Description:
Cellular tumor antigen p53 (Tumor suppressor p53).
Molecular weight: 43458
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
base-excision repair( GO:0006284 ) nucleotide-excision repair (and GO:0045001, a synonym)( GO:0006289 )
Important dates:
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
01-NOV-1990, sequence version 2.
07-FEB-2006, entry version 73.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Glires Rodentia Sciurognathi Muroidea Muridae Murinae Mus.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein P53_MOUSE:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X00876 | CAA25420.1 | - |
| EMBL | X00877 | CAA25420.1 | JOINED |
| EMBL | X00878 | CAA25420.1 | JOINED |
| EMBL | X00879 | CAA25420.1 | JOINED |
| EMBL | X00880 | CAA25420.1 | JOINED |
| EMBL | X00881 | CAA25420.1 | JOINED |
| EMBL | X00882 | CAA25420.1 | JOINED |
| EMBL | X00883 | CAA25420.1 | JOINED |
| EMBL | X00884 | CAA25420.1 | JOINED |
| EMBL | X00885 | CAA25420.1 | JOINED |
| EMBL | X01237 | CAA25625.1 | - |
| EMBL | X00741 | CAA25323.1 | - |
| EMBL | M13872 | AAA39881.1 | - |
| EMBL | M13873 | AAA39882.1 | - |
| EMBL | M13874 | AAA39883.1 | ALT_SEQ |
| EMBL | AB021961 | BAA82344.1 | - |
| EMBL | AF151353 | AAD39535.1 | - |
| EMBL | AB017815 | BAA82339.1 | - |
| EMBL | AB017816 | BAA82340.1 | - |
| EMBL | AB020317 | BAA82343.1 | - |
| EMBL | BC005448 | AAH05448.1 | - |
| EMBL | S77930 | AAB21108.2.1 | - |
| PIR | A22739 | DNMS53. | |
| PDB | 1HU8 | X-ray | A/B/C=99-284. |
| IntAct | P02340 | -.1 | |
| TRANSFAC | T01806 | -. | |
| Ensembl | ENSMUSG00000059552 | Mus musculus.1 | |
| MGI | MGI:98834 | Trp53.1 | |
| GO | GO:0005829 | C:cytosol | IDA. |
| GO | GO:0005739 | C:mitochondrion | ISS. |
| GO | GO:0005730 | C:nucleolus | ISS. |
| GO | GO:0005657 | C:replication fork | IDA. |
| GO | GO:0005524 | F:ATP binding | ISS. |
| GO | GO:0005507 | F:copper ion binding | ISS. |
| GO | GO:0000739 | F:DNA strand annealing activity | ISS. |
| GO | GO:0005515 | F:protein binding | ISS. |
| GO | GO:0003700 | F:transcription factor activity | IDA. |
| GO | GO:0006915 | P:apoptosis | ISS. |
| GO | GO:0006284 | P:base-excision repair | ISS. |
| GO | GO:0008635 | P:caspase activation via cytochrome c | ISS. |
| GO | GO:0007569 | P:cell aging | ISS. |
| GO | GO:0007050 | P:cell cycle arrest | ISS. |
| GO | GO:0030154 | P:cell differentiation | ISS. |
| GO | GO:0042771 | P:DNA damage response, signal transduction by... | IMP. |
| GO | GO:0043066 | P:negative regulation of apoptosis | IMP. |
| GO | GO:0030308 | P:negative regulation of cell growth | ISS. |
| GO | GO:0008156 | P:negative regulation of DNA replication | IDA. |
| GO | GO:0048147 | P:negative regulation of fibroblast prolifera... | IMP. |
| GO | GO:0006289 | P:nucleotide-excision repair | ISS. |
| GO | GO:0045941 | P:positive regulation of transcription | IDA. |
| GO | GO:0000060 | P:protein-nucleus import, translocation | IDA. |
| GO | GO:0042127 | P:regulation of cell proliferation | IMP. |
| GO | GO:0006355 | P:regulation of transcription, DNA-dependent | IDA. |
| GO | GO:0006974 | P:response to DNA damage stimulus | IDA. |
| GO | GO:0009411 | P:response to UV | IMP. |
| GO | GO:0010165 | P:response to X-ray | IDA. |
| InterPro | IPR002117 | P53. | |
| InterPro | IPR011615 | P53_DNA_bd. | |
| InterPro | IPR012346 | P53_RUNT_DNA_bd. | |
| InterPro | IPR010991 | p53_tetrameristn. | |
| Pfam | PF00870 | P53 | 1. |
| Pfam | PF07710 | P53_tetramer | 1. |
| PRINTS | PR00386 | P53SUPPRESSR. | |
| ProDom | PD002681 | P53 | 1. |
| PROSITE | PS00348 | P53 | 1. |
Keywords:
3D-structure; Acetylation; Activator; Anti-oncogene; Apoptosis; Cell cycle; Disease mutation; DNA-binding; Metal-binding; Nuclear protein; Phosphorylation; Transcription; Transcription regulation; Zinc.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=85027173; PubMed=6092064;
RA Bienz B., Zakut-Houri R., Givol D., Oren M.;
RT "Analysis of the gene coding for the murine cellular tumour antigen
RT p53.";
RL EMBO J. 3:2179-2183(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=84068204; PubMed=6646235;
RA Zakut-Houri R., Oren M., Bienz B., Lavie V., Hazum S., Givol D.;
RT "A single gene and a pseudogene for the cellular tumour antigen p53.";
RL Nature 306:594-597(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=84272240; PubMed=6379601;
RA Jenkins J.R., Rudge K., Redmond S., Wade-Evans A.;
RT "Cloning and expression analysis of full length mouse cDNA sequences
RT encoding the transformation associated protein p53.";
RL Nucleic Acids Res. 12:5609-5626(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE (CLONES PCD53; P53-M11 AND P53-M8).
RX MEDLINE=87064640; PubMed=3023970;
RA Arai N., Nomura D., Yokota K., Wolf D., Brill E., Shohat O.,
RA Rotter V.;
RT "Immunologically distinct p53 molecules generated by alternative
RT splicing.";
RL Mol. Cell. Biol. 6:3232-3239(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE, AND VARIANT VAL-135.
RX MEDLINE=88221682; PubMed=3329909;
RA Chumakov P.M.;
RT "Primary structure of DNA complementary to mRNA of murine oncoprotein
RT p53.";
RL Bioorg. Khim. 13:1691-1694(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=SCID;
RA Araki R., Fukumura R., Fujimori A., Tatsumi K., Abe M.;
RT "Cell cycle in DNA-PKcs knock-out mice.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=99330047; PubMed=10403253; DOI=10.1038/21913;
RA Jimenez G.S., Bryntesson F., Torres-Arzayus M.I., Priestley A.,
RA Beeche M., Saito S., Sakaguchi K., Appella E., Jeggo P.A.,
RA Taccioli G.E., Wahl G.M., Hubank M.;
RT "DNA-dependent protein kinase is not required for the p53-dependent
RT response to DNA damage.";
RL Nature 400:81-83(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Mammary carcinoma;
RA Araki R., Fukumura R., Fujimori A., Tatsumi K., Abe M.;
RT "Characterization of DNA-PKcs null mutant SX9.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=129/SvJ; TISSUE=Lung fibroblast;
RA Fujimori A., Abe M.;
RT "p53 in 129-SVJ mice.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [11]
RP NUCLEOTIDE SEQUENCE OF 222-258.
RX MEDLINE=92115342; PubMed=1766680;
RA Burns P.A., Kemp C.J., Gannon J.V., Lane D.P., Bremner R., Balmain A.;
RT "Loss of heterozygosity and mutational alterations of the p53 gene in
RT skin tumours of interspecific hybrid mice.";
RL Oncogene 6:2363-2369(1991).
RN [12]
RP INTERACTION WITH HIPK1, AND PHOSPHORYLATION.
RX MEDLINE=22608637; PubMed=12702766; DOI=10.1073/pnas.0530308100;
RA Kondo S., Lu Y., Debbas M., Lin A.W., Sarosi I., Itie A., Wakeham A.,
RA Tuan J., Saris C., Elliott G., Ma W., Benchimol S., Lowe S.W.,
RA Mak T.W., Thukral S.K.;
RT "Characterization of cells and gene-targeted mice deficient for the
RT p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1).";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5431-5436(2003).
RN [13]
RP INTERACTION WITH AXIN1, AND IDENTIFICATION IN A COMPLEX WITH HIPK2 AND
RP AXIN1.
RX PubMed=15526030; DOI=10.1038/sj.emboj.7600475;
RA Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.-M.,
RA Cheung P.-Y., Wu Z., Ye Z., Li P., Han J., Lin S.-C.;
RT "Axin stimulates p53 functions by activation of HIPK2 kinase through
RT multimeric complex formation.";
RL EMBO J. 23:4583-4594(2004).
RN [14]
RP PHOSPHORYLATION SITES, AND RNA-BINDING.
RX MEDLINE=86149247; PubMed=3006031;
RA Samad A., Anderson C.W., Carroll R.B.;
RT "Mapping of phosphomonoester and apparent phosphodiester bonds of the
RT oncogene product p53 from simian virus 40-transformed 3T3 cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:897-901(1986).
RN [15]
RP PHOSPHORYLATION SITES.
RX MEDLINE=91006019; PubMed=2145148;
RA Meek D.W., Simon S., Kikkawa U., Eckhart W.;
RT "The p53 tumour suppressor protein is phosphorylated at serine 389 by
RT casein kinase II.";
RL EMBO J. 9:3253-3260(1990).
RN [16]
RP DEACETYLATION BY SIRT1.
RX MEDLINE=21526626; PubMed=11672522; DOI=10.1016/S0092-8674(01)00524-4;
RA Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A.,
RA Guarente L., Gu W.;
RT "Negative control of p53 by Sir2alpha promotes cell survival under
RT stress.";
RL Cell 107:137-148(2001).
RN [17]
RP IDENTIFICATION IN A COMPLEX WITH CABLES1 AND TP73.
RX MEDLINE=21659718; PubMed=11706030; DOI=10.1074/jbc.M108535200;
RA Tsuji K., Mizumoto K., Yamochi T., Nishimoto I., Matsuoka M.;
RT "Differential effect of ik3-1/cables on p53- and p73-induced cell
RT death.";
RL J. Biol. Chem. 277:2951-2957(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 99-284.
RX MEDLINE=21192265; PubMed=11152481; DOI=10.1074/jbc.M011644200;
RA Zhao K., Chai X., Johnston K., Clements A., Marmorstein R.;
RT "Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A
RT resolution.";
RL J. Biol. Chem. 276:12120-12127(2001).
Feature:
CHAIN 1 390 Cellular tumor antigen p53.
/FTId=PRO_0000185709.
DNA_BIND 99 289 By similarity.
REGION 1 45 Transcription activation (acidic).
REGION 63 107 Interaction with WWOX (By similarity).
REGION 97 367 Interaction with HIPK1.
REGION 113 289 Interaction with AXIN1.
REGION 316 357 Interaction with HIPK2 (By similarity).
REGION 322 353 Oligomerization.
REGION 365 384 Basic (repression of DNA-binding).
MOTIF 302 318 Bipartite nuclear localization signal (By
similarity).
MOTIF 336 347 Nuclear export signal (By similarity).
METAL 173 173 Zinc.
METAL 176 176 Zinc.
METAL 235 235 Zinc.
METAL 239 239 Zinc.
BINDING 389 389 5'-phospho-RNA (covalent).
MOD_RES 18 18 Phosphoserine (by PRPK) (By similarity).
MOD_RES 21 21 Phosphothreonine (by VRK1) (By
similarity).
MOD_RES 302 302 N6-acetyllysine (By similarity).
MOD_RES 312 312 Phosphoserine.
MOD_RES 370 370 N6-acetyllysine (By similarity).
MOD_RES 379 379 N6-acetyllysine (By similarity).
VARIANT 135 135 A -> V (can cooperate with an activated
Ras to transform fibroblasts).
VARIANT 168 168 E -> G (in clone P53-M11).
VARIANT 191 191 L -> R.
CONFLICT 48 48 Q -> R (in Ref. 3).
CONFLICT 79 81 PVA -> QW (in Ref. 3).
STRAND 100 100
TURN 103 104
STRAND 107 110
STRAND 115 115
STRAND 117 118
STRAND 120 124
TURN 125 128
STRAND 129 132
TURN 134 135
STRAND 138 143
STRAND 145 146
TURN 150 151
STRAND 153 162
TURN 163 164
STRAND 165 165
TURN 166 167
STRAND 168 168
HELIX 174 177
TURN 178 178
STRAND 179 179
STRAND 184 186
TURN 188 189
STRAND 191 196
STRAND 198 198
STRAND 201 204
TURN 206 208
STRAND 211 216
TURN 222 223
STRAND 225 233
STRAND 235 235
TURN 237 238
TURN 240 245
STRAND 248 255
TURN 257 258
STRAND 259 259
STRAND 261 271
STRAND 273 273
HELIX 275 280
TURN 281 282
Comments:
-!- 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 p53/TP73. Interacts with histone acetyltransferases
EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them
to promoters. Interacts with ING4 and this interaction may be
indirect. C-terminus interacts with TAF1, when TAF1 is part of the
TFIID complex. Interacts with P53DINP1. Interacts with WWOX (By
similarity). Interacts with HIPK1, HIPK2 and AXIN1. Probably part
of a complex consisiting of TP53, HIPK2 and AXIN1.
-!- INTERACTION:
Q07817-1:BCL2L1 (xeno); NbExp=2; IntAct=EBI-474016, EBI-287195;
-!- SUBCELLULAR LOCATION: Cytoplasmic and nuclear (By similarity).
-!- PTM: Phosphorylated. Phosphorylation on Ser residues mediates
transcriptional activation. Phosphorylated on Thr-21 by VRK1,
which may prevent the interaction with MDM2 (By similarity).
Phosphorylated by HIPK1.
-!- PTM: Acetylated. Its deacetylation by SIRT1 impairs its ability to
induce proapoptotic program and modulate cell senescence.
-!- DISEASE: 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.
-!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator.
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Sequence length: 390
MTAMEESQSD ISLELPLSQE TFSGLWKLLP PEDILPSPHC MDDLLLPQDV EEFFEGPSEA
LRVSGAPAAQ DPVTETPGPV APAPATPWPL SSFVPSQKTY QGNYGFHLGF LQSGTAKSVM
CTYSPPLNKL FCQLAKTCPV QLWVSATPPA GSRVRAMAIY KKSQHMTEVV RRCPHHERCS
DGDGLAPPQH LIRVEGNLYP EYLEDRQTFR HSVVVPYEPP EAGSEYTTIH YKYMCNSSCM
GGMNRRPILT IITLEDSSGN LLGRDSFEVR VCACPGRDRR TEEENFRKKE VLCPELPPGS
AKRALPTCTS ASPPQKKKPL DGEYFTLKIR GRKRFEMFRE LNEALELKDA HATEESGDSR
AHSSYLKTKK GQSTSRHKKT MVKKVGPDSD