LT_POVLY
ID LT_POVLY Reviewed; 697 AA.
AC P04008;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-1986, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS B-lymphotropic polyomavirus (LPV).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; unclassified Polyomaviridae.
OX NCBI_TaxID=332091;
OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2998001; DOI=10.1016/0042-6822(85)90108-4;
RA Pawlita M., Clad A., zur Hausen H.;
RT "Complete DNA sequence of lymphotropic papovavirus: prototype of a new
RT species of the polyomavirus genus.";
RL Virology 143:196-211(1985).
RN [2]
RP SEQUENCE REVISION.
RA Pawlita M., Clad A., zur Hausen H.;
RL Submitted (AUG-2013) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3495678; DOI=10.7883/yoken1952.39.151;
RA Furuno A., Kanda T., Yoshiike K.;
RT "Monkey B-lymphotropic papovavirus genome: the entire DNA sequence and
RT variable regions.";
RL Jpn. J. Med. Sci. Biol. 39:151-161(1986).
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=P04008-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P04009-1; 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; K02562; AAA47059.2; -; Genomic_DNA.
DR EMBL; M30540; AAA47065.1; -; Genomic_DNA.
DR PIR; A03610; TVVPTL.
DR RefSeq; NP_848008.2; NC_004763.2.
DR SMR; P04008; -.
DR GeneID; 1494439; -.
DR KEGG; vg:1494439; -.
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; IPR003593; AAA+_ATPase.
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; SM00382; AAA; 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 Acetylation; Alternative splicing; ATP-binding; DNA replication;
KW DNA-binding; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW 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; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..697
FT /note="Large T antigen"
FT /id="PRO_0000115041"
FT DOMAIN 12..75
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 463..623
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 203..323
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 330..422
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 131..135
FT /note="Binding to host RB1 protein and transforming
FT activity"
FT /evidence="ECO:0000250"
FT REGION 136..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 188..196
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 172..188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 367
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 370
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 382
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 489..496
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT MOD_RES 1
FT /note="N-acetylmethionine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 134
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 140
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 187
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
SQ SEQUENCE 697 AA; 79762 MW; B62BB85D9A294588 CRC64;
MDQTLSKEER NELMDLLQIT RAAWGNLSMM KKAYKNVSKL YHPDKGGDSA KMQRLNELFQ
RVQVTLMEIR SQCGSSSSQG YFSEDFYFGP TTFQYSPMDR DAVREDLPNP GEGSWGKWWR
EFVNRQCCDD LFCSETMSSS SDEDTPPAAQ PPPPPAPSPE EEDEIEFVEE TPSSCDGSSS
QSSYTCTPPK RKKTEEKKPD DFPVCLYSFL SHAIYSNKTM NSFLIYTTLE KARQLYKTVE
KSKIVVDFKA SFSYQDEEGE GCLLFLITLG KHRVSAVKHF CVSQCTFSFI HCKAVVKPLE
LYKTLSKPPF KLLEENKPGV SMFEFQEEKE QSVNWQEICN FANEANISDV LLLLGIYIDF
AVEPGKCGKC EKKQHKFHYN YHKAHHANAC LFLESRAQKN ICQQAVDQVL AAKRLKLVEC
SRIELLEERF LQLFDEMDDF LHGEIEILRW MAGVAWYTIL LDNSWDVFQN ILQLITTSQP
KKRNVLIKGP INSGKTTLAS AFMHFFDGKA LNINCPADKL SFELGCAIDQ FCVLLDDVKG
QITLNKHLQP GQGVNNLDNL RDHLDGTIKV NLEKKHVNKR SQIFPPVIMT MNEYLLPPTI
GVRFALHLHL KPKAYLKQSL EKSDLVAKRI LNSGYTILLL LLWYNPVDSF TPKVQEKVVQ
WKETLEKYVS ITQFGNIQQN IIDGKDPLHG IVIEEQM
