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Database: UniProt
Entry: Q06186
LinkDB: Q06186
Original site: Q06186 
ID   HBEGF_MOUSE             Reviewed;         208 AA.
AC   Q06186;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   13-FEB-2019, entry version 151.
DE   RecName: Full=Proheparin-binding EGF-like growth factor;
DE   Contains:
DE     RecName: Full=Heparin-binding EGF-like growth factor;
DE              Short=HB-EGF;
DE              Short=HBEGF;
DE   Flags: Precursor;
GN   Name=Hbegf; Synonyms=Dtr, Hegfl;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Macrophage;
RX   PubMed=7678488; DOI=10.1006/bbrc.1993.1020;
RA   Abraham J.A., Damm D., Bajardi A., Miller J., Klagsbrun M.,
RA   Ezekowitz R.A.B.;
RT   "Heparin-binding EGF-like growth factor: characterization of rat and
RT   mouse cDNA clones, protein domain conservation across species, and
RT   transcript expression in tissues.";
RL   Biochem. Biophys. Res. Commun. 190:125-133(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ;
RX   PubMed=8647467; DOI=10.1016/0378-1119(95)00861-6;
RA   Harding P.A., Brigstock D.R., Shen L., Crissman-Combs M.A.,
RA   Besner G.E.;
RT   "Characterization of the gene encoding murine heparin-binding
RT   epidermal growth factor-like growth factor.";
RL   Gene 169:291-292(1996).
CC   -!- FUNCTION: Growth factor that mediates its effects via EGFR, ERBB2
CC       and ERBB4. Required for normal cardiac valve formation and normal
CC       heart function. Promotes smooth muscle cell proliferation. May be
CC       involved in macrophage-mediated cellular proliferation. It is
CC       mitogenic for fibroblasts, but not endothelial cells. It is able
CC       to bind EGF receptor/EGFR with higher affinity than EGF itself and
CC       is a far more potent mitogen for smooth muscle cells than EGF.
CC       Also acts as a diphtheria toxin receptor.
CC   -!- SUBUNIT: Interacts with FBLN1 (By similarity). Interacts with EGFR
CC       and ERBB4. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Heparin-binding EGF-like growth factor:
CC       Secreted, extracellular space. Note=Mature HB-EGF is released into
CC       the extracellular space and probably binds to a receptor.
CC   -!- SUBCELLULAR LOCATION: Proheparin-binding EGF-like growth factor:
CC       Cell membrane; Single-pass type I membrane protein.
CC   -!- TISSUE SPECIFICITY: Most abundant in kidney, skeletal muscle,
CC       lung, spleen, brain and heart.
CC   -!- PTM: O-glycosylated. {ECO:0000250}.
DR   EMBL; L36027; AAC42069.1; -; Genomic_DNA.
DR   EMBL; L36024; AAC42069.1; JOINED; Genomic_DNA.
DR   EMBL; L36025; AAC42069.1; JOINED; Genomic_DNA.
DR   EMBL; L36026; AAC42069.1; JOINED; Genomic_DNA.
DR   EMBL; L07264; AAA37542.1; -; mRNA.
DR   EMBL; U39192; AAC52617.1; -; Genomic_DNA.
DR   EMBL; U39189; AAC52617.1; JOINED; Genomic_DNA.
DR   EMBL; U39190; AAC52617.1; JOINED; Genomic_DNA.
DR   EMBL; U39191; AAC52617.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS29153.1; -.
DR   PIR; JC1410; JC1410.
DR   RefSeq; NP_034545.1; NM_010415.2.
DR   UniGene; Mm.289681; -.
DR   ProteinModelPortal; Q06186; -.
DR   SMR; Q06186; -.
DR   STRING; 10090.ENSMUSP00000025363; -.
DR   iPTMnet; Q06186; -.
DR   PhosphoSitePlus; Q06186; -.
DR   PaxDb; Q06186; -.
DR   PeptideAtlas; Q06186; -.
DR   PRIDE; Q06186; -.
DR   Ensembl; ENSMUST00000025363; ENSMUSP00000025363; ENSMUSG00000024486.
DR   GeneID; 15200; -.
DR   KEGG; mmu:15200; -.
DR   UCSC; uc008enl.2; mouse.
DR   CTD; 1839; -.
DR   MGI; MGI:96070; Hbegf.
DR   eggNOG; ENOG410IMHM; Eukaryota.
DR   eggNOG; ENOG41120D3; LUCA.
DR   GeneTree; ENSGT00940000156901; -.
DR   HOGENOM; HOG000026782; -.
DR   HOVERGEN; HBG053952; -.
DR   InParanoid; Q06186; -.
DR   KO; K08523; -.
DR   OMA; YSYDHTT; -.
DR   OrthoDB; 1348306at2759; -.
DR   PhylomeDB; Q06186; -.
DR   TreeFam; TF332773; -.
DR   Reactome; R-MMU-1227986; Signaling by ERBB2.
DR   Reactome; R-MMU-1236394; Signaling by ERBB4.
DR   Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR   Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR   Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-MMU-177929; Signaling by EGFR.
DR   Reactome; R-MMU-179812; GRB2 events in EGFR signaling.
DR   Reactome; R-MMU-180292; GAB1 signalosome.
DR   Reactome; R-MMU-180336; SHC1 events in EGFR signaling.
DR   Reactome; R-MMU-182971; EGFR downregulation.
DR   Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling.
DR   Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-MMU-212718; EGFR interacts with phospholipase C-gamma.
DR   Reactome; R-MMU-2179392; EGFR Transactivation by Gastrin.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-MMU-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-MMU-8857538; PTK6 promotes HIF1A stabilization.
DR   Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR   PMAP-CutDB; Q06186; -.
DR   PRO; PR:Q06186; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   Bgee; ENSMUSG00000024486; Expressed in 247 organ(s), highest expression level in decidua.
DR   ExpressionAtlas; Q06186; baseline and differential.
DR   Genevisible; Q06186; MM.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
DR   GO; GO:0008083; F:growth factor activity; IDA:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; NAS:UniProtKB.
DR   GO; GO:0001832; P:blastocyst growth; TAS:UniProtKB.
DR   GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR   GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:MGI.
DR   GO; GO:0051545; P:negative regulation of elastin biosynthetic process; ISO:MGI.
DR   GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0051549; P:positive regulation of keratinocyte migration; IMP:UniProtKB.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:UniProtKB.
DR   GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR   GO; GO:0008016; P:regulation of heart contraction; IMP:MGI.
DR   GO; GO:0035313; P:wound healing, spreading of epidermal cells; IMP:UniProtKB.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR015497; EGF_rcpt_ligand.
DR   PANTHER; PTHR10740; PTHR10740; 1.
DR   Pfam; PF00008; EGF; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Complete proteome; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Growth factor; Heparin-binding; Membrane;
KW   Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    208       Proheparin-binding EGF-like growth
FT                                factor.
FT                                /FTId=PRO_0000302804.
FT   PROPEP       24     62       {ECO:0000250}.
FT                                /FTId=PRO_0000007614.
FT   CHAIN        63    148       Heparin-binding EGF-like growth factor.
FT                                /FTId=PRO_0000007615.
FT   PROPEP      149    208       C-terminal. {ECO:0000255}.
FT                                /FTId=PRO_0000007616.
FT   TOPO_DOM     24    160       Extracellular. {ECO:0000255}.
FT   TRANSMEM    161    184       Helical. {ECO:0000255}.
FT   TOPO_DOM    185    208       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      104    144       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   CARBOHYD     85     85       O-linked (GalNAc...) threonine.
FT                                {ECO:0000250}.
FT   DISULFID    108    121       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    116    132       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    134    143       {ECO:0000255|PROSITE-ProRule:PRU00076}.
SQ   SEQUENCE   208 AA;  22808 MW;  7086934E23D25F8E CRC64;
     MKLLPSVMLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGSTNQL LPTGGDRAQG
     VQDLEGTDLN LFKVAFSSKP QGLATPSKER NGKKKKKGKG LGKKRDPCLR KYKDYCIHGE
     CRYLQEFRTP SCKCLPGYHG HRCHGLTLPV ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG
     LLMFRYHRRG GYDLESEEKV KLGVASSH
//
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