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P03074

- LT_POVM3

UniProt

P03074 - LT_POVM3

Protein

Large T antigen

Gene
N/A
Organism
Murine polyomavirus (strain 3) (MPyV)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 93 (01 Oct 2014)
      Sequence version 2 (10 Jul 2007)
      Previous versions | rss
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    Functioni

    Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi293 – 407115T-ag OBDPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri416 – 51095T-ag D1-typePROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi575 – 5828ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DNA replication origin binding Source: InterPro
    3. hydrolase activity Source: UniProtKB-KW
    4. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. DNA replication Source: UniProtKB-KW
    2. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
    3. suppression by virus of host JAK1 activity Source: UniProtKB-KW
    4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    DNA replication, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host JAK1 by virus, Modulation of host cell cycle by virus, Viral immunoevasion

    Keywords - Ligandi

    ATP-binding, DNA-binding, Metal-binding, Nucleotide-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Large T antigen (EC:3.6.4.-)
    Short name:
    LT
    Short name:
    LT-AG
    OrganismiMurine polyomavirus (strain 3) (MPyV)
    Taxonomic identifieri10635 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePolyomaviridaePolyomavirus
    Virus hostiMus musculus (Mouse) [TaxID: 10090]
    ProteomesiUP000006847: Genome

    Subcellular locationi

    Host nucleus By similarity

    GO - Cellular componenti

    1. host cell nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 782782Large T antigenPRO_0000115042Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine; by hostBy similarity
    Modified residuei278 – 2781Phosphothreonine; by hostBy similarity

    Post-translational modificationi

    Phosphorylated on both serine and threonine residues. Small t antigen inhibits the dephosphorylation by the AC form of PP2A By similarity.By similarity
    O-Glycosylated near the C-terminal region.By similarity
    Acetylated by CBP in a TP53-dependent manner.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Expressioni

    Keywords - Developmental stagei

    Early protein

    Interactioni

    Subunit structurei

    Forms homohexamers in the presence of ATP. Interacts with host HDAC1. Interacts (via LXCXE domain) with host RB1; the interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Interacts (via LXCXE domain) with host pRB-related proteins RBL1 and RBL2. Interacts (via C-terminus) with host TOP1 and POLA1 allowing DNA replication. Interacts with host preinitiation complex components TBP, TFIIA and TFIID to regulate transcription initiation By similarity.By similarity

    Protein-protein interaction databases

    MINTiMINT-580307.

    Structurei

    Secondary structure

    1
    782
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi7 – 1711
    Beta strandi21 – 233
    Helixi27 – 4014
    Helixi43 – 453
    Helixi49 – 6921

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FAFNMR-A1-79[»]
    4FB3X-ray3.79A/B/E290-420[»]
    ProteinModelPortaliP03074.
    SMRiP03074. Positions 1-79.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03074.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini12 – 7564JAdd
    BLAST
    Domaini549 – 709161SF3 helicasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni142 – 1465Binding to host RB1 protein and transforming activityBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi279 – 2868Nuclear localization signalBy similarity

    Domaini

    The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation.By similarity
    The LXCXE motif specifically binds to host pRB, RBL1, and RBL2.By similarity
    The zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication. The hexamers are required for subsequent alterations in the structure of origin DNA By similarity.By similarity
    The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity.By similarity

    Sequence similaritiesi

    Contains 1 J domain.Curated
    Contains 1 SF3 helicase domain.PROSITE-ProRule annotation
    Contains 1 T-ag D1-type zinc finger.PROSITE-ProRule annotation
    Contains 1 T-ag OBD DNA-binding domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri416 – 51095T-ag D1-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Family and domain databases

    Gene3Di1.10.10.510. 1 hit.
    1.10.287.110. 1 hit.
    3.40.50.300. 1 hit.
    InterProiIPR001623. DnaJ_domain.
    IPR014015. Helicase_SF3_DNA-vir.
    IPR010932. Lg_T_Ag_Polyomavir_C.
    IPR027417. P-loop_NTPase.
    IPR003133. T_Ag_DNA-bd.
    IPR017910. Znf_lg_T-Ag_D1-typ.
    [Graphical view]
    PfamiPF06431. Polyoma_lg_T_C. 1 hit.
    PF02217. T_Ag_DNA_bind. 1 hit.
    [Graphical view]
    SMARTiSM00271. DnaJ. 1 hit.
    [Graphical view]
    SUPFAMiSSF46565. SSF46565. 1 hit.
    SSF52540. SSF52540. 1 hit.
    PROSITEiPS51206. SF3_HELICASE_1. 1 hit.
    PS51287. T_AG_OBD. 1 hit.
    PS51341. ZF_LTAG_D1. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform Large T antigen (identifier: P03074-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA    50
    LMQELNSLWG TFKTEVYNLR MNLGGTGFQG SPPRTAERGT EESGHSPLHD 100
    DYWSFSYGSK YFTREWNDFF RKWDPSYQSP PKTAESSEQP DLFCYEEPLL 150
    SPNPSSPTDT PAHTAGRRRN PCVAEPDDSI SPDPPRTPVS RKRPRPAGAT 200
    GGGGGGVHAN GGSVFGHPTG GTSTPAHPPP YHSQGGSESM GGSDSSGFAE 250
    GSFRSDPRCE SENESYSQSC SQSSFNATPP KKAREDPAPS DFPSSLTGYL 300
    SHAIYSNKTF PAFLVYSTKE KCKQLYDTIG KFRPEFKCLV HYEEGGMLFF 350
    LTMTKHRVSA VKNYCSKLCS VSFLMCKAVT KPMECYQVVT AAPFQLITEN 400
    KPGLHQFEFT DEPEEQKAVD WIMVADFALE NNLDDPLLIM GYYLDFAKEV 450
    PSCIKCSKEE TRLQIHWKNH RKHAENADLF LNCKAQKTIC QQAADGVLAS 500
    RRLKLVECTR SQLLKERLQQ SLLRLKELGS SDALLYLAGV AWYQCLLEDF 550
    PQTLFKMLKL LTENVPKRRN ILFRGPVNSG KTGLAAALIS LLGGKSLNIN 600
    CPADKLAFEL GVAQDQFVVC FEDVKGQIAL NKQLQPGMGV ANLDNLRDYL 650
    DGSVKVNLEK KHSNKRSQLF PPCVCTMNEY LLPQTVWARF HMVLDFTCKP 700
    HLAQSLEKCE FLQRERIIQS GDTLALLLIW NFTSDVFDPD IQGLVKEVRD 750
    QFASECSYSL FCDILCNVQE GDDPLKDICE YS 782
    Length:782
    Mass (Da):87,662
    Last modified:July 10, 2007 - v2
    Checksum:i5E24E1F8A586C7A9
    GO
    Isoform Middle T antigen (identifier: P03076-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry P03076.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:421
    Mass (Da):48,694
    GO
    Isoform Small t antigen (identifier: P68834-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry P68834.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:195
    Mass (Da):22,811
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02289 Genomic DNA. Translation: AAA46872.1.
    U27812 Genomic DNA. Translation: AAA93241.1.
    U27813 Genomic DNA. Translation: AAA93245.1.
    AF442959 Genomic DNA. Translation: AAL35609.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02289 Genomic DNA. Translation: AAA46872.1 .
    U27812 Genomic DNA. Translation: AAA93241.1 .
    U27813 Genomic DNA. Translation: AAA93245.1 .
    AF442959 Genomic DNA. Translation: AAL35609.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FAF NMR - A 1-79 [» ]
    4FB3 X-ray 3.79 A/B/E 290-420 [» ]
    ProteinModelPortali P03074.
    SMRi P03074. Positions 1-79.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-580307.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P03074.

    Family and domain databases

    Gene3Di 1.10.10.510. 1 hit.
    1.10.287.110. 1 hit.
    3.40.50.300. 1 hit.
    InterProi IPR001623. DnaJ_domain.
    IPR014015. Helicase_SF3_DNA-vir.
    IPR010932. Lg_T_Ag_Polyomavir_C.
    IPR027417. P-loop_NTPase.
    IPR003133. T_Ag_DNA-bd.
    IPR017910. Znf_lg_T-Ag_D1-typ.
    [Graphical view ]
    Pfami PF06431. Polyoma_lg_T_C. 1 hit.
    PF02217. T_Ag_DNA_bind. 1 hit.
    [Graphical view ]
    SMARTi SM00271. DnaJ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46565. SSF46565. 1 hit.
    SSF52540. SSF52540. 1 hit.
    PROSITEi PS51206. SF3_HELICASE_1. 1 hit.
    PS51287. T_AG_OBD. 1 hit.
    PS51341. ZF_LTAG_D1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The nucleotide sequence and genome organization of the polyoma early region: extensive nucleotide and amino acid homology with SV40."
      Friedmann T., Esty A., LaPorte P., Deininger P.L.
      Cell 17:715-724(1979) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The nucleotide sequence and restriction enzyme sites of the polyoma genome."
      Deininger P.L., Esty A., LaPorte P., Hsu H., Friedmann T.
      Nucleic Acids Res. 8:855-860(1980) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: A3.
    3. "Genetic and structural analysis of a virulence determinant in polyomavirus VP1."
      Bauer P.H., Bronson R.T., Fung S.C., Freund R., Stehle T., Harrison S.C., Benjamin T.L.
      J. Virol. 69:7925-7931(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: Isolate LID and Isolate PTA.
    4. Clark B.E., Griffin B.E.
      Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: BG.
    5. "NMR structure of the N-terminal J domain of murine polyomavirus T antigens. Implications for DnaJ-like domains and for mutations of T antigens."
      Berjanskii M.V., Riley M.I., Xie A., Semenchenko V., Folk W.R., Van Doren S.R.
      J. Biol. Chem. 275:36094-36103(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-79.

    Entry informationi

    Entry nameiLT_POVM3
    AccessioniPrimary (citable) accession number: P03074
    Secondary accession number(s): Q76TX5, Q76W02, Q89471
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 10, 2007
    Last modified: October 1, 2014
    This is version 93 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3