LT_POVBK
ID LT_POVBK Reviewed; 695 AA.
AC P03071;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS BK polyomavirus (BKPyV) (Human polyomavirus 1).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Betapolyomavirus.
OX NCBI_TaxID=1891762;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Dunlop;
RX PubMed=229976; DOI=10.1016/0092-8674(79)90209-5;
RA Seif I., Khoury G., Dhar R.;
RT "The genome of human papovavirus BKV.";
RL Cell 18:963-977(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MM;
RX PubMed=228391; DOI=10.1126/science.228391;
RA Yang R.C.A., Wu R.;
RT "BK virus DNA: complete nucleotide sequence of a human tumor virus.";
RL Science 206:456-462(1979).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MM;
RX PubMed=6246273; DOI=10.1128/jvi.34.2.416-430.1980;
RA Yang R.C.A., Young A., Wu R.;
RT "BK virus DNA sequence coding for the t and T antigens and evaluation of
RT methods for determining sequence homology.";
RL J. Virol. 34:416-430(1980).
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=P03071-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P03082-1; 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; V01108; CAA24300.1; -; Genomic_DNA.
DR EMBL; V01109; CAA24302.1; -; Genomic_DNA.
DR PIR; C03632; TVVPTB.
DR RefSeq; YP_717940.1; NC_001538.1. [P03071-1]
DR SMR; P03071; -.
DR GeneID; 29031009; -.
DR KEGG; vg:29031009; -.
DR Proteomes; UP000008475; Genome.
DR Proteomes; UP000008990; 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:0004386; F:helicase activity; IEA:UniProtKB-KW.
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 3: Inferred from homology;
KW Acetylation; Activator; Alternative splicing; ATP-binding; DNA replication;
KW DNA-binding; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein;
KW Helicase; 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; Transcription; Transcription regulation;
KW Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..695
FT /note="Large T antigen"
FT /id="PRO_0000115037"
FT DOMAIN 12..75
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 402..562
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 141..256
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 267..359
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 105..109
FT /note="Binding to host RB1 protein and transforming
FT activity"
FT /evidence="ECO:0000250"
FT REGION 117..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 634..695
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 127..134
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 643..668
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 304
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 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 428..435
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 114
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 122
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 125
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 126
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 687
FT /note="N6-acetyllysine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 691
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250"
FT VARIANT 34
FT /note="Missing (in strain: MM)"
FT VARIANT 260
FT /note="S -> N (in strain: MM)"
FT VARIANT 335
FT /note="Q -> K (in strain: MM)"
FT VARIANT 337
FT /note="S -> V (in strain: MM)"
FT VARIANT 446
FT /note="G -> R (in strain: MM)"
SQ SEQUENCE 695 AA; 80505 MW; 8521A1807116A347 CRC64;
MDKVLNREES MELMDLLGLE RAAWGNLPLM RKAYLRKCKE FHPDKGGDED KMKRMNTLYK
KMEQDVKVAH QPDFGTWSSS EVPTYGTEEW ESWWSSFNEK WDEDLFCHED MFASDEEATA
DSQHSTPPKK KRKVEDPKDF PSDLHQFLSQ AVFSNRTLAC FAVYTTKEKA QILYKKLMEK
YSVTFISRHM CAGHNIIFFL TPHRHRVSAI NNFCQKLCTF SFLICKGVNK EYLLYSALTR
DPYHTIEESI QGGLKEHDFS PEEPEETKQV SWKLITEYAV ETKCEDVFLL LGMYLEFQYN
VEECKKCQKK DQPYHFKYHE KHFANAIIFA ESKNQKSICQ QAVDTVLAKK RVDTLHMTRE
EMLTERFNHI LDKMDLIFGA HGNAVLEQYM AGVAWLHCLL PKMDSVIFDF LHCIVFNVPK
RRYWLFKGPI DSGKTTLAAG LLDLCGGKAL NVNLPMERLT FELGVAIDQY MVVFEDVKGT
GAESKDLPSG HGINNLDSLR DYLDGSVKVN LEKKHLNKRT QIFPPGLVTM NEYPVPKTLQ
ARFVRQIDFR PKIYLRKSLQ NSEFLLEKRI LQSGMTLLLL LIWFRPVADF ATDIQSRIVE
WKERLDSEIS MYTFSRMKYN ICMGKCILDI TREEDSETED SGHGSSTESQ SQCSSQVSDT
SAPAEDSQRS DPHSQELHLC KGFQCFKRPK TPPPK
