ID ST_SV40 Reviewed; 174 AA.
AC P03081;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 22-FEB-2023, entry version 130.
DE RecName: Full=Small t antigen;
DE Short=ST;
DE Short=ST-AG;
OS Simian virus 40 (SV40).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Betapolyomavirus.
OX NCBI_TaxID=1891767;
OH NCBI_TaxID=9539; Macaca (macaques).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=205947; DOI=10.1126/science.205947;
RA Reddy V.B., Thimmappaya B., Dhar R., Subramanian K.N., Zain B.S., Pan J.,
RA Ghosh P.K., Celma M.L., Weissman S.M.;
RT "The genome of simian virus 40.";
RL Science 200:494-502(1978).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ACETYLATION AT MET-1.
RC STRAIN=776;
RX PubMed=205802; DOI=10.1038/273113a0;
RA Fiers W., Contreras R., Haegeman G., Rogiers R., van de Voorde A.,
RA van Heuverswyn H., van Herreweghe J., Volckaert G., Ysebaert M.;
RT "Complete nucleotide sequence of SV40 DNA.";
RL Nature 273:113-120(1978).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=6323762; DOI=10.1128/jvi.50.2.623-628.1984;
RA Ellman M., Bikel I., Figge J., Roberts T., Schlossman R., Livingston D.M.;
RT "Localization of the simian virus 40 Small t antigen in the nucleus and
RT cytoplasm of monkey and mouse cells.";
RL J. Virol. 50:623-628(1984).
RN [4]
RP INHIBITION OF HOST PP2A ACTIVITY.
RX PubMed=1848668; DOI=10.1128/mcb.11.4.1996-2003.1991;
RA Scheidtmann K.H., Mumby M.C., Rundell K., Walter G.;
RT "Dephosphorylation of simian virus 40 large-T antigen and p53 protein by
RT protein phosphatase 2A: inhibition by small-t antigen.";
RL Mol. Cell. Biol. 11:1996-2003(1991).
RN [5]
RP INTERACTION WITH HOST PP2A.
RX PubMed=1706474; DOI=10.1128/mcb.11.4.1988-1995.1991;
RA Yang S.-L., Lickteig R.L., Estes R., Rundell K., Walter G., Mumby M.C.;
RT "Control of protein phosphatase 2A by simian virus 40 small-t antigen.";
RL Mol. Cell. Biol. 11:1988-1995(1991).
RN [6]
RP INTERACTION WITH HOST PP2A.
RX PubMed=8107228; DOI=10.1128/jvi.68.3.1675-1681.1994;
RA Mungre S., Enderle K., Turk B., Porras A., Wu Y.Q., Mumby M.C., Rundell K.;
RT "Mutations which affect the inhibition of protein phosphatase 2A by simian
RT virus 40 small-t antigen in vitro decrease viral transformation.";
RL J. Virol. 68:1675-1681(1994).
RN [7]
RP FUNCTION.
RX PubMed=8794333; DOI=10.1128/jvi.70.10.6902-6908.1996;
RA Porras A., Bennett J., Howe A., Tokos K., Bouck N., Henglein B.,
RA Sathyamangalam S., Thimmapaya B., Rundell K.;
RT "A novel simian virus 40 early-region domain mediates transactivation of
RT the cyclin A promoter by small-t antigen and is required for transformation
RT in small-t antigen-dependent assays.";
RL J. Virol. 70:6902-6908(1996).
RN [8]
RP FUNCTION.
RX PubMed=8917510; DOI=10.1073/pnas.93.23.12861;
RA Watanabe G., Howe A., Lee R.J., Albanese C., Shu I.W., Karnezis A.N.,
RA Zon L., Kyriakis J., Rundell K., Pestell R.G.;
RT "Induction of cyclin D1 by simian virus 40 small tumor antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12861-12866(1996).
RN [9]
RP DOMAIN.
RX PubMed=9108037; DOI=10.1073/pnas.94.8.3679;
RA Kelley W.L., Georgopoulos C.;
RT "The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens
RT can functionally replace the J-domain of the Escherichia coli DnaJ
RT molecular chaperone.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3679-3684(1997).
RN [10]
RP FUNCTION.
RX PubMed=15890927; DOI=10.1128/jvi.79.11.6882-6889.2005;
RA Yu Y., Kudchodkar S.B., Alwine J.C.;
RT "Effects of simian virus 40 large and small tumor antigens on mammalian
RT target of rapamycin signaling: small tumor antigen mediates
RT hypophosphorylation of eIF4E-binding protein 1 late in infection.";
RL J. Virol. 79:6882-6889(2005).
RN [11]
RP FUNCTION.
RX PubMed=15680424; DOI=10.1016/j.virol.2004.12.017;
RA Skoczylas C., Henglein B., Rundell K.;
RT "PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is
RT mediated by a cell cycle-regulated E2F site.";
RL Virology 332:596-601(2005).
RN [12]
RP FUNCTION.
RX PubMed=17936323; DOI=10.1016/j.virol.2007.09.008;
RA Fahrbach K.M., Katzman R.B., Rundell K.;
RT "Role of SV40 ST antigen in the persistent infection of mesothelial
RT cells.";
RL Virology 370:255-263(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 87-174.
RX PubMed=17529992; DOI=10.1038/nsmb1254;
RA Chen Y., Xu Y., Bao Q., Xing Y., Li Z., Lin Z., Stock J.B., Jeffrey P.D.,
RA Shi Y.;
RT "Structural and biochemical insights into the regulation of protein
RT phosphatase 2A by small t antigen of SV40.";
RL Nat. Struct. Mol. Biol. 14:527-534(2007).
CC -!- FUNCTION: Promotes efficient viral genome replication by accelerating
CC both G1 and S phase progression of the cell cycle. Inhibits host PP2A
CC by binding to the A subunit, thereby displacing lower affinity
CC regulatory B subunit. Inactivation of PP2A in turn results in the
CC transactivation of cyclin A and cyclin D1 promoters. Late during the
CC infection cycle, ST may induce dephosphorylation of host eIF4E-binding
CC protein EIF4EBP1 leading to the inhibition of cap-dependent
CC translation. May establish and maintain high levels of viral genomes
CC during persistent infection in cell culture.
CC {ECO:0000269|PubMed:15680424, ECO:0000269|PubMed:15890927,
CC ECO:0000269|PubMed:17936323, ECO:0000269|PubMed:8794333,
CC ECO:0000269|PubMed:8917510}.
CC -!- SUBUNIT: Interacts with host PPP2R1A; the interaction inhibits PP2A
CC activity. {ECO:0000269|PubMed:1706474, ECO:0000269|PubMed:8107228}.
CC -!- INTERACTION:
CC P03081; P30153: PPP2R1A; Xeno; NbExp=5; IntAct=EBI-1266256, EBI-302388;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:6323762}. Host
CC nucleus {ECO:0000269|PubMed:6323762}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=Small t antigen;
CC IsoId=P03081-1; Sequence=Displayed;
CC Name=Large T antigen;
CC IsoId=P03070-1; Sequence=External;
CC Name=17kT antigen;
CC IsoId=P03070-2; Sequence=External;
CC Name=SELP;
CC IsoId=P0C6L2-1; Sequence=External;
CC -!- DOMAIN: The common region of SV40 ST, 17kT and LT proteins comprises
CC the J domain. This domain is essential for multiple viral activities,
CC including virion assembly, viral DNA replication, transformation and
CC transcriptional activation. This domain is also required for cyclin A-
CC transactivating activity of ST. {ECO:0000269|PubMed:9108037}.
CC -!- MISCELLANEOUS: [Isoform Small t antigen]: Produced by alternative
CC splicing.
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DR EMBL; J02400; AAB59925.1; -; Genomic_DNA.
DR PIR; C03631; TVVPA4.
DR RefSeq; YP_003708383.1; NC_001669.1.
DR PDB; 2PF4; X-ray; 3.10 A; E/F/G/H=1-174.
DR PDB; 2PKG; X-ray; 3.30 A; C/D=87-174.
DR PDBsum; 2PF4; -.
DR PDBsum; 2PKG; -.
DR SMR; P03081; -.
DR DIP; DIP-29393N; -.
DR IntAct; P03081; 3.
DR MINT; P03081; -.
DR iPTMnet; P03081; -.
DR OrthoDB; 14669at10239; -.
DR EvolutionaryTrace; P03081; -.
DR Proteomes; UP000007705; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR CDD; cd06257; DnaJ; 1.
DR Gene3D; 1.10.287.110; DnaJ domain; 1.
DR Gene3D; 1.20.120.1860; Small t-antigen, unique domain; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR003354; Papo_T_antigen.
DR InterPro; IPR036092; Papo_T_antigensf.
DR Pfam; PF02380; Papo_T_antigen; 1.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF46565; Chaperone J-domain; 1.
DR SUPFAM; SSF161240; T-antigen specific domain-like; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation;
KW Alternative splicing; Early protein;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host nucleus;
KW Host-virus interaction; Metal-binding; Oncogene; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..174
FT /note="Small t antigen"
FT /id="PRO_0000115061"
FT DOMAIN 12..75
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT ZN_FING 103..116
FT /note="C4-type; atypical"
FT ZN_FING 122..143
FT /note="H1C3-type; atypical"
FT MOD_RES 1
FT /note="N-acetylmethionine; by host"
FT /evidence="ECO:0000269|PubMed:205802"
FT TURN 2..4
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 7..15
FT /evidence="ECO:0007829|PDB:2PF4"
FT TURN 16..18
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:2PF4"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 54..69
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:2PF4"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:2PKG"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:2PF4"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:2PKG"
FT HELIX 114..125
FT /evidence="ECO:0007829|PDB:2PF4"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:2PF4"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:2PKG"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:2PF4"
FT HELIX 154..164
FT /evidence="ECO:0007829|PDB:2PF4"
SQ SEQUENCE 174 AA; 20449 MW; 91EC925ED2E29668 CRC64;
MDKVLNREES LQLMDLLGLE RSAWGNIPLM RKAYLKKCKE FHPDKGGDEE KMKKMNTLYK
KMEDGVKYAH QPDFGGFWDA TEVFASSLNP GVDAMYCKQW PECAKKMSAN CICLLCLLRM
KHENRKLYRK DPLVWVDCYC FDCFRMWFGL DLCEGTLLLW CDIIGQTTYR DLKL
//
