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Protein

Large T antigen

Gene
N/A
Organism
Murine polyomavirus (strain A2) (MPyV)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Protein inferred from homologyi

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)DescriptionActionsGraphical viewLength
DNA bindingi293 – 406T-ag OBDPROSITE-ProRule annotationAdd BLAST114
Zinc fingeri415 – 508T-ag D1-typePROSITE-ProRule annotationAdd BLAST94
Nucleotide bindingi573 – 580ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Hydrolase
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
LigandATP-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 A2) (MPyV)
Taxonomic identifieri10636 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePolyomaviridae
Virus hostiMus musculus (Mouse) [TaxID: 10090]
Proteomesi
  • UP000008479 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001150431 – 785Large T antigenAdd BLAST785

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; by hostBy similarity1
Modified residuei278Phosphothreonine; by hostBy similarity1

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

Proteomic databases

PRIDEiP03073.

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

Structurei

3D structure databases

ProteinModelPortaliP03073.
SMRiP03073.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 75JAdd BLAST64
Domaini547 – 707SF3 helicasePROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni142 – 146Binding to host RB1 protein and transforming activityBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi279 – 286Nuclear localization signalBy similarity8

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri415 – 508T-ag D1-typePROSITE-ProRule annotationAdd BLAST94

Keywords - Domaini

Zinc-finger

Phylogenomic databases

OrthoDBiVOG0900002Y.

Family and domain databases

Gene3Di1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
InterProiView protein in InterPro
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.
PfamiView protein in Pfam
PF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
SMARTiView protein in SMART
SM00271. DnaJ. 1 hit.
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Large T antigen (identifier: P03073-1) [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 VKNYCSKLCR SFLMCKAVTK PMECYQVVTA APFQLITENK
410 420 430 440 450
PGLHQFEFTD EPEEQKAVDW IMVADFALEN NLDDPLLIMG YYLDFAKEVP
460 470 480 490 500
SCIKCSKEET RLQIHWKNHR KHAENADLFL NCKAQKTICQ QAAASLASRR
510 520 530 540 550
LKLVECTRSQ LLKERLQQSL LRLKELGSSD ALLYLAGVAW YQCLLEDFPQ
560 570 580 590 600
TLFKMLKLLT ENVPKRRNIL FRGPVNSGKT GLAAALISLL GGKSLNINCP
610 620 630 640 650
ADKLAFELGV AQDQFVVCFE DVKGQIALNK QLQPGMGVAN LDNLRTTWNG
660 670 680 690 700
SVKVNLEKKH SNKRSQLFPP CVCTMNEYLL PQTVWARFHM VLDFTCKPHL
710 720 730 740 750
AQSLEKCEFL QRERIIQSGD TLALLLIWNF TSDVFDPDIQ GLVKEVRDQF
760 770 780
ASECSYSLFC DILCNVQEGD DPLKDICDIA EYTVY
Length:785
Mass (Da):88,091
Last modified:July 21, 1986 - v1
Checksum:i34E00D0612BA7E93
GO
Isoform Middle T antigen (identifier: P03077-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P03077.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:421
Mass (Da):48,622
GO
Isoform Small t antigen (identifier: P68835-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P68835.
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
J02288 Genomic DNA. Translation: AAB59901.1.
PIRiD03635. TVVPT.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02288 Genomic DNA. Translation: AAB59901.1.
PIRiD03635. TVVPT.

3D structure databases

ProteinModelPortaliP03073.
SMRiP03073.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiP03073.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

OrthoDBiVOG0900002Y.

Family and domain databases

Gene3Di1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
InterProiView protein in InterPro
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.
PfamiView protein in Pfam
PF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
SMARTiView protein in SMART
SM00271. DnaJ. 1 hit.
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiLT_POVMA
AccessioniPrimary (citable) accession number: P03073
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 12, 2017
This is version 101 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.