Homo sapiens L. (human) [HSA]

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. Implicated in Notch signaling cross-over. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.

STRUCTURE SIMILARITY:
Belongs to the p53 family.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylated by HIPK1 (By similarity). 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. Phosphorylated on Thr-55 by TAF1, which promotes MDM2-mediated degradation. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP.
Monomethylated at Lys-372 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370. Dimethylated at Lys-373 by EHMT1 and EHMT2. Monomethylated at Lys-382 by SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-370 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation.
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-291 and Lys-292, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to its stabilization. Ubiquitinated by TRIM24, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilization. Isoform 4 is monoubiquitinated in an MDM2-independent manner.
Dephosphorylated by PP2A-PPP2R5C holoenzyme at Thr-55. SV40 small T antigen inhibits the dephosphorylation by the AC form of PP2A.
Acetylated. Acetylation of Lys-382 by CREBBP enhances transcriptional activity. Deacetylation of Lys-382 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence.
Sumoylated by SUMO1.
May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line.


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


RELATED DISEASE(S):
choroid plexus papilloma
breast cancer (BC)
COLORECTAL CANCER
Li-Fraumeni syndrome-2
esophageal squamous cell carcinoma
osteogenic sarcoma
head and neck squamous cell carcinomas
lung cancer


Amino acids sequence

        10         20         30         40         50         60
MEEPQSDPSV EPPLSQETFS DLWKLLPENN VLSPLPSQAM DDLMLSPDDI EQWFTEDPGP
        70         80         90        100        110        120
DEAPRMPEAA PPVAPAPAAP TPAAPAPAPS WPLSSSVPSQ KTYQGSYGFR LGFLHSGTAK
       130        140        150        160        170        180
SVTCTYSPAL NKMFCQLAKT CPVQLWVDST PPPGTRVRAM AIYKQSQHMT EVVRRCPHHE
       190        200        210        220        230        240
RCSDSDGLAP PQHLIRVEGN LRVEYLDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS
       250        260        270        280        290        300
SCMGGMNRRP ILTIITLEDS SGNLLGRNSF EVRVCACPGR DRRTEEENLR KKGEPHHELP
       310        320        330        340        350        360
PGSTKRALPN NTSSSPQPKK KPLDGEYFTL QIRGRERFEM FRELNEALEL KDAQAGKEPG
       370        380        390
GSRAHSSHLK SKKGQSTSRH KKLMFKTEGP DSD  

Encoded by TP53 gene

FULL NAME: tumor protein p53


OTHER NAME(S):
FLJ92943
LFS1
P53
TRP53


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. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Alterations of this gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome. Multiple p53 variants due to alternative promoters and multiple alternative splicing have been found. These variants encode distinct isoforms, which can regulate p53 transcriptional activity. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggaggagc cgcagtcaga tcctagcgtc gagccccctc tgagtcagga aacattttca
        70         80         90        100        110        120
gacctatgga aactacttcc tgaaaacaac gttctgtccc ccttgccgtc ccaagcaatg
       130        140        150        160        170        180
gatgatttga tgctgtcccc ggacgatatt gaacaatggt tcactgaaga cccaggtcca
       190        200        210        220        230        240
gatgaagctc ccagaatgcc agaggctgct ccccccgtgg cccctgcacc agcagctcct
       250        260        270        280        290        300
acaccggcgg cccctgcacc agccccctcc tggcccctgt catcttctgt cccttcccag
       310        320        330        340        350        360
aaaacctacc agggcagcta cggtttccgt ctgggcttct tgcattctgg gacagccaag
       370        380        390        400        410        420
tctgtgactt gcacgtactc ccctgccctc aacaagatgt tttgccaact ggccaagacc
       430        440        450        460        470        480
tgccctgtgc agctgtgggt tgattccaca cccccgcccg gcacccgcgt ccgcgccatg
       490        500        510        520        530        540
gccatctaca agcagtcaca gcacatgacg gaggttgtga ggcgctgccc ccaccatgag
       550        560        570        580        590        600
cgctgctcag atagcgatgg tctggcccct cctcagcatc ttatccgagt ggaaggaaat
       610        620        630        640        650        660
ttgcgtgtgg agtatttgga tgacagaaac acttttcgac atagtgtggt ggtgccctat
       670        680        690        700        710        720
gagccgcctg aggttggctc tgactgtacc accatccact acaactacat gtgtaacagt
       730        740        750        760        770        780
tcctgcatgg gcggcatgaa ccggaggccc atcctcacca tcatcacact ggaagactcc
       790        800        810        820        830        840
agtggtaatc tactgggacg gaacagcttt gaggtgcgtg tttgtgcctg tcctgggaga
       850        860        870        880        890        900
gaccggcgca cagaggaaga gaatctccgc aagaaagggg agcctcacca cgagctgccc
       910        920        930        940        950        960
ccagggagca ctaagcgagc actgcccaac aacaccagct cctctcccca gccaaagaag
       970        980        990       1000       1010       1020
aaaccactgg atggagaata tttcaccctt cagatccgtg ggcgtgagcg cttcgagatg
      1030       1040       1050       1060       1070       1080
ttccgagagc tgaatgaggc cttggaactc aaggatgccc aggctgggaa ggagccaggg
      1090       1100       1110       1120       1130       1140
gggagcaggg ctcactccag ccacctgaag tccaaaaagg gtcagtctac ctcccgccat
      1150       1160       1170       1180
aaaaaactca tgttcaagac agaagggcct gactcagact ga 

Last modification date: Oct. 2, 2011