P53_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: P53_RAT
• UniProt AC: P10361
• Protein Name: Cellular tumor antigen p53
• Gene Name: Tp53
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 391
• Subcellular Localization: Cytoplasm . Nucleus . Nucleus, PML body . Endoplasmic reticulum . Mitochondrion matrix . Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress. Transloca
• Protein Description: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2..
• Protein Sequence: MEDSQSDMSIELPLSQETFSCLWKLLPPDDILPTTATGSPNSMEDLFLPQDVAELLEGPEEALQVSAPAAQEPGTEAPAPVAPASATPWPLSSSVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSISLNKLFCQLAKTCPVQLWVTSTPPPGTRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNPYAEYLDDRQTFRHSVVVPYEPPEVGSDYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEEHCPELPPGSAKRALPTSTSSSPQQKKKPLDGEYFTLKIRGRERFEMFRELNEALELKDARAAEESGDSRAHSSYPKTKKGQSTSRHKKPMIKKVGPDSD

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	Phosphorylation	----MEDSQSDMSIE ----CCCCCCCEEEE	20.48	18697815
6	Phosphorylation	--MEDSQSDMSIELP --CCCCCCCEEEEEE	38.95	7862459
9	Phosphorylation	EDSQSDMSIELPLSQ CCCCCCEEEEEECCH	20.22	7862459
15	Phosphorylation	MSIELPLSQETFSCL EEEEEECCHHHHHHH	24.83	18032786
18	Phosphorylation	ELPLSQETFSCLWKL EEECCHHHHHHHHHH	17.14	-
20	Phosphorylation	PLSQETFSCLWKLLP ECCHHHHHHHHHHCC	18.73	22817900
39	Phosphorylation	LPTTATGSPNSMEDL CCCCCCCCCCCHHHH	19.29	7862459
118	Acetylation	FLQSGTAKSVMCTYS EECCCCCCEEEEEEE	43.34	128769
181	Phosphorylation	CPHHERCSDGDGLAP CCCCCCCCCCCCCCC	51.34	-
213	Phosphorylation	DRQTFRHSVVVPYEP CCCCEEEEEEECCCC	16.61	27097102
218	Phosphorylation	RHSVVVPYEPPEVGS EEEEEECCCCCCCCC	29.47	27097102
225	Phosphorylation	YEPPEVGSDYTTIHY CCCCCCCCCCEEEEE	32.40	27097102
227	Phosphorylation	PPEVGSDYTTIHYKY CCCCCCCCEEEEEEE	13.89	27097102
228	Phosphorylation	PEVGSDYTTIHYKYM CCCCCCCEEEEEEEE	25.02	27097102
229	Phosphorylation	EVGSDYTTIHYKYMC CCCCCCEEEEEEEEC	10.26	27097102
232	Phosphorylation	SDYTTIHYKYMCNSS CCCEEEEEEEECCCC	10.44	27097102
267	Phosphorylation	GNLLGRDSFEVRVCA CCCCCCCCEEEEEEE	23.19	-
282	Phosphorylation	CPGRDRRTEEENFRK CCCCCCCCHHHHHHH	48.95	-
303	Acetylation	ELPPGSAKRALPTST CCCCCCHHHCCCCCC	39.64	-
308	Phosphorylation	SAKRALPTSTSSSPQ CHHHCCCCCCCCCCC	45.55	23984901
309	Phosphorylation	AKRALPTSTSSSPQQ HHHCCCCCCCCCCCC	25.09	23984901
310	Phosphorylation	KRALPTSTSSSPQQK HHCCCCCCCCCCCCC	34.80	23984901
311	Phosphorylation	RALPTSTSSSPQQKK HCCCCCCCCCCCCCC	28.69	28432305
312	Phosphorylation	ALPTSTSSSPQQKKK CCCCCCCCCCCCCCC	46.24	28432305
313	Phosphorylation	LPTSTSSSPQQKKKP CCCCCCCCCCCCCCC	26.88	27097102
319	Acetylation	SSPQQKKKPLDGEYF CCCCCCCCCCCCCCE	58.82	-
331	Methylation	EYFTLKIRGRERFEM CCEEEEECCHHHHHH	36.21	-
333	Methylation	FTLKIRGRERFEMFR EEEEECCHHHHHHHH	23.28	-
335	Methylation	LKIRGRERFEMFREL EEECCHHHHHHHHHH	31.31	-
368	"N6,N6-dimethyllysine"	RAHSSYPKTKKGQST CCCCCCCCCCCCCCC	65.82	-
368	Methylation	RAHSSYPKTKKGQST CCCCCCCCCCCCCCC	65.82	-
370	Methylation	HSSYPKTKKGQSTSR CCCCCCCCCCCCCCC	62.12	-
371	Acetylation	SSYPKTKKGQSTSRH CCCCCCCCCCCCCCC	68.37	60335
371	"N6,N6-dimethyllysine"	SSYPKTKKGQSTSRH CCCCCCCCCCCCCCC	68.37	-
371	Methylation	SSYPKTKKGQSTSRH CCCCCCCCCCCCCCC	68.37	-
376	Phosphorylation	TKKGQSTSRHKKPMI CCCCCCCCCCCCCCC	37.32	22817900
379	Acetylation	GQSTSRHKKPMIKKV CCCCCCCCCCCCCCC	58.42	60365
380	Acetylation	QSTSRHKKPMIKKVG CCCCCCCCCCCCCCC	33.42	60305
380	Methylation	QSTSRHKKPMIKKVG CCCCCCCCCCCCCCC	33.42	-
380	"N6,N6-dimethyllysine"	QSTSRHKKPMIKKVG CCCCCCCCCCCCCCC	33.42	-
390	Phosphorylation	IKKVGPDSD------ CCCCCCCCC------	48.64	18697815

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
6	S	Phosphorylation	Kinase	CK1_GROUP	-	PhosphoELM
6	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
9	S	Phosphorylation	Kinase	CK1_GROUP	-	PhosphoELM
9	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
9	S	Phosphorylation	Kinase	HIPK4	Q4V793	Uniprot
15	S	Phosphorylation	Kinase	PRKDC	-	PhosphoELM
15	S	Phosphorylation	Kinase	AMPK	Q09137	Uniprot
15	S	Phosphorylation	Kinase	ATM	-	Uniprot
15	S	Phosphorylation	Kinase	NUAK1	-	Uniprot
15	S	Phosphorylation	Kinase	PRPK	-	Uniprot
15	S	Phosphorylation	Kinase	CDK5	Q03114	Uniprot
15	S	Phosphorylation	Kinase	ATM	Q13315	PSP
15	S	Phosphorylation	Kinase	PRKDC	D3ZTN0	GPS
18	T	Phosphorylation	Kinase	CK1	-	Uniprot
18	T	Phosphorylation	Kinase	VRK2	-	Uniprot
18	T	Phosphorylation	Kinase	VRK1	-	Uniprot
20	S	Phosphorylation	Kinase	CK1	-	Uniprot
20	S	Phosphorylation	Kinase	CHEK2	-	Uniprot
20	S	Phosphorylation	Kinase	PLK3	Q9R011	Uniprot
39	S	Phosphorylation	Kinase	MAPKAPK5	-	Uniprot
181	S	Phosphorylation	Kinase	AURKB	O55099	Uniprot
267	S	Phosphorylation	Kinase	AURKB	O55099	Uniprot
282	T	Phosphorylation	Kinase	AURKB	O55099	Uniprot
313	S	Phosphorylation	Kinase	CDK1	P39951	Uniprot
313	S	Phosphorylation	Kinase	CDK2	Q63699	Uniprot
313	S	Phosphorylation	Kinase	AURKA	P59241	Uniprot
390	S	Phosphorylation	Kinase	CK2	-	Uniprot
390	S	Phosphorylation	Kinase	NUAK1	-	Uniprot
390	S	Phosphorylation	Kinase	CDK2	Q63699	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo11	Q7TSL3	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Huwe1	P51593	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
9	S	Phosphorylation	Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter (By similarity).	-
15	S	Phosphorylation	Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes.	-
15	S	Phosphorylation	Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (By similarity).	-
15	S	Phosphorylation	Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP.	-
15	S	Oxidation	Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes.	-
18	T	Phosphorylation	Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2.	-
20	S	ubiquitylation	Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2.	-
20	S	Phosphorylation	Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis.	-
20	S	Phosphorylation	Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2.	-
24	K	ubiquitylation	Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (By similarity).	-
313	S	Phosphorylation	Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage (By similarity).	-
331	R	Methylation	Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity).	-
333	R	Methylation	Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity).	-
335	R	Methylation	Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity).	-
368	K	Methylation	Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity).	-
368	K	Methylation	Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity.	-
368	K	Methylation	Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368.	-
370	K	Methylation	Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation.	-
370	K	Methylation	Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368.	-
371	K	Methylation	Dimethylated at Lys-371 by EHMT1 and EHMT2.	-
380	K	Methylation	Monomethylated at Lys-380 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity.	-
384	K	Sumoylation	Sumoylated at Lys-384 by UBC9 (By similarity).	-
390	S	Phosphorylation	Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage (By similarity).	-
390	S	Phosphorylation	Phosphorylated on Ser-390 following UV but not gamma irradiation.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of P53_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HS90A_RAT	Hsp90aa1	physical	9488468
HSP74_RAT	Hspa4	physical	9488468
CP27B_RAT	Cyp27b1	physical	9488468
UBC_RAT	Ubc	physical	22046440
TCP4_RAT	Sub1	physical	17130840
UBC_RAT	Ubc	physical	16330492
SUMO1_RAT	Sumo1	physical	19819240
CCNG1_RAT	Ccng1	physical	11983168

Drug and Disease Associations

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