P10361 (P53_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 163. History...
Names and origin
|Protein names||Recommended name:|
Cellular tumor antigen p53
Tumor suppressor p53
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||391 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity.
Binds 1 zinc ion per subunit By similarity.
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 TP53INP1. Part of a complex consisting of TP53, HIPK2 and AXIN1. Interacts with WWOX. Interacts with USP7 and SYVN1. Interacts with BANP. Interacts with ARMD10, E4F1, CDKN2AIP, NUAK1, UHRF2 and STK11/LKB1. Interacts with CHD8, leading to recruit histone H1 and prevent transactivation activity By similarity. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction By similarity. Interacts with HSP90AB1. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts with AURKA, DAXX, BRD7 and TRIM24. Interacts (when monomethylated at Lys-380) with L3MBTL1. Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage. Interacts with CDK5 in neurons. Interacts with AURKB, SETD2, UHRF2 and NOC2L. Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2. Interacts with PRKCG. Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA). Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion By similarity. Interacts with KAT6A By similarity. Interacts with UBC9 By similarity. Forms a complex with UBC9 and PRKRA By similarity. Interacts with ZNF385B; the interaction is direct By similarity. Interacts with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest By similarity. Interacts with ANKRD2 By similarity. Interacts with RFFL (via RING-type zinc finger); involved in p53/TP53 ubiquitination By similarity. Ref.5
Cytoplasm By similarity. Nucleus By similarity. Endoplasmic reticulum By similarity. Mitochondrion matrix. Note: Interaction with BANP promotes nuclear localization. Translocates to mitochondria upon oxidative stress By similarity. Ref.6
The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase By similarity.
Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter By similarity. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-390 following UV but not gamma irradiation. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP. 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. Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage By similarity.
Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence 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-289 and Lys-290, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24 and RFFL, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it By similarity.
Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368. Dimethylated at Lys-371 by EHMT1 and EHMT2. Monomethylated at Lys-380 by SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation By similarity.
Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 By similarity.
|Involvement in 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.
Belongs to the p53 family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 391||391||Cellular tumor antigen p53||PRO_0000185712|
|DNA binding||100 – 290||191||By similarity|
|Region||1 – 47||47||Transcription activation (acidic)|
|Region||64 – 108||45||Interaction with WWOX By similarity|
|Region||98 – 368||271||Interaction with HIPK1 By similarity|
|Region||98 – 298||201||Required for interaction with ZNF385A By similarity|
|Region||111 – 234||124||Required for interaction with FBXO42 By similarity|
|Region||114 – 290||177||Interaction with AXIN1 By similarity|
|Region||254 – 292||39||Interaction with E4F1 By similarity|
|Region||271 – 278||8||Interaction with DNA By similarity|
|Region||317 – 358||42||Interaction with HIPK2 By similarity|
|Region||323 – 354||32||Oligomerization|
|Region||357 – 361||5||Interaction with USP7 By similarity|
|Region||366 – 385||20||Basic (repression of DNA-binding)|
|Motif||303 – 319||17||Bipartite nuclear localization signal By similarity|
|Motif||337 – 348||12||Nuclear export signal By similarity|
|Motif||368 – 370||3||[KR]-[STA]-K motif|
|Metal binding||174||1||Zinc By similarity|
|Metal binding||177||1||Zinc By similarity|
|Metal binding||236||1||Zinc By similarity|
|Metal binding||240||1||Zinc By similarity|
|Site||118||1||Interaction with DNA By similarity|
Amino acid modifications
|Modified residue||9||1||Phosphoserine; by HIPK4 By similarity|
|Modified residue||15||1||Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM By similarity|
|Modified residue||18||1||Phosphothreonine; by CK1, VRK1 and VRK2 By similarity|
|Modified residue||20||1||Phosphoserine; by CHEK2, CK1 and PLK3 By similarity|
|Modified residue||39||1||Phosphoserine; by MAPKAPK5 By similarity|
|Modified residue||118||1||N6-acetyllysine; by KAT6A By similarity|
|Modified residue||181||1||Phosphoserine; by AURKB By similarity|
|Modified residue||267||1||Phosphoserine; by AURKB By similarity|
|Modified residue||282||1||Phosphothreonine; by AURKB By similarity|
|Modified residue||303||1||N6-acetyllysine By similarity|
|Modified residue||313||1||Phosphoserine; by AURKA, CDK1 and CDK2 By similarity|
|Modified residue||368||1||N6,N6-dimethyllysine; alternate By similarity|
|Modified residue||368||1||N6-methyllysine; by SMYD2; alternate By similarity|
|Modified residue||370||1||N6-methyllysine; by SETD7 By similarity|
|Modified residue||371||1||N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate By similarity|
|Modified residue||371||1||N6-acetyllysine; alternate By similarity|
|Modified residue||379||1||N6-acetyllysine By similarity|
|Modified residue||380||1||N6,N6-dimethyllysine; alternate By similarity|
|Modified residue||380||1||N6-acetyllysine; by KAT6A; alternate By similarity|
|Modified residue||380||1||N6-methyllysine; by SETD8; alternate By similarity|
|Modified residue||390||1||Phosphoserine; by CK2, CDK2 and NUAK1 By similarity|
|Cross-link||289||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||290||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||384||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Natural variant||103||1||G → S.|
|Natural variant||256||1||E → G.|
|Sequence conflict||174||1||C → W in AAA41788. Ref.2|
|||"Nucleotide sequence of a cDNA encoding the rat p53 nuclear oncoprotein."|
Nucleic Acids Res. 16:11384-11384(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Structure of the rat p53 tumor suppressor gene."|
Hulla J.E., Schneider R.P.
Nucleic Acids Res. 21:713-717(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53."|
Mathupala S.P., Heese C., Pedersen P.L.
J. Biol. Chem. 272:22776-22780(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart and Thymus.
|||"Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell."|
Sepehrnia B., Paz I.B., Dasgupta G., Momand J.
J. Biol. Chem. 271:15084-15090(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HSP90AB1.
|||"p53 opens the mitochondrial permeability transition pore to trigger necrosis."|
Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M.
Cell 149:1536-1548(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|X13058 mRNA. Translation: CAA31457.1.|
L07910 L07909 Genomic DNA. Translation: AAA41788.1.
U90328 mRNA. Translation: AAB80959.1.
BC081788 mRNA. Translation: AAH81788.2.
BC098663 mRNA. Translation: AAH98663.1.
|RefSeq||NP_112251.2. NM_030989.3. |
3D structure databases
|SMR||P10361. Positions 93-288, 317-358. |
Protein-protein interaction databases
|BioGrid||246960. 9 interactions.|
|IntAct||P10361. 4 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756. |
|UCSC||RGD:3889. rat. |
|RGD||3889. Tp53. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.520. 1 hit. |
184.108.40.206. 1 hit.
|InterPro||IPR008967. p53-like_TF_DNA-bd. |
|PANTHER||PTHR11447. PTHR11447. 1 hit. |
|Pfam||PF00870. P53. 1 hit. |
PF08563. P53_TAD. 1 hit.
PF07710. P53_tetramer. 1 hit.
|PRINTS||PR00386. P53SUPPRESSR. |
|SUPFAM||SSF47719. SSF47719. 1 hit. |
SSF49417. SSF49417. 1 hit.
|PROSITE||PS00348. P53. 1 hit. |
|Accession||Primary (citable) accession number: P10361|
Secondary accession number(s): O09168, Q4KMA9, Q66HM0
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families