LT_POVM3
ID LT_POVM3 Reviewed; 782 AA.
AC P0DOJ5; P03074; Q76TX5; Q76W02; Q89471;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS Murine polyomavirus (strain A3) (MPyV).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Alphapolyomavirus.
OX NCBI_TaxID=157703;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=225042; DOI=10.1016/0092-8674(79)90278-2;
RA Friedmann T., Esty A., LaPorte P., Deininger P.L.;
RT "The nucleotide sequence and genome organization of the polyoma early
RT region: extensive nucleotide and amino acid homology with SV40.";
RL Cell 17:715-724(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6253927;
RA Deininger P.L., Esty A., LaPorte P., Hsu H., Friedmann T.;
RT "The nucleotide sequence and restriction enzyme sites of the polyoma
RT genome.";
RL Nucleic Acids Res. 8:855-860(1980).
RN [3]
RP STRUCTURE BY NMR OF 1-79.
RX PubMed=10950962; DOI=10.1074/jbc.m006572200;
RA Berjanskii M.V., Riley M.I., Xie A., Semenchenko V., Folk W.R.,
RA Van Doren S.R.;
RT "NMR structure of the N-terminal J domain of murine polyomavirus T
RT antigens. Implications for DnaJ-like domains and for mutations of T
RT antigens.";
RL J. Biol. Chem. 275:36094-36103(2000).
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=P0DOJ5-1, P03074-1;
CC Sequence=Displayed;
CC Name=Middle T antigen;
CC IsoId=P0DOJ8-1, P03076-1;
CC Sequence=External;
CC Name=Small t antigen;
CC IsoId=P68834-1; 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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J02289; AAA46872.1; -; Genomic_DNA.
DR PDB; 1FAF; NMR; -; A=1-79.
DR PDBsum; 1FAF; -.
DR SMR; P0DOJ5; -.
DR Proteomes; UP000006847; 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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW DNA replication; 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..782
FT /note="Large T antigen"
FT /id="PRO_0000442782"
FT DOMAIN 12..75
FT /note="J"
FT DOMAIN 549..709
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 293..407
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 416..510
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 453
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 456
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 466
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 470
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 575..582
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"
FT HELIX 7..17
FT /evidence="ECO:0007829|PDB:1FAF"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:1FAF"
FT HELIX 27..40
FT /evidence="ECO:0007829|PDB:1FAF"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:1FAF"
FT HELIX 49..69
FT /evidence="ECO:0007829|PDB:1FAF"
SQ SEQUENCE 782 AA; 87662 MW; 5E24E1F8A586C7A9 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
VKNYCSKLCS VSFLMCKAVT KPMECYQVVT AAPFQLITEN KPGLHQFEFT DEPEEQKAVD
WIMVADFALE NNLDDPLLIM GYYLDFAKEV PSCIKCSKEE TRLQIHWKNH RKHAENADLF
LNCKAQKTIC QQAADGVLAS RRLKLVECTR SQLLKERLQQ SLLRLKELGS SDALLYLAGV
AWYQCLLEDF PQTLFKMLKL LTENVPKRRN ILFRGPVNSG KTGLAAALIS LLGGKSLNIN
CPADKLAFEL GVAQDQFVVC FEDVKGQIAL NKQLQPGMGV ANLDNLRDYL DGSVKVNLEK
KHSNKRSQLF PPCVCTMNEY LLPQTVWARF HMVLDFTCKP HLAQSLEKCE FLQRERIIQS
GDTLALLLIW NFTSDVFDPD IQGLVKEVRD QFASECSYSL FCDILCNVQE GDDPLKDICE
YS
