Reviewed,
UniProtKB/Swiss-Prot P04637 (P53_HUMAN)
Last modified
November 25, 2008.
Version 152.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (7) |
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Names and origin
| Protein names | Recommended name: Cellular tumor antigen p53 Alternative name(s): Tumor suppressor p53 Phosphoprotein p53 Antigen NY-CO-13 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 393 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (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. |
| Subunit structure | Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 By similarity. Binds DNA as a homotetramer. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. In vitro, the interaction of TP53 with cancer-associated/HPV (E6) viral proteins leads to ubiquitination and degradation of TP53 giving a possible model for cell growth regulation. This complex formation requires an additional factor, E6-AP, which stably associates with TP53 in the presence of E6. C-terminus interacts with TAF1, when TAF1 is part of the TFIID complex. Interacts with ING4 and this interaction may be indirect. Found in a complex with CABLES1 and TP73. Interacts with HIPK1, HIPK2, and P53DINP1. Interacts with WWOX. May interacts with HCV core protein. Interacts with USP7 and SYVN1. Interacts with HSP90AB1 By similarity. Interacts with ARMC10, BANP, CDKN2AIP and E4F1. |
| Subcellular location | Cytoplasm. Nucleus. Endoplasmic reticulum. Note= Interaction with BANP promotes nuclear localization. |
| Domain | The nuclear export signal acts as a transcriptional repression domain. |
| Post-translational modification | 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. 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, which may prevent the interaction with 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. Dephosphorylated by PP2A. SV40 small T antigen inhibits the dephosphorylation by the AC form of PP2A. May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line. Ubiquitinated by SYVN1, which leads to proteasomal degradation. Monomethylated at Lys-372 by SETD7, leading to stabilize it and increase transcriptional activation. Monomethylated at Lys-370 by SMYD2, leading to decrease DNA-binding activity and subsequent transcriptional regulation activity. Lys-372 monomethylation prevents the interaction with SMYD2 and subsequenct monomethylation at Lys-370. |
| Involvement in disease | TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. Defects in TP53 are involved in esophageal squamous cell carcinoma (ESCC) [MIM:133239]. ESCC is a tumor of the esophagus. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:151623]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (Ref.95 and Ref.98) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. Defects in TP53 may be associated with nasopharyngeal carcinoma [MIM:161550]; also known as nasopharyngeal cancer. Defects in TP53 are found in Barrett metaplasia; also known as Barrett esophagus. It is a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:275355]. Defects in TP53 are involved in oral squamous cell carcinoma (OSCC). Cigarette smoke is a prime mutagenic agent in cancer of the aerodigestive tract. Defects in TP53 are a cause of lung cancer [MIM:211980]. Defects in TP53 are a cause of choroid plexus papilloma [MIM:260500]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood. Defects in TP53 are a cause of one form of hereditary adrenocortical carcinoma (ADCC) [MIM:202300]. ADCC is a rare childhood tumor, representing about 0.4% of childhood tumors, with a high incidence of associated tumors. ADCC occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome [MIM:130650] and is a component tumor in Li-Fraumeni syndrome [MIM:151623]. |
| Sequence similarities | Belongs to the p53 family. |
Ontologies
Binary interactions
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P04637-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P04637-2) Also known as: I9RET; The sequence of this isoform differs from the canonical sequence as follows: 332-341: IRGRERFEMF → DGTSFQKENC 342-393: Missing. | ||||||
| Notes: Seems to be non-functional. Expressed in quiescent lymphocytes. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 393 | 393 | Cellular tumor antigen p53 | PRO_0000185703 | |||||
Regions | |||||||||
| DNA binding | 102 – 292 | 191 | |||||||
| Region | 1 – 83 | 83 | Interaction with HRMT1L2 | ||||||
| Region | 1 – 44 | 44 | Transcription activation (acidic) | ||||||
| Region | 66 – 110 | 45 | Interaction with WWOX | ||||||
| Region | 100 – 370 | 271 | Interaction with HIPK1 By similarity | ||||||
| Region | 116 – 292 | 177 | Interaction with AXIN1 By similarity | ||||||
| Region | 241 – 248 | 8 | Interacts with the 53BP2 SH3 domain | ||||||
| Region | 256 – 294 | 39 | Interaction with E4F1 | ||||||
| Region | 300 – 393 | 94 | Interaction with CARM1 | ||||||
| Region | 319 – 360 | 42 | Interaction with HIPK2 | ||||||
| Region | 325 – 356 | 32 | Oligomerization | ||||||
| Region | 359 – 363 | 5 | Interaction with USP7 | ||||||
| Region | 368 – 387 | 20 | Basic (repression of DNA-binding) | ||||||
| Motif | 305 – 321 | 17 | Bipartite nuclear localization signal | ||||||
| Motif | 339 – 350 | 12 | Nuclear export signal | ||||||
| Motif | 370 – 372 | 3 | [KR]-[STA]-K motif | ||||||
Sites | |||||||||
| Metal binding | 176 | 1 | Zinc | ||||||
| Metal binding | 179 | 1 | Zinc | ||||||
| Metal binding | 238 | 1 | Zinc | ||||||
| Metal binding | 242 | 1 | Zinc | ||||||
Amino acid modifications | |||||||||
| Modified residue | 9 | 1 | Phosphoserine; by HIPK4 | ||||||
| Modified residue | 15 | 1 | Phosphoserine; by PRPK | ||||||
| Modified residue | 18 | 1 | Phosphothreonine; by VRK1 | ||||||
| Modified residue | 46 | 1 | Phosphoserine; by HIPK2 | ||||||
| Modified residue | 55 | 1 | Phosphothreonine; by TAF1 | ||||||
| Modified residue | 99 | 1 | Phosphoserine | ||||||
| Modified residue | 305 | 1 | N6-acetyllysine | ||||||
| Modified residue | 315 | 1 | Phosphoserine; by CDC2 | ||||||
| Modified residue | 370 | 1 | N6-methyllysine | ||||||
| Modified residue | 372 | 1 | N6-methyllysine | ||||||
| Modified residue | 373 | 1 | N6-acetyllysine | ||||||
| Modified residue | 382 | 1 | N6-acetyllysine | ||||||
| Modified residue | 392 | 1 | O-(5'-phospho-RNA)-serine | ||||||
| Modified residue | 392 | 1 | Phosphoserine; by CK2 | ||||||
Natural variations | |||||||||
| Alternative sequence | 332 – 341 | 10 | IRGRERFEMF → DGTSFQKENC in isoform 2. | VSP_006535 | |||||
| Alternative sequence | 342 – 393 | 52 | Missing in isoform 2. | VSP_006536 | |||||
| Natural variant | 5 | 1 | Q → H in a sporadic cancer; somatic mutation. | VAR_044543 | |||||
| Natural variant | 6 | 1 | S → L in a sporadic cancer; somatic mutation. | VAR_044544 | |||||
| Natural variant | 7 | 1 | D → H in a sporadic cancer; somatic mutation. | VAR_005851 | |||||
| Natural variant | 8 | 1 | P → S in a sporadic cancer; somatic mutation. | VAR_044545 | |||||
| Natural variant | 10 | 1 | V → I in a sporadic cancer; somatic mutation. | VAR_044546 | |||||
| Natural variant | 11 | 1 | E → K in sporadic cancers; somatic mutation. | VAR_044547 | |||||
| Natural variant | 11 | 1 | E → Q in sporadic cancers; somatic mutation. | VAR_044548 | |||||
| Natural variant | 15 | 1 | S → R in a sporadic cancer; somatic mutation. | VAR_044549 | |||||
| Natural variant | 16 | 1 | Q → L in a sporadic cancer; somatic mutation. | VAR_044550 | |||||
| Natural variant | 17 | 1 | E → D in a sporadic cancer; somatic mutation. | VAR_044551 | |||||
| Natural variant | 24 | 1 | K → N in a sporadic cancer; somatic mutation. | VAR_044552 | |||||
| Natural variant | 28 | 1 | E → A in a sporadic cancer; somatic mutation. | VAR_044553 | |||||
| Natural variant | 29 – 30 | 2 | NN → KD in a sporadic cancer; somatic mutation. | VAR_047158 | |||||
| Natural variant | 31 | 1 | V → I in sporadic cancers; somatic mutation. | VAR_044554 | |||||
| Natural variant | 33 | 1 | S → T in a sporadic cancer; somatic mutation. | VAR_044555 | |||||
| Natural variant | 34 | 1 | P → L in a sporadic cancer; somatic mutation. | VAR_044556 | |||||
| Natural variant | 35 | 1 | L → F in sporadic cancers; somatic mutation. | VAR_005852 | |||||
| Natural variant | 36 | 1 | P → L in a sporadic cancer; somatic mutation. | VAR_044557 | |||||
| Natural variant | 37 | 1 | S → P in a sporadic cancer; somatic mutation. | VAR_044558 | |||||
| Natural variant | 37 | 1 | S → T in a sporadic cancer; somatic mutation. | VAR_044559 | |||||
| Natural variant | 39 | 1 | A → P in a sporadic cancer; somatic mutation. | VAR_044560 | |||||
| Natural variant | 39 | 1 | A → V in a sporadic cancer; somatic mutation. | VAR_044561 | |||||
| Natural variant | 42 | 1 | D → Y in a sporadic cancer; somatic mutation. | VAR_044562 | |||||
| Natural variant | 43 | 1 | L → S in a sporadic cancer; somatic mutation. | VAR_005853 | |||||
| Natural variant | 44 | 1 | M → I in a sporadic cancer; somatic mutation. | VAR_044563 | |||||
| Natural variant | 44 | 1 | M → T in a sporadic cancer; somatic mutation. | VAR_044564 | |||||
| Natural variant | 44 | 1 | M → V in a sporadic cancer; somatic mutation. | VAR_044565 | |||||
| Natural variant | 45 | 1 | L → M in a sporadic cancer; somatic mutation. | VAR_044566 | |||||
| Natural variant | 46 | 1 | S → F in sporadic cancers; somatic mutation. | VAR_044567 | |||||
| Natural variant | 46 | ||||||||