dbPTM

LT_SV40 - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	LT_SV40
UniProt AC	P03070
Protein Name	Large T antigen
Gene Name
Organism	Simian virus 40 (SV40).
Sequence Length	708
Subcellular Localization	Host nucleus .
Protein 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.; Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain..
Protein Sequence	MDKVLNREESLQLMDLLGLERSAWGNIPLMRKAYLKKCKEFHPDKGGDEEKMKKMNTLYKKMEDGVKYAHQPDFGGFWDATEIPTYGTDEWEQWWNAFNEENLFCSEEMPSSDDEATADSQHSTPPKKKRKVEDPKDFPSELLSFLSHAVFSNRTLACFAIYTTKEKAALLYKKIMEKYSVTFISRHNSYNHNILFFLTPHRHRVSAINNYAQKLCTFSFLICKGVNKEYLMYSALTRDPFSVIEESLPGGLKEHDFNPEEAEETKQVSWKLVTEYAMETKCDDVLLLLGMYLEFQYSFEMCLKCIKKEQPSHYKYHEKHYANAAIFADSKNQKTICQQAVDTVLAKKRVDSLQLTREQMLTNRFNDLLDRMDIMFGSTGSADIEEWMAGVAWLHCLLPKMDSVVYDFLKCMVYNIPKKRYWLFKGPIDSGKTTLAAALLELCGGKALNVNLPLDRLNFELGVAIDQFLVVFEDVKGTGGESRDLPSGQGINNLDNLRDYLDGSVKVNLEKKHLNKRTQIFPPGIVTMNEFSVPKTLQARFVKQIDFRAKDYLKHCLERSEFLLEKRIIQSGIALLLMLIWYRPVAEFAQSIQSRIVEWKERLDKEFSLSVYQKMKFNVAMGIGVLDWLRNSDDDDEDSQENADKNEDGGEKNMEDSGHETGIDSQSQGSFQAPQSSQSVHDHNQPYHICRGFTCFKKPPTPPPEPET

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDKVLNRE -------CCCCCCHH	11.53	205802
106	Phosphorylation	NEENLFCSEEMPSSD CHHCCCCCCCCCCCC	29.29	2838952
112	Phosphorylation	CSEEMPSSDDEATAD CCCCCCCCCCCCCCC	43.12	2838952
120	Phosphorylation	DDEATADSQHSTPPK CCCCCCCCCCCCCCC	27.59	2160857
123	Phosphorylation	ATADSQHSTPPKKKR CCCCCCCCCCCCCCC	34.67	2838952
124	Phosphorylation	TADSQHSTPPKKKRK CCCCCCCCCCCCCCC	41.30	2552322
639	Phosphorylation	SDDDDEDSQENADKN CCCCCHHHHHCHHCC	37.03	2160857
665	Phosphorylation	GHETGIDSQSQGSFQ CCCCCCCCCCCCCCC	29.79	1654434
667	Phosphorylation	ETGIDSQSQGSFQAP CCCCCCCCCCCCCCC	40.22	1654434
676	Phosphorylation	GSFQAPQSSQSVHDH CCCCCCCCCCCCCCC	29.32	2838952
677	Phosphorylation	SFQAPQSSQSVHDHN CCCCCCCCCCCCCCC	22.64	2838952
679	Phosphorylation	QAPQSSQSVHDHNQP CCCCCCCCCCCCCCC	24.30	2838952
697	Acetylation	CRGFTCFKKPPTPPP ECCCCCCCCCCCCCC	67.52	15254196
701	Phosphorylation	TCFKKPPTPPPEPET CCCCCCCCCCCCCCC	57.88	2838952

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
120	S	Phosphorylation	Kinase	ATM	-	GPS
665	S	Phosphorylation	Kinase	PRKDC	-	PhosphoELM
667	S	Phosphorylation	Kinase	PRKDC	-	PhosphoELM
677	S	Phosphorylation	Kinase	PRKDC	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of LT_SV40 !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of LT_SV40 !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P53_HUMAN	TP53	physical	10570441
RB_HUMAN	RB1	physical	10570441
E2F1_HUMAN	E2F1	physical	9205103

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of LT_SV40

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Complete nucleotide sequence of SV40 DNA."; Fiers W., Contreras R., Haegeman G., Rogiers R., van de Voorde A.,van Heuverswyn H., van Herreweghe J., Volckaert G., Ysebaert M.; Nature 273:113-120(1978). Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ACETYLATION AT MET-1.	205802 [Abstract]
Phosphorylation
Reference	PubMed
"Mechanisms of simian virus 40 T-antigen activation by phosphorylationof threonine 124."; McVey D., Woelker B., Tegtmeyer P.; J. Virol. 70:3887-3893(1996). Cited for: PHOSPHORYLATION AT THR-124, AND MUTAGENESIS OF THR-124.	8648725 [Abstract]
"Phosphorylation of large tumour antigen by cdc2 stimulates SV40 DNAreplication."; McVey D., Brizuela L., Mohr I., Marshak D.R., Gluzman Y., Beach D.; Nature 341:503-507(1989). Cited for: PROTEIN SEQUENCE OF 102-118, AND PHOSPHORYLATION AT THR-124 BY CDC2.	2552322 [Abstract]