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Trp53 |
Protein FULL name:
cellular tumor antigen p53 isoform a [Mus musculus].
Trp53 (Mus musculus) is product of expression of Trp53 gene.
FUNCTION: 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.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: Binds DNA as a homotetramer. Found in a complex with CABLES1 and TP73. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. The C-terminus interacts with TAF1, when TAF1 is part of the TFIID complex. Interacts with HIPK1, HIPK2, AXIN1, and P53DINP1. Part of a complex consisting of TP53, HIPK2 and AXIN1. Interacts with WWOX. Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction (By similarity). Directly interacts with FBXO42; leading to ubiquination and degradation of TP53 (By similarity). Interacts with BANP, CDKN2AIP and E4F1. Interacts with CHD8, leading to recruit histone H1 and prevent transactivation activity.
INTERACTION: P03070:- (xeno); NbExp=6; IntAct=EBI-474016, EBI-617698; Q13315:ATM (xeno); NbExp=1; IntAct=EBI-474016, EBI-495465; O70445:Bard1; NbExp=1; IntAct=EBI-474016, EBI-1790207; Q07817-1:BCL2L1 (xeno); NbExp=2; IntAct=EBI-474016, EBI-287195; O96017:CHEK2 (xeno); NbExp=1; IntAct=EBI-474016, EBI-1180783; Q09472:EP300 (xeno); NbExp=1; IntAct=EBI-474016, EBI-447295; O54992:Mapkapk5; NbExp=1; IntAct=EBI-474016, EBI-1202132; P23804:Mdm2; NbExp=1; IntAct=EBI-474016, EBI-641788; Q8N2W9:PIAS4 (xeno); NbExp=2; IntAct=EBI-474016, EBI-473160; P63087-1:Ppp1cc; NbExp=1; IntAct=EBI-474016, EBI-450267; Q61466:Smarcd1; NbExp=1; IntAct=EBI-474016, EBI-371529; Q99986:VRK1 (xeno); NbExp=1; IntAct=EBI-474016, EBI-1769146;
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Endoplasmic reticulum (By similarity). Note=Interaction with BANP promotes nuclear localization (By similarity).
DOMAIN: The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase (By similarity).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP (By similarity). Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-386 following UV but not gamma irradiation. Phosphorylated by HIPK1.
PTM: Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence.
PTM: Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1 at Lys-285 and Lys-286, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it (By similarity).
PTM: Monomethylated at Lys-366 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys- 364 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-366 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-364 (By similarity).
PTM: Sumoylated by SUMO1 (By similarity).
PTM: Demethylation of di-methylated Lys-364 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity).
DISEASE: Note=p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.
SIMILARITY: Belongs to the p53 family.
| NCBI GenPept GI number(s): |
148747262 |
| Species: | Mus musculus |
Links to other databases:
| Database | ID | Link |
| Uniprot | P02340 |
P02340 |
| PFAM: | - |
P02340 (Link - using uniprot id) |
| InterPro: | - |
P02340 (Link - using uniprot id) |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDV EEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTY QGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPA GSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYP EYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILT IITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGS AKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDA HATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD |
Trp53 (Mus musculus) is able to recognize following damages:
Trp53 (Mus musculus) belongs to following protein families:
References:
| Title | Authors | Journal |
| Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. | DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ | Proc Natl Acad Sci U S A May 1, 1979 |
| A single gene and a pseudogene for the cellular tumour antigen p53. | Zakut-Houri R, Oren M, Bienz B, Lavie V, Hazum S, Givol D | Nature Jan. 1, 1983 |
| Cloning and expression analysis of full length mouse cDNA sequences encoding the transformation associated protein p53. | Jenkins JR, Rudge K, Redmond S, Wade-Evans A | Nucleic Acids Res July 25, 1984 |
| Analysis of the gene coding for the murine cellular tumour antigen p53. | Bienz B, Zakut-Houri R, Givol D, Oren M | EMBO J Sept. 1, 1984 |
| Mapping of phosphomonoester and apparent phosphodiester bonds of the oncogene product p53 from simian virus 40-transformed 3T3 cells. | Samad A, Anderson CW, Carroll RB | Proc Natl Acad Sci U S A Jan. 1, 1986 |
| Immunologically distinct p53 molecules generated by alternative splicing. | Arai N, Nomura D, Yokota K, Wolf D, Brill E, Shohat O, Rotter V | Mol Cell Biol Sept. 1, 1986 |
| [Primary structure of DNA complementary to mRNA of murine oncoprotein p53] | Chumakov PM | Bioorg Khim Dec. 1, 1987 |
| The p53 tumour suppressor protein is phosphorylated at serine 389 by casein kinase II. | Meek DW, Simon S, Kikkawa U, Eckhart W | EMBO J Oct. 1, 1990 |
| Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice. | Burns PA, Kemp CJ, Gannon JV, Lane DP, Bremner R, Balmain A | Oncogene Dec. 1, 1991 |
| p53 is covalently linked to 5.8S rRNA. | Fontoura BM, Sorokina EA, David E, Carroll RB | Mol Cell Biol Nov. 1, 1992 |
| DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage. | Jimenez GS, Bryntesson F, Torres-Arzayus MI, Priestley A, Beeche M, Saito S, Sakaguchi K, Appella E, Jeggo PA, Taccioli GE, Wahl GM, Hubank M | Nature July 1, 1999 |
| p53 is involved in the p120E4F-mediated growth arrest. | Sandy P, Gostissa M, Fogal V, Cecco LD, Szalay K, Rooney RJ, Schneider C, Del Sal G | Oncogene Feb. 13, 2000 |
| Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution. | Zhao K, Chai X, Johnston K, Clements A, Marmorstein R | J Biol Chem April 13, 2001 |
| Negative control of p53 by Sir2alpha promotes cell survival under stress. | Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W | Cell Oct. 19, 2001 |
| Differential effect of ik3-1/cables on p53- and p73-induced cell death. | Tsuji K, Mizumoto K, Yamochi T, Nishimoto I, Matsuoka M | J Biol Chem Feb. 25, 2002 |
| Direct interaction with and activation of p53 by SMAR1 retards cell-cycle progression at G2/M phase and delays tumor growth in mice. | Kaul R, Mukherjee S, Ahmed F, Bhat MK, Chhipa R, Galande S, Chattopadhyay S | Int J Cancer Jan. 20, 2003 |
| Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1). | Kondo S, Lu Y, Debbas M, Lin AW, Sarosi I, Itie A, Wakeham A, Tuan J, Saris C, Elliott G, Ma W, Benchimol S, Lowe SW, Mak TW, Thukral SK | Proc Natl Acad Sci U S A April 1, 2003 |
| Identification and characterization of murine mHAUSP encoding a deubiquitinating enzyme that regulates the status of p53 ubiquitination. | Lim SK, Shin JM, Kim YS, Baek KH | Int J Oncol Jan. 1, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation. | Rui Y, Xu Z, Lin S, Li Q, Rui H, Luo W, Zhou HM, Cheung PY, Wu Z, Ye Z, Li P, Han J, Lin SC | EMBO J Nov. 24, 2004 |
| Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9. | Arai S, Matsushita A, Du K, Yagi K, Okazaki Y, Kurokawa R | FEBS Lett Dec. 11, 2007 |
| CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. | Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI | Nat Cell Biol Jan. 1, 2009 |
Last modification of this entry: Oct. 6, 2010.
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