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Q8WWG1

- NRG4_HUMAN

UniProt

Q8WWG1 - NRG4_HUMAN

Protein

Pro-neuregulin-4, membrane-bound isoform

Gene

NRG4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
  1. Functioni

    Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors By similarity.By similarity

    GO - Biological processi

    1. epidermal growth factor receptor signaling pathway Source: Reactome
    2. Fc-epsilon receptor signaling pathway Source: Reactome
    3. fibroblast growth factor receptor signaling pathway Source: Reactome
    4. innate immune response Source: Reactome
    5. neurotrophin TRK receptor signaling pathway Source: Reactome
    6. phosphatidylinositol-mediated signaling Source: Reactome

    Keywords - Molecular functioni

    Growth factor

    Enzyme and pathway databases

    ReactomeiREACT_115596. Signaling by ERBB4.
    REACT_115755. Signaling by ERBB2.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115961. PI3K events in ERBB4 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116005. SHC1 events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_116022. Nuclear signaling by ERBB4.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiQ8WWG1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pro-neuregulin-4, membrane-bound isoform
    Short name:
    Pro-NRG4
    Cleaved into the following chain:
    Neuregulin-4
    Short name:
    NRG-4
    Gene namesi
    Name:NRG4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:29862. NRG4.

    Subcellular locationi

    Chain Pro-neuregulin-4, membrane-bound isoform : Cell membrane By similarity; Single-pass type I membrane protein By similarity
    Note: Does not seem to be active.By similarity

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA142671246.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 115115Pro-neuregulin-4, membrane-bound isoformPRO_0000019485Add
    BLAST
    Chaini1 – 6161Neuregulin-4PRO_0000019486Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi9 ↔ 23PROSITE-ProRule annotation
    Disulfide bondi17 ↔ 34PROSITE-ProRule annotation
    Disulfide bondi36 ↔ 45PROSITE-ProRule annotation
    Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.By similarity
    Extensive glycosylation precedes the proteolytic cleavage.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiQ8WWG1.

    Expressioni

    Gene expression databases

    ArrayExpressiQ8WWG1.
    BgeeiQ8WWG1.
    CleanExiHS_NRG4.
    GenevestigatoriQ8WWG1.

    Organism-specific databases

    HPAiHPA010957.

    Interactioni

    Subunit structurei

    Interacts with ERBB4.By similarity

    Protein-protein interaction databases

    IntActiQ8WWG1. 2 interactions.
    STRINGi9606.ENSP00000378367.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8WWG1.
    SMRiQ8WWG1. Positions 15-46.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 6262ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini84 – 11532CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei63 – 8321Helical; Note=Internal signal sequenceSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 4642EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization By similarity.By similarity
    ERBB receptor binding is elicited entirely by the EGF-like domain.By similarity

    Sequence similaritiesi

    Belongs to the neuregulin family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG42904.
    HOGENOMiHOG000113853.
    HOVERGENiHBG006533.
    InParanoidiQ8WWG1.
    KOiK05458.
    OMAiPMENKLA.
    OrthoDBiEOG73806M.
    PhylomeDBiQ8WWG1.

    Family and domain databases

    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    [Graphical view]
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    PROSITEiPS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8WWG1-1 [UniParc]FASTAAdd to Basket

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    MPTDHEEPCG PSHKSFCLNG GLCYVIPTIP SPFCRCVENY TGARCEEVFL    50
    PGSSIQTKSN LFEAFVALAV LVTLIIGAFY FLCRKGHFQR ASSVQYDINL 100
    VETSSTSAHH SHEQH 115
    Length:115
    Mass (Da):12,722
    Last modified:March 1, 2002 - v1
    Checksum:i72F962E2D0F37AC3
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC087456 Genomic DNA. No translation available.
    CH471136 Genomic DNA. Translation: EAW99227.1.
    BC017568 mRNA. Translation: AAH17568.1.
    CCDSiCCDS10288.1.
    RefSeqiNP_612640.1. NM_138573.3.
    UniGeneiHs.732438.

    Genome annotation databases

    EnsembliENST00000394907; ENSP00000378367; ENSG00000169752.
    ENST00000566417; ENSP00000457335; ENSG00000169752.
    GeneIDi145957.
    KEGGihsa:145957.
    UCSCiuc002bbo.3. human.

    Polymorphism databases

    DMDMi28201832.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC087456 Genomic DNA. No translation available.
    CH471136 Genomic DNA. Translation: EAW99227.1 .
    BC017568 mRNA. Translation: AAH17568.1 .
    CCDSi CCDS10288.1.
    RefSeqi NP_612640.1. NM_138573.3.
    UniGenei Hs.732438.

    3D structure databases

    ProteinModelPortali Q8WWG1.
    SMRi Q8WWG1. Positions 15-46.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q8WWG1. 2 interactions.
    STRINGi 9606.ENSP00000378367.

    Polymorphism databases

    DMDMi 28201832.

    Proteomic databases

    PRIDEi Q8WWG1.

    Protocols and materials databases

    DNASUi 145957.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000394907 ; ENSP00000378367 ; ENSG00000169752 .
    ENST00000566417 ; ENSP00000457335 ; ENSG00000169752 .
    GeneIDi 145957.
    KEGGi hsa:145957.
    UCSCi uc002bbo.3. human.

    Organism-specific databases

    CTDi 145957.
    GeneCardsi GC15M076233.
    HGNCi HGNC:29862. NRG4.
    HPAi HPA010957.
    MIMi 610894. gene.
    neXtProti NX_Q8WWG1.
    PharmGKBi PA142671246.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42904.
    HOGENOMi HOG000113853.
    HOVERGENi HBG006533.
    InParanoidi Q8WWG1.
    KOi K05458.
    OMAi PMENKLA.
    OrthoDBi EOG73806M.
    PhylomeDBi Q8WWG1.

    Enzyme and pathway databases

    Reactomei REACT_115596. Signaling by ERBB4.
    REACT_115755. Signaling by ERBB2.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115961. PI3K events in ERBB4 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116005. SHC1 events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_116022. Nuclear signaling by ERBB4.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki Q8WWG1.

    Miscellaneous databases

    GeneWikii NRG4.
    GenomeRNAii 145957.
    NextBioi 85235.
    PROi Q8WWG1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8WWG1.
    Bgeei Q8WWG1.
    CleanExi HS_NRG4.
    Genevestigatori Q8WWG1.

    Family and domain databases

    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    [Graphical view ]
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    PROSITEi PS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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: Liver.

    Entry informationi

    Entry nameiNRG4_HUMAN
    AccessioniPrimary (citable) accession number: Q8WWG1
    Secondary accession number(s): A6NIE8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 2003
    Last sequence update: March 1, 2002
    Last modified: October 1, 2014
    This is version 110 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: 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