LT_POVJC
ID LT_POVJC Reviewed; 688 AA.
AC P03072;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Large T antigen;
DE Short=LT;
DE Short=LT-AG;
DE EC=3.6.4.-;
OS JC polyomavirus (JCPyV) (JCV).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Betapolyomavirus.
OX NCBI_TaxID=10632;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6086957; DOI=10.1128/jvi.51.2.458-469.1984;
RA Frisque R.J., Bream G.L., Cannella M.T.;
RT "Human polyomavirus JC virus genome.";
RL J. Virol. 51:458-469(1984).
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 TP53,
CC inhibiting TP53 binding to DNA. Interacts with host preinitiation
CC complex components TBP, TFIIA and TFIID to regulate transcription
CC initiation. {ECO:0000250|UniProtKB:P03070}.
CC -!- INTERACTION:
CC P03072; Q00577: PURA; Xeno; NbExp=4; IntAct=EBI-8658901, EBI-1045860;
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=P03072-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P03083-1; 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; J02226; AAA82102.1; -; Genomic_DNA.
DR PIR; A03609; TVVPTJ.
DR RefSeq; NP_043512.1; NC_001699.1. [P03072-1]
DR PDB; 4LIF; X-ray; 2.60 A; A=132-261.
DR PDB; 4LMD; X-ray; 1.50 A; A/B=132-261.
DR PDB; 4NBP; X-ray; 1.32 A; A=132-261.
DR PDB; 5CYN; X-ray; 2.70 A; A=132-261.
DR PDB; 5J40; X-ray; 2.17 A; A=261-628.
DR PDB; 5J47; X-ray; 1.99 A; A=261-628.
DR PDB; 5J4V; X-ray; 2.94 A; A=261-628.
DR PDB; 5J4Y; X-ray; 2.59 A; A=261-628.
DR PDBsum; 4LIF; -.
DR PDBsum; 4LMD; -.
DR PDBsum; 4NBP; -.
DR PDBsum; 5CYN; -.
DR PDBsum; 5J40; -.
DR PDBsum; 5J47; -.
DR PDBsum; 5J4V; -.
DR PDBsum; 5J4Y; -.
DR SMR; P03072; -.
DR IntAct; P03072; 1.
DR MINT; P03072; -.
DR BindingDB; P03072; -.
DR ChEMBL; CHEMBL4523163; -.
DR DNASU; 1489517; -.
DR GeneID; 1489517; -.
DR KEGG; vg:1489517; -.
DR Proteomes; UP000008478; 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 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 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..688
FT /note="Large T antigen"
FT /id="PRO_0000115040"
FT DOMAIN 12..75
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 401..561
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DNA_BIND 140..255
FT /note="T-ag OBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00620"
FT ZN_FING 266..358
FT /note="T-ag D1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT REGION 115..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 105..109
FT /note="LXCXE motif"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOTIF 126..133
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT COMPBIAS 642..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00671"
FT BINDING 427..434
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 114
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 121
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 124
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 125
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 660
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 680
FT /note="N6-acetyllysine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT MOD_RES 684
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03070"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 157..165
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 166..179
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 193..204
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 222..229
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 230..236
FT /evidence="ECO:0007829|PDB:4NBP"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:4NBP"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 286..294
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:5J4Y"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 304..308
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 318..329
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 334..355
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 358..376
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 385..398
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 402..415
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 420..426
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:5J4Y"
FT HELIX 433..444
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 455..462
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 471..476
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 491..495
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 499..503
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 525..529
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 536..539
FT /evidence="ECO:0007829|PDB:5J47"
FT STRAND 543..547
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 552..559
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 563..566
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 573..583
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 594..607
FT /evidence="ECO:0007829|PDB:5J47"
FT HELIX 610..621
FT /evidence="ECO:0007829|PDB:5J47"
SQ SEQUENCE 688 AA; 79311 MW; 4A55A72F0C10F516 CRC64;
MDKVLNREES MELMDLLGLD RSAWGNIPVM RKAYLKKCKE LHPDKGGDED KMKRMNFLYK
KMEQGVKVAH QPDFGTWNSS EVPTYGTDEW ESWWNTFNEK WDEDLFCHEE MFASDDENTG
SQHSTPPKKK KKVEDPKDFP VDLHAFLSQA VFSNRTVASF AVYTTKEKAQ ILYKKLMEKY
SVTFISRHGF GGHNILFFLT PHRHRVSAIN NYCQKLCTFS FLICKGVNKE YLFYSALCRQ
PYAVVEESIQ GGLKEHDFNP EEPEETKQVS WKLVTQYALE TKCEDVFLLM GMYLDFQENP
QQCKKCEKKD QPNHFNHHEK HYYNAQIFAD SKNQKSICQQ AVDTVAAKQR VDSIHMTREE
MLVERFNFLL DKMDLIFGAH GNAVLEQYMA GVAWIHCLLP QMDTVIYDFL KCIVLNIPKK
RYWLFKGPID SGKTTLAAAL LDLCGGKSLN VNMPLERLNF ELGVGIDQFM VVFEDVKGTG
AESRDLPSGH GISNLDCLRD YLDGSVKVNL ERKHQNKRTQ VFPPGIVTMN EYSVPRTLQA
RFVRQIDFRP KAYLRKSLSC SEYLLEKRIL QSGMTLLLLL IWFRPVADFA AAIHERIVQW
KERLDLEISM YTFSTMKANV GMGRPILDFP REEDSEAEDS GHGSSTESQS QCFSQVSEAS
GADTQENCTF HICKGFQCFK KPKTPPPK
