CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002039
UniProt Accession
Genbank Protein ID
 J02400 
Genbank Nucleotide ID
Protein Name
 Large T antigen 
Protein Synonyms/Alias
 LT; LT-AG 
Gene Name
  
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Simian virus 40 (SV40) 
NCBI Taxa ID
 10633 
Lysine Modification
Position
Peptide
Type
References
697CRGFTCFKKPPTPPPacetylation[1, 2]
Reference
 [1] p53 targets simian virus 40 large T antigen for acetylation by CBP.
 Poulin DL, Kung AL, DeCaprio JA.
 J Virol. 2004 Aug;78(15):8245-53. [PMID: 15254196]
 [2] Targeting of p300/CREB binding protein coactivators by simian virus 40 is mediated through p53.
 Borger DR, DeCaprio JA.
 J Virol. 2006 May;80(9):4292-303. [PMID: 16611888] 
Functional Description
 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. May inactivate the growth- suppressing properties of the E3 ubiquitin ligase CUL7. 
Sequence Annotation
 DOMAIN 12 75 J.
 DOMAIN 400 560 SF3 helicase.
 DNA_BIND 139 254 T-ag OBD.
 ZN_FING 265 357 T-ag D1-type.
 NP_BIND 426 433 ATP (Potential).
 REGION 63 89 Binding of LT to the CUL7 complex.
 REGION 337 672 Binding to host TP53 protein.
 REGION 418 616 ATPase activity.
 REGION 627 708 C-terminal region.
 REGION 699 708 CPD.
 MOTIF 103 107 LXCXE motif.
 MOTIF 125 132 Nuclear localization signal.
 MOD_RES 1 1 N-acetylmethionine; by host.
 MOD_RES 106 106 Phosphoserine; by host.
 MOD_RES 112 112 Phosphoserine; by host.
 MOD_RES 120 120 Phosphoserine; by host.
 MOD_RES 123 123 Phosphoserine; by host.
 MOD_RES 124 124 Phosphothreonine; by host.
 MOD_RES 639 639 Phosphoserine; by host.
 MOD_RES 676 676 Phosphoserine; by host.
 MOD_RES 677 677 Phosphoserine; by host.
 MOD_RES 679 679 Phosphoserine; by host.
 MOD_RES 697 697 N6-acetyllysine; by host.
 MOD_RES 701 701 Phosphothreonine; by host.  
Keyword
 3D-structure; Acetylation; Activator; Alternative initiation; Alternative splicing; ATP-binding; Complete proteome; Direct protein sequencing; DNA replication; DNA-binding; Early protein; G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein; Helicase; Host nucleus; Host-virus interaction; Hydrolase; Inhibition of host innate immune response by virus; Inhibition of host interferon signaling pathway by virus; Inhibition of host JAK1 by virus; Metal-binding; Modulation of host cell cycle by virus; Modulation of host E3 ubiquitin ligases by virus; Modulation of host ubiquitin pathway by virus; Nucleotide-binding; Oncogene; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 708 AA 
Protein Sequence
MDKVLNREES LQLMDLLGLE RSAWGNIPLM RKAYLKKCKE FHPDKGGDEE KMKKMNTLYK 60
KMEDGVKYAH QPDFGGFWDA TEIPTYGTDE WEQWWNAFNE ENLFCSEEMP SSDDEATADS 120
QHSTPPKKKR KVEDPKDFPS ELLSFLSHAV FSNRTLACFA IYTTKEKAAL LYKKIMEKYS 180
VTFISRHNSY NHNILFFLTP HRHRVSAINN YAQKLCTFSF LICKGVNKEY LMYSALTRDP 240
FSVIEESLPG GLKEHDFNPE EAEETKQVSW KLVTEYAMET KCDDVLLLLG MYLEFQYSFE 300
MCLKCIKKEQ PSHYKYHEKH YANAAIFADS KNQKTICQQA VDTVLAKKRV DSLQLTREQM 360
LTNRFNDLLD RMDIMFGSTG SADIEEWMAG VAWLHCLLPK MDSVVYDFLK CMVYNIPKKR 420
YWLFKGPIDS GKTTLAAALL ELCGGKALNV NLPLDRLNFE LGVAIDQFLV VFEDVKGTGG 480
ESRDLPSGQG INNLDNLRDY LDGSVKVNLE KKHLNKRTQI FPPGIVTMNE FSVPKTLQAR 540
FVKQIDFRAK DYLKHCLERS EFLLEKRIIQ SGIALLLMLI WYRPVAEFAQ SIQSRIVEWK 600
ERLDKEFSLS VYQKMKFNVA MGIGVLDWLR NSDDDDEDSQ ENADKNEDGG EKNMEDSGHE 660
TGIDSQSQGS FQAPQSSQSV HDHNQPYHIC RGFTCFKKPP TPPPEPET 708 
Gene Ontology
 GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003688; F:DNA replication origin binding; IEA:InterPro.
 GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
 GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
 GO:0039649; P:modulation by virus of host ubiquitin-protein ligase activity; IEA:UniProtKB-KW.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0039576; P:suppression by virus of host JAK1 activity; IEA:UniProtKB-KW.
 GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR001623; DnaJ_domain.
 IPR014015; Helicase_SF3_DNA-vir.
 IPR016392; Lg_T_Ag_polyomavir.
 IPR010932; Lg_T_Ag_Polyomavir_C.
 IPR027417; P-loop_NTPase.
 IPR003133; T_Ag_DNA-bd.
 IPR017910; Znf_lg_T-Ag_D1-typ. 
Pfam
 PF00226; DnaJ
 PF06431; Polyoma_lg_T_C
 PF02217; T_Ag_DNA_bind 
SMART
 SM00271; DnaJ 
PROSITE
 PS00636; DNAJ_1
 PS50076; DNAJ_2
 PS51206; SF3_HELICASE_1
 PS51287; T_AG_OBD
 PS51341; ZF_LTAG_D1 
PRINTS