Protein: Large T antigen (LT) (LT-AG) (EC 5.6.2.4) (DNA 3'-5' helicase large T antigen) (P03070)
Organism: Simian virus 40 (SV40)
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. 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.
Subcellular location: Host nucleus {ECO:0000269|PubMed:3027978, ECO:0000269|PubMed:6096007}.
Sequence: MDKVLNREESLQLMDLLGLERSAWGNIPLMRKAYLKKCKEFHPDKGGDEEKMKKMNTLYKKMEDGVKYAHQPDFGGFWDATEIPTYGTDEWEQWWNAFNEENLFCSEEMPSSDDEATADSQHSTPPKKKRKVEDPKDFPSELLSFLSHAVFSNRTLACFAIYTTKEKAALLYKKIMEKYSVTFISRHNSYNHNILFFLTPHRHRVSAINNYAQKLCTFSFLICKGVNKEYLMYSALTRDPFSVIEESLPGGLKEHDFNPEEAEETKQVSWKLVTEYAMETKCDDVLLLLGMYLEFQYSFEMCLKCIKKEQPSHYKYHEKHYANAAIFADSKNQKTICQQAVDTVLAKKRVDSLQLTREQMLTNRFNDLLDRMDIMFGSTGSADIEEWMAGVAWLHCLLPKMDSVVYDFLKCMVYNIPKKRYWLFKGPIDSGKTTLAAALLELCGGKALNVNLPLDRLNFELGVAIDQFLVVFEDVKGTGGESRDLPSGQGINNLDNLRDYLDGSVKVNLEKKHLNKRTQIFPPGIVTMNEYSVPKTLQARFVKQIDFRPKDYLKHCLERSEFLLEKRIIQSGIALLLMLIWYRPVAEFAQSIQSRIVEWKERLDKEFSLSVYQKMKFNVAMGIGVLDWLRNSDDDDEDSQENADKNEDGGEKNMEDSGHETGIDSQSQGSFQAPQSSQSVHDHNQPYHICRGFTCFKKPPTPPPEPET
InterPro domains: - IPR014015: Helicase, superfamily 3, DNA virus (domain) [400-560]
- IPR016392: Large T antigen, polyomaviridae (family) [1-629]
- IPR037102: Zinc finger, large T-antigen D1 domain superfamily (homologous_superfamily) [256-355]
- IPR036869: Chaperone J-domain superfamily (homologous_superfamily) [1-106]
- IPR001623: DnaJ domain (domain) [11-75]
- IPR010932: Large T antigen, polyomavirus, C-terminal (domain) [265-681]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [266-626]
- IPR003133: T antigen, Ori-binding (domain) [136-254]
- IPR017910: Zinc finger, large T-antigen D1-type (domain) [265-357]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0016032 (viral process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019058 (viral life cycle), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019079 (viral genome replication), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0039693 (viral DNA genome replication), GO:0006139 (nucleobase-containing compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0006259 (DNA metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0071897 (DNA biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0018995 (host cellular component), GO:0033643 (host cell part), GO:0043657 (host cell), GO:0033646 (host intracellular part), GO:0043656 (host intracellular region), GO:0033647 (host intracellular organelle), GO:0030430 (host cell cytoplasm), GO:0033648 (host intracellular membrane-bounded organelle), GO:0042025 (host cell nucleus)