LT_POVMK
ID LT_POVMK Reviewed; 648 AA.
AC P24597;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS Murine polyomavirus (strain Kilham) (MPyV) (Murine pneumotropic virus).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Betapolyomavirus.
OX NCBI_TaxID=10638;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1849675; DOI=10.1016/0042-6822(91)90879-g;
RA Mayer M., Doerries K.;
RT "Nucleotide sequence and genome organization of the murine polyomavirus,
RT Kilham strain.";
RL Virology 181:469-480(1991).
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=2;
CC Name=Large T antigen;
CC IsoId=P24597-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P24598-1; 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; M55904; AAA46551.1; -; Genomic_DNA.
DR PIR; A37945; TVVPMK.
DR RefSeq; NP_041232.1; NC_001505.2.
DR SMR; P24597; -.
DR PRIDE; P24597; -.
DR GeneID; 29031024; -.
DR KEGG; vg:29031024; -.
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; 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; 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..648
FT /note="Large T antigen"
FT /id="PRO_0000115045"
FT DOMAIN 12..75
FT /note="J"
FT DOMAIN 418..573
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 154..272
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 281..373
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 112..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 103..107
FT /note="LXCXE motif"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOTIF 140..147
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 321
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 444..451
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 112
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 139
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
SQ SEQUENCE 648 AA; 74708 MW; 6F7FEF95A8AB255A CRC64;
MDHQLTREES QRLMHLLKLP MEQYGNFPLM RKAFLRACKI VHPDKGGSDE LSQELISLYR
RLEESLPCLS TQDFIETDIL QIPSYGTPEW DEWWKEFNKD FDLFCNEAFD RSDDEQEPQP
DDSAPIILSP TYPARSQATP PKKKAKMDSP NDMPADLMEY LSCAILSNKT LPCFLIYTTL
EKVELLYNKL SEEVLSPRFN QVDHKYGRKY VPIFIITGTK HRVSAVFNYC ATYCSVSFIV
VKGVIKEYPL YCHLCVEPYS VLQESIEELN SEFFDAPEDA AKNVNWVAIS EYALKINCDD
IYLLMGLYKE FQSPVPNCSK CENRMLTNHF KFHKEHHENA FYLQLVENQK TICQQAVDGV
IATKTVDMAQ MTRNEQLAAR FDKLFERLEV ILSAQSSYTI SMFMAGIVWF ENLFPGQSFK
DLLLELLECM VSNIPKRRYW LFTGPVNTGK TTLAAAVLDL GGTIYISDCY LIELEVANSQ
IHGCVEVLAE KVKIRLPPGQ GINNLDNLRD HLDGAVKVNL EKKHLNKKTQ IFPPGIVTSN
EYFIPFTLRV RFCKKLVFKF SKYQYLSLKK TECLGRYRIL QNGCTLLLLL IYHCDLDDFA
ESIQGKVRAW KERVNSEISV STYLEMRQCC LEGRYSVCTK YSNANTAQ
