ID   E1BIN8_BOVIN            Unreviewed;       208 AA.
AC   E1BIN8;
DT   02-NOV-2010, integrated into UniProtKB/TrEMBL.
DT   02-NOV-2010, sequence version 1.
DT   27-MAR-2024, entry version 84.
DE   RecName: Full=Proheparin-binding EGF-like growth factor {ECO:0000256|ARBA:ARBA00040098};
GN   Name=HBEGF {ECO:0000313|Ensembl:ENSBTAP00000029015.3,
GN   ECO:0000313|VGNC:VGNC:29765};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913 {ECO:0000313|Ensembl:ENSBTAP00000029015.3, ECO:0000313|Proteomes:UP000009136};
RN   [1] {ECO:0000313|Ensembl:ENSBTAP00000029015.3, ECO:0000313|Proteomes:UP000009136}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000029015.3,
RC   ECO:0000313|Proteomes:UP000009136};
RA   Rosen B.D., Bickhart D.M., Koren S., Schnabel R.D., Hall R., Zimin A.,
RA   Dreischer C., Schultheiss S., Schroeder S.G., Elsik C.G., Couldrey C.,
RA   Liu G.E., Van Tassell C.P., Phillippy A.M., Smith T.P.L., Medrano J.F.;
RT   "ARS-UCD1.2.";
RL   Submitted (MAR-2018) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|Ensembl:ENSBTAP00000029015.3}
RP   IDENTIFICATION.
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000029015.3};
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
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. {ECO:0000256|ARBA:ARBA00037587}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-
CC       pass type I membrane protein {ECO:0000256|ARBA:ARBA00004479}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00076}.
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DR   RefSeq; NP_001137562.1; NM_001144090.1.
DR   AlphaFoldDB; E1BIN8; -.
DR   SMR; E1BIN8; -.
DR   STRING; 9913.ENSBTAP00000029015; -.
DR   PaxDb; 9913-ENSBTAP00000029015; -.
DR   Ensembl; ENSBTAT00000029015.4; ENSBTAP00000029015.3; ENSBTAG00000021766.4.
DR   GeneID; 522921; -.
DR   KEGG; bta:522921; -.
DR   CTD; 1839; -.
DR   VEuPathDB; HostDB:ENSBTAG00000021766; -.
DR   VGNC; VGNC:29765; HBEGF.
DR   eggNOG; ENOG502S0ZP; Eukaryota.
DR   GeneTree; ENSGT00940000156901; -.
DR   HOGENOM; CLU_096527_2_0_1; -.
DR   InParanoid; E1BIN8; -.
DR   OMA; YSYDHTT; -.
DR   OrthoDB; 5322886at2759; -.
DR   TreeFam; TF332773; -.
DR   Reactome; R-BTA-1227986; Signaling by ERBB2.
DR   Reactome; R-BTA-1236394; Signaling by ERBB4.
DR   Reactome; R-BTA-1250196; SHC1 events in ERBB2 signaling.
DR   Reactome; R-BTA-1250342; PI3K events in ERBB4 signaling.
DR   Reactome; R-BTA-1250347; SHC1 events in ERBB4 signaling.
DR   Reactome; R-BTA-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-BTA-177929; Signaling by EGFR.
DR   Reactome; R-BTA-179812; GRB2 events in EGFR signaling.
DR   Reactome; R-BTA-180292; GAB1 signalosome.
DR   Reactome; R-BTA-180336; SHC1 events in EGFR signaling.
DR   Reactome; R-BTA-182971; EGFR downregulation.
DR   Reactome; R-BTA-1963640; GRB2 events in ERBB2 signaling.
DR   Reactome; R-BTA-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-BTA-212718; EGFR interacts with phospholipase C-gamma.
DR   Reactome; R-BTA-2179392; EGFR Transactivation by Gastrin.
DR   Reactome; R-BTA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-BTA-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-BTA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-BTA-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-BTA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-BTA-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-BTA-8857538; PTK6 promotes HIF1A stabilization.
DR   Reactome; R-BTA-8863795; Downregulation of ERBB2 signaling.
DR   Reactome; R-BTA-9009391; Extra-nuclear estrogen signaling.
DR   Proteomes; UP000009136; Chromosome 7.
DR   Bgee; ENSBTAG00000021766; Expressed in oocyte and 104 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR   GO; GO:0005154; F:epidermal growth factor receptor binding; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR   GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR   GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IEA:Ensembl.
DR   GO; GO:0060326; P:cell chemotaxis; IEA:Ensembl.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0038134; P:ERBB2-EGFR signaling pathway; IEA:Ensembl.
DR   GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IEA:Ensembl.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR   GO; GO:0051549; P:positive regulation of keratinocyte migration; IEA:Ensembl.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0090303; P:positive regulation of wound healing; IEA:Ensembl.
DR   GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl.
DR   GO; GO:0035313; P:wound healing, spreading of epidermal cells; IEA:Ensembl.
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   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
PE   4: Predicted;
KW   Disulfide bond {ECO:0000256|PROSITE-ProRule:PRU00076};
KW   EGF-like domain {ECO:0000256|PROSITE-ProRule:PRU00076};
KW   Growth factor {ECO:0000256|ARBA:ARBA00023030};
KW   Membrane {ECO:0000256|SAM:Phobius};
KW   Reference proteome {ECO:0000313|Proteomes:UP000009136};
KW   Signal {ECO:0000256|SAM:SignalP}; Transmembrane {ECO:0000256|SAM:Phobius};
KW   Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           24..208
FT                   /note="Proheparin-binding EGF-like growth factor"
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5003144130"
FT   TRANSMEM        162..186
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   DOMAIN          104..144
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000259|PROSITE:PS50026"
FT   REGION          36..55
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        37..52
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        134..143
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00076"
SQ   SEQUENCE   208 AA;  23093 MW;  B73E5A104B563B77 CRC64;
     MKLLPSVVLK LFLAAVLSAL VTGESLERLR RGLAAGTSNL DTPTQSTDQL LPAGGGQGRE
     VLDLEEANLD LFRAAFSSKP QALATPSKEE RGKRKKKGKG LGKKRNPCLR RYKDFCIHGE
     CKYVKELRVP TCICHPGYHG ERCHGLSLPV KNRLYTYDHT TILVVVAVVL SSVCLLVIMG
     LLMFWYHRRG GYDVENEEKV KLGMTTSH
//