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P03074

- LT_POVM3

UniProt

P03074 - LT_POVM3

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Protein
Large T antigen
Gene
N/A
Organism
Murine polyomavirus (strain 3) (MPyV)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

Functioni

Isoform large T 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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi293 – 407115T-ag OBD
Add
BLAST
Zinc fingeri416 – 51095T-ag D1-type
Add
BLAST
Nucleotide bindingi575 – 5828ATP Reviewed prediction

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA replication origin binding Source: InterPro
  3. hydrolase activity Source: UniProtKB-KW
  4. metal ion binding Source: UniProtKB-KW
Complete GO annotation...

GO - Biological processi

  1. DNA replication Source: UniProtKB-KW
  2. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
  3. suppression by virus of host JAK1 activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

DNA 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

Keywords - Ligandi

ATP-binding, DNA-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Large T antigen (EC:3.6.4.-)
Short name:
LT
Short name:
LT-AG
OrganismiMurine polyomavirus (strain 3) (MPyV)
Taxonomic identifieri10635 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePolyomaviridaePolyomavirus
Virus hostiMus musculus (Mouse) [TaxID: 10090]
ProteomesiUP000006847: Genome

Subcellular locationi

Host nucleus By similarity

GO - Cellular componenti

  1. host cell nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 782782Large T antigen
PRO_0000115042Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine; by host By similarity
Modified residuei278 – 2781Phosphothreonine; by host By similarity

Post-translational modificationi

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.

Keywords - PTMi

Acetylation, Phosphoprotein

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

MINTiMINT-580307.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi7 – 1711
Beta strandi21 – 233
Helixi27 – 4014
Helixi43 – 453
Helixi49 – 6921

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FAFNMR-A1-79[»]
4FB3X-ray3.79A/B/E290-420[»]
ProteinModelPortaliP03074.
SMRiP03074. Positions 1-79.

Miscellaneous databases

EvolutionaryTraceiP03074.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 7564J
Add
BLAST
Domaini549 – 709161SF3 helicase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni142 – 1465Binding to host RB1 protein and transforming activity By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi279 – 2868Nuclear localization signal By similarity

Domaini

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.

Sequence similaritiesi

Contains 1 J domain.

Keywords - Domaini

Zinc-finger

Family and domain databases

Gene3Di1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR001623. 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]
PfamiPF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
[Graphical view]
SMARTiSM00271. DnaJ. 1 hit.
[Graphical view]
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform Large T antigen (identifier: P03074-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA    50
LMQELNSLWG TFKTEVYNLR MNLGGTGFQG SPPRTAERGT EESGHSPLHD 100
DYWSFSYGSK YFTREWNDFF RKWDPSYQSP PKTAESSEQP DLFCYEEPLL 150
SPNPSSPTDT PAHTAGRRRN PCVAEPDDSI SPDPPRTPVS RKRPRPAGAT 200
GGGGGGVHAN GGSVFGHPTG GTSTPAHPPP YHSQGGSESM GGSDSSGFAE 250
GSFRSDPRCE SENESYSQSC SQSSFNATPP KKAREDPAPS DFPSSLTGYL 300
SHAIYSNKTF PAFLVYSTKE KCKQLYDTIG KFRPEFKCLV HYEEGGMLFF 350
LTMTKHRVSA VKNYCSKLCS VSFLMCKAVT KPMECYQVVT AAPFQLITEN 400
KPGLHQFEFT DEPEEQKAVD WIMVADFALE NNLDDPLLIM GYYLDFAKEV 450
PSCIKCSKEE TRLQIHWKNH RKHAENADLF LNCKAQKTIC QQAADGVLAS 500
RRLKLVECTR SQLLKERLQQ SLLRLKELGS SDALLYLAGV AWYQCLLEDF 550
PQTLFKMLKL LTENVPKRRN ILFRGPVNSG KTGLAAALIS LLGGKSLNIN 600
CPADKLAFEL GVAQDQFVVC FEDVKGQIAL NKQLQPGMGV ANLDNLRDYL 650
DGSVKVNLEK KHSNKRSQLF PPCVCTMNEY LLPQTVWARF HMVLDFTCKP 700
HLAQSLEKCE FLQRERIIQS GDTLALLLIW NFTSDVFDPD IQGLVKEVRD 750
QFASECSYSL FCDILCNVQE GDDPLKDICE YS 782
Length:782
Mass (Da):87,662
Last modified:July 10, 2007 - v2
Checksum:i5E24E1F8A586C7A9
GO
Isoform Middle T antigen (identifier: P03076-1) [UniParc]FASTAAdd to Basket

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.
Length:421
Mass (Da):48,694
GO
Isoform Small t antigen (identifier: P68834-1) [UniParc]FASTAAdd to Basket

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.
Length:195
Mass (Da):22,811
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02289 Genomic DNA. Translation: AAA46872.1.
U27812 Genomic DNA. Translation: AAA93241.1.
U27813 Genomic DNA. Translation: AAA93245.1.
AF442959 Genomic DNA. Translation: AAL35609.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FAF NMR - A 1-79 [» ]
4FB3 X-ray 3.79 A/B/E 290-420 [» ]
ProteinModelPortali P03074.
SMRi P03074. Positions 1-79.
ModBasei Search...

Protein-protein interaction databases

MINTi MINT-580307.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P03074.

Family and domain databases

Gene3Di 1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
3.40.50.300. 1 hit.
InterProi IPR001623. 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 ]
Pfami PF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
[Graphical view ]
SMARTi SM00271. DnaJ. 1 hit.
[Graphical view ]
SUPFAMi SSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEi PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiLT_POVM3
AccessioniPrimary (citable) accession number: P03074
Secondary accession number(s): Q76TX5, Q76W02, Q89471
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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