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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei164 – 1641Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

GO - Molecular functioni

  1. inward rectifier potassium channel activity Source: ProtInc
  2. PDZ domain binding Source: UniProtKB

GO - Biological processi

  1. potassium ion import Source: GO_Central
  2. potassium ion transport Source: ProtInc
  3. regulation of ion transmembrane transport Source: GO_Central
  4. synaptic transmission Source: Reactome
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

ReactomeiREACT_25004. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
REACT_75831. Activation of G protein gated Potassium channels.
REACT_75870. Classical Kir channels.

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
ProteomesiUP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:6265. KCNJ4.

Subcellular locationi

  1. Cell membrane; Multi-pass membrane protein
  2. Cell junctionsynapsepostsynaptic cell membrane By similarity; Multi-pass membrane protein By similarity
  3. Cytoplasmic vesicle membrane By similarity

  4. Note: TAX1BP3 binding promotes dissociation of KCNJ4 from LIN7 famaly members and KCNJ4 internalization.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5555CytoplasmicBy similarityAdd
BLAST
Transmembranei56 – 8025Helical; Name=M1By similarityAdd
BLAST
Topological domaini81 – 12040ExtracellularBy similarityAdd
BLAST
Intramembranei121 – 13212Helical; Pore-forming; Name=H5By similarityAdd
BLAST
Intramembranei133 – 1397Pore-formingBy similarity
Topological domaini140 – 1489ExtracellularBy similarity
Transmembranei149 – 17022Helical; Name=M2By similarityAdd
BLAST
Topological domaini171 – 445275CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. basolateral plasma membrane Source: UniProtKB
  2. cell junction Source: UniProtKB-KW
  3. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  4. plasma membrane Source: Reactome
  5. postsynaptic membrane Source: UniProtKB-SubCell
  6. 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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi117 – 1171H → E: Loss of pH-sensitivity. 1 Publication

Organism-specific databases

PharmGKBiPA30048.

Polymorphism and mutation databases

BioMutaiKCNJ4.
DMDMi1352483.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445Inward rectifier potassium channel 4PRO_0000154930Add
BLAST

Proteomic databases

PaxDbiP48050.
PRIDEiP48050.

PTM databases

PhosphoSiteiP48050.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP48050.
CleanExiHS_KCNJ4.
ExpressionAtlasiP48050. baseline and differential.
GenevestigatoriP48050.

Organism-specific databases

HPAiHPA003270.

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

Protein-protein interaction databases

BioGridi109963. 11 interactions.
IntActiP48050. 3 interactions.
MINTiMINT-159020.
STRINGi9606.ENSP00000306497.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3GJ9X-ray2.80C/D436-445[»]
ProteinModelPortaliP48050.
SMRiP48050. Positions 18-357.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP48050.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni91 – 11121Val/Gly/Ala/Pro stretchAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi134 – 1396Selectivity filterBy similarity
Motifi443 – 4453PDZ-bindingSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi102 – 1054Poly-Gly
Compositional biasi362 – 3687Poly-Pro
Compositional biasi383 – 3908Poly-Glu
Compositional biasi391 – 3999Poly-Ala

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

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48050.
KOiK04998.
OMAiFFHGDLD.
OrthoDBiEOG7XPZ5K.
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. 1 hit.
PTHR11767:SF13. PTHR11767:SF13. 1 hit.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti16 – 172KR → NG in AAC60632 (PubMed:8051145).Curated
Sequence conflicti107 – 1071A → D in AAA66076 (PubMed:8034048).Curated
Sequence conflicti350 – 3501A → G in AAC60632 (PubMed:8051145).Curated
Sequence conflicti392 – 3921A → S in AAA66076 (PubMed:8034048).Curated
Sequence conflicti395 – 3951A → S in AAA66076 (PubMed:8034048).Curated
Sequence conflicti396 – 3961A → R (PubMed:8051145).Curated
Sequence conflicti398 – 3981A → G (PubMed:8051145).Curated

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.
UCSCiuc003avs.1. human.

Polymorphism and mutation databases

BioMutaiKCNJ4.

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
EntryMethodResolution (Å)ChainPositionsPDBsum
3GJ9X-ray2.80C/D436-445[»]
ProteinModelPortaliP48050.
SMRiP48050. Positions 18-357.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109963. 11 interactions.
IntActiP48050. 3 interactions.
MINTiMINT-159020.
STRINGi9606.ENSP00000306497.

Chemistry

BindingDBiP48050.
ChEMBLiCHEMBL2146347.
GuidetoPHARMACOLOGYi432.

PTM databases

PhosphoSiteiP48050.

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.
UCSCiuc003avs.1. human.

Organism-specific databases

CTDi3761.
GeneCardsiGC22M038822.
H-InvDBHIX0175381.
HGNCiHGNC:6265. KCNJ4.
HPAiHPA003270.
MIMi600504. gene.
neXtProtiNX_P48050.
PharmGKBiPA30048.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG72812.
GeneTreeiENSGT00760000118842.
HOGENOMiHOG000237325.
HOVERGENiHBG006178.
InParanoidiP48050.
KOiK04998.
OMAiFFHGDLD.
OrthoDBiEOG7XPZ5K.
PhylomeDBiP48050.
TreeFamiTF313676.

Enzyme and pathway databases

ReactomeiREACT_25004. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
REACT_75831. Activation of G protein gated Potassium channels.
REACT_75870. Classical Kir channels.

Miscellaneous databases

EvolutionaryTraceiP48050.
GeneWikiiKCNJ4.
GenomeRNAii3761.
NextBioi14745.
PROiP48050.
SOURCEiSearch...

Gene expression databases

BgeeiP48050.
CleanExiHS_KCNJ4.
ExpressionAtlasiP48050. baseline and differential.
GenevestigatoriP48050.

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. 1 hit.
PTHR11767:SF13. PTHR11767:SF13. 1 hit.
PfamiPF01007. IRK. 1 hit.
[Graphical view]
PIRSFiPIRSF005465. GIRK_kir. 1 hit.
PRINTSiPR01326. KIR23CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure and characterization of a small-conductance inwardly rectifying potassium channel from human hippocampus."
    Perier F., Radeke C.M., Vandenberg C.A.
    Proc. Natl. Acad. Sci. U.S.A. 91:6240-6244(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Hippocampus.
  2. "Cloning a novel human brain inward rectifier potassium channel and its functional expression in Xenopus oocytes."
    Tang W., Yang X.-C.
    FEBS Lett. 348:239-243(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Cloning and expression of a novel human brain inward rectifier potassium channel."
    Makhina E.N., Kelly A.J., Lopatin A.N., Mercer R.W., Nichols C.G.
    J. Biol. Chem. 269:20468-20474(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Hippocampus.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "The DNA sequence of human chromosome 22."
    Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
    , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
    Nature 402:489-495(1999) [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].
    Tissue: Brain.
  7. "Identification and molecular localization of a pH-sensing domain for the inward rectifier potassium channel HIR."
    Coulter K.L., Perier F., Radeke C.M., Vandenberg C.A.
    Neuron 15:1157-1168(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-117.
  8. "Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome."
    Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A., Rajan S., Derst C., Veh R.W., Daut J.
    Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCNJ2 AND KCNJ12.
  9. "Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1."
    Yan X., Zhou H., Zhang J., Shi C., Xie X., Wu Y., Tian C., Shen Y., Long J.
    J. Mol. Biol. 392:967-976(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 436-445 IN COMPLEX WITH TAX1BP3, INTERACTION WITH TAX1BP3.

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: April 29, 2015
This is version 144 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

External Data

Dasty 3

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 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.