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P22459

- KCNA4_HUMAN

UniProt

P22459 - KCNA4_HUMAN

Protein

Potassium voltage-gated channel subfamily A member 4

Gene

KCNA4

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 2 (30 Nov 2010)
      Previous versions | rss
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    Functioni

    Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.

    GO - Molecular functioni

    1. potassium ion binding Source: InterPro
    2. protein binding Source: UniProtKB
    3. voltage-gated potassium channel activity Source: ProtInc

    GO - Biological processi

    1. potassium ion transport Source: ProtInc
    2. protein homooligomerization Source: InterPro
    3. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel, Potassium channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_75770. Voltage gated Potassium channels.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Potassium voltage-gated channel subfamily A member 4
    Alternative name(s):
    HPCN2
    Voltage-gated K(+) channel HuKII
    Voltage-gated potassium channel HBK4
    Voltage-gated potassium channel HK1
    Voltage-gated potassium channel subunit Kv1.4
    Gene namesi
    Name:KCNA4
    Synonyms:KCNA4L
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:6222. KCNA4.

    Subcellular locationi

    GO - Cellular componenti

    1. plasma membrane Source: Reactome
    2. voltage-gated potassium channel complex Source: ProtInc

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA207.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 653653Potassium voltage-gated channel subfamily A member 4PRO_0000053981Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei90 – 901Phosphoserine; by PKASequence Analysis
    Glycosylationi181 – 1811N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi352 – 3521N-linked (GlcNAc...)Sequence Analysis
    Modified residuei599 – 5991Phosphoserine; by PKASequence Analysis

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP22459.
    PRIDEiP22459.

    PTM databases

    PhosphoSiteiP22459.

    Expressioni

    Gene expression databases

    BgeeiP22459.
    CleanExiHS_KCNA4.
    GenevestigatoriP22459.

    Organism-specific databases

    HPAiCAB001977.
    HPA016422.

    Interactioni

    Subunit structurei

    Heterotetramer of potassium channel proteins. Binds PDZ domains of DLG1, DLG2 and DLG4. Interacts with SIGMAR1 By similarity. Part of a complex containing KCNA1, KCNAB1 and LGI1 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Dlg3Q629364EBI-631235,EBI-349596From a different organism.
    DLG4P783522EBI-631235,EBI-80389
    Dlg4P310163EBI-631235,EBI-375655From a different organism.

    Protein-protein interaction databases

    BioGridi109942. 16 interactions.
    IntActiP22459. 6 interactions.
    MINTiMINT-200816.
    STRINGi9606.ENSP00000328511.

    Structurei

    3D structure databases

    ProteinModelPortaliP22459.
    SMRiP22459. Positions 1-75, 175-571.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei308 – 32619Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei371 – 39222Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei404 – 42421Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei443 – 46119Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei478 – 49720Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei539 – 56123Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi524 – 5296Selectivity filterBy similarity
    Motifi651 – 6533PDZ-bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi62 – 654Poly-His
    Compositional biasi123 – 13715Poly-GluAdd
    BLAST
    Compositional biasi162 – 1654Poly-Gly
    Compositional biasi433 – 4364Poly-Gln

    Domaini

    The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
    The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1226.
    HOGENOMiHOG000231015.
    HOVERGENiHBG052230.
    InParanoidiP22459.
    KOiK04877.
    OMAiKKAHHRQ.
    OrthoDBiEOG7M0NRD.
    PhylomeDBiP22459.
    TreeFamiTF313103.

    Family and domain databases

    Gene3Di1.20.120.350. 1 hit.
    1.20.5.600. 1 hit.
    3.30.710.10. 1 hit.
    InterProiIPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR003091. K_chnl.
    IPR003968. K_chnl_volt-dep_Kv.
    IPR003972. K_chnl_volt-dep_Kv1.
    IPR020467. K_chnl_volt-dep_Kv1.4.
    IPR012897. K_chnl_volt-dep_Kv1.4_TID.
    IPR003131. T1-type_BTB.
    IPR028325. VG_K_chnl.
    [Graphical view]
    PANTHERiPTHR11537. PTHR11537. 1 hit.
    PfamiPF02214. BTB_2. 1 hit.
    PF00520. Ion_trans. 1 hit.
    PF07941. K_channel_TID. 1 hit.
    [Graphical view]
    PRINTSiPR00169. KCHANNEL.
    PR01511. KV14CHANNEL.
    PR01491. KVCHANNEL.
    PR01496. SHAKERCHANEL.
    SMARTiSM00225. BTB. 1 hit.
    [Graphical view]
    SUPFAMiSSF54695. SSF54695. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P22459-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA    50
    VEGSGGSGGG SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS 100
    SFPHCSDLMP SGSEEKILRE LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE 150
    CSYTDLLPQD EGGGGYSSVR YSDCCERVVI NVSGLRFETQ MKTLAQFPET 200
    LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR LKRPVNVPFD 250
    IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP 300
    ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL 350
    LNDTSAPHLE NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF 400
    KNIMNIIDIV SILPYFITLG TDLAQQQGGG NGQQQQAMSF AILRIIRLVR 450
    VFRIFKLSRH SKGLQILGHT LRASMRELGL LIFFLFIGVI LFSSAVYFAE 500
    ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV GSLCAIAGVL 550
    TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS 600
    TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE 650
    TDV 653
    Length:653
    Mass (Da):73,257
    Last modified:November 30, 2010 - v2
    Checksum:i5E511DB704CCA013
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti38 – 381A → R in AAA60034. (PubMed:2263489)Curated
    Sequence conflicti42 – 421A → R in AAA60034. (PubMed:2263489)Curated
    Sequence conflicti84 – 885RRRRQ → EEEAT in AAA60034. (PubMed:2263489)Curated
    Sequence conflicti304 – 3041S → D in AAA60034. (PubMed:2263489)Curated
    Sequence conflicti542 – 5421S → V in AAA60034. (PubMed:2263489)Curated
    Sequence conflicti631 – 6311G → A in AAA60034. (PubMed:2263489)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55514 mRNA. Translation: AAA60034.1.
    M60450 mRNA. Translation: AAA61275.1.
    L02751 mRNA. Translation: AAA36140.1.
    AC124657 Genomic DNA. No translation available.
    CCDSiCCDS41629.1.
    PIRiA39922.
    RefSeqiNP_002224.1. NM_002233.3.
    UniGeneiHs.592002.

    Genome annotation databases

    EnsembliENST00000328224; ENSP00000328511; ENSG00000182255.
    GeneIDi3739.
    KEGGihsa:3739.
    UCSCiuc001msk.3. human.

    Polymorphism databases

    DMDMi313104127.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55514 mRNA. Translation: AAA60034.1 .
    M60450 mRNA. Translation: AAA61275.1 .
    L02751 mRNA. Translation: AAA36140.1 .
    AC124657 Genomic DNA. No translation available.
    CCDSi CCDS41629.1.
    PIRi A39922.
    RefSeqi NP_002224.1. NM_002233.3.
    UniGenei Hs.592002.

    3D structure databases

    ProteinModelPortali P22459.
    SMRi P22459. Positions 1-75, 175-571.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109942. 16 interactions.
    IntActi P22459. 6 interactions.
    MINTi MINT-200816.
    STRINGi 9606.ENSP00000328511.

    Chemistry

    BindingDBi P22459.
    ChEMBLi CHEMBL2362996.
    GuidetoPHARMACOLOGYi 541.

    PTM databases

    PhosphoSitei P22459.

    Polymorphism databases

    DMDMi 313104127.

    Proteomic databases

    PaxDbi P22459.
    PRIDEi P22459.

    Protocols and materials databases

    DNASUi 3739.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000328224 ; ENSP00000328511 ; ENSG00000182255 .
    GeneIDi 3739.
    KEGGi hsa:3739.
    UCSCi uc001msk.3. human.

    Organism-specific databases

    CTDi 3739.
    GeneCardsi GC11M030031.
    H-InvDB HIX0036152.
    HGNCi HGNC:6222. KCNA4.
    HPAi CAB001977.
    HPA016422.
    MIMi 176266. gene.
    neXtProti NX_P22459.
    PharmGKBi PA207.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1226.
    HOGENOMi HOG000231015.
    HOVERGENi HBG052230.
    InParanoidi P22459.
    KOi K04877.
    OMAi KKAHHRQ.
    OrthoDBi EOG7M0NRD.
    PhylomeDBi P22459.
    TreeFami TF313103.

    Enzyme and pathway databases

    Reactomei REACT_75770. Voltage gated Potassium channels.

    Miscellaneous databases

    GeneWikii KCNA4.
    GenomeRNAii 3739.
    NextBioi 14635.
    PROi P22459.
    SOURCEi Search...

    Gene expression databases

    Bgeei P22459.
    CleanExi HS_KCNA4.
    Genevestigatori P22459.

    Family and domain databases

    Gene3Di 1.20.120.350. 1 hit.
    1.20.5.600. 1 hit.
    3.30.710.10. 1 hit.
    InterProi IPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR003091. K_chnl.
    IPR003968. K_chnl_volt-dep_Kv.
    IPR003972. K_chnl_volt-dep_Kv1.
    IPR020467. K_chnl_volt-dep_Kv1.4.
    IPR012897. K_chnl_volt-dep_Kv1.4_TID.
    IPR003131. T1-type_BTB.
    IPR028325. VG_K_chnl.
    [Graphical view ]
    PANTHERi PTHR11537. PTHR11537. 1 hit.
    Pfami PF02214. BTB_2. 1 hit.
    PF00520. Ion_trans. 1 hit.
    PF07941. K_channel_TID. 1 hit.
    [Graphical view ]
    PRINTSi PR00169. KCHANNEL.
    PR01511. KV14CHANNEL.
    PR01491. KVCHANNEL.
    PR01496. SHAKERCHANEL.
    SMARTi SM00225. BTB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54695. SSF54695. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4."
      Philipson L.H., Schaefer K., Lamendola J., Bell G.I., Steiner D.F.
      Nucleic Acids Res. 18:7160-7160(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Skeletal muscle.
    2. "Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle."
      Tamkun M.M., Knoth K.M., Walbridge J.A., Kroemer H., Roden D.M., Glover D.M.
      FASEB J. 5:331-337(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Heart.
    3. "Human potassium channel genes: molecular cloning and functional expression."
      Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K.
      Mol. Cell. Neurosci. 1:214-223(1990)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "NMR structure of inactivation gates from mammalian voltage-dependent potassium channels."
      Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R., Ruppersberg J.P., Kalbitzer H.R.
      Nature 385:272-275(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-37.

    Entry informationi

    Entry nameiKCNA4_HUMAN
    AccessioniPrimary (citable) accession number: P22459
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: November 30, 2010
    Last modified: October 1, 2014
    This is version 139 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3