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Protein

Large T antigen

Gene
N/A
Organism
JC polyomavirus (JCPyV) (JCV)
Status
Reviewed-Annotation score: 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 bindingi140 – 255116T-ag OBDPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri266 – 35893T-ag D1-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi427 – 4348ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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
OrganismiJC polyomavirus (JCPyV) (JCV)
Taxonomic identifieri10632 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePolyomaviridaePolyomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008478 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 688688Large T antigenPRO_0000115040Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine; by hostBy similarity
Modified residuei114 – 1141Phosphoserine; by hostBy similarity
Modified residuei121 – 1211Phosphoserine; by hostBy similarity
Modified residuei124 – 1241Phosphoserine; by hostBy similarity
Modified residuei125 – 1251Phosphothreonine; by hostBy similarity
Modified residuei660 – 6601Phosphoserine; by hostBy similarity
Modified residuei680 – 6801N6-acetyllysine; by hostBy similarity
Modified residuei684 – 6841Phosphothreonine; 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 TP53, inhibiting TP53 binding to DNA. Interacts with host preinitiation complex components TBP, TFIIA and TFIID to regulate transcription initiation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PURAQ005774EBI-8658901,EBI-1045860From a different organism.

Protein-protein interaction databases

IntActiP03072. 1 interaction.
MINTiMINT-110758.

Structurei

Secondary structure

1
688
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi137 – 1393Combined sources
Helixi141 – 1466Combined sources
Beta strandi157 – 1659Combined sources
Helixi166 – 17914Combined sources
Beta strandi183 – 1908Combined sources
Beta strandi193 – 20412Combined sources
Helixi206 – 2149Combined sources
Beta strandi218 – 2203Combined sources
Beta strandi222 – 2298Combined sources
Helixi230 – 2367Combined sources
Beta strandi243 – 2497Combined sources
Helixi255 – 2573Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LIFX-ray2.60A132-261[»]
4LMDX-ray1.50A/B132-261[»]
4NBPX-ray1.32A132-261[»]
5CYNX-ray2.70A132-261[»]
ProteinModelPortaliP03072.
SMRiP03072. Positions 7-119, 132-261, 266-628.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 7564JPROSITE-ProRule annotationAdd
BLAST
Domaini401 – 561161SF3 helicasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni105 – 1095Binding to host RB1 protein and transforming activityBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi126 – 1338Nuclear 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.PROSITE-ProRule annotation
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 fingeri266 – 35893T-ag D1-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

CDDicd06257. DnaJ. 1 hit.
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.
IPR016392. Lg_T_Ag_polyomavir.
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]
PIRSFiPIRSF003368. Large_T_antigen_polyomaV. 1 hit.
SMARTiSM00271. DnaJ. 1 hit.
[Graphical view]
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50076. DNAJ_2. 1 hit.
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Large T antigen (identifier: P03072-1) [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
MDKVLNREES MELMDLLGLD RSAWGNIPVM RKAYLKKCKE LHPDKGGDED
60 70 80 90 100
KMKRMNFLYK KMEQGVKVAH QPDFGTWNSS EVPTYGTDEW ESWWNTFNEK
110 120 130 140 150
WDEDLFCHEE MFASDDENTG SQHSTPPKKK KKVEDPKDFP VDLHAFLSQA
160 170 180 190 200
VFSNRTVASF AVYTTKEKAQ ILYKKLMEKY SVTFISRHGF GGHNILFFLT
210 220 230 240 250
PHRHRVSAIN NYCQKLCTFS FLICKGVNKE YLFYSALCRQ PYAVVEESIQ
260 270 280 290 300
GGLKEHDFNP EEPEETKQVS WKLVTQYALE TKCEDVFLLM GMYLDFQENP
310 320 330 340 350
QQCKKCEKKD QPNHFNHHEK HYYNAQIFAD SKNQKSICQQ AVDTVAAKQR
360 370 380 390 400
VDSIHMTREE MLVERFNFLL DKMDLIFGAH GNAVLEQYMA GVAWIHCLLP
410 420 430 440 450
QMDTVIYDFL KCIVLNIPKK RYWLFKGPID SGKTTLAAAL LDLCGGKSLN
460 470 480 490 500
VNMPLERLNF ELGVGIDQFM VVFEDVKGTG AESRDLPSGH GISNLDCLRD
510 520 530 540 550
YLDGSVKVNL ERKHQNKRTQ VFPPGIVTMN EYSVPRTLQA RFVRQIDFRP
560 570 580 590 600
KAYLRKSLSC SEYLLEKRIL QSGMTLLLLL IWFRPVADFA AAIHERIVQW
610 620 630 640 650
KERLDLEISM YTFSTMKANV GMGRPILDFP REEDSEAEDS GHGSSTESQS
660 670 680
QCFSQVSEAS GADTQENCTF HICKGFQCFK KPKTPPPK
Length:688
Mass (Da):79,311
Last modified:July 21, 1986 - v1
Checksum:i4A55A72F0C10F516
GO
Isoform Small t antigen (identifier: P03083-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P03083.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:172
Mass (Da):20,238
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02226 Genomic DNA. Translation: AAA82102.1.
PIRiA03609. TVVPTJ.
RefSeqiNP_043512.1. NC_001699.1. [P03072-1]

Genome annotation databases

GeneIDi1489517.
KEGGivg:1489517.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02226 Genomic DNA. Translation: AAA82102.1.
PIRiA03609. TVVPTJ.
RefSeqiNP_043512.1. NC_001699.1. [P03072-1]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LIFX-ray2.60A132-261[»]
4LMDX-ray1.50A/B132-261[»]
4NBPX-ray1.32A132-261[»]
5CYNX-ray2.70A132-261[»]
ProteinModelPortaliP03072.
SMRiP03072. Positions 7-119, 132-261, 266-628.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP03072. 1 interaction.
MINTiMINT-110758.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489517.
KEGGivg:1489517.

Family and domain databases

CDDicd06257. DnaJ. 1 hit.
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.
IPR016392. Lg_T_Ag_polyomavir.
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]
PIRSFiPIRSF003368. Large_T_antigen_polyomaV. 1 hit.
SMARTiSM00271. DnaJ. 1 hit.
[Graphical view]
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50076. DNAJ_2. 1 hit.
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLT_POVJC
AccessioniPrimary (citable) accession number: P03072
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 7, 2016
This is version 98 of the entry and version 1 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

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.