O88898 (P63_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 121.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Tumor protein 63 Short name=p63 Alternative name(s): Transformation-related protein 63 Short name=TP63 Tumor protein p73-like Short name=p73L | ||||
| Gene names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus![]() |
Protein attributes
| Sequence length | 680 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Activates transcription of the p21 promoter By similarity. Activates RIPK4 transcription. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 |
| Cofactor | Binds 1 zinc ion per subunit By similarity. |
| Subunit structure | Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity. Interacts with HIPK2. Interacts with SSRP1, leading to stimulate coactivator activity. Interacts with PDS5A. Interacts (via activation domain) with NOC2L By similarity. Interacts with WWP1. Ref.9 |
| Subcellular location | |
| Tissue specificity | Widely expressed, notably in thymus, prostate, placenta and skeletal muscle, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast and prostate express high levels of DeltaN-type isoforms. Ref.1 |
| Developmental stage | TA*-type isoforms are expressed from E7.5, prior to the onset of epithelial stratification, while DeltaN-type isoforms are expressed from E9.5. Ref.8 |
| Induction | Induced by DNA damaging agents. Ref.7 |
| Domain | The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms By similarity. |
| Post-translational modification | May be sumoylated By similarity. Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. Ref.9 |
| Sequence similarities | Belongs to the p53 family. Contains 1 SAM (sterile alpha motif) domain. |
| Sequence caution | The sequence BAC33397.1 differs from that shown. Reason: Intron retention. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 2 | EBI-2338025,EBI-2338025 | ||
| NQO1 | P15559 | 2 | EBI-2338228,EBI-3989435 | From a different organism. |
| TP53 | P04637 | 2 | EBI-2338025,EBI-366083 | From a different organism. |
Alternative products
| This entry describes 6 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O88898-1) Also known as: TA*-alpha; TA*p63alpha; 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. | ||||||
| Note: Produced by alternative promoter usage. | ||||||
| Isoform 2 (identifier: O88898-2) Also known as: DeltaN-alpha; The sequence of this isoform differs from the canonical sequence as follows: 1-108: MNFETSRCAT...QDSDLSDPMW → MLYLENNAQTQFSE | ||||||
| Note: Produced by alternative promoter usage. | ||||||
| Isoform 3 (identifier: O88898-3) Also known as: TA*-beta; TA*p63beta; The sequence of this isoform differs from the canonical sequence as follows: 551-680: SFLARLGCSS...KQQRIKEEGE → RIWQV | ||||||
| Note: Produced by alternative splicing of isoform 1. | ||||||
| Isoform 4 (identifier: O88898-4) Also known as: DeltaN-beta; The sequence of this isoform differs from the canonical sequence as follows: 1-108: MNFETSRCAT...QDSDLSDPMW → MLYLENNAQTQFSE 551-680: SFLARLGCSS...KQQRIKEEGE → RIWQV | ||||||
| Note: Produced by alternative splicing of isoform 2. | ||||||
| Isoform 5 (identifier: O88898-5) Also known as: TA*-gamma; TA*p63gamma; The sequence of this isoform differs from the canonical sequence as follows: 373-377: GTKRP → A 450-680: QTSMQSQSSY...KQQRIKEEGE → HLLSACFRNE...SNPPNHSVYP | ||||||
| Note: Produced by alternative splicing of isoform 1. | ||||||
| Isoform 6 (identifier: O88898-6) Also known as: DeltaN-gamma; The sequence of this isoform differs from the canonical sequence as follows: 1-108: MNFETSRCAT...QDSDLSDPMW → MLYLENNAQTQFSE 373-377: GTKRP → A 450-680: QTSMQSQSSY...KQQRIKEEGE → HLLSACFRNE...SNPPNHSVYP | ||||||
| Note: Produced by alternative splicing of isoform 2. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 680 | 680 | Tumor protein 63 | PRO_0000185730 | |||||
Regions | |||||||||
| Domain | 541 – 607 | 67 | SAM | ||||||
| DNA binding | 170 – 362 | 193 | By similarity | ||||||
| Region | 1 – 107 | 107 | Transcription activation By similarity | ||||||
| Region | 352 – 388 | 37 | Interaction with HIPK2 By similarity | ||||||
| Region | 394 – 443 | 50 | Oligomerization By similarity | ||||||
| Region | 610 – 680 | 71 | Transactivation inhibition By similarity | ||||||
| Compositional bias | 437 – 444 | 8 | Poly-Gln | ||||||
Sites | |||||||||
| Metal binding | 244 | 1 | Zinc By similarity | ||||||
| Metal binding | 247 | 1 | Zinc By similarity | ||||||
| Metal binding | 308 | 1 | Zinc By similarity | ||||||
| Metal binding | 312 | 1 | Zinc By similarity | ||||||
Amino acid modifications | |||||||||
| Cross-link | 676 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 108 | 108 | MNFET…SDPMW → MLYLENNAQTQFSE in isoform 2, isoform 4 and isoform 6. | VSP_012471 | |||||
| Alternative sequence | 373 – 377 | 5 | GTKRP → A in isoform 5 and isoform 6. | VSP_012472 | |||||
| Alternative sequence | 450 – 680 | 231 | QTSMQ…KEEGE → HLLSACFRNELVEPRGEAPT QSDVFFRHSNPPNHSVYP in isoform 5 and isoform 6. | VSP_012473 | |||||
| Alternative sequence | 551 – 680 | 130 | SFLAR…KEEGE → RIWQV in isoform 3 and isoform 4. | VSP_012474 | |||||
Experimental info | |||||||||
| Mutagenesis | 543 | 1 | Y → F: Abolishes interaction with WWP1. Ref.9 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities." Yang A., Kaghad M., Wang Y., Gillett E., Fleming M.D., Doetsch V., Andrews N.C., Caput D., McKeon F. Mol. Cell 2:305-316(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6), TISSUE SPECIFICITY. |
| [2] | "A second p53-related protein, p73L, with high homology to p73." Senoo M., Seki N., Ohira M., Sugano S., Watanabe M., Tachibana M., Tanaka T., Shinkai Y., Kato H. Biochem. Biophys. Res. Commun. 248:603-607(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thymus. |
| [3] | Kui J.S., Wang J.H., Zhang M.Q., Mills A.A. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-376 (ISOFORMS 2 AND 4). Strain: C57BL/6J. Tissue: Head. |
| [5] | "p63 is a p53 homologue required for limb and epidermal morphogenesis." Mills A.A., Zheng B., Wang X.-J., Vogel H., Roop D.R., Bradley A. Nature 398:708-713(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN EPITHELIAL MORPHOGENESIS. |
| [6] | "p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development." Yang A., Schweitzer R., Sun D., Kaghad M., Walker N., Bronson R.T., Tabin C., Sharpe A., Caput D., Crum C., McKeon F. Nature 398:714-718(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN EPITHELIAL MORPHOGENESIS. |
| [7] | "p63 and p73 are required for p53-dependent apoptosis in response to DNA damage." Flores E.R., Tsai K.Y., Crowley D., Sengupta S., Yang A., McKeon F., Jacks T. Nature 416:560-564(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TP53 DEPENDENT APOPTOSIS, INDUCTION. |
| [8] | "p63 is the molecular switch for initiation of an epithelial stratification program." Koster M.I., Kim S., Mills A.A., DeMayo F.J., Roop D.R. Genes Dev. 18:126-131(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN EPITHELIAL MORPHOGENESIS, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE. |
| [9] | "WW domain-containing E3 ubiquitin protein ligase 1 targets p63 transcription factor for ubiquitin-mediated proteasomal degradation and regulates apoptosis." Li Y., Zhou Z., Chen C. Cell Death Differ. 15:1941-1951(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH WWP1, MUTAGENESIS OF TYR-543. |
| [10] | "Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus." Mitchell K., O'Sullivan J., Missero C., Blair E., Richardson R., Anderson B., Antonini D., Murray J.C., Shanske A.L., Schutte B.C., Romano R.A., Sinha S., Bhaskar S.S., Black G.C., Dixon J., Dixon M.J. Am. J. Hum. Genet. 90:69-75(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RIPK4 TRANSACTIVATION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF075434 mRNA. Translation: AAC62639.1. AF075435 mRNA. Translation: AAC62640.1. AF075436 mRNA. Translation: AAC62641.1. AF075437 mRNA. Translation: AAC62642.1. AF075438 mRNA. Translation: AAC62643.1. AF075439 mRNA. Translation: AAC62644.1. AB010152 mRNA. Translation: BAA32432.1. AF533892 Genomic DNA. Translation: AAP87982.1. AF533892 Genomic DNA. Translation: AAP87985.1. AF533892 Genomic DNA. Translation: AAP87983.1. AF533892 Genomic DNA. Translation: AAP87984.1. AF533892 Genomic DNA. Translation: AAP87986.1. AF533892 Genomic DNA. Translation: AAP87987.1. AK048623 mRNA. Translation: BAC33397.1. Sequence problems. |
| IPI | IPI00126538. IPI00135459. IPI00135460. IPI00515553. IPI00515634. IPI00896016. |
| RefSeq | NP_001120731.1. NM_001127259.1. NP_001120732.1. NM_001127260.1. NP_001120733.1. NM_001127261.1. NP_001120734.1. NM_001127262.1. NP_001120736.1. NM_001127264.1. NP_001120737.1. NM_001127265.1. NP_035771.1. NM_011641.2. |
| UniGene | Mm.20894. |
3D structure databases | |
| ProteinModelPortal | O88898. |
| SMR | O88898. Positions 153-437, 545-611. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O88898. 4 interactions. |
PTM databases | |
| PhosphoSite | O88898. |
Proteomic databases | |
| PaxDb | O88898. |
| PRIDE | O88898. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSMUST00000040231; ENSMUSP00000038117; ENSMUSG00000022510. ENSMUST00000065523; ENSMUSP00000067005; ENSMUSG00000022510. ENSMUST00000115304; ENSMUSP00000110959; ENSMUSG00000022510. ENSMUST00000115308; ENSMUSP00000110963; ENSMUSG00000022510. ENSMUST00000115310; ENSMUSP00000110965; ENSMUSG00000022510. |
| GeneID | 22061. |
| KEGG | mmu:22061. |
| UCSC | uc007yuo.2. mouse. uc007yup.2. mouse. uc007yuq.2. mouse. uc007yut.2. mouse. uc007yuu.2. mouse. uc007yuv.2. mouse. |
Organism-specific databases | |
| CTD | 22061. |
| MGI | MGI:1330810. Trp63. |
Phylogenomic databases | |
| eggNOG | NOG80479. |
| GeneTree | ENSGT00390000015092. |
| HOVERGEN | HBG005201. |
| InParanoid | O88898. |
| KO | K10149. |
| OMA | GTTNKIE. |
| OrthoDB | EOG4V6ZG6. |
Gene expression databases | |
| ArrayExpress | O88898. |
| Bgee | O88898. |
| CleanEx | MM_TRP63. |
| Genevestigator | O88898. |
| GermOnline | ENSMUSG00000022510. Mus musculus. |
Family and domain databases | |
| Gene3D | 1.10.150.50. 1 hit. 2.60.40.720. 1 hit. 4.10.170.10. 1 hit. |
| InterPro | IPR008967. p53-like_TF_DNA-bd. IPR012346. p53/RUNT-type_TF_DNA-bd. IPR011615. p53_DNA-bd. IPR010991. p53_tetrameristn. IPR002117. p53_tumour_suppressor. IPR001660. SAM. IPR013761. SAM/pointed. IPR011510. SAM_2. [Graphical view] |
| PANTHER | PTHR11447. PTHR11447. 1 hit. |
| Pfam | PF00870. P53. 1 hit. PF07710. P53_tetramer. 1 hit. PF07647. SAM_2. 1 hit. [Graphical view] |
| PRINTS | PR00386. P53SUPPRESSR. |
| SMART | SM00454. SAM. 1 hit. [Graphical view] |
| SUPFAM | SSF49417. P53_like_DNA_bnd. 1 hit. SSF47719. p53_tetrameristn. 1 hit. SSF47769. SAM_homology. 1 hit. |
| PROSITE | PS00348. P53. 1 hit. PS50105. SAM_DOMAIN. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 301864. |
| SOURCE | Search... |
Entry information
| Entry name | P63_MOUSE | ||||||||
| Accession | Primary (citable) accession number: O88898 Secondary accession number(s): O88897 Q9QWZ0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
