Mus musculus L. (mouse) [MMU]

FULL NAME: Cellular tumor antigen p53


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.

STRUCTURE SIMILARITY:
Belongs to the p53 family.


POST-TRANSLATIONAL MODIFICATION:
Sumoylated by SUMO1 (By similarity).
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. Ubiquitinated by TRIM24, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it (By similarity).
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. Dimethylated at Lys-367 EHMT1 and EHMT2. Monomethylated at Lys-376 SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-364 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity).
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. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2 (By similarity). Phosphorylated on Ser-386 following UV but not gamma irradiation. Phosphorylated by HIPK1.
Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence.


RELATED PATHWAY(S):
DNA damage response (DDR)


Amino acids sequence

        10         20         30         40         50         60
MTAMEESQSD ISLELPLSQE TFSGLWKLLP PEDILPSPHC MDDLLLPQDV EEFFEGPSEA
        70         80         90        100        110        120
LRVSGAPAAQ DPVTETPGPV APAPATPWPL SSFVPSQKTY QGNYGFHLGF LQSGTAKSVM
       130        140        150        160        170        180
CTYSPPLNKL FCQLAKTCPV QLWVSATPPA GSRVRAMAIY KKSQHMTEVV RRCPHHERCS
       190        200        210        220        230        240
DGDGLAPPQH LIRVEGNLYP EYLEDRQTFR HSVVVPYEPP EAGSEYTTIH YKYMCNSSCM
       250        260        270        280        290        300
GGMNRRPILT IITLEDSSGN LLGRDSFEVR VCACPGRDRR TEEENFRKKE VLCPELPPGS
       310        320        330        340        350        360
AKRALPTCTS ASPPQKKKPL DGEYFTLKIR GRKRFEMFRE LNEALELKDA HATEESGDSR
       370        380
AHSSLQPRAF QALIKEESPN C   

Encoded by Trp53 gene

FULL NAME: transformation related protein 53


OTHER NAME(S):
Tp53
bbl
bfy
bhy
p44
p53


DESCRIPTION:
This gene encodes tumor protein p53, which responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing transcription activation, DNA-binding, and oligomerization domains. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mice deficient for this gene are developmentally normal but are susceptible to spontaneous tumors. Evidence to date shows that this gene contains one promoter, in contrast to alternative promoters of the human gene, and transcribes a few of splice variants which encode different isoforms, although the biological validity or the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgactgcca tggaggagtc acagtcggat atcagcctcg agctccctct gagccaggag
        70         80         90        100        110        120
acattttcag gcttatggaa actacttcct ccagaagata tcctgccatc acctcactgc
       130        140        150        160        170        180
atggacgatc tgttgctgcc ccaggatgtt gaggagtttt ttgaaggccc aagtgaagcc
       190        200        210        220        230        240
ctccgagtgt caggagctcc tgcagcacag gaccctgtca ccgagacccc tgggccagtg
       250        260        270        280        290        300
gcccctgccc cagccactcc atggcccctg tcatcttttg tcccttctca aaaaacttac
       310        320        330        340        350        360
cagggcaact atggcttcca cctgggcttc ctgcagtctg ggacagccaa gtctgttatg
       370        380        390        400        410        420
tgcacgtact ctcctcccct caataagcta ttctgccagc tggcgaagac gtgccctgtg
       430        440        450        460        470        480
cagttgtggg tcagcgccac acctccagct gggagccgtg tccgcgccat ggccatctac
       490        500        510        520        530        540
aagaagtcac agcacatgac ggaggtcgtg agacgctgcc cccaccatga gcgctgctcc
       550        560        570        580        590        600
gatggtgatg gcctggctcc tccccagcat cttatccggg tggaaggaaa tttgtatccc
       610        620        630        640        650        660
gagtatctgg aagacaggca gacttttcgc cacagcgtgg tggtacctta tgagccaccc
       670        680        690        700        710        720
gaggccggct ctgagtatac caccatccac tacaagtaca tgtgtaatag ctcctgcatg
       730        740        750        760        770        780
gggggcatga accgccgacc tatccttacc atcatcacac tggaagactc cagtgggaac
       790        800        810        820        830        840
cttctgggac gggacagctt tgaggttcgt gtttgtgcct gccctgggag agaccgccgt
       850        860        870        880        890        900
acagaagaag aaaatttccg caaaaaggaa gtcctttgcc ctgaactgcc cccagggagc
       910        920        930        940        950        960
gcaaagagag cgctgcccac ctgcacaagc gcctctcccc cgcaaaagaa aaaaccactt
       970        980        990       1000       1010       1020
gatggagagt atttcaccct caagatccgc gggcgtaaac gcttcgagat gttccgggag
      1030       1040       1050       1060       1070       1080
ctgaatgagg ccttagagtt aaaggatgcc catgctacag aggagtctgg agacagcagg
      1090       1100       1110       1120       1130       1140
gctcactcca gcctccagcc tagagccttc caagccttga tcaaggagga aagcccaaac

tgctag     

Last modification date: Oct. 2, 2011