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   24-JAN-2024, entry version 177.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   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 mouse
RT   cDNA clones, protein domain conservation across species, and transcript
RT   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., Besner G.E.;
RT   "Characterization of the gene encoding murine heparin-binding epidermal
RT   growth factor-like growth factor.";
RL   Gene 169:291-292(1996).
CC   -!- FUNCTION: Growth factor that mediates its effects via EGFR, ERBB2 and
CC       ERBB4. Required for normal cardiac valve formation and normal heart
CC       function. Promotes smooth muscle cell proliferation. May be involved in
CC       macrophage-mediated cellular proliferation. It is mitogenic for
CC       fibroblasts, but not endothelial cells. It is able to bind EGF
CC       receptor/EGFR with higher affinity than EGF itself and is a far more
CC       potent mitogen for smooth muscle cells than EGF. Also acts as a
CC       diphtheria toxin receptor.
CC   -!- SUBUNIT: Interacts with FBLN1 (By similarity). Interacts with EGFR and
CC       ERBB4. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Heparin-binding EGF-like growth factor]:
CC       Secreted, extracellular space. Note=Mature HB-EGF is released into the
CC       extracellular space and probably binds to a receptor.
CC   -!- SUBCELLULAR LOCATION: [Proheparin-binding EGF-like growth factor]: Cell
CC       membrane; Single-pass type I membrane protein.
CC   -!- TISSUE SPECIFICITY: Most abundant in kidney, skeletal muscle, lung,
CC       spleen, brain and heart.
CC   -!- PTM: O-glycosylated. {ECO:0000250}.
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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   AlphaFoldDB; Q06186; -.
DR   SMR; Q06186; -.
DR   STRING; 10090.ENSMUSP00000025363; -.
DR   GlyCosmos; Q06186; 1 site, No reported glycans.
DR   GlyGen; Q06186; 1 site.
DR   iPTMnet; Q06186; -.
DR   PhosphoSitePlus; Q06186; -.
DR   PaxDb; 10090-ENSMUSP00000025363; -.
DR   PeptideAtlas; Q06186; -.
DR   ProteomicsDB; 271492; -.
DR   Antibodypedia; 26845; 528 antibodies from 32 providers.
DR   DNASU; 15200; -.
DR   Ensembl; ENSMUST00000025363.7; ENSMUSP00000025363.6; ENSMUSG00000024486.7.
DR   GeneID; 15200; -.
DR   KEGG; mmu:15200; -.
DR   UCSC; uc008enl.2; mouse.
DR   AGR; MGI:96070; -.
DR   CTD; 1839; -.
DR   MGI; MGI:96070; Hbegf.
DR   VEuPathDB; HostDB:ENSMUSG00000024486; -.
DR   eggNOG; ENOG502S0ZP; Eukaryota.
DR   GeneTree; ENSGT00940000156901; -.
DR   HOGENOM; CLU_096527_2_0_1; -.
DR   InParanoid; Q06186; -.
DR   OMA; YSYDHTT; -.
DR   OrthoDB; 5322886at2759; -.
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   Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR   BioGRID-ORCS; 15200; 3 hits in 79 CRISPR screens.
DR   ChiTaRS; Hbegf; mouse.
DR   PRO; PR:Q06186; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q06186; Protein.
DR   Bgee; ENSMUSG00000024486; Expressed in tarsal region and 227 other cell types or tissues.
DR   ExpressionAtlas; Q06186; baseline and differential.
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:0005886; C: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:0048018; F:receptor ligand activity; IDA:MGI.
DR   GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IDA:MGI.
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:0038134; P:ERBB2-EGFR signaling pathway; IMP:MGI.
DR   GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IMP: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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   PANTHER; PTHR10740:SF4; PROHEPARIN-BINDING EGF-LIKE GROWTH FACTOR; 1.
DR   PANTHER; PTHR10740; TRANSFORMING GROWTH FACTOR ALPHA; 1.
DR   Pfam; PF00008; EGF; 1.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   Genevisible; Q06186; MM.
PE   2: Evidence at transcript level;
KW   Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Growth factor; Heparin-binding; Membrane; Reference proteome; Secreted;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..208
FT                   /note="Proheparin-binding EGF-like growth factor"
FT                   /id="PRO_0000302804"
FT   PROPEP          24..62
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000007614"
FT   CHAIN           63..148
FT                   /note="Heparin-binding EGF-like growth factor"
FT                   /id="PRO_0000007615"
FT   PROPEP          149..208
FT                   /note="C-terminal"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000007616"
FT   TOPO_DOM        24..160
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        161..184
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        185..208
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          104..144
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REGION          35..57
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          80..104
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        39..55
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        90..104
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        85
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000250"
FT   DISULFID        108..121
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        116..132
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        134..143
FT                   /evidence="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
//