Detail Information for IndEnz0002010578
IED ID IndEnz0002010578
Enzyme Type ID protease010578
Protein Name Cellular tumor antigen p53
Tumor suppressor p53
Gene Name Tp53 P53
Organism Rattus norvegicus (Rat)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat)
Enzyme Sequence MEDSQSDMSIELPLSQETFSCLWKLLPPDDILPTTATGSPNSMEDLFLPQDVAELLEGPEEALQVSAPAAQEPGTEAPAPVAPASATPWPLSSSVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSISLNKLFCQLAKTCPVQLWVTSTPPPGTRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNPYAEYLDDRQTFRHSVVVPYEPPEVGSDYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEEHCPELPPGSAKRALPTSTSSSPQQKKKPLDGEYFTLKIRGRERFEMFRELNEALELKDARAAEESGDSRAHSSYPKTKKGQSTSRHKKPMIKKVGPDSD
Enzyme Length 391
Uniprot Accession Number P10361
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding DNA_BIND 100..290; /evidence=ECO:0000250
EC Number
Enzyme Function 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. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By similarity). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By similarity). 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 seems to have an effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. {ECO:0000250|UniProtKB:P02340, ECO:0000250|UniProtKB:P04637}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Chain (1); Compositional bias (3); Cross-link (4); DNA binding (1); Metal binding (4); Modified residue (25); Motif (3); Natural variant (2); Region (16); Sequence conflict (1); Site (1)
Keywords Acetylation;Activator;Apoptosis;Biological rhythms;Cell cycle;Cytoplasm;Cytoskeleton;DNA-binding;Endoplasmic reticulum;Isopeptide bond;Metal-binding;Methylation;Mitochondrion;Necrosis;Nucleus;Phosphoprotein;Reference proteome;Repressor;Transcription;Transcription regulation;Tumor suppressor;Ubl conjugation;Zinc
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. Nucleus, PML body {ECO:0000250|UniProtKB:P04637}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix {ECO:0000250|UniProtKB:P04637}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:P04637}. Note=Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress. Translocates to mitochondria in response to mitomycin C treatment (By similarity). {ECO:0000250|UniProtKB:P04637}.
Modified Residue MOD_RES 9; /note="Phosphoserine; by HIPK4"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 15; /note="Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 18; /note="Phosphothreonine; by CK1, VRK1 and VRK2"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 20; /note="Phosphoserine; by CHEK2, CK1 and PLK3"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 39; /note="Phosphoserine; by MAPKAPK5"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 118; /note="N6-acetyllysine; by KAT6A"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 181; /note="Phosphoserine; by AURKB"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 267; /note="Phosphoserine; by AURKB"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 282; /note="Phosphothreonine; by AURKB"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 303; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 313; /note="Phosphoserine; by AURKA, CDK1 and CDK2"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 319; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:P02340"; MOD_RES 331; /note="Omega-N-methylarginine"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 333; /note="Symmetric dimethylarginine"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 335; /note="Symmetric dimethylarginine"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 368; /note="N6,N6-dimethyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 368; /note="N6-methyllysine; by SMYD2; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 370; /note="N6-methyllysine; by SETD7"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 371; /note="N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 371; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 379; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 380; /note="N6,N6-dimethyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 380; /note="N6-acetyllysine; by KAT6A; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 380; /note="N6-methyllysine; by KMT5A; alternate"; /evidence="ECO:0000250|UniProtKB:P04637"; MOD_RES 390; /note="Phosphoserine; by CK2, CDK2 and NUAK1"; /evidence="ECO:0000250|UniProtKB:P04637"
Post Translational Modification PTM: 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. 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). Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P04637}.; PTM: 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 KMT5A, 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). Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity). {ECO:0000250|UniProtKB:P04637}.; PTM: Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 (By similarity). {ECO:0000250}.; PTM: 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, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P02340, ECO:0000250|UniProtKB:P04637}.; PTM: Acetylated. Acetylation by CREBBP enhances transcriptional activity. Acetylation by EP300. Deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner. {ECO:0000250|UniProtKB:P04637}.
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 10329733; 10564948; 11278372; 11295070; 11502571; 11773703; 11827957; 11958430; 11973333; 12143041; 12163498; 12167434; 12215673; 12464630; 12503078; 12506145; 12527914; 12534344; 12538352; 12549819; 12654005; 12835324; 12850271; 12869365; 14514686; 14576152; 14685795; 14695767; 14739302; 14962081; 15002037; 15033826; 15122989; 15199126; 15315938; 15632413; 15735701; 15782130; 15829407; 15872011; 15922606; 15990448; 16000635; 16005638; 16118209; 16204796; 16207712; 16282427; 16328969; 16330492; 16392041; 16427076; 16491117; 16544096; 16614397; 16688778; 16690610; 16729028; 16760664; 16817227; 16914427; 16937528; 17060322; 17234627; 17289031; 17368433; 17418105; 17431217; 17442733; 17466256; 17470299; 17516866; 17540029; 17542038; 17546582; 17556661; 17571083; 17594519; 17595763; 17600529; 17651018; 17659301; 17661174; 17699727; 17724205; 17881359; 17901943; 17962954; 17998337; 18026139; 18037131; 18057955; 18083315; 18093815; 18162465; 18181021; 18263706; 18279588; 18311796; 18317410; 18335527; 18336558; 18337831; 18408766; 18497077; 18516675; 18555008; 18614532; 18649423; 18656278; 18691572; 18724031; 18753141; 18775851; 18924150; 18945670; 18948218; 19052818; 19059678; 19111121; 19136059; 19168033; 19170070; 19305162; 19330797; 19349302; 19513548; 19576024; 19618124; 19684617; 19765618; 19797907; 19819240; 19910580; 19950214; 20032585; 20062521; 20094059; 20113312; 20385474; 20413784; 20424134; 20483005; 20506231; 20515733; 20530960; 20569441; 20594980; 20650967; 20703075; 20720180; 20855262; 20935146; 20961644; 20972911; 21164280; 21178334; 21181359; 21187408; 21189548; 21376104; 21498419; 21546003; 21656845; 21712954; 21748659; 21792911; 21854749; 21908547; 21912060; 21959983; 21965303; 22011578; 22023760; 22046440; 22073357; 22154326; 22294442; 22296365; 22319579; 22330834; 22405968; 22420318; 22505033; 22514887; 22515118; 22559303; 22738191; 22763759; 22791818; 22801079; 22806321; 22833673; 22884071; 22917926; 22954396; 22977862; 23051735; 23059819; 23069657; 23164821; 23402272; 23538210; 23568954; 23588680; 23595775; 23608382; 23625637; 23631263; 23648705; 23657598; 23678040; 23714159; 23714208; 23810908; 23941874; 23948959; 24043441; 24189031; 24223793; 24269759; 24312187; 24421392; 24567336; 24670206; 24704558; 24763879; 24817286; 24828139; 24986327; 25247799; 25356872; 25470941; 25506925; 25547174; 25655048; 25767724; 25773675; 25791630; 25811670; 25936182; 26004897; 26059825; 26111627; 26302161; 26353976; 26384650; 26400065; 26426258; 26431790; 26439224; 26456506; 26497030; 26553132; 26571802; 26675978; 26714124; 26792455; 26968221; 27008853; 27013579; 27031958; 27046449; 27221738; 27387128; 27528400; 27553877; 27584794; 27665784; 27703600; 27878231; 27881147; 28002632; 28093932; 28100501; 28131915; 28220272; 28220578; 28237798; 28358926; 28414026; 28486954; 28573231; 28634073; 28678856; 28800961; 28834365; 28885617; 29039595; 29048679; 29199862; 29286111; 29333769; 29344658; 29429512; 29498408; 29504377; 29546074; 29620173; 29978915; 30488170; 30502252; 30511343; 30514107; 30514679; 30592279; 30887692; 30949500; 30968966; 30998966; 31032366; 31420372; 31432116; 31638262; 31787253; 31973811; 32000560; 32026570; 32314164; 32329863; 32344470; 32462563; 32554484; 32770526; 32810137; 33028080; 33159115; 33336750; 34064070; 8389468; 9485768;
Motif MOTIF 303..319; /note=Bipartite nuclear localization signal; /evidence=ECO:0000250; MOTIF 337..348; /note=Nuclear export signal; /evidence=ECO:0000250; MOTIF 368..370; /note=[KR]-[STA]-K motif
Gene Encoded By
Mass 43,451
Kinetics
Metal Binding METAL 174; /note=Zinc; /evidence=ECO:0000250; METAL 177; /note=Zinc; /evidence=ECO:0000250; METAL 236; /note=Zinc; /evidence=ECO:0000250; METAL 240; /note=Zinc; /evidence=ECO:0000250
Rhea ID
Cross Reference Brenda