48050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109963. 10 interactors.
IntActiP48050. 3 interactors.
MINTiMINT-159020.
STRINGi9606.ENSP00000306497.

Chemistry databases

BindingDBiP48050.
ChEMBLiCHEMBL2146347.
GuidetoPHARMACOLOGYi432.

PTM databases

iPTMnetiP48050.
PhosphoSitePlusiP48050.

Polymorphism and mutation databases

BioMutaiKCNJ4.
DMDMi1352483.

Proteomic databases

PaxDbiP48050.
PRIDEiP48050.

Protocols and materials databases

DNASUi3761.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303592; ENSP00000306497; ENSG00000168135.
GeneIDi3761.
KEGGihsa:3761.
UCSCiuc003avt.3. human.

Organism-specific databases

CTDi3761.
DisGeNETi3761.
GeneCardsiKCNJ4.
H-InvDBHIX0175381.
HGNCiHGNC:6265. KCNJ4.
MIMi600504. gene.
neXtProtiNX_P48050.
OpenTargetsiENSG00000168135.
PharmGKBiPA30048.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3827. Eukaryota.
ENOG410XQ62. LUCA.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48050.
KOiK04998.
OMAiHAPRRKH.
OrthoDBiEOG091G08HC.
PhylomeDBiP48050.
TreeFamiTF313676.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168135-MONOMER.
ReactomeiR-HSA-1296041. Activation of G protein gated Potassium channels.
R-HSA-1296053. Classical Kir channels.
R-HSA-5576886. Phase 4 - resting membrane potential.
R-HSA-997272. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.

Miscellaneous databases

EvolutionaryTraceiP48050.
GeneWikiiKCNJ4.
GenomeRNAii3761.
PROiP48050.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168135.
CleanExiHS_KCNJ4.
ExpressionAtlasiP48050. baseline and differential.
GenevisibleiP48050. HS.

Family and domain databases

Gene3Di2.60.40.1400. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003273. K_chnl_inward-rec_Kir2.3.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]
PANTHERiPTHR11767. PTHR11767. 3 hits.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01326. KIR23CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNJ4_HUMAN
AccessioniPrimary (citable) accession number: P48050
Secondary accession number(s): Q14D44
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.