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Q06186

- HBEGF_MOUSE

UniProt

Q06186 - HBEGF_MOUSE

Protein

Proheparin-binding EGF-like growth factor

Gene

Hbegf

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor.

    GO - Molecular functioni

    1. epidermal growth factor receptor binding Source: UniProtKB
    2. growth factor activity Source: UniProtKB
    3. heparin binding Source: UniProtKB

    GO - Biological processi

    1. angiogenesis Source: UniProtKB
    2. blastocyst growth Source: UniProtKB
    3. cell migration Source: UniProtKB
    4. epidermal growth factor receptor signaling pathway Source: MGI
    5. negative regulation of elastin biosynthetic process Source: Ensembl
    6. positive regulation of cell growth Source: Ensembl
    7. positive regulation of keratinocyte migration Source: UniProtKB
    8. positive regulation of protein kinase B signaling Source: Ensembl
    9. positive regulation of smooth muscle cell proliferation Source: UniProtKB
    10. positive regulation of wound healing Source: Ensembl
    11. regulation of heart contraction Source: MGI
    12. wound healing, spreading of epidermal cells Source: UniProtKB

    Keywords - Molecular functioni

    Growth factor

    Keywords - Ligandi

    Heparin-binding

    Enzyme and pathway databases

    ReactomeiREACT_188191. Signaling by ERBB2.
    REACT_188528. GRB2 events in ERBB2 signaling.
    REACT_188574. SHC1 events in ERBB2 signaling.
    REACT_188579. Signaling by ERBB4.
    REACT_188580. SHC1 events in ERBB4 signaling.
    REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198350. EGFR Transactivation by Gastrin.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_203296. PI3K events in ERBB4 signaling.
    REACT_215348. PI3K events in ERBB2 signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Proheparin-binding EGF-like growth factor
    Cleaved into the following chain:
    Heparin-binding EGF-like growth factor
    Short name:
    HB-EGF
    Short name:
    HBEGF
    Gene namesi
    Name:Hbegf
    Synonyms:Dtr, Hegfl
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 18

    Organism-specific databases

    MGIiMGI:96070. Hbegf.

    Subcellular locationi

    Chain Heparin-binding EGF-like growth factor : Secretedextracellular space
    Note: Mature HB-EGF is released into the extracellular space and probably binds to a receptor.

    GO - Cellular componenti

    1. cell surface Source: Ensembl
    2. extracellular region Source: Reactome
    3. extracellular space Source: BHF-UCL
    4. integral component of plasma membrane Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 208185Proheparin-binding EGF-like growth factorPRO_0000302804Add
    BLAST
    Propeptidei24 – 6239By similarityPRO_0000007614Add
    BLAST
    Chaini63 – 14886Heparin-binding EGF-like growth factorPRO_0000007615Add
    BLAST
    Propeptidei149 – 20860C-terminalSequence AnalysisPRO_0000007616Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi85 – 851O-linked (GalNAc...)By similarity
    Disulfide bondi108 ↔ 121PROSITE-ProRule annotation
    Disulfide bondi116 ↔ 132PROSITE-ProRule annotation
    Disulfide bondi134 ↔ 143PROSITE-ProRule annotation

    Post-translational modificationi

    O-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiQ06186.

    PTM databases

    PhosphoSiteiQ06186.

    Miscellaneous databases

    PMAP-CutDBQ06186.

    Expressioni

    Tissue specificityi

    Most abundant in kidney, skeletal muscle, lung, spleen, brain and heart.

    Gene expression databases

    ArrayExpressiQ06186.
    BgeeiQ06186.
    CleanExiMM_HBEGF.
    GenevestigatoriQ06186.

    Interactioni

    Subunit structurei

    Interacts with FBLN1 By similarity. Interacts with EGFR and ERBB4.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000025363.

    Structurei

    3D structure databases

    ProteinModelPortaliQ06186.
    SMRiQ06186. Positions 107-147.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 160137ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini185 – 20824CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei161 – 18424HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini104 – 14441EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG45526.
    HOGENOMiHOG000026782.
    HOVERGENiHBG053952.
    InParanoidiQ06186.
    KOiK08523.
    OMAiYSYDHTT.
    OrthoDBiEOG7VQJGP.
    PhylomeDBiQ06186.
    TreeFamiTF332773.

    Family and domain databases

    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR015497. EGF_rcpt_ligand.
    [Graphical view]
    PANTHERiPTHR10740. PTHR10740. 1 hit.
    PfamiPF00008. EGF. 1 hit.
    [Graphical view]
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    PROSITEiPS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 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.

    Q06186-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKLLPSVMLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGSTNQL    50
    LPTGGDRAQG VQDLEGTDLN LFKVAFSSKP QGLATPSKER NGKKKKKGKG 100
    LGKKRDPCLR KYKDYCIHGE CRYLQEFRTP SCKCLPGYHG HRCHGLTLPV 150
    ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG LLMFRYHRRG GYDLESEEKV 200
    KLGVASSH 208
    Length:208
    Mass (Da):22,808
    Last modified:February 1, 1995 - v1
    Checksum:i7086934E23D25F8E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36027
    , L36024, L36025, L36026 Genomic DNA. Translation: AAC42069.1.
    L07264 mRNA. Translation: AAA37542.1.
    U39192
    , U39189, U39190, U39191 Genomic DNA. Translation: AAC52617.1.
    CCDSiCCDS29153.1.
    PIRiJC1410.
    RefSeqiNP_034545.1. NM_010415.2.
    UniGeneiMm.289681.

    Genome annotation databases

    EnsembliENSMUST00000025363; ENSMUSP00000025363; ENSMUSG00000024486.
    GeneIDi15200.
    KEGGimmu:15200.
    UCSCiuc008enl.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36027
    , L36024 , L36025 , L36026 Genomic DNA. Translation: AAC42069.1 .
    L07264 mRNA. Translation: AAA37542.1 .
    U39192
    , U39189 , U39190 , U39191 Genomic DNA. Translation: AAC52617.1 .
    CCDSi CCDS29153.1.
    PIRi JC1410.
    RefSeqi NP_034545.1. NM_010415.2.
    UniGenei Mm.289681.

    3D structure databases

    ProteinModelPortali Q06186.
    SMRi Q06186. Positions 107-147.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000025363.

    PTM databases

    PhosphoSitei Q06186.

    Proteomic databases

    PRIDEi Q06186.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000025363 ; ENSMUSP00000025363 ; ENSMUSG00000024486 .
    GeneIDi 15200.
    KEGGi mmu:15200.
    UCSCi uc008enl.2. mouse.

    Organism-specific databases

    CTDi 1839.
    MGIi MGI:96070. Hbegf.

    Phylogenomic databases

    eggNOGi NOG45526.
    HOGENOMi HOG000026782.
    HOVERGENi HBG053952.
    InParanoidi Q06186.
    KOi K08523.
    OMAi YSYDHTT.
    OrthoDBi EOG7VQJGP.
    PhylomeDBi Q06186.
    TreeFami TF332773.

    Enzyme and pathway databases

    Reactomei REACT_188191. Signaling by ERBB2.
    REACT_188528. GRB2 events in ERBB2 signaling.
    REACT_188574. SHC1 events in ERBB2 signaling.
    REACT_188579. Signaling by ERBB4.
    REACT_188580. SHC1 events in ERBB4 signaling.
    REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198350. EGFR Transactivation by Gastrin.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_203296. PI3K events in ERBB4 signaling.
    REACT_215348. PI3K events in ERBB2 signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Miscellaneous databases

    NextBioi 287735.
    PMAP-CutDB Q06186.
    PROi Q06186.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q06186.
    Bgeei Q06186.
    CleanExi MM_HBEGF.
    Genevestigatori Q06186.

    Family and domain databases

    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR015497. EGF_rcpt_ligand.
    [Graphical view ]
    PANTHERi PTHR10740. PTHR10740. 1 hit.
    Pfami PF00008. EGF. 1 hit.
    [Graphical view ]
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    PROSITEi PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues."
      Abraham J.A., Damm D., Bajardi A., Miller J., Klagsbrun M., Ezekowitz R.A.B.
      Biochem. Biophys. Res. Commun. 190:125-133(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Macrophage.
    2. "Characterization of the gene encoding murine heparin-binding epidermal growth factor-like growth factor."
      Harding P.A., Brigstock D.R., Shen L., Crissman-Combs M.A., Besner G.E.
      Gene 169:291-292(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/SvJ.

    Entry informationi

    Entry nameiHBEGF_MOUSE
    AccessioniPrimary (citable) accession number: Q06186
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 120 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3