VGF_VACCW
ID VGF_VACCW Reviewed; 140 AA.
AC P01136; Q76ZJ8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 113.
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-1; OrderedLocusNames=VACWR009;
GN and
GN Name=VGF-2; OrderedLocusNames=VACWR210;
OS Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain
OS WR)).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=10254;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7143577; DOI=10.1128/jvi.44.2.637-646.1982;
RA Venkatesan S., Gershowitz A., Moss B.;
RT "Complete nucleotide sequences of two adjacent early vaccinia virus genes
RT located within the inverted terminal repetition.";
RL J. Virol. 44:637-646(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Esposito J.J., Frace A.M., Sammons S.A., Olsen-Rasmussen M., Osborne J.,
RA Wohlhueter R.;
RT "Sequencing of the coding region of Vaccinia-WR to an average 9-fold
RT redundancy and an error rate of 0.16/10kb.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=3339716; DOI=10.1128/jvi.62.3.866-874.1988;
RA Buller R.M., Chakrabarti S., Cooper J.A., Twardzik D.R., Moss B.;
RT "Deletion of the vaccinia virus growth factor gene reduces virus
RT virulence.";
RL J. Virol. 62:866-874(1988).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=2739561; DOI=10.1016/0882-4010(89)90071-5;
RA Lai A.C., Pogo B.G.;
RT "Attenuated deletion mutants of vaccinia virus lacking the vaccinia growth
RT factor are defective in replication in vivo.";
RL Microb. Pathog. 6:219-226(1989).
RN [5]
RP FUNCTION, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=3339713; DOI=10.1128/jvi.62.3.1080-1083.1988;
RA Chang W., Lim J.G., Hellstrom I., Gentry L.E.;
RT "Characterization of vaccinia virus growth factor biosynthetic pathway with
RT an antipeptide antiserum.";
RL J. Virol. 62:1080-1083(1988).
RN [6]
RP FUNCTION.
RX PubMed=2229050; DOI=10.1016/s0021-9258(17)30598-7;
RA Lin Y.Z., Ke X.H., Tam J.P.;
RT "Growth inhibition by vaccinia virus growth factor.";
RL J. Biol. Chem. 265:18884-18890(1990).
RN [7]
RP FUNCTION.
RX PubMed=15025565; DOI=10.1042/bj20031375;
RA Andrade A.A., Silva P.N., Pereira A.C., De Sousa L.P., Ferreira P.C.,
RA Gazzinelli R.T., Kroon E.G., Ropert C., Bonjardim C.A.;
RT "The vaccinia virus-stimulated mitogen-activated protein kinase (MAPK)
RT pathway is required for virus multiplication.";
RL Biochem. J. 381:437-446(2004).
RN [8]
RP FUNCTION.
RX PubMed=20512239; DOI=10.1590/s0074-02762010000300005;
RA Andrade A.A., Brasil B.S., Pereira A.C., Ferreira P.C., Kroon E.G.,
RA Bonjardim C.A.;
RT "Vaccinia virus regulates expression of p21WAF1/Cip1 in A431 cells.";
RL Mem. Inst. Oswaldo Cruz 105:269-277(2010).
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. {ECO:0000269|PubMed:15025565,
CC ECO:0000269|PubMed:20512239, ECO:0000269|PubMed:2229050,
CC ECO:0000269|PubMed:3339713}.
CC -!- SUBUNIT: Vaccinia growth factor interacts with host EGFR and promotes
CC EGFR dimerization.
CC -!- SUBCELLULAR LOCATION: [Pro-vaccinia growth factor]: Host membrane
CC {ECO:0000269|PubMed:3339713}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:3339713}.
CC -!- SUBCELLULAR LOCATION: [Vaccinia growth factor]: Secreted
CC {ECO:0000269|PubMed:3339713}.
CC -!- DISRUPTION PHENOTYPE: Higher doses of VGF- virus than WT virus are
CC required for intracranial lethality in mice and for production of skin
CC lesions in rabbits. No effect in cell culture.
CC {ECO:0000269|PubMed:2739561, ECO:0000269|PubMed:3339716}.
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DR EMBL; J02421; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY243312; AAO89288.1; -; Genomic_DNA.
DR EMBL; AY243312; AAO89489.1; -; Genomic_DNA.
DR PIR; A01391; WMVZ9.
DR RefSeq; YP_232891.1; NC_006998.1.
DR RefSeq; YP_233092.1; NC_006998.1.
DR SMR; P01136; -.
DR DNASU; 3707587; -.
DR DNASU; 3707624; -.
DR GeneID; 3707587; -.
DR GeneID; 3707624; -.
DR KEGG; vg:3707587; -.
DR KEGG; vg:3707624; -.
DR Proteomes; UP000000344; 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 1: Evidence at protein level;
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-vaccinia growth factor"
FT /id="PRO_0000007599"
FT CHAIN 19..96
FT /note="Vaccinia growth factor"
FT /evidence="ECO:0000255"
FT /id="PRO_0000412918"
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; 15524 MW; F47C814309B8DCEF CRC64;
MSMKYLMLLF AAMIIRSFAD SGNAIETTSP EITNATTDIP AIRLCGPEGD GYCLHGDCIH
ARDIDGMYCR CSHGYTGIRC QHVVLVDYQR SENPNTTTSY IPSPGIMLVL VGIIIITCCL
LSVYRFTRRT KLPIQDMVVP
