LT_SV40
ID LT_SV40 Reviewed; 708 AA.
AC P03070;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
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 PROTEIN SEQUENCE (ISOFORM 17KT ANTIGEN), AND ALTERNATIVE SPLICING.
RX PubMed=8223482; DOI=10.1002/j.1460-2075.1993.tb06162.x;
RA Zerrahn J., Knippschild U., Winkler T., Deppert W.;
RT "Independent expression of the transforming amino-terminal domain of SV40
RT large I antigen from an alternatively spliced third SV40 early mRNA.";
RL EMBO J. 12:4739-4746(1993).
RN [4]
RP PROTEIN SEQUENCE OF 102-118, AND PHOSPHORYLATION AT THR-124 BY CDC2.
RX PubMed=2552322; DOI=10.1038/341503a0;
RA McVey D., Brizuela L., Mohr I., Marshak D.R., Gluzman Y., Beach D.;
RT "Phosphorylation of large tumour antigen by cdc2 stimulates SV40 DNA
RT replication.";
RL Nature 341:503-507(1989).
RN [5]
RP INTERACTION WITH HOST TP53.
RX PubMed=218111; DOI=10.1038/278261a0;
RA Lane D.P., Crawford L.V.;
RT "T antigen is bound to a host protein in SV40-transformed cells.";
RL Nature 278:261-263(1979).
RN [6]
RP DNA-BINDING, AND DOMAIN.
RX PubMed=6298451; DOI=10.1128/jvi.46.1.143-150.1983;
RA DeLucia A.L., Lewton B.A., Tjian R., Tegtmeyer P.;
RT "Topography of simian virus 40 A protein-DNA complexes: arrangement of
RT pentanucleotide interaction sites at the origin of replication.";
RL J. Virol. 46:143-150(1983).
RN [7]
RP NUCLEAR LOCALIZATION SIGNAL, AND SUBCELLULAR LOCATION.
RX PubMed=6096007; DOI=10.1016/0092-8674(84)90457-4;
RA Kalderon D., Roberts B.L., Richardson W.D., Smith A.E.;
RT "A short amino acid sequence able to specify nuclear location.";
RL Cell 39:499-509(1984).
RN [8]
RP INTERACTION WITH HOST POLA1.
RX PubMed=3025630; DOI=10.1128/mcb.6.11.4077-4087.1986;
RA Smale S.T., Tjian R.;
RT "T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA
RT replication.";
RL Mol. Cell. Biol. 6:4077-4087(1986).
RN [9]
RP GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=3027978; DOI=10.1016/0042-6822(87)90407-7;
RA Schmitt M.K., Mann K.;
RT "Glycosylation of simian virus 40 T antigen and localization of
RT glycosylated T antigen in the nuclear matrix.";
RL Virology 156:268-281(1987).
RN [10]
RP INTERACTION WITH HOST RB PROTEIN.
RX PubMed=2839300; DOI=10.1016/0092-8674(88)90559-4;
RA Decaprio J.A., Ludlow J.W., Figge J., Shew J.-Y., Huang C.-M., Lee W.-H.,
RA Marsilio E., Paucha E., Livingston D.M.;
RT "SV40 large tumor antigen forms a specific complex with the product of the
RT retinoblastoma susceptibility gene.";
RL Cell 54:275-283(1988).
RN [11]
RP PHOSPHORYLATION AT SER-106; SER-112; SER-123; THR-124; SER-676; SER-677;
RP SER-679 AND THR-701.
RX PubMed=2838952; DOI=10.1016/0042-6822(88)90653-8;
RA Graesser F.A., Scheidmann K.H., Tuazon P.T., Traugh J.A., Walter G.;
RT "In vitro phosphorylation of SV40 large T antigen.";
RL Virology 165:13-22(1988).
RN [12]
RP ACTIVATION OF DNA REPLICATION BY HOST PP2A.
RX PubMed=2555176; DOI=10.1002/j.1460-2075.1989.tb08568.x;
RA Virshup D.M., Kauffman M.G., Kelly T.J.;
RT "Activation of SV40 DNA replication in vitro by cellular protein
RT phosphatase 2A.";
RL EMBO J. 8:3891-3898(1989).
RN [13]
RP INTERACTION WITH HOST RBL1.
RX PubMed=2546678; DOI=10.1016/0092-8674(89)90839-8;
RA Dyson N., Buchkovich K., Whyte P., Harlow E.;
RT "The cellular 107K protein that binds to adenovirus E1A also associates
RT with the large T antigens of SV40 and JC virus.";
RL Cell 58:249-255(1989).
RN [14]
RP PHOSPHORYLATION AT SER-106; SER-112; SER-120; SER-123; THR-124; SER-639;
RP SER-677; SER-679 AND THR-701.
RX PubMed=2160857; DOI=10.1016/0092-8674(90)90179-i;
RA Prives C.;
RT "The replication functions of SV40 T antigen are regulated by
RT phosphorylation.";
RL Cell 61:735-738(1990).
RN [15]
RP DOMAIN.
RX PubMed=2173794; DOI=10.1128/jvi.64.12.6291-6296.1990;
RA Hoess A., Moarefi I.F., Fanning E., Arthur A.K.;
RT "The finger domain of simian virus 40 large T antigen controls DNA-binding
RT specificity.";
RL J. Virol. 64:6291-6296(1990).
RN [16]
RP DOMAIN.
RX PubMed=1851875; DOI=10.1128/jvi.65.6.3167-3174.1991;
RA Loeber G., Stenger J.E., Ray S., Parsons R.E., Anderson M.E., Tegtmeyer P.;
RT "The zinc finger region of simian virus 40 large T antigen is needed for
RT hexamer assembly and origin melting.";
RL J. Virol. 65:3167-3174(1991).
RN [17]
RP DEPHOSPHORYLATION BY HOST PP2A.
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 [18]
RP DEPHOSPHORYLATION BY HOST PP2A.
RX PubMed=1848320; DOI=10.1128/jvi.65.4.2098-2101.1991;
RA Scheidtmann K.H., Virshup D.M., Kelly T.J.;
RT "Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen
RT specifically at residues involved in regulation of DNA-binding activity.";
RL J. Virol. 65:2098-2101(1991).
RN [19]
RP INTERACTION WITH HOST RB1.
RX PubMed=1316611; DOI=10.1073/pnas.89.10.4549;
RA Chellappan S., Kraus V.B., Kroger B., Munger K., Howley P.M., Phelps W.C.,
RA Nevins J.R.;
RT "Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7
RT protein share the capacity to disrupt the interaction between transcription
RT factor E2F and the retinoblastoma gene product.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4549-4553(1992).
RN [20]
RP PHOSPHORYLATION AT THR-124, AND MUTAGENESIS OF THR-124.
RX PubMed=8648725; DOI=10.1128/jvi.70.6.3887-3893.1996;
RA McVey D., Woelker B., Tegtmeyer P.;
RT "Mechanisms of simian virus 40 T-antigen activation by phosphorylation of
RT threonine 124.";
RL J. Virol. 70:3887-3893(1996).
RN [21]
RP FUNCTION, AND INTERACTION WITH HOST TBP AND TFIID.
RX PubMed=8647434; DOI=10.1101/gad.10.11.1369;
RA Damania B., Alwine J.C.;
RT "TAF-like function of SV40 large T antigen.";
RL Genes Dev. 10:1369-1381(1996).
RN [22]
RP FUNCTION, AND INTERACTION WITH HOST TFIIA.
RX PubMed=9632777; DOI=10.1128/mcb.18.7.3926;
RA Damania B., Lieberman P., Alwine J.C.;
RT "Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA
RT complex on the TATA element.";
RL Mol. Cell. Biol. 18:3926-3935(1998).
RN [23]
RP DOMAIN.
RX PubMed=9488456; DOI=10.1128/mcb.18.3.1408;
RA Zalvide J., Stubdal H., DeCaprio J.A.;
RT "The J domain of simian virus 40 large T antigen is required to
RT functionally inactivate RB family proteins.";
RL Mol. Cell. Biol. 18:1408-1415(1998).
RN [24]
RP DOMAIN, AND SUBUNIT.
RX PubMed=11909532; DOI=10.1016/s0960-9822(02)00696-6;
RA VanLoock M.S., Alexandrov A., Yu X., Cozzarelli N.R., Egelman E.H.;
RT "SV40 large T antigen hexamer structure: domain organization and DNA-
RT induced conformational changes.";
RL Curr. Biol. 12:472-476(2002).
RN [25]
RP ACETYLATION AT LYS-697.
RX PubMed=15254196; DOI=10.1128/jvi.78.15.8245-8253.2004;
RA Poulin D.L., Kung A.L., DeCaprio J.A.;
RT "p53 targets simian virus 40 large T antigen for acetylation by CBP.";
RL J. Virol. 78:8245-8253(2004).
RN [26]
RP FUNCTION OF ISOFORM 17KT.
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 [27]
RP FUNCTION, INTERACTION WITH HUMAN FBW7GAMMA ISOFORM, AND MUTAGENESIS OF
RP THR-701.
RX PubMed=15611062; DOI=10.1074/jbc.m413377200;
RA Welcker M., Clurman B.E.;
RT "The SV40 large T antigen contains a decoy phosphodegron that mediates its
RT interactions with Fbw7/hCdc4.";
RL J. Biol. Chem. 280:7654-7658(2005).
RN [28]
RP INTERACTION WITH HUMAN CUL7, IDENTIFICATION IN A SCF(CUL7)-LIKE COMPLEX,
RP AND MUTAGENESIS OF PHE-98.
RX PubMed=16140746; DOI=10.1128/jvi.79.18.11685-11692.2005;
RA Kasper J.S., Kuwabara H., Arai T., Ali S.H., DeCaprio J.A.;
RT "Simian virus 40 large T antigen's association with the CUL7 SCF complex
RT contributes to cellular transformation.";
RL J. Virol. 79:11685-11692(2005).
RN [29]
RP FUNCTION, AND INTERACTION WITH HOST HDAC1.
RX PubMed=17341466; DOI=10.1093/nar/gkl1113;
RA Valls E., Blanco-Garcia N., Aquizu N., Piedra D., Estaras C.,
RA de la Cruz X., Martinez-Balbas M.A.;
RT "Involvement of chromatin and histone deacetylation in SV40 T antigen
RT transcription regulation.";
RL Nucleic Acids Res. 35:1958-1968(2007).
RN [30]
RP INTERACTION WITH HOST TOP1.
RX PubMed=18003733; DOI=10.1128/jvi.01314-07;
RA Khopde S., Simmons D.T.;
RT "Simian virus 40 DNA replication is dependent on an interaction between
RT topoisomerase I and the C-terminal end of T antigen.";
RL J. Virol. 82:1136-1145(2008).
RN [31]
RP FUNCTION, AND INTERACTION WITH HUMAN BUB1.
RX PubMed=18922873; DOI=10.1128/jvi.01515-08;
RA Hein J., Boichuk S., Wu J., Cheng Y., Freire R., Jat P.S., Roberts T.M.,
RA Gjoerup O.V.;
RT "Simian virus 40 large T antigen disrupts genome integrity and activates a
RT DNA damage response via Bub1 binding.";
RL J. Virol. 83:117-127(2009).
RN [32]
RP INTERACTION WITH HOST FAM111A, AND C-TERMINAL REGION.
RX PubMed=23093934; DOI=10.1371/journal.ppat.1002949;
RA Fine D.A., Rozenblatt-Rosen O., Padi M., Korkhin A., James R.L.,
RA Adelmant G., Yoon R., Guo L., Berrios C., Zhang Y., Calderwood M.A.,
RA Velmurgan S., Cheng J., Marto J.A., Hill D.E., Cusick M.E., Vidal M.,
RA Florens L., Washburn M.P., Litovchick L., DeCaprio J.A.;
RT "Identification of FAM111A as an SV40 host range restriction and adenovirus
RT helper factor.";
RL PLoS Pathog. 8:E1002949-E1002949(2012).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 7-117, AND DOMAIN.
RX PubMed=11226179; DOI=10.1093/emboj/20.1.295;
RA Kim H.-Y., Ahn B.-Y., Cho Y.;
RT "Structural basis for the inactivation of retinoblastoma tumor suppressor
RT by SV40 large T antigen.";
RL EMBO J. 20:295-304(2001).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 260-627.
RX PubMed=12774115; DOI=10.1038/nature01691;
RA Li D., Zhao R., Lilyestrom W., Gai D., Zhang R., DeCaprio J.A., Fanning E.,
RA Jochimiak A., Szakonyi G., Chen X.S.;
RT "Structure of the replicative helicase of the oncoprotein SV40 large tumour
RT antigen.";
RL Nature 423:512-518(2003).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 251-627.
RX PubMed=15454080; DOI=10.1016/j.cell.2004.09.017;
RA Gai D., Zhao R., Li D., Finkielstein C.V., Chen X.S.;
RT "Mechanisms of conformational change for a replicative hexameric helicase
RT of SV40 large tumor antigen.";
RL Cell 119:47-60(2004).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 251-627.
RX PubMed=16951253; DOI=10.1101/gad.1456306;
RA Lilyestrom W., Klein M.G., Zhang R., Joachimiak A., Chen X.S.;
RT "Crystal structure of SV40 large T-antigen bound to p53: interplay between
RT a viral oncoprotein and a cellular tumor suppressor.";
RL Genes Dev. 20:2373-2382(2006).
CC -!- FUNCTION: Isoform large T antigen is a key early protein essential for
CC both driving viral replication and inducing cellular transformation.
CC Plays a role in viral genome replication by driving entry of quiescent
CC cells into the cell cycle and by autoregulating the synthesis of viral
CC early mRNA. Displays highly oncogenic activities by corrupting the host
CC cellular checkpoint mechanisms that guard cell division and the
CC transcription, replication, and repair of DNA. Participates in the
CC modulation of cellular gene expression preceeding viral DNA
CC replication. This step involves binding to host key cell cycle
CC regulators retinoblastoma protein RB1/pRb and TP53. Induces the
CC disassembly of host E2F1 transcription factors from RB1, thus promoting
CC transcriptional activation of E2F1-regulated S-phase genes. Inhibits
CC host TP53 binding to DNA, abrogating the ability of TP53 to stimulate
CC gene expression. Plays the role of a TFIID-associated factor (TAF) in
CC transcription initiation for all three RNA polymerases, by stabilizing
CC the TBP-TFIIA complex on promoters. Initiates viral DNA replication and
CC unwinding via interactions with the viral origin of replication. Binds
CC two adjacent sites in the SV40 origin. The replication fork movement is
CC facilitated by Large T antigen helicase activity. Activates the
CC transcription of viral late mRNA, through host TBP and TFIIA
CC stabilization. Interferes with histone deacetylation mediated by HDAC1,
CC leading to activation of transcription. May inactivate the growth-
CC suppressing properties of the E3 ubiquitin ligase CUL7.
CC {ECO:0000269|PubMed:15611062, ECO:0000269|PubMed:17341466,
CC ECO:0000269|PubMed:18922873, ECO:0000269|PubMed:8647434,
CC ECO:0000269|PubMed:9632777}.
CC -!- FUNCTION: Isoform 17kT antigen targets host RBL2 for degradation and
CC promotes cell proliferation. Transactivates host cyclin A promoter
CC through its J domain. {ECO:0000269|PubMed:15680424}.
CC -!- SUBUNIT: Isoform large T antigen forms homohexamers in the presence of
CC ATP. Interacts with host HDAC1. Interacts (via LXCXE domain) with host
CC RB1; the interaction induces the aberrant dissociation of RB1-E2F1
CC complex thereby disrupting RB1's activity. Interacts (via LXCXE domain)
CC with host pRB-related proteins RBL1 and RBL2. Interacts (via C-
CC terminus) with host TOP1 and POLA1 allowing DNA replication. Interacts
CC with host TP53, inhibiting TP53 binding to DNA. Interacts with host
CC preinitiation complex components TBP, TFIIA and TFIID to regulate
CC transcription initiation. LT interacts (via CPD region) with host
CC FBW7gamma isoform (via WD repeats); seems to function as a competitive
CC inhibitor of FBW7gamma function for physiologic substrates. LT
CC interacts with host E3 ubiquitin ligase CUL7; this interaction seems to
CC inhibit CUL7. Component of a SCF(CUL7)-like complex composed of SV40 Lt
CC and host proteins CUL7, SKP1, RBX1, and FBXW8. LT interacts with host
CC BUB1; this interaction induces activation of a DNA damage response and
CC promotes p53 stabilization and phosphorylation (Probable). Interacts
CC with host FAM111A and this interaction is required for efficient viral
CC replication and sustained viral gene expression in restrictive cell
CC types. {ECO:0000269|PubMed:11909532, ECO:0000269|PubMed:1316611,
CC ECO:0000269|PubMed:15611062, ECO:0000269|PubMed:16140746,
CC ECO:0000269|PubMed:17341466, ECO:0000269|PubMed:18003733,
CC ECO:0000269|PubMed:18922873, ECO:0000269|PubMed:218111,
CC ECO:0000269|PubMed:23093934, ECO:0000269|PubMed:2546678,
CC ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:3025630,
CC ECO:0000269|PubMed:8647434, ECO:0000269|PubMed:9632777, ECO:0000305}.
CC -!- INTERACTION:
CC P03070; P03070: -; NbExp=2; IntAct=EBI-617698, EBI-617698;
CC P03070; O43683: BUB1; Xeno; NbExp=2; IntAct=EBI-617698, EBI-748936;
CC P03070; P20248: CCNA2; Xeno; NbExp=2; IntAct=EBI-617698, EBI-457097;
CC P03070; P00546: CDC28; Xeno; NbExp=3; IntAct=EBI-617698, EBI-4253;
CC P03070; P06493: CDK1; Xeno; NbExp=2; IntAct=EBI-617698, EBI-444308;
CC P03070; Q92793: CREBBP; Xeno; NbExp=2; IntAct=EBI-617698, EBI-81215;
CC P03070; Q09472: EP300; Xeno; NbExp=2; IntAct=EBI-617698, EBI-447295;
CC P03070; P35568: IRS1; Xeno; NbExp=2; IntAct=EBI-617698, EBI-517592;
CC P03070; P52292: KPNA2; Xeno; NbExp=2; IntAct=EBI-617698, EBI-349938;
CC P03070; P52293: Kpna2; Xeno; NbExp=3; IntAct=EBI-617698, EBI-3043908;
CC P03070; O00629: KPNA4; Xeno; NbExp=2; IntAct=EBI-617698, EBI-396343;
CC P03070; P01106: MYC; Xeno; NbExp=2; IntAct=EBI-617698, EBI-447544;
CC P03070; P09884: POLA1; Xeno; NbExp=6; IntAct=EBI-617698, EBI-850026;
CC P03070; Q00577: PURA; Xeno; NbExp=2; IntAct=EBI-617698, EBI-1045860;
CC P03070; P06400: RB1; Xeno; NbExp=6; IntAct=EBI-617698, EBI-491274;
CC P03070; P27694: RPA1; Xeno; NbExp=3; IntAct=EBI-617698, EBI-621389;
CC P03070; P02340: Tp53; Xeno; NbExp=19; IntAct=EBI-617698, EBI-474016;
CC P03070; P04637: TP53; Xeno; NbExp=22; IntAct=EBI-617698, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:3027978,
CC ECO:0000269|PubMed:6096007}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=Large T antigen;
CC IsoId=P03070-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P03081-1; Sequence=External;
CC Name=17kT antigen;
CC IsoId=P03070-2; Sequence=VSP_035893, VSP_035894;
CC Name=SELP;
CC IsoId=P0C6L2-1; Sequence=External;
CC -!- DOMAIN: The J domain is essential for multiple viral activities,
CC including virion assembly, viral DNA replication, transformation and
CC transcriptional activation. {ECO:0000269|PubMed:9488456}.
CC -!- DOMAIN: The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.
CC {ECO:0000269|PubMed:11226179}.
CC -!- DOMAIN: The origin-binding domain (T-ag OBD) interacts specifically
CC with several pentameric sequences 5'-GAGGC-3' in the SV40 origin of DNA
CC replication. {ECO:0000269|PubMed:6298451}.
CC -!- DOMAIN: The zinc finger region contributes to protein-protein
CC interactions essential for the assembly of stable T-antigen hexamers at
CC the origin of replication. The hexamers are required for subsequent
CC alterations in the structure of origin DNA (PubMed:2173794,
CC PubMed:1851875). {ECO:0000269|PubMed:1851875,
CC ECO:0000269|PubMed:2173794}.
CC -!- DOMAIN: The C-terminal region is involved in interaction with host
CC FAM111A. It is also required for the host range and adenovirus helper
CC functions of the virus (PubMed:23093934).
CC {ECO:0000269|PubMed:23093934}.
CC -!- DOMAIN: The ATP binding/ATPase domain is required for proper hexamer
CC assembly and helicase activity. {ECO:0000269|PubMed:11909532}.
CC -!- DOMAIN: Cdc4 phospho-degron (CPD) region is involved in interaction
CC with host FBW7gamma isoform.
CC -!- PTM: Phosphorylated on both serine and threonine residues.
CC Phosphorylation on Ser-120 and Ser-123 inhibits viral replication,
CC while phosphorylation on Thr-124 enhances replication by activating the
CC DNA-binding domain. Phosphorylation on Thr-701 is required for binding
CC to host FBW7gamma isoform. Dephosphorylated preferentially by PP2A on
CC Ser-120, Ser-123, Ser-677 and perhaps Ser-679. Small t antigen inhibits
CC the dephosphorylation by the AC form of PP2A.
CC {ECO:0000269|PubMed:2160857, ECO:0000269|PubMed:2552322,
CC ECO:0000269|PubMed:2838952, ECO:0000269|PubMed:8648725}.
CC -!- PTM: O-Glycosylated near the C-terminal region.
CC {ECO:0000269|PubMed:3027978}.
CC -!- PTM: Acetylated by CBP in a TP53-dependent manner.
CC {ECO:0000269|PubMed:15254196, ECO:0000269|PubMed:205802}.
CC -!- MISCELLANEOUS: The sequence shown is that of strain 776. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 17kT antigen]: Produced by alternative
CC splicing. {ECO:0000305}.
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DR EMBL; J02400; AAB59924.1; -; Genomic_DNA.
DR RefSeq; YP_003708382.1; NC_001669.1.
DR PDB; 1EJL; X-ray; 2.80 A; A/B=126-132.
DR PDB; 1GH6; X-ray; 3.20 A; A=7-117.
DR PDB; 1N25; X-ray; 2.80 A; A/B=260-627.
DR PDB; 1Q1S; X-ray; 2.30 A; A/B=110-133.
DR PDB; 1Q1T; X-ray; 2.50 A; A/B=110-134.
DR PDB; 1SVL; X-ray; 1.95 A; A/B/C=251-627.
DR PDB; 1SVM; X-ray; 1.94 A; A/B/C/D/E/F=251-627.
DR PDB; 1SVO; X-ray; 2.60 A; A/B=251-627.
DR PDB; 1TBD; NMR; -; A=131-260.
DR PDB; 1Z1D; NMR; -; B=131-259.
DR PDB; 2FUF; X-ray; 1.45 A; A=131-259.
DR PDB; 2H1L; X-ray; 3.16 A; A/B/C/D/E/F/G/H/I/J/K/L=260-627.
DR PDB; 2IF9; X-ray; 2.59 A; A/B=131-260.
DR PDB; 2IPR; X-ray; 1.50 A; A/B=131-259.
DR PDB; 2ITJ; X-ray; 2.50 A; A/B=131-259.
DR PDB; 2ITL; X-ray; 1.65 A; A/B=131-259.
DR PDB; 2NL8; X-ray; 2.30 A; A=131-259.
DR PDB; 2NTC; X-ray; 2.40 A; A/B=131-260.
DR PDB; 2TBD; NMR; -; A=131-260.
DR PDB; 3QK2; X-ray; 1.64 A; A=131-260.
DR PDB; 3QN2; X-ray; 1.66 A; A=131-260.
DR PDB; 4E2I; X-ray; 5.00 A; A/B/C/D/E/F/G/H/I/J/K/L=266-627.
DR PDB; 4FGN; X-ray; 3.20 A; A/B=131-260.
DR PDB; 4GDF; X-ray; 2.80 A; A/B/E/F=131-627.
DR PDB; 4RXH; X-ray; 1.76 A; A/C=125-132.
DR PDB; 5D9I; X-ray; 1.70 A; A/B=131-260.
DR PDBsum; 1EJL; -.
DR PDBsum; 1GH6; -.
DR PDBsum; 1N25; -.
DR PDBsum; 1Q1S; -.
DR PDBsum; 1Q1T; -.
DR PDBsum; 1SVL; -.
DR PDBsum; 1SVM; -.
DR PDBsum; 1SVO; -.
DR PDBsum; 1TBD; -.
DR PDBsum; 1Z1D; -.
DR PDBsum; 2FUF; -.
DR PDBsum; 2H1L; -.
DR PDBsum; 2IF9; -.
DR PDBsum; 2IPR; -.
DR PDBsum; 2ITJ; -.
DR PDBsum; 2ITL; -.
DR PDBsum; 2NL8; -.
DR PDBsum; 2NTC; -.
DR PDBsum; 2TBD; -.
DR PDBsum; 3QK2; -.
DR PDBsum; 3QN2; -.
DR PDBsum; 4E2I; -.
DR PDBsum; 4FGN; -.
DR PDBsum; 4GDF; -.
DR PDBsum; 4RXH; -.
DR PDBsum; 5D9I; -.
DR BMRB; P03070; -.
DR SMR; P03070; -.
DR BioGRID; 3509198; 5.
DR DIP; DIP-24251N; -.
DR IntAct; P03070; 60.
DR MINT; P03070; -.
DR BindingDB; P03070; -.
DR ChEMBL; CHEMBL1075257; -.
DR GlyConnect; 326; 1 O-Linked glycan.
DR iPTMnet; P03070; -.
DR PRIDE; P03070; -.
DR ABCD; P03070; 3 sequenced antibodies.
DR EvolutionaryTrace; P03070; -.
DR Proteomes; UP000007705; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003688; F:DNA replication origin binding; IEA:InterPro.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0039686; P:bidirectional double-stranded viral DNA replication; IDA:UniProtKB.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:UniProtKB.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0039649; P:modulation by virus of host ubiquitin-protein ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0039576; P:suppression by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039693; P:viral DNA genome replication; IDA:UniProtKB.
DR CDD; cd06257; DnaJ; 1.
DR DisProt; DP01618; -.
DR Gene3D; 1.10.10.510; -; 1.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR IDEAL; IID90002; -.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR014015; Helicase_SF3_DNA-vir.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR016392; Lg_T_Ag_polyomavir.
DR InterPro; IPR010932; Lg_T_Ag_Polyomavir_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR003133; T_Ag_DNA-bd.
DR InterPro; IPR017910; Znf_lg_T-Ag_D1-typ.
DR InterPro; IPR037102; Znf_lg_T-Ag_D1_dom_sf.
DR Pfam; PF06431; Polyoma_lg_T_C; 1.
DR Pfam; PF02217; T_Ag_DNA_bind; 1.
DR PIRSF; PIRSF003368; Large_T_antigen_polyomaV; 1.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS51206; SF3_HELICASE_1; 1.
DR PROSITE; PS51287; T_AG_OBD; 1.
DR PROSITE; PS51341; ZF_LTAG_D1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation;
KW Alternative splicing; ATP-binding; Direct protein sequencing;
KW DNA replication; DNA-binding; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein;
KW Helicase; Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host JAK1 by virus; Metal-binding;
KW Modulation of host cell cycle by virus;
KW Modulation of host E3 ubiquitin ligases by virus;
KW Modulation of host ubiquitin pathway by virus; Nucleotide-binding;
KW Oncogene; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..708
FT /note="Large T antigen"
FT /id="PRO_0000115046"
FT DOMAIN 12..75
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 400..560
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 139..254
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 265..357
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 63..89
FT /note="Binding of LT to the CUL7 complex"
FT REGION 109..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..672
FT /note="Binding to host TP53 protein"
FT REGION 418..616
FT /note="ATPase activity"
FT REGION 627..708
FT /note="C-terminal region"
FT REGION 630..685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 699..708
FT /note="CPD"
FT MOTIF 103..107
FT /note="LXCXE motif"
FT /evidence="ECO:0000269|PubMed:11226179"
FT MOTIF 125..132
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:6096007"
FT COMPBIAS 120..134
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 645..659
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..684
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 426..433
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT MOD_RES 1
FT /note="N-acetylmethionine; by host"
FT /evidence="ECO:0000269|PubMed:205802"
FT MOD_RES 106
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT MOD_RES 112
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT MOD_RES 120
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857"
FT MOD_RES 123
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT MOD_RES 124
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2552322, ECO:0000269|PubMed:2838952,
FT ECO:0000269|PubMed:8648725"
FT MOD_RES 639
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857"
FT MOD_RES 676
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2838952"
FT MOD_RES 677
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT MOD_RES 679
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT MOD_RES 697
FT /note="N6-acetyllysine; by host"
FT /evidence="ECO:0000269|PubMed:15254196"
FT MOD_RES 701
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:2160857,
FT ECO:0000269|PubMed:2838952"
FT VAR_SEQ 132..135
FT /note="VEDP -> ALLT (in isoform 17kT antigen)"
FT /evidence="ECO:0000303|PubMed:8223482"
FT /id="VSP_035893"
FT VAR_SEQ 136..708
FT /note="Missing (in isoform 17kT antigen)"
FT /evidence="ECO:0000303|PubMed:8223482"
FT /id="VSP_035894"
FT VARIANT 531
FT /note="Y -> F"
FT VARIANT 549
FT /note="P -> A"
FT MUTAGEN 98
FT /note="F->A: Complete loss of interaction with host CUL7."
FT /evidence="ECO:0000269|PubMed:16140746"
FT MUTAGEN 124
FT /note="T->A: 200-fold reduction in phosphorylation by CDC2.
FT No DNA replication activation."
FT /evidence="ECO:0000269|PubMed:8648725"
FT MUTAGEN 679
FT /note="S->A: Enhanced DNA replication."
FT MUTAGEN 701
FT /note="T->A: Complete loss of interaction with host
FT FBW7gamma isoform."
FT /evidence="ECO:0000269|PubMed:15611062"
FT HELIX 7..16
FT /evidence="ECO:0007829|PDB:1GH6"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:1GH6"
FT TURN 37..40
FT /evidence="ECO:0007829|PDB:1GH6"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:1GH6"
FT TURN 48..52
FT /evidence="ECO:0007829|PDB:1GH6"
FT HELIX 53..67
FT /evidence="ECO:0007829|PDB:1GH6"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:1GH6"
FT HELIX 91..102
FT /evidence="ECO:0007829|PDB:1GH6"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 140..145
FT /evidence="ECO:0007829|PDB:2FUF"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:2FUF"
FT STRAND 182..189
FT /evidence="ECO:0007829|PDB:2FUF"
FT STRAND 192..203
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 205..215
FT /evidence="ECO:0007829|PDB:2FUF"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4GDF"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 229..236
FT /evidence="ECO:0007829|PDB:2FUF"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:2FUF"
FT HELIX 270..279
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 285..293
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:1SVM"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:1SVO"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 333..354
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 357..375
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:1SVL"
FT HELIX 384..394
FT /evidence="ECO:0007829|PDB:1SVM"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 401..414
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 428..431
FT /evidence="ECO:0007829|PDB:1N25"
FT HELIX 432..443
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:2H1L"
FT TURN 454..456
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 457..461
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 462..464
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:1SVM"
FT TURN 479..484
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 490..495
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 498..502
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 535..538
FT /evidence="ECO:0007829|PDB:1SVM"
FT STRAND 541..546
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 551..558
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 562..565
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 572..582
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 585..587
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 593..606
FT /evidence="ECO:0007829|PDB:1SVM"
FT HELIX 609..621
FT /evidence="ECO:0007829|PDB:1SVM"
SQ SEQUENCE 708 AA; 81624 MW; 3E37D4BAFC5D59BD CRC64;
MDKVLNREES LQLMDLLGLE RSAWGNIPLM RKAYLKKCKE FHPDKGGDEE KMKKMNTLYK
KMEDGVKYAH QPDFGGFWDA TEIPTYGTDE WEQWWNAFNE ENLFCSEEMP SSDDEATADS
QHSTPPKKKR KVEDPKDFPS ELLSFLSHAV FSNRTLACFA IYTTKEKAAL LYKKIMEKYS
VTFISRHNSY NHNILFFLTP HRHRVSAINN YAQKLCTFSF LICKGVNKEY LMYSALTRDP
FSVIEESLPG GLKEHDFNPE EAEETKQVSW KLVTEYAMET KCDDVLLLLG MYLEFQYSFE
MCLKCIKKEQ PSHYKYHEKH YANAAIFADS KNQKTICQQA VDTVLAKKRV DSLQLTREQM
LTNRFNDLLD RMDIMFGSTG SADIEEWMAG VAWLHCLLPK MDSVVYDFLK CMVYNIPKKR
YWLFKGPIDS GKTTLAAALL ELCGGKALNV NLPLDRLNFE LGVAIDQFLV VFEDVKGTGG
ESRDLPSGQG INNLDNLRDY LDGSVKVNLE KKHLNKRTQI FPPGIVTMNE YSVPKTLQAR
FVKQIDFRPK DYLKHCLERS EFLLEKRIIQ SGIALLLMLI WYRPVAEFAQ SIQSRIVEWK
ERLDKEFSLS VYQKMKFNVA MGIGVLDWLR NSDDDDEDSQ ENADKNEDGG EKNMEDSGHE
TGIDSQSQGS FQAPQSSQSV HDHNQPYHIC RGFTCFKKPP TPPPEPET
