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Reviewed, UniProtKB/Swiss-Prot P03070 (LT_SV40)

Last modified June 16, 2009. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Large T antigen
      Short name=LT-AG
      Short name=LT
    EC=3.6.1.-
OrganismSimian virus 40 (SV40)
Taxonomic identifier10633 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stagePolyomaviridaePolyomavirus
Virus hostMacaca (macaques) [TaxID: 9539]

Protein attributes

Sequence length708 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Isoform large T antigen plays a role in virion assembly. Autoregulates the synthesis of the viral early mRNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription. Ref.21 Ref.22 Ref.23 Ref.26 Ref.27

Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain. Ref.21 Ref.22 Ref.23 Ref.26 Ref.27

Subunit structure

Isoform large T antigen forms homohexamers in the presence of ATP. Interacts with host HDAC1. Interacts (via LXCXE domain) with host RB1; the interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Interacts (via LXCXE domain) with host pRB-related proteins RBL1 and RBL2. Interacts (via C-terminus) with host TOP1 and POLA1 allowing DNA replication. Interacts with host TP53, inhibiting TP53 binding to DNA. Interacts with host preinitiation complex components TBP, TFIIA and TFIID to regulate transcription initiation. Ref.21 Ref.22 Ref.27 Ref.5 Ref.8 Ref.10 Ref.13 Ref.19 Ref.28

Subcellular location

Host nucleus. Ref.9

Domain

The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation. Ref.23 Ref.15 Ref.16 Ref.24

The LXCXE motif specifically binds to host pRB, RBL1, and RBL2. Ref.23 Ref.15 Ref.16 Ref.24

The origin-binding domain (T-ag OBD) interacts specifically with several pentameric sequences 5'-GAGGC-3' in the SV40 origin of DNA replication. Ref.23 Ref.15 Ref.16 Ref.24

The zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication. The hexamers are required for subsequent alterations in the structure of origin DNA. Ref.23 Ref.15 Ref.16 Ref.24

The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity. Ref.23 Ref.15 Ref.16 Ref.24

Post-translational modification

Phosphorylated on both serine and threonine residues. Phosphorylation on Ser-120 and Ser-123 inhibits viral replication, while phosphorylation on Thr-124 enhances replication by activating the DNA-binding domain. Dephosphorylated preferentially by PP2A on Ser-120, Ser-123, Ser-677 and perhaps Ser-679. Small t antigen inhibits the dephosphorylation by the AC form of PP2A. Ref.4 Ref.11 Ref.14 Ref.17 Ref.18 Ref.20

O-Glycosylated near the C-terminal region. Ref.9

Acetylated by CBP in a TP53-dependent manner.

Sequence similarities

Contains 1 J domain.

Contains 1 SF3 helicase domain.

Contains 1 T-ag D1-type zinc finger.

Contains 1 T-ag OBD DNA-binding domain.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MYCP011061EBI-617698,EBI-447544From a different organism.
TP53P046373EBI-617698,EBI-366083From a different organism.
Tp53P023406EBI-617698,EBI-474016From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform Large T antigen (identifier: P03070-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Small t antigen (identifier: P03081-1)

The sequence of this isoform can be found in the external entry P03081-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative splicing.
Isoform 17kT antigen (identifier: P03070-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-135: VEDP → ALLT
     136-708: Missing.
Note: Produced by alternative splicing.
Isoform SELP (identifier: P0C6L2-1)

The sequence of this isoform can be found in the external entry P0C6L2-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 708708Large T antigen
PRO_0000115046

Regions

Domain12 – 7564J
Domain400 – 560161SF3 helicase
DNA binding139 – 254116T-ag OBD Ref.6
Zinc finger265 – 35793T-ag D1-type
Nucleotide binding426 – 4338ATP Potential
Region337 – 672336Binding to host TP53 protein
Region418 – 616199ATPase actvity
Motif103 – 1075LXCXE motif
Motif125 – 1328Nuclear localization signal Ref.7
Compositional bias633 – 6386Poly-Asp

Amino acid modifications

Modified residue11N-acetylmethionine; by host
Modified residue1061Phosphoserine; by host
Modified residue1121Phosphoserine; by host
Modified residue1201Phosphoserine; by host
Modified residue1231Phosphoserine; by host
Modified residue1241Phosphothreonine; by host
Modified residue6391Phosphoserine; by host
Modified residue6761Phosphoserine; by host
Modified residue6771Phosphoserine; by host
Modified residue6791Phosphoserine; by host
Modified residue6971N6-acetyllysine; by host
Modified residue7011Phosphothreonine; by host

Natural variations

Alternative sequence132 – 1354VEDP → ALLT in isoform 17kT antigen.
VSP_035893
Alternative sequence136 – 708573Missing in isoform 17kT antigen.
VSP_035894
Natural variant5311F → Y in strain: 776.
Natural variant5491A → P in strain: 776.
Natural variant5521Y → P in strain: 776.

Experimental info

Mutagenesis1241T → A: 200-fold reduction in phosphorylation by CDC2. No DNA replication activation. Ref.20
Mutagenesis6791S → A: Enhanced DNA replication.

Secondary structure

..................................................................................................... 708
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Large T antigen [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: CB81306EF9E4E2C0

FASTA70881,582
        10         20         30         40         50         60 
MDKVLNREES LQLMDLLGLE RSAWGNIPLM RKAYLKKCKE FHPDKGGDEE KMKKMNTLYK 

        70         80         90        100        110        120 
KMEDGVKYAH QPDFGGFWDA TEIPTYGTDE WEQWWNAFNE ENLFCSEEMP SSDDEATADS 

       130        140        150        160        170        180 
QHSTPPKKKR KVEDPKDFPS ELLSFLSHAV FSNRTLACFA IYTTKEKAAL LYKKIMEKYS 

       190        200        210        220        230        240 
VTFISRHNSY NHNILFFLTP HRHRVSAINN YAQKLCTFSF LICKGVNKEY LMYSALTRDP 

       250        260        270        280        290        300 
FSVIEESLPG GLKEHDFNPE EAEETKQVSW KLVTEYAMET KCDDVLLLLG MYLEFQYSFE 

       310        320        330        340        350        360 
MCLKCIKKEQ PSHYKYHEKH YANAAIFADS KNQKTICQQA VDTVLAKKRV DSLQLTREQM 

       370        380        390        400        410        420 
LTNRFNDLLD RMDIMFGSTG SADIEEWMAG VAWLHCLLPK MDSVVYDFLK CMVYNIPKKR 

       430        440        450        460        470        480 
YWLFKGPIDS GKTTLAAALL ELCGGKALNV NLPLDRLNFE LGVAIDQFLV VFEDVKGTGG 

       490        500        510        520        530        540 
ESRDLPSGQG INNLDNLRDY LDGSVKVNLE KKHLNKRTQI FPPGIVTMNE FSVPKTLQAR 

       550        560        570        580        590        600 
FVKQIDFRAK DYLKHCLERS EFLLEKRIIQ SGIALLLMLI WYRPVAEFAQ SIQSRIVEWK 

       610        620        630        640        650        660 
ERLDKEFSLS VYQKMKFNVA MGIGVLDWLR NSDDDDEDSQ ENADKNEDGG EKNMEDSGHE 

       670        680        690        700 
TGIDSQSQGS FQAPQSSQSV HDHNQPYHIC RGFTCFKKPP TPPPEPET 

« Hide

Isoform Small t antigen.

See P03081.

FASTA
Isoform 17kT antigen.

Checksum: 34517296D3E87E4F
Show »

FASTA13515,754
Isoform SELP.

See P0C6L2.

FASTA

References

[1]"The genome of simian virus 40."
Reddy V.B., Thimmappaya B., Dhar R., Subramanian K.N., Zain B.S., Pan J., Ghosh P.K., Celma M.L., Weissman S.M.
Science 200:494-502(1978) [PubMed: 205947] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Complete nucleotide sequence of SV40 DNA."
Fiers W., Contreras R., Haegeman G., Rogiers R., van de Voorde A., van Heuverswyn H., van Herreweghe J., Volckaert G., Ysebaert M.
Nature 273:113-120(1978) [PubMed: 205802] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ACETYLATION AT MET-1.
Strain: 776.
[3]"Independent expression of the transforming amino-terminal domain of SV40 large I antigen from an alternatively spliced third SV40 early mRNA."
Zerrahn J., Knippschild U., Winkler T., Deppert W.
EMBO J. 12:4739-4746(1993) [PubMed: 8223482] [Abstract]
Cited for: PROTEIN SEQUENCE (ISOFORM 17KT ANTIGEN), ALTERNATIVE SPLICING.
[4]"Phosphorylation of large tumour antigen by cdc2 stimulates SV40 DNA replication."
McVey D., Brizuela L., Mohr I., Marshak D.R., Gluzman Y., Beach D.
Nature 341:503-507(1989) [PubMed: 2552322] [Abstract]
Cited for: PROTEIN SEQUENCE OF 102-118, PHOSPHORYLATION AT THR-124 BY CDC2.
[5]"T antigen is bound to a host protein in SV40-transformed cells."
Lane D.P., Crawford L.V.
Nature 278:261-263(1979) [PubMed: 218111] [Abstract]
Cited for: INTERACTION WITH HOST TP53.
[6]"Topography of simian virus 40 A protein-DNA complexes: arrangement of pentanucleotide interaction sites at the origin of replication."
DeLucia A.L., Lewton B.A., Tjian R., Tegtmeyer P.
J. Virol. 46:143-150(1983) [PubMed: 6298451] [Abstract]
Cited for: DNA-BINDING.
[7]"A short amino acid sequence able to specify nuclear location."
Kalderon D., Roberts B.L., Richardson W.D., Smith A.E.
Cell 39:499-509(1984) [PubMed: 6096007] [Abstract]
Cited for: NUCLEAR LOCALIZATION SIGNAL.
[8]"T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication."
Smale S.T., Tjian R.
Mol. Cell. Biol. 6:4077-4087(1986) [PubMed: 3025630] [Abstract]
Cited for: INTERACTION WITH HOST POLA1.
[9]"Glycosylation of simian virus 40 T antigen and localization of glycosylated T antigen in the nuclear matrix."
Schmitt M.K., Mann K.
Virology 156:268-281(1987) [PubMed: 3027978] [Abstract]
Cited for: GLYCOSYLATION, SUBCELLULAR LOCATION.
[10]"SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene."
Decaprio J.A., Ludlow J.W., Figge J., Shew J.-Y., Huang C.-M., Lee W.-H., Marsilio E., Paucha E., Livingston D.M.
Cell 54:275-283(1988) [PubMed: 2839300] [Abstract]
Cited for: INTERACTION WITH HOST RB PROTEIN.
[11]"In vitro phosphorylation of SV40 large T antigen."
Graesser F.A., Scheidmann K.H., Tuazon P.T., Traugh J.A., Walter G.
Virology 165:13-22(1988) [PubMed: 2838952] [Abstract]
Cited for: PHOSPHORYLATION.
[12]"Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A."
Virshup D.M., Kauffman M.G., Kelly T.J.
EMBO J. 8:3891-3898(1989) [PubMed: 2555176] [Abstract]
Cited for: ACTIVATION OF DNA REPLICATION BY HOST PP2A.
[13]"The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus."
Dyson N., Buchkovich K., Whyte P., Harlow E.
Cell 58:249-255(1989) [PubMed: 2546678] [Abstract]
Cited for: INTERACTION WITH HOST RBL1.
[14]"The replication functions of SV40 T antigen are regulated by phosphorylation."
Prives C.
Cell 61:735-738(1990) [PubMed: 2160857] [Abstract]
Cited for: PHOSPHORYLATION.
[15]"The finger domain of simian virus 40 large T antigen controls DNA-binding specificity."
Hoess A., Moarefi I.F., Fanning E., Arthur A.K.
J. Virol. 64:6291-6296(1990) [PubMed: 2173794] [Abstract]
Cited for: ZINC-FINGER DOMAIN.
[16]"The zinc finger region of simian virus 40 large T antigen is needed for hexamer assembly and origin melting."
Loeber G., Stenger J.E., Ray S., Parsons R.E., Anderson M.E., Tegtmeyer P.
J. Virol. 65:3167-3174(1991) [PubMed: 1851875] [Abstract]
Cited for: ZINC-FINGER DOMAIN.
[17]"Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen."
Scheidtmann K.H., Mumby M.C., Rundell K., Walter G.
Mol. Cell. Biol. 11:1996-2003(1991) [PubMed: 1848668] [Abstract]
Cited for: DEPHOSPHORYLATION BY HOST PP2A.
[18]"Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity."
Scheidtmann K.H., Virshup D.M., Kelly T.J.
J. Virol. 65:2098-2101(1991) [PubMed: 1848320] [Abstract]
Cited for: DEPHOSPHORYLATION BY HOST PP2A.
[19]"Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product."
Chellappan S., Kraus V.B., Kroger B., Munger K., Howley P.M., Phelps W.C., Nevins J.R.
Proc. Natl. Acad. Sci. U.S.A. 89:4549-4553(1992) [PubMed: 1316611] [Abstract]
Cited for: INTERACTION WITH HOST RB1.
[20]"Mechanisms of simian virus 40 T-antigen activation by phosphorylation of threonine 124."
McVey D., Woelker B., Tegtmeyer P.
J. Virol. 70:3887-3893(1996) [PubMed: 8648725] [Abstract]
Cited for: PHOSPHORYLATION AT THR-124, MUTAGENESIS OF THR-124.
[21]"TAF-like function of SV40 large T antigen."
Damania B., Alwine J.C.
Genes Dev. 10:1369-1381(1996) [PubMed: 8647434] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST TBP AND TFIID.
[22]"Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element."
Damania B., Lieberman P., Alwine J.C.
Mol. Cell. Biol. 18:3926-3935(1998) [PubMed: 9632777] [Abstract]
Cited for: FUNCTION IN TRANSCRIPTION INITIATION, INTERACTION WITH HOST TFIIA.
[23]"The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins."
Zalvide J., Stubdal H., DeCaprio J.A.
Mol. Cell. Biol. 18:1408-1415(1998) [PubMed: 9488456] [Abstract]
Cited for: J DOMAIN FUNCTION.
[24]"SV40 large T antigen hexamer structure: domain organization and DNA-induced conformational changes."
VanLoock M.S., Alexandrov A., Yu X., Cozzarelli N.R., Egelman E.H.
Curr. Biol. 12:472-476(2002) [PubMed: 11909532] [Abstract]
Cited for: ATPASE DOMAIN.
[25]"p53 targets simian virus 40 large T antigen for acetylation by CBP."
Poulin D.L., Kung A.L., DeCaprio J.A.
J. Virol. 78:8245-8253(2004) [PubMed: 15254196] [Abstract]
Cited for: ACETYLATION.
[26]"PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site."
Skoczylas C., Henglein B., Rundell K.
Virology 332:596-601(2005) [PubMed: 15680424] [Abstract]
Cited for: FUNCTION OF ISOFORM 17KT.
[27]"Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation."
Valls E., Blanco-Garcia N., Aquizu N., Piedra D., Estaras C., de la Cruz X., Martinez-Balbas M.A.
Nucleic Acids Res. 35:1958-1968(2007) [PubMed: 17341466] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST HDAC1.
[28]"Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen."
Khopde S., Simmons D.T.
J. Virol. 82:1136-1145(2008) [PubMed: 18003733] [Abstract]
Cited for: INTERACTION WITH HOST TOP1.
[29]"Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen."
Kim H.-Y., Ahn B.-Y., Cho Y.
EMBO J. 20:295-304(2001) [PubMed: 11226179] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 7-117.
[30]"Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen."
Li D., Zhao R., Lilyestrom W., Gai D., Zhang R., DeCaprio J.A., Fanning E., Jochimiak A., Szakonyi G., Chen X.S.
Nature 423:512-518(2003) [PubMed: 12774115] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 260-627.
[31]"Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen."
Gai D., Zhao R., Li D., Finkielstein C.V., Chen X.S.
Cell 119:47-60(2004) [PubMed: 15454080] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 251-627.
[32]"Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor."
Lilyestrom W., Klein M.G., Zhang R., Joachimiak A., Chen X.S.
Genes Dev. 20:2373-2382(2006) [PubMed: 16951253] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 251-627.
+Additional computationally mapped references.

Cross-references

Sequence databases

J02400 Genomic DNA. Translation: AAB59924.1.
RefSeqNP_043127.1.

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1EJLX-ray2.80A/B126-132[»]
1GH6X-ray3.20A7-117[»]
1N25X-ray2.80A/B260-627[»]
1Q1SX-ray2.30A/B112-133[»]
1Q1TX-ray2.50A/B112-133[»]
1SVLX-ray1.95A/B/C251-627[»]
1SVMX-ray1.94A/B/C/D/E/F251-627[»]
1SVOX-ray2.60A/B251-627[»]
1TBDNMR-A131-260[»]
1Z1DNMR-B131-259[»]
2FUFX-ray1.45A131-259[»]
2H1LX-ray3.16A/B/C/D/E/F/G/H/I/J/K/L260-627[»]
2IF9X-ray2.59A/B131-260[»]
2IPRX-ray1.50A/B131-259[»]
2ITJX-ray2.50A/B131-259[»]
2ITLX-ray1.65A/B131-259[»]
2NL8X-ray2.30A131-259[»]
2NTCX-ray2.40A/B131-260[»]
2TBDNMR-A131-260[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:24251N.
IntActP03070. 4 interactions.

PTM databases

GlycoSuiteDBP03070.

Genome annotation databases

GeneID1489531.

Family and domain databases

InterProIPR001623. DnaJ_N.
IPR018253. Heat_shock_DnaJ_CS.
IPR014015. Helicase_SF3_DNA-vir.
IPR016392. Lg_T_Ag_polyomavir.
IPR010932. Lg_T_Ag_Polyomavir_C.
IPR003133. T_Ag_DNA_bd.
IPR017910. Znf_lg_T-Ag_D1-typ.
[Graphical view]
Gene3DG3DSA:1.10.287.110. DnaJ_N. 1 hit.
PfamPF00226. DnaJ. 1 hit.
PF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
[Graphical view]
PIRSFPIRSF003368. Large_T_antigen_polyomaV. 1 hit.
SMARTSM00271. DnaJ. 1 hit.
[Graphical view]
PROSITEPS00636. DNAJ_1. False negative.
PS50076. DNAJ_2. 1 hit.
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameLT_SV40
AccessionPrimary (citable) accession number: P03070
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1996
Last modified: June 16, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectVirus (Virus annotation project)

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents