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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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi293 – 407115T-ag OBDPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri416 – 51095T-ag D1-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi575 – 5828ATPPROSITE-ProRule annotation

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

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-KW
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 antigenPRO_0000115042Add
BLAST

Amino acid modifications

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

Protein-protein interaction databases

MINTiMINT-580307.

Structurei

Secondary structure

1
782
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi7 – 1711Combined sources
Beta strandi21 – 233Combined sources
Helixi27 – 4014Combined sources
Helixi43 – 453Combined sources
Helixi49 – 6921Combined sources

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP03074.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 7564JAdd
BLAST
Domaini549 – 709161SF3 helicasePROSITE-ProRule annotationAdd
BLAST

Region

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

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi279 – 2868Nuclear localization signalBy 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).By similarity
The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity.By similarity

Sequence similaritiesi

Contains 1 J domain.Curated
Contains 1 SF3 helicase domain.PROSITE-ProRule annotation
Contains 1 T-ag D1-type zinc finger.PROSITE-ProRule annotation
Contains 1 T-ag OBD DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri416 – 51095T-ag D1-typePROSITE-ProRule annotationAdd
BLAST

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

        10         20         30         40         50
MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA
60 70 80 90 100
LMQELNSLWG TFKTEVYNLR MNLGGTGFQG SPPRTAERGT EESGHSPLHD
110 120 130 140 150
DYWSFSYGSK YFTREWNDFF RKWDPSYQSP PKTAESSEQP DLFCYEEPLL
160 170 180 190 200
SPNPSSPTDT PAHTAGRRRN PCVAEPDDSI SPDPPRTPVS RKRPRPAGAT
210 220 230 240 250
GGGGGGVHAN GGSVFGHPTG GTSTPAHPPP YHSQGGSESM GGSDSSGFAE
260 270 280 290 300
GSFRSDPRCE SENESYSQSC SQSSFNATPP KKAREDPAPS DFPSSLTGYL
310 320 330 340 350
SHAIYSNKTF PAFLVYSTKE KCKQLYDTIG KFRPEFKCLV HYEEGGMLFF
360 370 380 390 400
LTMTKHRVSA VKNYCSKLCS VSFLMCKAVT KPMECYQVVT AAPFQLITEN
410 420 430 440 450
KPGLHQFEFT DEPEEQKAVD WIMVADFALE NNLDDPLLIM GYYLDFAKEV
460 470 480 490 500
PSCIKCSKEE TRLQIHWKNH RKHAENADLF LNCKAQKTIC QQAADGVLAS
510 520 530 540 550
RRLKLVECTR SQLLKERLQQ SLLRLKELGS SDALLYLAGV AWYQCLLEDF
560 570 580 590 600
PQTLFKMLKL LTENVPKRRN ILFRGPVNSG KTGLAAALIS LLGGKSLNIN
610 620 630 640 650
CPADKLAFEL GVAQDQFVVC FEDVKGQIAL NKQLQPGMGV ANLDNLRDYL
660 670 680 690 700
DGSVKVNLEK KHSNKRSQLF PPCVCTMNEY LLPQTVWARF HMVLDFTCKP
710 720 730 740 750
HLAQSLEKCE FLQRERIIQS GDTLALLLIW NFTSDVFDPD IQGLVKEVRD
760 770 780
QFASECSYSL FCDILCNVQE GDDPLKDICE YS
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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...
MobiDBi 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: November 26, 2014
This is version 95 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