ID   VGF_VACCA               Reviewed;         140 AA.
AC   O57166;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   29-SEP-2021, entry version 90.
DE   RecName: Full=Pro-vaccinia growth factor;
DE            Short=Pro-VGF;
DE   Contains:
DE     RecName: Full=Vaccinia growth factor;
DE              Short=VGF;
DE     AltName: Full=Secreted epidermal growth factor-like;
DE   Flags: Precursor;
GN   Name=VGF; OrderedLocusNames=MVA005R, ACAM3000_MVA_005;
OS   Vaccinia virus (strain Ankara) (VACV).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX   NCBI_TaxID=126794;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=9601507; DOI=10.1006/viro.1998.9123;
RA   Antoine G., Scheiflinger F., Dorner F., Falkner F.G.;
RT   "The complete genomic sequence of the modified vaccinia Ankara strain:
RT   comparison with other orthopoxviruses.";
RL   Virology 244:365-396(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Isolate Acambis 3000;
RA   Esposito J.J., Frace M., Sammons S.A., Olsen-Rasmussen M.S., Osborne J.,
RA   Khristova M., Wohlhueter R.M.;
RL   Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Vaccinia growth factor stimulates cellular proliferation
CC       (hyperplasia) around infected cells. This effect is beneficial for
CC       virus replication in vivo, because poxviruses replicate possibly better
CC       in proliferating cells than in quiescent cells. Acts by binding host
CC       EGFR, inducing its dimerization, autophosphorylation and leading to
CC       activation of several cellular pathways regulating cell proliferation
CC       or cell survival. The activation by host EGFR of mitogen activated
CC       protein kinases (MAPK) and extracellular-signal regulated kinases (ERK)
CC       are essential for the positive effect of vaccinia growth factor on
CC       poxvirus virulence in vivo (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Vaccinia growth factor interacts with host EGFR and promotes
CC       EGFR dimerization. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Pro-vaccinia growth factor]: Host membrane
CC       {ECO:0000250|UniProtKB:P01136}; Single-pass type I membrane protein
CC       {ECO:0000250|UniProtKB:P01136}.
CC   -!- SUBCELLULAR LOCATION: [Vaccinia growth factor]: Secreted
CC       {ECO:0000250|UniProtKB:P01136}.
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DR   EMBL; U94848; AAB96482.1; -; Genomic_DNA.
DR   EMBL; AY603355; AAT10402.1; -; Genomic_DNA.
DR   PIR; T30766; T30766.
DR   SMR; O57166; -.
DR   Proteomes; UP000159908; Genome.
DR   Proteomes; UP000172909; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0007176; P:regulation of epidermal growth factor-activated receptor activity; IEA:InterPro.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR015497; EGF_rcpt_ligand.
DR   InterPro; IPR011170; GF_C11R.
DR   PANTHER; PTHR10740; PTHR10740; 1.
DR   PIRSF; PIRSF001779; GF_C11R; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
PE   3: Inferred from homology;
KW   Disulfide bond; EGF-like domain; Glycoprotein; Growth factor;
KW   Host membrane; Host-virus interaction; Membrane; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..140
FT                   /note="Pro-vaccinia growth factor"
FT                   /id="PRO_0000007595"
FT   CHAIN           19..96
FT                   /note="Vaccinia growth factor"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000412914"
FT   TOPO_DOM        19..100
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        101..121
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        122..140
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          41..81
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   SITE            96..97
FT                   /note="Cleavage (By host protease)"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        34
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        95
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        45..58
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        53..69
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        71..80
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ   SEQUENCE   140 AA;  15532 MW;  E0834FA8D51BD8BF CRC64;
     MLINYLMLLF AAMIIRSFAD SGNAIETTSP EITNATTDIP AIRLCGPEGD GYCLHGDCIH
     ARDIDGMYCR CSHGYTGIRC QHVVLVDYQR SEKPNTTTSY IPSPGIMLVL VGIIIITCCL
     LSVYRFTRRT KLPIQDMVVP