P53_HORSE
ID P53_HORSE Reviewed; 280 AA.
AC P79892; Q29481;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Cellular tumor antigen p53;
DE AltName: Full=Tumor suppressor p53;
DE Flags: Fragment;
GN Name=TP53; Synonyms=P53;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-263.
RC TISSUE=Spleen;
RX PubMed=8913276; DOI=10.1016/0304-3835(96)04359-5;
RA Pazzi K.A., Kraegel S.A., Griffey S.M., Theon A.P., Madewell B.R.;
RT "Analysis of the equine tumor suppressor gene p53 in the normal horse and
RT in eight cutaneous squamous cell carcinomas.";
RL Cancer Lett. 107:125-130(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 76-280.
RX PubMed=8722575; DOI=10.3109/10425179609010208;
RA Nasir L., Reid S.W.;
RT "Nucleotide sequence of exons 5 to 9 of the p53 tumour-suppressor gene of
RT the horse (Equus caballus).";
RL DNA Seq. 6:185-187(1996).
CC -!- FUNCTION: Acts as a tumor suppressor in many tumor types; induces
CC growth arrest or apoptosis depending on the physiological circumstances
CC and cell type. Involved in cell cycle regulation as a trans-activator
CC that acts to negatively regulate cell division by controlling a set of
CC genes required for this process. One of the activated genes is an
CC inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be
CC mediated either by stimulation of BAX and FAS antigen expression, or by
CC repression of Bcl-2 expression. Its pro-apoptotic activity is activated
CC via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By
CC similarity). However, this activity is inhibited when the interaction
CC with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By
CC similarity). In cooperation with mitochondrial PPIF is involved in
CC activating oxidative stress-induced necrosis; the function is largely
CC independent of transcription. Prevents CDK7 kinase activity when
CC associated to CAK complex in response to DNA damage, thus stopping cell
CC cycle progression. Induces the transcription of long intergenic non-
CC coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21
CC participates in TP53-dependent transcriptional repression leading to
CC apoptosis and seems to have an effect on cell-cycle regulation.
CC Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated
CC transcriptional activation of PER2. {ECO:0000250|UniProtKB:P02340,
CC ECO:0000250|UniProtKB:P04637}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Forms homodimers and homotetramers (By similarity). Binds DNA
CC as a homotetramer. Interacts with AXIN1. Probably part of a complex
CC consisting of TP53, HIPK2 and AXIN1. Interacts with histone
CC acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and
CC recruits them to promoters. Interacts (via C-terminus) with TAF1; when
CC TAF1 is part of the TFIID complex. Interacts with ING4; this
CC interaction may be indirect. Found in a complex with CABLES1 and TP73.
CC Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX.
CC Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with
CC CHD8; leading to recruit histone H1 and prevent transactivation
CC activity. Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1,
CC UHRF2 and E4F. Interacts with YWHAZ; the interaction enhances TP53
CC transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits
CC this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-
CC terminus). Interacts with MKRN1. Interacts with PML (via C-terminus).
CC Interacts with MDM2; leading to ubiquitination and proteasomal
CC degradation of TP53. Directly interacts with FBXO42; leading to
CC ubiquitination and degradation of TP53. Interacts (phosphorylated by
CC ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-
CC induced TP53-dependent inhibition of cell proliferation. Interacts with
CC PPP2R2A. Interacts with AURKA, DAXX, BRD7 and TRIM24. Interacts (when
CC monomethylated) with L3MBTL1. Interacts with GRK5. Binds to the CAK
CC complex (CDK7, cyclin H and MAT1) in response to DNA damage. Interacts
CC with CDK5 in neurons. Interacts with AURKB, SETD2, UHRF2 and NOC2L.
CC Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination
CC by MDM2. Interacts with PTK2B/PYK2; this promotes ubiquitination by
CC MDM2. Interacts with PRKCG. Interacts with PPIF; the association
CC implicates preferentially tetrameric TP53, is induced by oxidative
CC stress and is impaired by cyclosporin A (CsA). Interacts with SNAI1;
CC the interaction induces SNAI1 degradation via MDM2-mediated
CC ubiquitination and inhibits SNAI1-induced cell invasion. Interacts with
CC KAT6A. Interacts with UBC9. Interacts with ZNF385B; the interaction is
CC direct. Interacts (via DNA-binding domain) with ZNF385A; the
CC interaction is direct and enhances p53/TP53 transactivation functions
CC on cell-cycle arrest target genes, resulting in growth arrest (By
CC similarity). Interacts with ANKRD2. Interacts with RFFL and RNF34;
CC involved in p53/TP53 ubiquitination. Interacts with MTA1 and COP1.
CC Interacts with CCAR2 (via N-terminus). Interacts with MORC3. Interacts
CC (via C-terminus) with POU4F2 (via C-terminus). Interacts (via
CC oligomerization region) with NOP53; the interaction is direct and may
CC prevent the MDM2-mediated proteasomal degradation of TP53. Interacts
CC with AFG1L; mediates mitochondrial translocation of TP53. Interacts
CC with UBD (By similarity). Interacts with TAF6 (By similarity).
CC Interacts with C10orf90/FATS; the interaction inhibits binding of TP53
CC and MDM2 (By similarity). Interacts with NUPR1; interaction is stress-
CC dependent. Forms a complex with EP300 and NUPR1; this complex binds
CC CDKN1A promoter leading to transcriptional induction of CDKN1A (By
CC similarity). Interacts with PRMT5 in response to DNA damage; the
CC interaction is TTC5/STRAP dependent (By similarity). Interacts with
CC PPP1R13L (via SH3 domain and ANK repeats); the interaction inhibits
CC pro-apoptotic activity of p53/TP53 (By similarity). Interacts with
CC PPP1R13B/ASPP1 and TP53BP2/ASPP2; the interactions promotes pro-
CC apoptotic activity (By similarity). When phosphorylated, interacts with
CC DDX3X and gamma-tubulin (By similarity). Interacts with KAT7/HBO1;
CC leading to inhibit histone acetyltransferase activity of KAT7/HBO1 (By
CC similarity). Interacts with S100A4; this interaction promotes TP53
CC degradation (By similarity). Interacts with TTC5/STRAP; the interaction
CC may result in increased mitochondrial-dependent apoptosis (By
CC similarity). Interacts with NQO1; this interaction is NADH-dependent,
CC stabilizes TP53 in response to oxidative stress and protects it from
CC ubiquitin-independent degradation by the 20S proteasome.
CC {ECO:0000250|UniProtKB:P02340, ECO:0000250|UniProtKB:P04637,
CC ECO:0000250|UniProtKB:P10361}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus
CC {ECO:0000250|UniProtKB:P04637}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P04637}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P04637}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P04637}.
CC Note=Interaction with BANP promotes nuclear localization. Recruited
CC into PML bodies together with CHEK2. Translocates to mitochondria upon
CC oxidative stress. Translocates to mitochondria in response to mitomycin
CC C treatment (By similarity). {ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Phosphorylated by VRK1, which may prevent the interaction with
CC MDM2. Phosphorylated by CHEK2 in response to DNA damage, which prevents
CC ubiquitination by MDM2. Phosphorylated by PLK3 in response to reactive
CC oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably
CC phosphorylated on by CDK7 in a CAK complex in response to DNA damage.
CC Phosphorylated by CK2 following UV but not gamma irradiation.
CC Stabilized by CDK5-mediated phosphorylation in response to genotoxic
CC and oxidative stresses at Ser-9, leading to accumulation of p53/TP53,
CC particularly in the nucleus, thus inducing the transactivation of
CC p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-9 in response to
CC genotoxic stress. Phosphorylated at Ser-266 by CDK2 in response to DNA-
CC damage (By similarity). {ECO:0000250}.
CC -!- PTM: Monomethylated by SETD7, leading to stabilization and increased
CC transcriptional activation. Monomethylated by SMYD2, leading to
CC decreased DNA-binding activity and subsequent transcriptional
CC regulation activity. Monomethylation by SETD7 prevents interaction with
CC SMYD2 and subsequent monomethylation by SMYD2 (By similarity).
CC Dimethylated by EHMT1 and EHMT2. Monomethylated by KMT5A, promoting
CC interaction with L3MBTL1 and leading to repress transcriptional
CC activity. Demethylation by KDM1A prevents interaction with TP53BP1 and
CC represses TP53-mediated transcriptional activation (By similarity).
CC Methylated by PRMT5; methylation is increased after DNA damage and
CC might possibly affect TP53 target gene specificity (By similarity).
CC {ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Sumoylated with SUMO1. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal
CC degradation. Ubiquitinated by RFWD3, which works in cooperation with
CC MDM2 and may catalyze the formation of short polyubiquitin chains on
CC p53/TP53 that are not targeted to the proteasome. Ubiquitinated by
CC MKRN1, which leads to proteasomal degradation. Deubiquitinated by
CC USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34
CC and RNF125, which leads to proteasomal degradation. Ubiquitination by
CC TOPORS induces degradation. Deubiquitination by USP7, leading to
CC stabilize it. Ubiquitinated by COP1, which leads to proteasomal
CC degradation (By similarity). Ubiquitination and subsequent proteasomal
CC degradation is negatively regulated by CCAR2 (By similarity).
CC Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-
CC linkage independent and non-proteolytic, leading to TP53 stabilization
CC (By similarity). {ECO:0000250|UniProtKB:P02340,
CC ECO:0000250|UniProtKB:P04637}.
CC -!- DISEASE: Note=p53 is found in increased amounts in a wide variety of
CC transformed cells. p53 is frequently mutated or inactivated in many
CC types of cancer.
CC -!- SIMILARITY: Belongs to the p53 family. {ECO:0000305}.
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DR EMBL; S83123; AAB46899.1; -; mRNA.
DR EMBL; U37120; AAB18936.1; -; Genomic_DNA.
DR AlphaFoldDB; P79892; -.
DR SMR; P79892; -.
DR STRING; 9796.ENSECAP00000032751; -.
DR PaxDb; P79892; -.
DR InParanoid; P79892; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0048512; P:circadian behavior; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd08367; P53; 1.
DR Gene3D; 2.60.40.720; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR012346; p53/RUNT-type_TF_DNA-bd_sf.
DR InterPro; IPR011615; p53_DNA-bd.
DR InterPro; IPR002117; p53_tumour_suppressor.
DR PANTHER; PTHR11447; PTHR11447; 1.
DR Pfam; PF00870; P53; 1.
DR PRINTS; PR00386; P53SUPPRESSR.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS00348; P53; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Apoptosis; Biological rhythms; Cell cycle;
KW Cytoplasm; Cytoskeleton; DNA-binding; Endoplasmic reticulum;
KW Isopeptide bond; Metal-binding; Mitochondrion; Necrosis; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc.
FT CHAIN <1..>280
FT /note="Cellular tumor antigen p53"
FT /id="PRO_0000185702"
FT DNA_BIND 52..243
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT REGION 26..60
FT /note="Interaction with WWOX"
FT /evidence="ECO:0000250"
FT REGION 50..251
FT /note="Required for interaction with ZNF385A"
FT /evidence="ECO:0000250"
FT REGION 63..187
FT /note="Required for interaction with FBXO42"
FT /evidence="ECO:0000250"
FT REGION 207..245
FT /note="Interaction with E4F1"
FT /evidence="ECO:0000250"
FT REGION 224..231
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 234..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..>280
FT /note="Oligomerization"
FT MOTIF 256..272
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 234..251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT SITE 70
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 9
FT /note="Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 70
FT /note="N6-acetyllysine; by KAT6A"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 133
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 220
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 235
FT /note="Phosphothreonine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 256
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 266
FT /note="Phosphoserine; by AURKA, CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P02340"
FT CROSSLNK 242
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 243
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CONFLICT 79
FT /note="T -> A (in Ref. 2; AAB18936)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="L -> M (in Ref. 2; AAB18936)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="A -> V (in Ref. 2; AAB18936)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="G -> A (in Ref. 2; AAB18936)"
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 280
SQ SEQUENCE 280 AA; 30985 MW; 040F12030B5ACEE9 CRC64;
PAVNNLLLSP DVVNWLDEGP DEAPRMPAAP APLAPAPATS WPLSSFVPSQ KTYPGCYGFR
LGFLNSGTAK SVTCTYSPTL NKLFCQLAKT CPVQLLVSSP PPPGTRVRAM AIYKKSEFMT
EVVRRCPHHE RCSDSSDGLA PPQHLIRVEG NLRAEYLDDR NTFRHSVVVP YEPPEVGSDC
TTIHYNFMCN SSCMGGMNRR PILTIITLED SSGNLLGRNS FEVRVCACPG RDRRTEEENF
RKKEEPCPEP PPRSTKRVLS SNTSSSPPQK KKPLDGEYFT
