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P03074 (LT_POVM3) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Large T antigen

Short name=LT
Short name=LT-AG
EC=3.6.4.-
OrganismMurine polyomavirus (strain 3) (MPyV) [Complete proteome]
Taxonomic identifier10635 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stagePolyomaviridaePolyomavirus
Virus hostMus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length782 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Isoform largeT antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. 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 By similarity.

Subunit structure

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 preinitiation complex components TBP, TFIIA and TFIID to regulate transcription initiation By similarity.

Subcellular location

Host nucleus By similarity.

Domain

The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation By similarity.

The LXCXE motif specifically binds to host pRB, RBL1, and RBL2 By similarity.

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 By similarity.

The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity By similarity.

Post-translational modification

Phosphorylated on both serine and threonine residues. Small t antigen inhibits the dephosphorylation by the AC form of PP2A By similarity.

O-Glycosylated near the C-terminal region By similarity.

Acetylated by CBP in a TP53-dependent manner By similarity.

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

Keywords
   Biological processDNA replication
G1/S host cell cycle checkpoint dysregulation by virus
Host-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host interferon signaling pathway by virus
Inhibition of host JAK1 by virus
Modulation of host cell cycle by virus
Viral immunoevasion
   Cellular componentHost nucleus
   Coding sequence diversityAlternative splicing
   Developmental stageEarly protein
   DiseaseOncogene
   DomainZinc-finger
   LigandATP-binding
DNA-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host G1/S transition checkpoint

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host JAK1 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA replication origin binding

Inferred from electronic annotation. Source: InterPro

hydrolase activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Large T antigen (identifier: P03074-1)

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 Middle T antigen (identifier: P03076-1)

The sequence of this isoform can be found in the external entry P03076.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoform Small t antigen (identifier: P68834-1)

The sequence of this isoform can be found in the external entry P68834.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 782782Large T antigen
PRO_0000115042

Regions

Domain12 – 7564J
Domain549 – 709161SF3 helicase
DNA binding293 – 407115T-ag OBD
Zinc finger416 – 51095T-ag D1-type
Nucleotide binding575 – 5828ATP Potential
Region142 – 1465Binding to host RB1 protein and transforming activity By similarity
Motif279 – 2868Nuclear localization signal By similarity

Amino acid modifications

Modified residue11N-acetylmethionine; by host By similarity
Modified residue2781Phosphothreonine; by host By similarity

Secondary structure

........... 782
Helix Strand Turn

Details...

Sequences

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

Last modified July 10, 2007. Version 2.
Checksum: 5E24E1F8A586C7A9

FASTA78287,662
        10         20         30         40         50         60 
MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA LMQELNSLWG 

        70         80         90        100        110        120 
TFKTEVYNLR MNLGGTGFQG SPPRTAERGT EESGHSPLHD DYWSFSYGSK YFTREWNDFF 

       130        140        150        160        170        180 
RKWDPSYQSP PKTAESSEQP DLFCYEEPLL SPNPSSPTDT PAHTAGRRRN PCVAEPDDSI 

       190        200        210        220        230        240 
SPDPPRTPVS RKRPRPAGAT GGGGGGVHAN GGSVFGHPTG GTSTPAHPPP YHSQGGSESM 

       250        260        270        280        290        300 
GGSDSSGFAE GSFRSDPRCE SENESYSQSC SQSSFNATPP KKAREDPAPS DFPSSLTGYL 

       310        320        330        340        350        360 
SHAIYSNKTF PAFLVYSTKE KCKQLYDTIG KFRPEFKCLV HYEEGGMLFF LTMTKHRVSA 

       370        380        390        400        410        420 
VKNYCSKLCS VSFLMCKAVT KPMECYQVVT AAPFQLITEN KPGLHQFEFT DEPEEQKAVD 

       430        440        450        460        470        480 
WIMVADFALE NNLDDPLLIM GYYLDFAKEV PSCIKCSKEE TRLQIHWKNH RKHAENADLF 

       490        500        510        520        530        540 
LNCKAQKTIC QQAADGVLAS RRLKLVECTR SQLLKERLQQ SLLRLKELGS SDALLYLAGV 

       550        560        570        580        590        600 
AWYQCLLEDF PQTLFKMLKL LTENVPKRRN ILFRGPVNSG KTGLAAALIS LLGGKSLNIN 

       610        620        630        640        650        660 
CPADKLAFEL GVAQDQFVVC FEDVKGQIAL NKQLQPGMGV ANLDNLRDYL DGSVKVNLEK 

       670        680        690        700        710        720 
KHSNKRSQLF PPCVCTMNEY LLPQTVWARF HMVLDFTCKP HLAQSLEKCE FLQRERIIQS 

       730        740        750        760        770        780 
GDTLALLLIW NFTSDVFDPD IQGLVKEVRD QFASECSYSL FCDILCNVQE GDDPLKDICE 


YS 

« Hide

Isoform Middle T antigen [UniParc].

See P03076.

Isoform Small t antigen [UniParc].

See P68834.

References

[1]"The nucleotide sequence and genome organization of the polyoma early region: extensive nucleotide and amino acid homology with SV40."
Friedmann T., Esty A., LaPorte P., Deininger P.L.
Cell 17:715-724(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The nucleotide sequence and restriction enzyme sites of the polyoma genome."
Deininger P.L., Esty A., LaPorte P., Hsu H., Friedmann T.
Nucleic Acids Res. 8:855-860(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: A3.
[3]"Genetic and structural analysis of a virulence determinant in polyomavirus VP1."
Bauer P.H., Bronson R.T., Fung S.C., Freund R., Stehle T., Harrison S.C., Benjamin T.L.
J. Virol. 69:7925-7931(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate LID and Isolate PTA.
[4]Clark B.E., Griffin B.E.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: BG.
[5]"NMR structure of the N-terminal J domain of murine polyomavirus T antigens. Implications for DnaJ-like domains and for mutations of T antigens."
Berjanskii M.V., Riley M.I., Xie A., Semenchenko V., Folk W.R., Van Doren S.R.
J. Biol. Chem. 275:36094-36103(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-79.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02289 Genomic DNA. Translation: AAA46872.1.
U27812 Genomic DNA. Translation: AAA93241.1.
U27813 Genomic DNA. Translation: AAA93245.1.
AF442959 Genomic DNA. Translation: AAL35609.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FAFNMR-A1-79[»]
4FB3X-ray3.79A/B/E290-420[»]
ProteinModelPortalP03074.
SMRP03074. Positions 1-79.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-580307.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
3.40.50.300. 1 hit.
InterProIPR001623. DnaJ_domain.
IPR014015. Helicase_SF3_DNA-vir.
IPR010932. Lg_T_Ag_Polyomavir_C.
IPR027417. P-loop_NTPase.
IPR003133. T_Ag_DNA-bd.
IPR017910. Znf_lg_T-Ag_D1-typ.
[Graphical view]
PfamPF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
[Graphical view]
SMARTSM00271. DnaJ. 1 hit.
[Graphical view]
SUPFAMSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03074.

Entry information

Entry nameLT_POVM3
AccessionPrimary (citable) accession number: P03074
Secondary accession number(s): Q76TX5, Q76W02, Q89471
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 10, 2007
Last modified: April 16, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references