LT_POVMA
ID LT_POVMA Reviewed; 785 AA.
AC P03073;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS Murine polyomavirus (strain A2) (MPyV).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Alphapolyomavirus.
OX NCBI_TaxID=10636;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6243401; DOI=10.1038/283445a0;
RA Soeda E., Arrand J.R., Smolar N., Walsh J.E., Griffin B.E.;
RT "Coding potential and regulatory signals of the polyoma virus genome.";
RL Nature 283:445-453(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. {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
CC preinitiation complex components TBP, TFIIA and TFIID to regulate
CC transcription initiation. {ECO:0000250|UniProtKB:P03070}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P03070}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Large T antigen;
CC IsoId=P03073-1; Sequence=Displayed;
CC Name=Middle T antigen;
CC IsoId=P03077-1; Sequence=External;
CC Name=Small t antigen;
CC IsoId=P68835-1; 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}.
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DR EMBL; J02288; AAB59901.1; -; Genomic_DNA.
DR PIR; D03635; TVVPT.
DR BMRB; P03073; -.
DR SMR; P03073; -.
DR Proteomes; UP000008479; 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 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; 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; 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; Reference proteome; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..785
FT /note="Large T antigen"
FT /id="PRO_0000115043"
FT DOMAIN 12..75
FT /note="J"
FT DOMAIN 547..707
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 293..406
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 415..508
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 74..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 142..146
FT /note="LXCXE motif"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOTIF 279..286
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT COMPBIAS 216..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 452
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 469
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 573..580
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|UniProtKB:P03070"
FT MOD_RES 278
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
SQ SEQUENCE 785 AA; 88091 MW; 34E00D0612BA7E93 CRC64;
MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA LMQELNSLWG
TFKTEVYNLR MNLGGTGFQG SPPRTAERGT EESGHSPLHD DYWSFSYGSK YFTREWNDFF
RKWDPSYQSP PKTAESSEQP DLFCYEEPLL SPNPSSPTDT PAHTAGRRRN PCVAEPDDSI
SPDPPRTPVS RKRPRPAGAT GGGGGGVHAN GGSVFGHPTG GTSTPAHPPP YHSQGGSESM
GGSDSSGFAE GSFRSDPRCE SENESYSQSC SQSSFNATPP KKAREDPAPS DFPSSLTGYL
SHAIYSNKTF PAFLVYSTKE KCKQLYDTIG KFRPEFKCLV HYEEGGMLFF LTMTKHRVSA
VKNYCSKLCR SFLMCKAVTK PMECYQVVTA APFQLITENK PGLHQFEFTD EPEEQKAVDW
IMVADFALEN NLDDPLLIMG YYLDFAKEVP SCIKCSKEET RLQIHWKNHR KHAENADLFL
NCKAQKTICQ QAAASLASRR LKLVECTRSQ LLKERLQQSL LRLKELGSSD ALLYLAGVAW
YQCLLEDFPQ TLFKMLKLLT ENVPKRRNIL FRGPVNSGKT GLAAALISLL GGKSLNINCP
ADKLAFELGV AQDQFVVCFE DVKGQIALNK QLQPGMGVAN LDNLRTTWNG SVKVNLEKKH
SNKRSQLFPP CVCTMNEYLL PQTVWARFHM VLDFTCKPHL AQSLEKCEFL QRERIIQSGD
TLALLLIWNF TSDVFDPDIQ GLVKEVRDQF ASECSYSLFC DILCNVQEGD DPLKDICDIA
EYTVY
