HBEGF_CHICK
ID HBEGF_CHICK Reviewed; 212 AA.
AC Q9W7C5;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 132.
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=HEGFL;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RC STRAIN=White leghorn;
RX PubMed=10318950; DOI=10.1073/pnas.96.10.5716;
RA Fu S., Bottoli I., Goller M., Vogt P.K.;
RT "Heparin-binding epidermal growth factor-like growth factor, a v-Jun target
RT gene, induces oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:5716-5721(1999).
RN [2]
RP FUNCTION INTERACTION WITH CNIH2, AND DEVELOPMENTAL STAGE.
RX PubMed=17229890; DOI=10.1091/mbc.e06-08-0733;
RA Hoshino H., Uchida T., Otsuki T., Kawamoto S., Okubo K., Takeichi M.,
RA Chisaka O.;
RT "Cornichon-like protein facilitates secretion of HB-EGF and regulates
RT proper development of cranial nerves.";
RL Mol. Biol. Cell 18:1143-1152(2007).
CC -!- FUNCTION: May be involved in macrophage-mediated cellular
CC proliferation. It is mitogenic for fibroblasts and smooth muscle but
CC not endothelial cells. It is able to bind EGF receptor/EGFR with higher
CC affinity than EGF itself and is a far more potent mitogen for smooth
CC muscle cells than EGF (By similarity). Plays an important role in the
CC proper development of cranial nerves by inhibiting the migration of the
CC cranial neural crest cells (NCCs) into the odd-numbered neuromeres (r3
CC and r5) of the hindbrain Plays a role in mediating v-Jun-induced
CC oncogenic transformation. {ECO:0000250, ECO:0000269|PubMed:10318950,
CC ECO:0000269|PubMed:17229890}.
CC -!- SUBUNIT: Interacts with CNIH2.
CC -!- SUBCELLULAR LOCATION: [Heparin-binding EGF-like growth factor]:
CC Secreted, extracellular space {ECO:0000250}. Note=Mature HB-EGF is
CC released into the extracellular space and probably binds to a receptor.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Proheparin-binding EGF-like growth factor]: Cell
CC membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed uniformly in the embryonic hindbrain.
CC {ECO:0000269|PubMed:17229890}.
CC -!- INDUCTION: Strongly induced in embryonic fibroblasts transformed by v-
CC Jun. {ECO:0000269|PubMed:10318950}.
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DR EMBL; AF131224; AAD29416.1; -; mRNA.
DR RefSeq; NP_990180.1; NM_204849.1.
DR AlphaFoldDB; Q9W7C5; -.
DR SMR; Q9W7C5; -.
DR BioGRID; 675932; 1.
DR STRING; 9031.ENSGALP00000001399; -.
DR PaxDb; Q9W7C5; -.
DR Ensembl; ENSGALT00000001401; ENSGALP00000001399; ENSGALG00000000949.
DR GeneID; 395654; -.
DR KEGG; gga:395654; -.
DR CTD; 1839; -.
DR VEuPathDB; HostDB:geneid_395654; -.
DR eggNOG; ENOG502S0ZP; Eukaryota.
DR GeneTree; ENSGT00940000156901; -.
DR HOGENOM; CLU_096527_2_0_1; -.
DR InParanoid; Q9W7C5; -.
DR OMA; YSYDHTT; -.
DR OrthoDB; 1348306at2759; -.
DR PhylomeDB; Q9W7C5; -.
DR TreeFam; TF332773; -.
DR Reactome; R-GGA-1227986; Signaling by ERBB2.
DR Reactome; R-GGA-1236394; Signaling by ERBB4.
DR Reactome; R-GGA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-GGA-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-GGA-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-GGA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-GGA-179812; GRB2 events in EGFR signaling.
DR Reactome; R-GGA-180292; GAB1 signalosome.
DR Reactome; R-GGA-180336; SHC1 events in EGFR signaling.
DR Reactome; R-GGA-182971; EGFR downregulation.
DR Reactome; R-GGA-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-GGA-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-GGA-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-GGA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-GGA-6785631; ERBB2 Regulates Cell Motility.
DR Reactome; R-GGA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-GGA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-GGA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-GGA-8863795; Downregulation of ERBB2 signaling.
DR PRO; PR:Q9W7C5; -.
DR Proteomes; UP000000539; Chromosome 13.
DR Bgee; ENSGALG00000000949; Expressed in liver and 11 other tissues.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0021545; P:cranial nerve development; IMP:UniProtKB.
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:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IBA:GO_Central.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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 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 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; EGF-like domain; Growth factor;
KW Heparin-binding; Membrane; Receptor; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..212
FT /note="Proheparin-binding EGF-like growth factor"
FT /id="PRO_0000408979"
FT CHAIN ?..152
FT /note="Heparin-binding EGF-like growth factor"
FT /id="PRO_0000408980"
FT PROPEP 153..212
FT /note="C-terminal"
FT /evidence="ECO:0000250"
FT /id="PRO_0000408981"
FT TOPO_DOM 19..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 108..148
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 82..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..108
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 112..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 120..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 138..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ SEQUENCE 212 AA; 22541 MW; E82A8D08F5297183 CRC64;
MDGRVVLIHA LLTAVCSAAV GKFGRDGPHG EALHNEVLLH EGGGVASVSA TAPLLGGIVE
KEGGGAASGD ALSELPRVAF LSKPQGPVTP KKKGNGNKRR KGKGLGKKRD PCLRKYKDFC
IHGECKYIRE LGAPSCICQP GYHGERCHGL LLPVEHPPST YDHTTALAVV AVVLSSLCLV
IITALLMFRC HKRGVYDVEN EEKIKLGITV NH
