LT_BFPYV
ID LT_BFPYV Reviewed; 587 AA.
AC P13894;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS Budgerigar fledgling disease virus (BFPyV) (Aves polyomavirus 1).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Gammapolyomavirus.
OX NCBI_TaxID=1891747;
OH NCBI_TaxID=9224; Psittacidae (parrots).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2838972; DOI=10.1016/0042-6822(88)90660-5;
RA Rott O., Kroeger M., Mueller H., Hobom G.;
RT "The genome of budgerigar fledgling disease virus, an avian polyomavirus.";
RL Virology 165:74-86(1988).
RN [2]
RP SEQUENCE REVISION.
RA Stoll R., Dong L., Kouwenhoven B., Hobom G., Mueller H.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Large T antigen;
CC IsoId=P13894-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P13895-1; 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}.
CC -!- DOMAIN: The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.
CC {ECO:0000250}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The ATP binding/ATPase domain is required for proper hexamer
CC assembly and helicase activity. {ECO:0000250}.
CC -!- PTM: Phosphorylated on both serine and threonine residues. Small t
CC antigen inhibits the dephosphorylation by the AC form of PP2A (By
CC similarity). {ECO:0000250}.
CC -!- PTM: O-Glycosylated near the C-terminal region. {ECO:0000250}.
CC -!- PTM: Acetylated by CBP in a TP53-dependent manner. {ECO:0000250}.
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DR EMBL; M20775; AAB59760.1; -; Genomic_DNA.
DR PIR; D29194; TVVPBF.
DR SMR; P13894; -.
DR Proteomes; UP000134051; 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; 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; PF00226; DnaJ; 1.
DR Pfam; PF06431; Polyoma_lg_T_C; 1.
DR Pfam; PF02217; T_Ag_DNA_bind; 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 3: Inferred from homology;
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; Phosphoprotein;
KW Reference proteome; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..587
FT /note="Large T antigen"
FT /id="PRO_0000115035"
FT DOMAIN 6..82
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 360..520
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 102..219
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 221..319
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 58..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 258
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 261
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 275
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 386..393
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
SQ SEQUENCE 587 AA; 67133 MW; 73E5D71DA92EB873 CRC64;
MASLRRLTEL LCLPVTATAA DIKTAYRRTA LKYHPDKGGD EEKMKELNTL MEEFRETEGL
RADETLEDSD PEPEESGYAT FENVSVPDID GAFFKLMKLK KCMQTYFSVN ERRKQQSCPD
CHLLITSITK MPQLKAHLYE HFGIKGHIVA HWTGIALLVL QLEKPTRIST VHNFCKKYCT
ISICSVRGIK KNCVHALIKT LLDVPGLDLE ECSIDMNVVD EKQFMHAMLY DYAVQIDCTD
ALLLLAIYKR LAQPTDKCPE CQKDKDTVKR KRSTHIDDHP RHQHNASLFL HIKDQKRLCQ
CAVDAVLAEK RFRSATMTRD ERLKERFRTV LRNIQELLDG ETEAIDDFVT AILLFNMLFP
DVDVIVDILQ TMVKNPPKRR YYIFKGPVNT GKTTVAAAIL ALCTGASLNV NGTPDRLQFE
LGCAIDQFMV LFEDVKGTPE PDTNLPSGFG MVNLDNLRDH LEGSVPVNLE RKHQNKVSQI
FPPGIITMNN YVLPHTIQAR ARTLVNFKHI KVYAKALRNN ISVLEQRLIT KPETLLAYLL
IRPESEKEIS ADLRAEFLTV IENLKFEVDE RFFQYNNRLH EGLCVHE
