ID   VGF_VAR67               Reviewed;         140 AA.
AC   P0DOP9; P33804; Q76Q77; Q76UB3; Q89066; Q89756;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2019, sequence version 1.
DT   29-SEP-2021, entry version 10.
DE   RecName: Full=Pro-variola growth factor;
DE            Short=Pro-VGF;
DE   Contains:
DE     RecName: Full=Variola growth factor;
DE              Short=VGF;
DE     AltName: Full=Secreted epidermal growth factor-like;
DE   Flags: Precursor;
GN   ORFNames=B3R, B4R, C11R, D2L, D4R;
OS   Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX   NCBI_TaxID=587200;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA   Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT   "Genes of variola and vaccinia viruses necessary to overcome the host
RT   protective mechanisms.";
RL   FEBS Lett. 319:80-83(1993).
CC   -!- FUNCTION: Variola 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: Variola growth factor interacts with host EGFR and promotes
CC       EGFR dimerization. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Pro-variola growth factor]: Host membrane
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Variola growth factor]: Secreted.
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DR   EMBL; X69198; CAA48943.1; -; Genomic_DNA.
DR   PIR; B36837; B36837.
DR   RefSeq; NP_042046.1; NC_001611.1.
DR   SMR; P0DOP9; -.
DR   GeneID; 1486396; -.
DR   KEGG; vg:1486396; -.
DR   Proteomes; UP000002060; 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; Reference proteome;
KW   Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..140
FT                   /note="Pro-variola growth factor"
FT                   /id="PRO_0000007600"
FT   CHAIN           19..96
FT                   /note="Variola growth factor"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000412919"
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;  15772 MW;  03A134EA5A94E14A CRC64;
     MSMKYLMLLF AAMIIRSFAN SGNAIETTLS EITNTTTDIP AIRLCGPEGD RYCFHGICIH
     ARDIDGMYCR CSHGYTGIRC QHVVLVDYQR SEKPNTTTSY IPSPGIVLVL LVSIIVCCLL
     FVYRFTRRTN KLPLQDMVVP