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P48050

- KCNJ4_HUMAN

UniProt

P48050 - KCNJ4_HUMAN

Protein

Inward rectifier potassium channel 4

Gene

KCNJ4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    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
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. potassium ion transmembrane transport Source: GOC
    2. potassium ion transport Source: ProtInc
    3. synaptic transmission Source: Reactome

    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: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:6265. KCNJ4.

    Subcellular locationi

    Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane By similarity; Multi-pass membrane protein By similarity. Cytoplasmic vesicle membrane By similarity
    Note: TAX1BP3 binding promotes dissociation of KCNJ4 from LIN7 famaly members and KCNJ4 internalization.By similarity

    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

    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.

    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

    ArrayExpressiP48050.
    BgeeiP48050.
    CleanExiHS_KCNJ4.
    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:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3GJ9X-ray2.80C/D436-445[»]
    ProteinModelPortaliP48050.
    SMRiP48050. Positions 18-357.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP48050.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 5555CytoplasmicBy similarityAdd
    BLAST
    Topological domaini81 – 12040ExtracellularBy similarityAdd
    BLAST
    Topological domaini140 – 1489ExtracellularBy similarity
    Topological domaini171 – 445275CytoplasmicBy similarityAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei121 – 13212Helical; Pore-forming; Name=H5By similarityAdd
    BLAST
    Intramembranei133 – 1397Pore-formingBy similarity

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei56 – 8025Helical; Name=M1By similarityAdd
    BLAST
    Transmembranei149 – 17022Helical; Name=M2By similarityAdd
    BLAST

    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.
    HOGENOMiHOG000237325.
    HOVERGENiHBG006178.
    InParanoidiP48050.
    KOiK04998.
    OMAiKPYMTEE.
    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

    MHGHSRNGQA HVPRRKRRNR FVKKNGQCNV YFANLSNKSQ RYMADIFTTC    50
    VDTRWRYMLM IFSAAFLVSW LFFGLLFWCI AFFHGDLEAS PGVPAAGGPA 100
    AGGGGAAPVA PKPCIMHVNG FLGAFLFSVE TQTTIGYGFR CVTEECPLAV 150
    IAVVVQSIVG CVIDSFMIGT IMAKMARPKK RAQTLLFSHH AVISVRDGKL 200
    CLMWRVGNLR KSHIVEAHVR AQLIKPYMTQ EGEYLPLDQR DLNVGYDIGL 250
    DRIFLVSPII IVHEIDEDSP LYGMGKEELE SEDFEIVVIL EGMVEATAMT 300
    TQARSSYLAS EILWGHRFEP VVFEEKSHYK VDYSRFHKTY EVAGTPCCSA 350
    RELQESKITV LPAPPPPPSA FCYENELALM SQEEEEMEEE AAAAAAVAAG 400
    LGLEAGSKEE AGIIRMLEFG SHLDLERMQA SLPLDNISYR RESAI 445
    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:
    EMBL
    GenBank
    DDBJ
    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 databases

    DMDMi1352483.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS13971.1.
    PIRi A54852.
    I38521.
    RefSeqi NP_004972.1. NM_004981.1.
    NP_690607.1. NM_152868.2.
    UniGenei Hs.32505.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3GJ9 X-ray 2.80 C/D 436-445 [» ]
    ProteinModelPortali P48050.
    SMRi P48050. Positions 18-357.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109963. 11 interactions.
    IntActi P48050. 3 interactions.
    MINTi MINT-159020.
    STRINGi 9606.ENSP00000306497.

    Chemistry

    ChEMBLi CHEMBL2146347.
    GuidetoPHARMACOLOGYi 432.

    PTM databases

    PhosphoSitei P48050.

    Polymorphism databases

    DMDMi 1352483.

    Proteomic databases

    PaxDbi P48050.
    PRIDEi P48050.

    Protocols and materials databases

    DNASUi 3761.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000303592 ; ENSP00000306497 ; ENSG00000168135 .
    GeneIDi 3761.
    KEGGi hsa:3761.
    UCSCi uc003avs.1. human.

    Organism-specific databases

    CTDi 3761.
    GeneCardsi GC22M038822.
    H-InvDB HIX0175381.
    HGNCi HGNC:6265. KCNJ4.
    HPAi HPA003270.
    MIMi 600504. gene.
    neXtProti NX_P48050.
    PharmGKBi PA30048.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG72812.
    HOGENOMi HOG000237325.
    HOVERGENi HBG006178.
    InParanoidi P48050.
    KOi K04998.
    OMAi KPYMTEE.
    OrthoDBi EOG7XPZ5K.
    PhylomeDBi P48050.
    TreeFami TF313676.

    Enzyme and pathway databases

    Reactomei REACT_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

    EvolutionaryTracei P48050.
    GeneWikii KCNJ4.
    GenomeRNAii 3761.
    NextBioi 14745.
    PROi P48050.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P48050.
    Bgeei P48050.
    CleanExi HS_KCNJ4.
    Genevestigatori P48050.

    Family and domain databases

    Gene3Di 2.60.40.1400. 1 hit.
    InterProi IPR014756. 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 ]
    PANTHERi PTHR11767. PTHR11767. 1 hit.
    PTHR11767:SF13. PTHR11767:SF13. 1 hit.
    Pfami PF01007. IRK. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF005465. GIRK_kir. 1 hit.
    PRINTSi PR01326. KIR23CHANNEL.
    PR01320. KIRCHANNEL.
    SUPFAMi SSF81296. SSF81296. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 139 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