HBEGF_MOUSE
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 03-AUG-2022, entry version 169.
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 GlyGen; Q06186; 1 site.
DR iPTMnet; Q06186; -.
DR PhosphoSitePlus; Q06186; -.
DR PaxDb; Q06186; -.
DR PeptideAtlas; Q06186; -.
DR PRIDE; Q06186; -.
DR ProteomicsDB; 271492; -.
DR Antibodypedia; 26845; 400 antibodies from 31 providers.
DR DNASU; 15200; -.
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 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; 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 Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 15200; 2 hits in 74 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 224 other tissues.
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: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:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IBA:GO_Central.
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; 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; 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
