LT_POVBO
ID LT_POVBO Reviewed; 619 AA.
AC P24851; Q84248; Q90051;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS Bovine polyomavirus (BPyV) (Bos taurus polyomavirus 1).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Epsilonpolyomavirus.
OX NCBI_TaxID=1891754;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2167926; DOI=10.1099/0022-1317-71-8-1723;
RA Schuurman R., Sol C., van der Noordaa J.;
RT "The complete nucleotide sequence of bovine polyomavirus.";
RL J. Gen. Virol. 71:1723-1735(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-84, AND ALTERNATIVE SPLICING.
RX PubMed=1279101; DOI=10.1099/0022-1317-73-11-2879;
RA Schuurman R., Jacobs M., van Strien A., van der Noordaa J., Sol C.;
RT "Analysis of splice sites in the early region of bovine polyomavirus:
RT evidence for a unique pattern of large T mRNA splicing.";
RL J. Gen. Virol. 73:2879-2886(1992).
CC -!- FUNCTION: Isoform large T antigen is a key early protein essential for
CC both driving viral replication and inducing cellular transformation.
CC Plays a role in viral genome replication by driving entry of quiescent
CC cells into the cell cycle and by autoregulating the synthesis of viral
CC early mRNA. Displays highly oncogenic activities by corrupting the host
CC cellular checkpoint mechanisms that guard cell division and the
CC transcription, replication, and repair of DNA. Participates in the
CC modulation of cellular gene expression preceeding viral DNA
CC replication. This step involves binding to host key cell cycle
CC regulators retinoblastoma protein RB1/pRb and TP53. Induces the
CC disassembly of host E2F1 transcription factors from RB1, thus promoting
CC transcriptional activation of E2F1-regulated S-phase genes. Inhibits
CC host TP53 binding to DNA, abrogating the ability of TP53 to stimulate
CC gene expression. Plays the role of a TFIID-associated factor (TAF) in
CC transcription initiation for all three RNA polymerases, by stabilizing
CC the TBP-TFIIA complex on promoters. Initiates viral DNA replication and
CC unwinding via interactions with the viral origin of replication. Binds
CC two adjacent sites in the SV40 origin. The replication fork movement is
CC facilitated by Large T antigen helicase activity. Activates the
CC transcription of viral late mRNA, through host TBP and TFIIA
CC stabilization. Interferes with histone deacetylation mediated by HDAC1,
CC leading to activation of transcription. {ECO:0000250|UniProtKB:P03070}.
CC -!- SUBUNIT: Forms homohexamers in the presence of ATP. Interacts with host
CC HDAC1. Interacts (via LXCXE domain) with host RB1; the interaction
CC induces the aberrant dissociation of RB1-E2F1 complex thereby
CC disrupting RB1's activity. Interacts (via LXCXE domain) with host pRB-
CC related proteins RBL1 and RBL2. Interacts (via C-terminus) with host
CC TOP1 and POLA1 allowing DNA replication. Interacts with host TP53,
CC inhibiting TP53 binding to DNA. Interacts with host preinitiation
CC complex components TBP, TFIIA and TFIID to regulate transcription
CC initiation. {ECO:0000250|UniProtKB:P03070}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P03070}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Large T antigen;
CC IsoId=P24851-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P24852-1; Sequence=External;
CC -!- DOMAIN: The J domain is essential for multiple viral activities,
CC including virion assembly, viral DNA replication, transformation and
CC transcriptional activation. {ECO:0000250|UniProtKB:P03070}.
CC -!- DOMAIN: The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.
CC {ECO:0000250|UniProtKB:P03070}.
CC -!- DOMAIN: The zinc finger region contributes to protein-protein
CC interactions essential for the assembly of stable T-antigen hexamers at
CC the origin of replication. The hexamers are required for subsequent
CC alterations in the structure of origin DNA.
CC {ECO:0000250|UniProtKB:P03070}.
CC -!- DOMAIN: The ATP binding/ATPase domain is required for proper hexamer
CC assembly and helicase activity. {ECO:0000250|UniProtKB:P03070}.
CC -!- PTM: Phosphorylated on both serine and threonine residues. Small t
CC antigen inhibits the dephosphorylation by the AC form of PP2A.
CC {ECO:0000250|UniProtKB:P03070}.
CC -!- PTM: O-Glycosylated near the C-terminal region.
CC {ECO:0000250|UniProtKB:P03070}.
CC -!- PTM: Acetylated by CBP in a TP53-dependent manner.
CC {ECO:0000250|UniProtKB:P03070}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA03040.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; D13942; BAA03040.1; ALT_SEQ; Genomic_DNA.
DR EMBL; S48202; AAB24090.2; -; mRNA.
DR PIR; JU0357; TVVPBP.
DR RefSeq; NP_040788.2; NC_001442.1. [P24851-1]
DR SMR; P24851; -.
DR GeneID; 29031001; -.
DR KEGG; vg:29031001; -.
DR Proteomes; UP000008476; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003688; F:DNA replication origin binding; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039576; P:suppression by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd06257; DnaJ; 1.
DR Gene3D; 1.10.10.510; -; 1.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR014015; Helicase_SF3_DNA-vir.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR016392; Lg_T_Ag_polyomavir.
DR InterPro; IPR010932; Lg_T_Ag_Polyomavir_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR003133; T_Ag_DNA-bd.
DR InterPro; IPR017910; Znf_lg_T-Ag_D1-typ.
DR InterPro; IPR037102; Znf_lg_T-Ag_D1_dom_sf.
DR Pfam; PF06431; Polyoma_lg_T_C; 1.
DR Pfam; PF02217; T_Ag_DNA_bind; 1.
DR PIRSF; PIRSF003368; Large_T_antigen_polyomaV; 1.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS51206; SF3_HELICASE_1; 1.
DR PROSITE; PS51287; T_AG_OBD; 1.
DR PROSITE; PS51341; ZF_LTAG_D1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; DNA replication; DNA-binding;
KW Early protein; G1/S host cell cycle checkpoint dysregulation by virus;
KW Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host JAK1 by virus; Metal-binding;
KW Modulation of host cell cycle by virus; Nucleotide-binding; Oncogene;
KW Phosphoprotein; Reference proteome; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..619
FT /note="Large T antigen"
FT /id="PRO_0000115038"
FT DOMAIN 10..73
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 391..586
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 132..245
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 255..348
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 98..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 93..97
FT /note="LXCXE motif"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOTIF 121..128
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT COMPBIAS 106..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 417..424
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT MOD_RES 102
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 120
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
SQ SEQUENCE 619 AA; 70674 MW; 539CE547187CF015 CRC64;
MELTSEEYEE LRGLLGTPDI GNADTLKKAF LKACKVHHPD KGGNEEAMKR LLYLYNKAKI
AASATTSQVP EYGTSQWEQW WEEFNQGFDE QDLHCDEELE PSDNEEENPA GSQAPGSQAT
PPKKPRTSPD FPEVLKEYVS NALFTNRTYN CFIIFTTAEK GKELYPCIQA AYKCTFIALY
MYNGDSVLYI ITVGKHRVNA MENLCSKKCT VSFLQAKGVL KPQEAYNVCC TFELISQNIQ
GGLPSSFFNP VQEEEKSVNW KLISEFACSI KCTDPLLLMA LYLEFTTAPE ACKVCDNPRR
LEHRRHHTKD HTLNALLFQD SKTQKTICNQ ACDTVLAKRR LDMKTLTRNE LLVQRWQGLF
QEMEDLFGAR GEEHLAHRMA AVMWLNALHP NMPDVIFNYI KMVVENKPKQ RYLLLKGPVN
CGKTTVAAGL IGLCGGAYLN INCPPERLAF ELGMAIDQFT VVFEDVKGKK SSKSSLQTGI
GFENLDNLRD HLDGAVPVNL ERKHQNKVTQ IFPPGIVTCN EYDIPLTVKI RMYQKVELLH
NYNLYKSLKN TEEVGKKRYL QSGITWLLLL IYFRSVDDFT EKLQECVVKW KERIETEVGD
MWLLTMKENI EQGKNILEK
