P0DOJ5 · LT_POVM3

Function

function

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. Has processive 3'-5' DNA helicase activity which requires a short 3' single-stranded region and ATP. 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.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: DNA helicase activity requires Mg2+.

Features

Showing features for dna binding, binding site.

TypeIDPosition(s)Description
DNA binding293-407T-ag OBD
Binding site453Zn2+ (UniProtKB | ChEBI)
Binding site456Zn2+ (UniProtKB | ChEBI)
Binding site466Zn2+ (UniProtKB | ChEBI)
Binding site470Zn2+ (UniProtKB | ChEBI)
Binding site575-582ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componenthost cell nucleus
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionDNA replication origin binding
Molecular Functionhelicase activity
Molecular Functionisomerase activity
Molecular Functionmetal ion binding
Biological ProcessDNA replication
Biological Processsymbiont-mediated perturbation of host cell cycle G1/S transition checkpoint
Biological Processsymbiont-mediated suppression of host innate immune response
Biological Processsymbiont-mediated suppression of host JAK-STAT cascade via inhibition of JAK1 activity
Biological Processsymbiont-mediated suppression of host type I interferon-mediated signaling pathway
Biological Processvirus-mediated perturbation of host defense response

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Large T antigen
  • EC number
  • Short names
    LT; LT-AG
  • Alternative names
    • DNA 3'-5' helicase large T antigen

Organism names

Accessions

  • Primary accession
    P0DOJ5
  • Secondary accessions
    • P03074
    • Q76TX5
    • Q76W02
    • Q89471

Proteomes

Subcellular Location

Keywords

Phenotypes & Variants

Keywords

PTM/Processing

Features

Showing features for modified residue, chain.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine; by host
ChainPRO_00004427821-782Large T antigen
Modified residue278Phosphothreonine; by host

Post-translational modification

Phosphorylated on both serine and threonine residues. Small t antigen inhibits the dephosphorylation by the AC form of PP2A.
O-Glycosylated near the C-terminal region.
Acetylated by CBP in a TP53-dependent manner.

Keywords

Expression

Keywords

Interaction

Subunit

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.

Structure

Family & Domains

Features

Showing features for domain, region, motif, compositional bias, zinc finger.

TypeIDPosition(s)Description
Domain12-75J
Region74-97Disordered
Motif142-146LXCXE motif
Region145-291Disordered
Compositional bias216-250Polar residues
Compositional bias262-279Polar residues
Motif279-286Nuclear localization signal
Zinc finger416-510T-ag D1-type
Domain549-709SF3 helicase

Domain

The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation.
The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.
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.
The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity.

Keywords

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

P0DOJ5-1

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.

  • Name
    Large T antigen
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    782
  • Mass (Da)
    87,662
  • Last updated
    2017-12-20 v1
  • Checksum
    5E24E1F8A586C7A9
MDRVLSRADKERLLELLKLPRQLWGDFGRMQQAYKQQSLLLHPDKGGSHALMQELNSLWGTFKTEVYNLRMNLGGTGFQGSPPRTAERGTEESGHSPLHDDYWSFSYGSKYFTREWNDFFRKWDPSYQSPPKTAESSEQPDLFCYEEPLLSPNPSSPTDTPAHTAGRRRNPCVAEPDDSISPDPPRTPVSRKRPRPAGATGGGGGGVHANGGSVFGHPTGGTSTPAHPPPYHSQGGSESMGGSDSSGFAEGSFRSDPRCESENESYSQSCSQSSFNATPPKKAREDPAPSDFPSSLTGYLSHAIYSNKTFPAFLVYSTKEKCKQLYDTIGKFRPEFKCLVHYEEGGMLFFLTMTKHRVSAVKNYCSKLCSVSFLMCKAVTKPMECYQVVTAAPFQLITENKPGLHQFEFTDEPEEQKAVDWIMVADFALENNLDDPLLIMGYYLDFAKEVPSCIKCSKEETRLQIHWKNHRKHAENADLFLNCKAQKTICQQAADGVLASRRLKLVECTRSQLLKERLQQSLLRLKELGSSDALLYLAGVAWYQCLLEDFPQTLFKMLKLLTENVPKRRNILFRGPVNSGKTGLAAALISLLGGKSLNINCPADKLAFELGVAQDQFVVCFEDVKGQIALNKQLQPGMGVANLDNLRDYLDGSVKVNLEKKHSNKRSQLFPPCVCTMNEYLLPQTVWARFHMVLDFTCKPHLAQSLEKCEFLQRERIIQSGDTLALLLIWNFTSDVFDPDIQGLVKEVRDQFASECSYSLFCDILCNVQEGDDPLKDICEYS

P0DOJ8-1

The sequence of this isoform can be found in the external entry linked below. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

View isoform
  • Name
    Middle T antigen
  • See also
    sequence in UniParc or sequence clusters in UniRef

P68834-1

The sequence of this isoform can be found in the external entry linked below. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

View isoform
  • Name
    Small t antigen
  • See also
    sequence in UniParc or sequence clusters in UniRef

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias216-250Polar residues
Compositional bias262-279Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
J02289
EMBL· GenBank· DDBJ
AAA46872.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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