VGF_VARV
ID VGF_VARV Reviewed; 140 AA.
AC P0DOQ0; 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 11.
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.
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX NCBI_TaxID=10255;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Bangladesh-1975;
RX PubMed=8264798; DOI=10.1038/366748a0;
RA Massung R.F., Esposito J.J., Liu L.I., Qi J., Utterback T.R., Knight J.C.,
RA Aubin L., Yuran T.E., Parsons J.M., Loparev V.N., Selivanov N.A.,
RA Cavallaro K.F., Kerlavage A.R., Mahy B.W.J., Venter J.C.;
RT "Potential virulence determinants in terminal regions of variola smallpox
RT virus genome.";
RL Nature 366:748-751(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Congo-1965, Garcia-1966, and Somalia-1977;
RX PubMed=8661439; DOI=10.1006/viro.1996.0378;
RA Massung R.F., Loparev V.N., Knight J.C., Totmenin A.V., Chizhikov V.E.,
RA Parsons J.M., Safronov P.F., Gutorov V.V., Shchelkunov S.N., Esposito J.J.;
RT "Terminal region sequence variations in variola virus DNA.";
RL Virology 221:291-300(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Garcia-1966;
RX PubMed=10639322; DOI=10.1006/viro.1999.0086;
RA Shchelkunov S.N., Totmenin A.V., Loparev V.N., Safronov P.F., Gutorov V.V.,
RA Chizhikov V.E., Knight J.C., Parsons J.M., Massung R.F., Esposito J.J.;
RT "Alastrim smallpox variola minor virus genome DNA sequences.";
RL Virology 266:361-386(2000).
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; L22579; AAA60749.1; -; Genomic_DNA.
DR EMBL; U18337; AAA69306.1; -; Genomic_DNA.
DR EMBL; U18338; AAA69343.1; -; Genomic_DNA.
DR EMBL; U18340; AAA69412.1; -; Genomic_DNA.
DR EMBL; Y16780; CAB54597.1; -; Genomic_DNA.
DR PIR; C72150; C72150.
DR PIR; T28439; T28439.
DR SMR; P0DOQ0; -.
DR Proteomes; UP000111493; Genome.
DR Proteomes; UP000119805; 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-variola growth factor"
FT /id="PRO_0000448105"
FT CHAIN 19..96
FT /note="Variola growth factor"
FT /evidence="ECO:0000255"
FT /id="PRO_0000448106"
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"
FT VARIANT 113
FT /note="S -> G (in strain: Garcia-1966)"
SQ SEQUENCE 140 AA; 15704 MW; F9E4D05401715F05 CRC64;
MSMKYLMLLF AAMIIRSFAN SGNAIETTLS EITNTTTDIP AIRLCGPEGN GYCFHGICIH
ARDIDGMYCR CSHGYTGIRC QHVVLVDYQR SEKPNTTTSY IPSPGIVLVL LVSIIMCCLL
FVYRFTRRTN KLPLQDMVVP
