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UniProtKB - P03070 (LT_SV40)

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Protein

Large T antigen

Gene
N/A
Organism
Simian virus 40 (SV40)
Status
Reviewed-Annotation score: Annotation score: 5 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. May inactivate the growth-suppressing properties of the E3 ubiquitin ligase CUL7.
Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi139 – 254T-ag OBDPROSITE-ProRule annotationAdd BLAST116
Zinc fingeri265 – 357T-ag D1-typePROSITE-ProRule annotationAdd BLAST93
Nucleotide bindingi426 – 433ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DNA replication origin binding Source: InterPro
  • double-stranded DNA binding Source: UniProtKB
  • helicase activity Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • single-stranded DNA binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionActivator, DNA-binding, Helicase, 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, Modulation of host E3 ubiquitin ligases by virus, Modulation of host ubiquitin pathway by virus, Transcription, Transcription regulation, 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
OrganismiSimian virus 40 (SV40)
Taxonomic identifieri1891767 [NCBI]
Taxonomic lineageiViruses › dsDNA viruses, no RNA stage › Polyomaviridae ›
Virus hostiMacaca (macaques) [TaxID: 9539]
Proteomesi
  • UP000007705 Componenti: Genome

Subcellular locationi

  • Host nucleus 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi98F → A: Complete loss of interaction with host CUL7. 1 Publication1
Mutagenesisi124T → A: 200-fold reduction in phosphorylation by CDC2. No DNA replication activation. 1 Publication1
Mutagenesisi679S → A: Enhanced DNA replication. 1
Mutagenesisi701T → A: Complete loss of interaction with host FBW7gamma isoform. 1 Publication1

Keywords - Diseasei

Oncogene

Chemistry databases

ChEMBLiCHEMBL1075257.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001150461 – 708Large T antigenAdd BLAST708

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; by host1 Publication1
Modified residuei106Phosphoserine; by host2 Publications1
Modified residuei112Phosphoserine; by host2 Publications1
Modified residuei120Phosphoserine; by host1 Publication1
Modified residuei123Phosphoserine; by host2 Publications1
Modified residuei124Phosphothreonine; by host4 Publications1
Modified residuei639Phosphoserine; by host1 Publication1
Modified residuei676Phosphoserine; by host1 Publication1
Modified residuei677Phosphoserine; by host2 Publications1
Modified residuei679Phosphoserine; by host2 Publications1
Modified residuei697N6-acetyllysine; by host1 Publication1
Modified residuei701Phosphothreonine; by host2 Publications1

Post-translational modificationi

Phosphorylated on both serine and threonine residues. Phosphorylation on Ser-120 and Ser-123 inhibits viral replication, while phosphorylation on Thr-124 enhances replication by activating the DNA-binding domain. Phosphorylation on Thr-701 is required for binding to host FBW7gamma isoform. Dephosphorylated preferentially by PP2A on Ser-120, Ser-123, Ser-677 and perhaps Ser-679. Small t antigen inhibits the dephosphorylation by the AC form of PP2A.4 Publications
O-Glycosylated near the C-terminal region.1 Publication
Acetylated by CBP in a TP53-dependent manner.2 Publications

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP03070.

PTM databases

iPTMnetiP03070.
UniCarbKBiP03070.

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Isoform large T antigen 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. LT interacts (via CPD region) with host FBW7gamma isoform (via WD repeats); seems to function as a competitive inhibitor of FBW7gamma function for physiologic substrates. LT interacts with host E3 ubiquitin ligase CUL7; this interaction seems to inhibit CUL7. Component of a SCF(CUL7)-like complex composed of SV40 Lt and host proteins CUL7, SKP1, RBX1, and FBXW8. LT interacts with host BUB1; this interaction induces activation of a DNA damage response and promotes p53 stabilization and phosphorylation (Probable). Interacts with host FAM111A and this interaction is required for efficient viral replication and sustained viral gene expression in restrictive cell types.Curated13 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi3509198. 1 interactor.
DIPiDIP-24251N.
IntActiP03070. 59 interactors.
MINTiMINT-91005.

Chemistry databases

BindingDBiP03070.

Structurei

Secondary structure

1708
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi7 – 16Combined sources10
Helixi27 – 36Combined sources10
Turni37 – 40Combined sources4
Turni43 – 45Combined sources3
Turni48 – 52Combined sources5
Helixi53 – 67Combined sources15
Beta strandi87 – 89Combined sources3
Helixi91 – 102Combined sources12
Beta strandi136 – 138Combined sources3
Helixi140 – 145Combined sources6
Beta strandi156 – 163Combined sources8
Helixi165 – 178Combined sources14
Beta strandi182 – 189Combined sources8
Beta strandi192 – 203Combined sources12
Helixi205 – 215Combined sources11
Beta strandi217 – 219Combined sources3
Beta strandi221 – 227Combined sources7
Helixi229 – 236Combined sources8
Beta strandi242 – 248Combined sources7
Helixi251 – 254Combined sources4
Helixi270 – 279Combined sources10
Helixi285 – 293Combined sources9
Helixi294 – 296Combined sources3
Turni299 – 301Combined sources3
Helixi303 – 306Combined sources4
Helixi311 – 314Combined sources4
Helixi317 – 327Combined sources11
Helixi333 – 354Combined sources22
Helixi357 – 375Combined sources19
Beta strandi377 – 379Combined sources3
Helixi384 – 394Combined sources11
Turni395 – 397Combined sources3
Helixi401 – 414Combined sources14
Beta strandi421 – 425Combined sources5
Beta strandi428 – 431Combined sources4
Helixi432 – 443Combined sources12
Beta strandi446 – 448Combined sources3
Beta strandi450 – 452Combined sources3
Turni454 – 456Combined sources3
Helixi457 – 461Combined sources5
Helixi462 – 464Combined sources3
Beta strandi470 – 472Combined sources3
Turni479 – 484Combined sources6
Helixi490 – 495Combined sources6
Helixi498 – 502Combined sources5
Beta strandi507 – 509Combined sources3
Beta strandi512 – 514Combined sources3
Beta strandi517 – 519Combined sources3
Beta strandi524 – 528Combined sources5
Helixi535 – 538Combined sources4
Beta strandi541 – 546Combined sources6
Helixi551 – 558Combined sources8
Helixi562 – 565Combined sources4
Helixi572 – 582Combined sources11
Helixi585 – 587Combined sources3
Helixi590 – 592Combined sources3
Helixi593 – 606Combined sources14
Helixi609 – 621Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EJLX-ray2.80A/B126-132[»]
1GH6X-ray3.20A7-117[»]
1N25X-ray2.80A/B260-627[»]
1Q1SX-ray2.30A/B110-133[»]
1Q1TX-ray2.50A/B110-134[»]
1SVLX-ray1.95A/B/C251-627[»]
1SVMX-ray1.94A/B/C/D/E/F251-627[»]
1SVOX-ray2.60A/B251-627[»]
1TBDNMR-A131-260[»]
1Z1DNMR-B131-259[»]
2FUFX-ray1.45A131-259[»]
2H1LX-ray3.16A/B/C/D/E/F/G/H/I/J/K/L260-627[»]
2IF9X-ray2.59A/B131-260[»]
2IPRX-ray1.50A/B131-259[»]
2ITJX-ray2.50A/B131-259[»]
2ITLX-ray1.65A/B131-259[»]
2NL8X-ray2.30A131-259[»]
2NTCX-ray2.40A/B131-260[»]
2TBDNMR-A131-260[»]
3QK2X-ray1.64A131-260[»]
3QN2X-ray1.66A131-260[»]
4E2IX-ray5.00A/B/C/D/E/F/G/H/I/J/K/L266-627[»]
4FGNX-ray3.20A/B131-260[»]
4GDFX-ray2.80A/B/E/F131-627[»]
4RXHX-ray1.76A/C125-132[»]
5D9IX-ray1.70A/B131-260[»]
5TCTX-ray2.90A/B/C/D/E/F266-627[»]
ProteinModelPortaliP03070.
SMRiP03070.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03070.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 75JPROSITE-ProRule annotationAdd BLAST64
Domaini400 – 560SF3 helicasePROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni63 – 89Binding of LT to the CUL7 complexAdd BLAST27
Regioni337 – 672Binding to host TP53 proteinAdd BLAST336
Regioni418 – 616ATPase activityAdd BLAST199
Regioni627 – 708C-terminal regionAdd BLAST82
Regioni699 – 708CPD10

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi103 – 107LXCXE motif5
Motifi125 – 132Nuclear localization signal1 Publication8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi633 – 638Poly-Asp6

Domaini

The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation.1 Publication
The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.
The origin-binding domain (T-ag OBD) interacts specifically with several pentameric sequences 5'-GAGGC-3' in the SV40 origin of DNA replication.
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 (PubMed:2173794, PubMed:1851875).2 Publications
The C-terminal region is involved in interaction with host FAM111A. It is also required for the host range and adenovirus helper functions of the virus (PubMed:23093934).1 Publication
The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity.1 Publication
Cdc4 phospho-degron (CPD) region is involved in interaction with host FBW7gamma isoform.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri265 – 357T-ag D1-typePROSITE-ProRule annotationAdd BLAST93

Keywords - Domaini

Zinc-finger

Family and domain databases

CDDicd06257. DnaJ. 1 hit.
Gene3Di1.10.10.510. 1 hit.
1.10.287.110. 1 hit.
InterProiView protein in InterPro
IPR001623. 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.
PfamiView protein in Pfam
PF06431. Polyoma_lg_T_C. 1 hit.
PF02217. T_Ag_DNA_bind. 1 hit.
PIRSFiPIRSF003368. Large_T_antigen_polyomaV. 1 hit.
SMARTiView protein in SMART
SM00271. DnaJ. 1 hit.
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS50076. DNAJ_2. 1 hit.
PS51206. SF3_HELICASE_1. 1 hit.
PS51287. T_AG_OBD. 1 hit.
PS51341. ZF_LTAG_D1. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform Large T antigen (identifier: P03070-1) [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 LQLMDLLGLE RSAWGNIPLM RKAYLKKCKE FHPDKGGDEE 
        60         70         80         90        100
KMKKMNTLYK KMEDGVKYAH QPDFGGFWDA TEIPTYGTDE WEQWWNAFNE 
       110        120        130        140        150
ENLFCSEEMP SSDDEATADS QHSTPPKKKR KVEDPKDFPS ELLSFLSHAV 
       160        170        180        190        200
FSNRTLACFA IYTTKEKAAL LYKKIMEKYS VTFISRHNSY NHNILFFLTP 
       210        220        230        240        250
HRHRVSAINN YAQKLCTFSF LICKGVNKEY LMYSALTRDP FSVIEESLPG 
       260        270        280        290        300
GLKEHDFNPE EAEETKQVSW KLVTEYAMET KCDDVLLLLG MYLEFQYSFE 
       310        320        330        340        350
MCLKCIKKEQ PSHYKYHEKH YANAAIFADS KNQKTICQQA VDTVLAKKRV 
       360        370        380        390        400
DSLQLTREQM LTNRFNDLLD RMDIMFGSTG SADIEEWMAG VAWLHCLLPK 
       410        420        430        440        450
MDSVVYDFLK CMVYNIPKKR YWLFKGPIDS GKTTLAAALL ELCGGKALNV 
       460        470        480        490        500
NLPLDRLNFE LGVAIDQFLV VFEDVKGTGG ESRDLPSGQG INNLDNLRDY 
       510        520        530        540        550
LDGSVKVNLE KKHLNKRTQI FPPGIVTMNE FSVPKTLQAR FVKQIDFRAK 
       560        570        580        590        600
DYLKHCLERS EFLLEKRIIQ SGIALLLMLI WYRPVAEFAQ SIQSRIVEWK 
       610        620        630        640        650
ERLDKEFSLS VYQKMKFNVA MGIGVLDWLR NSDDDDEDSQ ENADKNEDGG 
       660        670        680        690        700
EKNMEDSGHE TGIDSQSQGS FQAPQSSQSV HDHNQPYHIC RGFTCFKKPP 

TPPPEPET
Length:708
Mass (Da):81,582
Last modified:February 1, 1996 - v2
Checksum:iCB81306EF9E4E2C0
GO
Isoform Small t antigen (identifier: P03081-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P03081.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative splicing.
Length:174
Mass (Da):20,449
GO
Isoform 17kT antigen (identifier: P03070-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     132-135: VEDP → ALLT
     136-708: Missing.

Note: Produced by alternative splicing.
Show »
Length:135
Mass (Da):15,754
Checksum:i34517296D3E87E4F
GO
Isoform SELP (identifier: P0C6L2-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P0C6L2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation.
Length:23
Mass (Da):2,705
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti531F → Y in strain: 776. 1
Natural varianti549A → P in strain: 776. 1
Natural varianti552Y → P in strain: 776. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035893132 – 135VEDP → ALLT in isoform 17kT antigen. 1 Publication4
Alternative sequenceiVSP_035894136 – 708Missing in isoform 17kT antigen. 1 PublicationAdd BLAST573

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02400 Genomic DNA. Translation: AAB59924.1.
RefSeqiYP_003708382.1. NC_001669.1.

Genome annotation databases

GeneIDi29031019.
KEGGivg:29031019.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

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.

Entry informationi

Entry nameiLT_SV40
AccessioniPrimary (citable) accession number: P03070
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1996
Last modified: July 5, 2017
This is version 157 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references