HBEGF_CHLAE
ID HBEGF_CHLAE Reviewed; 208 AA.
AC Q09118;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 AltName: Full=Diphtheria toxin receptor;
DE Short=DT-R;
DE Flags: Precursor;
GN Name=HBEGF; Synonyms=DTR, HEGFL;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1606612; DOI=10.1016/0092-8674(92)90623-k;
RA Naglich J.G., Metherall J.E., Russel D.W., Eidels L.;
RT "Expression cloning of a diphtheria toxin receptor: identity with a
RT heparin-binding EGF-like growth factor precursor.";
RL Cell 69:1051-1061(1992).
RN [2]
RP DOMAIN TOXIN BINDING.
RX PubMed=7826391; DOI=10.1006/bbrc.1995.1100;
RA Hooper K.P., Eidels L.;
RT "Localization of a critical diphtheria toxin-binding domain to the C-
RT terminus of the mature heparin-binding EGF-like growth factor region of the
RT diphtheria toxin receptor.";
RL Biochem. Biophys. Res. Commun. 206:710-717(1995).
RN [3]
RP DOMAIN TOXIN BINDING, AND MUTAGENESIS OF GLU-141.
RX PubMed=8607824; DOI=10.1006/bbrc.1996.0463;
RA Hooper K.P., Eidels L.;
RT "Glutamic acid 141 of the diphtheria toxin receptor (HB-EGF precursor) is
RT critical for toxin binding and toxin sensitivity.";
RL Biochem. Biophys. Res. Commun. 220:675-680(1996).
RN [4]
RP INTERACTION WITH FBLN1.
RX PubMed=11846885; DOI=10.1186/1471-2121-3-2;
RA Brooke J.S., Cha J.-H., Eidels L.;
RT "Latent transforming growth factor beta-binding protein-3 and fibulin-1C
RT interact with the extracellular domain of the heparin-binding EGF-like
RT growth factor precursor.";
RL BMC Cell Biol. 3:2-2(2002).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with EGFR and ERBB4 (By similarity). Interacts with
CC FBLN1. {ECO:0000250, ECO:0000269|PubMed:11846885}.
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 -!- PTM: O-glycosylated. {ECO:0000250}.
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DR EMBL; M93012; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A41914; A41914.
DR AlphaFoldDB; Q09118; -.
DR SMR; Q09118; -.
DR IntAct; Q09118; 1.
DR MINT; Q09118; -.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; IEA:UniProt.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
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; Glycoprotein;
KW Growth factor; Heparin-binding; Membrane; Receptor; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..208
FT /note="Proheparin-binding EGF-like growth factor"
FT /id="PRO_0000302802"
FT PROPEP 20..62
FT /evidence="ECO:0000250"
FT /id="PRO_0000007608"
FT CHAIN 63..148
FT /note="Heparin-binding EGF-like growth factor"
FT /id="PRO_0000007609"
FT PROPEP 149..208
FT /note="C-terminal"
FT /evidence="ECO:0000255"
FT /id="PRO_0000007610"
FT TOPO_DOM 20..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 34..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..148
FT /note="Toxin-binding domain"
FT SITE 141
FT /note="Plays a critical role in diphtheria toxin binding
FT and toxin sensitivity"
FT CARBOHYD 75
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
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"
FT MUTAGEN 141
FT /note="E->H: 100-fold less sensitive to the diphtheria
FT toxin and 12-fold decrease in toxin-binding."
FT /evidence="ECO:0000269|PubMed:8607824"
SQ SEQUENCE 208 AA; 22985 MW; 8D108289A0485AE9 CRC64;
MKLLPSVVLK LLLAAVLSAL VTGESLEQLR RGLAAGTSNP DPSTGSTDQL LRLGGGRDRK
VRDLQEADLD LLRVTLSSKP QALATPSKEE HGKRKKKGKG LGKKRDPCLR KYKDFCIHGE
CKYVKELRAP SCICHPGYHG ERCHGLSLPV ENRLYTYDHT TILAVVAVVL SSVCLLVIVG
LLMFRYHRRG GYDVENEEKV KLGMTNSH
