O88898
SS
Gene name |
Tp63 (P63, P73l, Tp73l, Trp63) |
Protein name |
Tumor protein 63 |
Names |
p63 , Transformation-related protein 63 , TP63 , Tumor protein p73-like , p73L |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22061 |
EC number |
|
Protein Class |
|
Descriptions
TAp63, the longest isoform of p63, is highly expressed in primary oocytes that are arrested in prophase of meiosis I. Autoinhibition of TAp63 is characterized by a reduction in affinity to DNA and activators such as p300. The transactivation (TA) domain configuration in TAp63 suppresses interaction with the acetyltransferase p300 by blocking the tetramerization interface of the tetramerization domain. This autoinhibition mechanism keeps TAp63 in a dimeric conformation, which significantly reduces its transcriptional activity compared to other forms. The proteolytic cleavage of TAp63 at either the C-terminus of the TA domain (66-67) or the N-terminus of the TI domain (591-592) results in a rapid conversion of the closed dimeric state into an open tetrameric conformation. In contrast, cleavage at the C-terminus of TAp63ɑ does not affect on the relief of autoinhibition. The detection of DNA damage initiates a kinase cascade that leads to sequential phosphorylation by Chk2 and CK1. This process results in the formation of an open and tetrameric state, which exhibits higher DNA binding affinity compared with the closed dimeric conformation.
Autoinhibitory domains (AIDs)
Target domain |
588-680 (Tetramerization domain) |
Relief mechanism |
PTM, Cleavage, Others |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
2 structures for O88898
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 5N2O | NMR | - | A | 545-609 | PDB |
| AF-O88898-F1 | Predicted | AlphaFoldDB |
28 variants for O88898
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389389469 | 18 | Y>H | No | EVA | |
| rs32471981 | 19 | I>F | No | EVA | |
| rs3389426735 | 31 | W>* | No | EVA | |
| rs3389325289 | 32 | K>I | No | EVA | |
| rs3389400754 | 40 | M>I | No | EVA | |
| rs3406774297 | 51 | S>I | No | EVA | |
| rs3413138537 | 86 | T>A | No | EVA | |
| rs3389325337 | 88 | K>N | No | EVA | |
| rs3389402810 | 95 | C>Y | No | EVA | |
| rs3389416257 | 110 | Q>* | No | EVA | |
| rs3389359438 | 167 | S>T | No | EVA | |
| rs3389402767 | 200 | K>M | No | EVA | |
| rs3389413639 | 209 | C>Y | No | EVA | |
| rs3389410073 | 221 | Q>* | No | EVA | |
| rs3389409997 | 268 | E>D | No | EVA | |
| rs3405102785 | 293 | P>L | No | EVA | |
| rs3389370512 | 298 | E>D | No | EVA | |
| rs3389389497 | 304 | Y>H | No | EVA | |
| rs3389359457 | 335 | L>V | No | EVA | |
| rs3389402722 | 345 | C>Y | No | EVA | |
| rs3389402745 | 422 | E>K | No | EVA | |
| rs3389370469 | 432 | I>F | No | EVA | |
| rs3389426667 | 440 | Q>K | No | EVA | |
| rs3389406645 | 455 | S>A | No | EVA | |
| rs3389400772 | 471 | S>N | No | EVA | |
| rs3389410057 | 474 | K>N | No | EVA | |
| rs3389370529 | 486 | Q>K | No | EVA | |
| rs3406843822 | 500 | G>V | No | EVA |
No associated diseases with O88898
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| chromatin | The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| dendrite | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
16 GO annotations of molecular function
| Name | Definition |
|---|---|
| chromatin binding | Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. |
| damaged DNA binding | Binding to damaged DNA. |
| DNA binding | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). |
| DNA-binding transcription activator activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II. |
| DNA-binding transcription factor activity | A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons. |
| DNA-binding transcription factor activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II. |
| double-stranded DNA binding | Binding to double-stranded DNA. |
| identical protein binding | Binding to an identical protein or proteins. |
| MDM2/MDM4 family protein binding | Binding to a member of the MDM2/MDM4 protein family, comprising negative regulators of p53. |
| metal ion binding | Binding to a metal ion. |
| p53 binding | Binding to one of the p53 family of proteins. |
| promoter-specific chromatin binding | Binding to a section of chromatin that is associated with gene promoter sequences of DNA. |
| protein domain specific binding | Binding to a specific domain of a protein. |
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II. |
| sequence-specific DNA binding | Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding. |
| WW domain binding | Binding to a WW domain of a protein, a small module composed of 40 amino acids and plays a role in mediating protein-protein interactions via proline-rich regions. |
60 GO annotations of biological process
| Name | Definition |
|---|---|
| anatomical structure formation involved in morphogenesis | The developmental process pertaining to the initial formation of an anatomical structure from unspecified parts. This process begins with the specific processes that contribute to the appearance of the discrete structure and ends when the structural rudiment is recognizable. An anatomical structure is any biological entity that occupies space and is distinguished from its surroundings. Anatomical structures can be macroscopic such as a carpel, or microscopic such as an acrosome. |
| animal organ morphogenesis | Morphogenesis of an animal organ. An organ is defined as a tissue or set of tissues that work together to perform a specific function or functions. Morphogenesis is the process in which anatomical structures are generated and organized. Organs are commonly observed as visibly distinct structures, but may also exist as loosely associated clusters of cells that work together to perform a specific function or functions. |
| apoptotic process | A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. |
| cellular senescence | A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest. |
| chromatin remodeling | A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication. |
| cloacal septation | The separation of the single opening of the digestive, urinary, and reproductive tracts, the cloaca, into multiple isolated openings during development. |
| cranial skeletal system development | The process whose specific outcome is the progression of a cranial skeletal system over time, from its formation to the mature structure. The cranial skeletal system is the skeletal subdivision of the head, and includes the skull (cranium plus mandible), pharyngeal and/or hyoid apparatus. |
| determination of adult lifespan | The pathways that regulate the duration of the adult phase of the life-cycle of an animal. |
| ectoderm and mesoderm interaction | A cell-cell signaling process occurring between the two gastrulation-generated layers of the ectoderm and the mesoderm. |
| embryonic forelimb morphogenesis | The process, occurring in the embryo, by which the anatomical structures of the forelimb are generated and organized. The forelimbs are the front limbs of an animal, e.g. the arms of a human. |
| embryonic hindlimb morphogenesis | The process, occurring in the embryo, by which the anatomical structures of the hindlimbs are generated and organized. The hindlimbs are the posterior limbs of an animal. |
| embryonic limb morphogenesis | The process, occurring in the embryo, by which the anatomical structures of the limb are generated and organized. A limb is an appendage of an animal used for locomotion or grasping. |
| epidermal cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of an epidermal cell, any of the cells making up the epidermis. |
| epidermal cell division | Any process resulting in the physical partitioning and separation of an epidermal cell, any of the cells making up the epidermis, into daughter cells. |
| epidermis development | The process whose specific outcome is the progression of the epidermis over time, from its formation to the mature structure. The epidermis is the outer epithelial layer of an animal, it may be a single layer that produces an extracellular material (e.g. the cuticle of arthropods) or a complex stratified squamous epithelium, as in the case of many vertebrate species. |
| epithelial cell development | The process whose specific outcome is the progression of an epithelial cell over time, from its formation to the mature structure. An epithelial cell is a cell usually found in a two-dimensional sheet with a free surface. |
| epithelial cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of an epithelial cell, any of the cells making up an epithelium. |
| establishment of planar polarity | Coordinated organization of groups of cells in the plane of an epithelium, such that they all orient to similar coordinates. |
| establishment of skin barrier | Establishment of the epithelial barrier, the functional barrier in the skin that limits its permeability. |
| female genitalia morphogenesis | The process in which the anatomical structures of female genitalia are generated and organized. |
| hair follicle development | The process whose specific outcome is the progression of the hair follicle over time, from its formation to the mature structure. A hair follicle is a tube-like opening in the epidermis where the hair shaft develops and into which the sebaceous glands open. |
| hair follicle morphogenesis | The process in which the anatomical structures of the hair follicle are generated and organized. |
| intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage, and ends when the execution phase of apoptosis is triggered. |
| keratinocyte differentiation | The process in which a relatively unspecialized cell acquires specialized features of a keratinocyte. |
| keratinocyte proliferation | The multiplication or reproduction of keratinocytes, resulting in the expansion of a cell population. Keratinocytes are epidermal cells which synthesize keratin and undergo a characteristic change as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. |
| morphogenesis of a polarized epithelium | The morphogenetic process in which the anatomical structures of a polarized epithelium are generated and organized. A polarized epithelium is an epithelium where the epithelial sheet is oriented with respect to the planar axis. |
| negative regulation of intracellular estrogen receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of an intracellular estrogen receptor signaling pathway. |
| negative regulation of keratinocyte differentiation | Any process that stops, prevents, or reduces the frequency, rate or extent of keratinocyte differentiation. |
| negative regulation of mesoderm development | Any process that stops, prevents or reduces the frequency, rate or extent of mesoderm development. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| neuron apoptotic process | Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. |
| Notch signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| odontogenesis of dentin-containing tooth | The process whose specific outcome is the progression of a dentin-containing tooth over time, from its formation to the mature structure. A dentin-containing tooth is a hard, bony organ borne on the jaw or other bone of a vertebrate, and is composed mainly of dentin, a dense calcified substance, covered by a layer of enamel. |
| pattern specification process | Any developmental process that results in the creation of defined areas or spaces within an organism to which cells respond and eventually are instructed to differentiate. |
| polarized epithelial cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a polarized epithelial cell. The polarized epithelial cell can be any of the cells within an epithelium where the epithelial sheet is oriented with respect to the planar axis. |
| positive regulation of apoptotic signaling pathway | Any process that activates or increases the frequency, rate or extent of apoptotic signaling pathway. |
| positive regulation of cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
| positive regulation of fibroblast apoptotic process | Any process that activates or increases the frequency, rate or extent of fibroblast apoptotic process. |
| positive regulation of keratinocyte proliferation | Any process that increases the rate, frequency or extent of keratinocyte proliferation. Keratinocyte proliferation is the multiplication or reproduction of keratinocytes, resulting in the expansion of a cell population. |
| positive regulation of Notch signaling pathway | Any process that activates or increases the frequency, rate or extent of the Notch signaling pathway. |
| positive regulation of osteoblast differentiation | Any process that activates or increases the frequency, rate or extent of osteoblast differentiation. |
| positive regulation of somatic stem cell population maintenance | Any process that activates or increases the frequency, rate or extent of somatic stem cell population maintenance. |
| positive regulation of stem cell proliferation | Any process that activates or increases the frequency, rate or extent of stem cell proliferation. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| post-anal tail morphogenesis | The process in which a post-anal tail is generated and organized. A post-anal tail is a muscular region of the body that extends posterior to the anus. The post-anal tail may aid locomotion and balance. |
| prostate gland development | The process whose specific outcome is the progression of the prostate gland over time, from its formation to the mature structure. The prostate gland is a partly muscular, partly glandular body that is situated near the base of the mammalian male urethra and secretes an alkaline viscid fluid which is a major constituent of the ejaculatory fluid. |
| prostatic bud formation | The morphogenetic process in which a region of the fetal urogenital sinus epithelium is specified to become the prostate, resulting in prostate bud outgrowth. |
| protein tetramerization | The formation of a protein tetramer, a macromolecular structure consisting of four noncovalently associated identical or nonidentical subunits. |
| proximal/distal pattern formation | The regionalization process in which specific areas of cell differentiation are determined along a proximal/distal axis. The proximal/distal axis is defined by a line that runs from main body (proximal end) of an organism outward (distal end). |
| regulation of epidermal cell division | Any process that modulates the frequency, rate or extent of the physical partitioning and separation of an epidermal cell into daughter cells. An epidermal cell is any of the cells that make up the epidermis. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| skeletal system development | The process whose specific outcome is the progression of the skeleton over time, from its formation to the mature structure. The skeleton is the bony framework of the body in vertebrates (endoskeleton) or the hard outer envelope of insects (exoskeleton or dermoskeleton). |
| skin epidermis development | The process whose specific outcome is the progression of the skin epidermis over time, from its formation to the mature structure. |
| skin morphogenesis | The process in which the anatomical structures of the skin are generated and organized. The skin is the external membranous integument of an animal. In vertebrates the skin generally consists of two layers, an outer nonsensitive and nonvascular epidermis (cuticle or skarfskin) composed of cells which are constantly growing and multiplying in the deeper, and being thrown off in the superficial layers, as well as an inner, sensitive and vascular dermis (cutis, corium or true skin) composed mostly of connective tissue. |
| spermatogenesis | The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa. |
| squamous basal epithelial stem cell differentiation involved in prostate gland acinus development | The process in which a relatively unspecialized epithelial cell acquires specialized features of a squamous basal epithelial stem cell of the prostate. |
| stem cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a stem cell. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells. |
| stem cell proliferation | The multiplication or reproduction of stem cells, resulting in the expansion of a stem cell population. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells. |
| sympathetic nervous system development | The process whose specific outcome is the progression of the sympathetic nervous system over time, from its formation to the mature structure. The sympathetic nervous system is one of the two divisions of the vertebrate autonomic nervous system (the other being the parasympathetic nervous system). The sympathetic preganglionic neurons have their cell bodies in the thoracic and lumbar regions of the spinal cord and connect to the paravertebral chain of sympathetic ganglia. Innervate heart and blood vessels, sweat glands, viscera and the adrenal medulla. Most sympathetic neurons, but not all, use noradrenaline as a post-ganglionic neurotransmitter. |
| transcription by RNA polymerase II | The synthesis of RNA from a DNA template by RNA polymerase II (RNAP II), originating at an RNA polymerase II promoter. Includes transcription of messenger RNA (mRNA) and certain small nuclear RNAs (snRNAs). |
6 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| O15350 | TP73 | Tumor protein p73 | Homo sapiens (Human) | SS |
| Q9H3D4 | TP63 | Tumor protein 63 | Homo sapiens (Human) | EV |
| P04637 | TP53 | Cellular tumor antigen p53 | Homo sapiens (Human) | EV |
| Q9JJP2 | Tp73 | Tumor protein p73 | Mus musculus (Mouse) | SS |
| Q9JJP6 | Tp63 | Tumor protein 63 | Rattus norvegicus (Rat) | SS |
| P10361 | Tp53 | Cellular tumor antigen p53 | Rattus norvegicus (Rat) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MNFETSRCAT | LQYCPDPYIQ | RFIETPAHFS | WKESYYRSAM | SQSTQTSEFL | SPEVFQHIWD |
| 70 | 80 | 90 | 100 | 110 | 120 |
| FLEQPICSVQ | PIELNFVDEP | SENGATNKIE | ISMDCIRMQD | SDLSDPMWPQ | YTNLGLLNSM |
| 130 | 140 | 150 | 160 | 170 | 180 |
| DQQIQNGSSS | TSPYNTDHAQ | NSVTAPSPYA | QPSSTFDALS | PSPAIPSNTD | YPGPHSFDVS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| FQQSSTAKSA | TWTYSTELKK | LYCQIAKTCP | IQIKVMTPPP | QGAVIRAMPV | YKKAEHVTEV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VKRCPNHELS | REFNEGQIAP | PSHLIRVEGN | SHAQYVEDPI | TGRQSVLVPY | EPPQVGTEFT |
| 310 | 320 | 330 | 340 | 350 | 360 |
| TVLYNFMCNS | SCVGGMNRRP | ILIIVTLETR | DGQVLGRRCF | EARICACPGR | DRKADEDSIR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KQQVSDSAKN | GDGTKRPFRQ | NTHGIQMTSI | KKRRSPDDEL | LYLPVRGRET | YEMLLKIKES |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LELMQYLPQH | TIETYRQQQQ | QQHQHLLQKQ | TSMQSQSSYG | NSSPPLNKMN | SMNKLPSVSQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LINPQQRNAL | TPTTMPEGMG | ANIPMMGTHM | PMAGDMNGLS | PTQALPPPLS | MPSTSHCTPP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| PPYPTDCSIV | SFLARLGCSS | CLDYFTTQGL | TTIYQIEHYS | MDDLASLKIP | EQFRHAIWKG |
| 610 | 620 | 630 | 640 | 650 | 660 |
| ILDHRQLHDF | SSPPHLLRTP | SGASTVSVGS | SETRGERVID | AVRFTLRQTI | SFPPRDEWND |
| 670 | |||||
| FNFDMDSRRN | KQQRIKEEGE |