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 27-MAR-2024, entry version 195. 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=3; 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=20; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 8. DR DIP; DIP-24251N; -. DR IntAct; P03070; 60. DR MINT; P03070; -. DR BindingDB; P03070; -. DR ChEMBL; CHEMBL1075257; -. DR GlyConnect; 326; 1 O-GlcNAc glycan. DR iPTMnet; P03070; -. DR ABCD; P03070; 3 sequenced antibodies. DR OrthoDB; 14669at10239; -. 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:0039576; P:disruption by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW. DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:UniProtKB. DR GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW. DR GO; GO:0039645; P:perturbation by virus of host G1/S transition checkpoint; 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; 3.40.1310.20; -; 1. DR Gene3D; 1.10.287.110; DnaJ domain; 1. DR Gene3D; 1.20.1050.70; Large T antigen, SV40, domain 3; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.10.10.510; Zinc finger, large T-antigen D1 domain; 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; Chaperone J-domain; 1. DR SUPFAM; SSF55464; Origin of replication-binding domain, RBD-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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; Interferon antiviral system evasion; KW Metal-binding; 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 //