P53_DANRE
ID P53_DANRE Reviewed; 373 AA.
AC P79734; Q7ZW62; Q90440;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cellular tumor antigen p53;
DE AltName: Full=Tumor suppressor p53;
GN Name=tp53; Synonyms=drp53;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9200835;
RA Cheng R., Ford B.L., O'Neal P.E., Mathews C.Z., Bradford C.S., Thongtan T.,
RA Barnes D.W., Hendricks J.D., Bailey G.S.;
RT "Zebrafish (Danio rerio) p53 tumor suppressor gene: cDNA sequence and
RT expression during embryogenesis.";
RL Mol. Mar. Biol. Biotechnol. 6:88-97(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bauer M.P., Goetz F.W.;
RT "Isolation of p53 in the zebrafish.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-212.
RA Winge P.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=12477391; DOI=10.1016/s0960-9822(02)01319-2;
RA Langheinrich U., Hennen E., Stott G., Vacun G.;
RT "Zebrafish as a model organism for the identification and characterization
RT of drugs and genes affecting p53 signaling.";
RL Curr. Biol. 12:2023-2028(2002).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF SER-26; ASN-168 AND MET-214.
RX PubMed=15630097; DOI=10.1073/pnas.0406252102;
RA Berghmans S., Murphey R.D., Wienholds E., Neuberg D., Kutok J.L.,
RA Fletcher C.D.M., Morris J.P., Liu T.X., Schulte-Merker S., Kanki J.P.,
RA Plasterk R., Zon L.I., Look A.T.;
RT "tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:407-412(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22952453; DOI=10.1371/journal.pgen.1002922;
RA Sorrells S., Carbonneau S., Harrington E., Chen A.T., Hast B., Milash B.,
RA Pyati U., Major M.B., Zhou Y., Zon L.I., Stewart R.A., Look A.T., Jette C.;
RT "Ccdc94 protects cells from ionizing radiation by inhibiting the expression
RT of p53.";
RL PLoS Genet. 8:E1002922-E1002922(2012).
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. {ECO:0000269|PubMed:12477391,
CC ECO:0000269|PubMed:15630097, ECO:0000269|PubMed:22952453}.
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: Binds DNA as a homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: In double morpholino knockdown of tp53 and yju2,
CC tp53 deficiency rescues animals from developmental neurodegeneration
CC observed on yju2 mutants and radiosensitivity.
CC {ECO:0000269|PubMed:22952453}.
CC -!- SIMILARITY: Belongs to the p53 family. {ECO:0000305}.
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DR EMBL; U60804; AAB40617.1; -; mRNA.
DR EMBL; AF365873; AAO85406.1; -; mRNA.
DR EMBL; U46693; AAA97408.1; -; mRNA.
DR RefSeq; NP_571402.1; NM_131327.2.
DR PDB; 4CZ5; X-ray; 1.02 A; A/B/C/D=301-330.
DR PDB; 4CZ6; X-ray; 1.53 A; A/B/C/D=301-330.
DR PDB; 4CZ7; X-ray; 1.10 A; A/B/C/D/E/F=301-330.
DR PDBsum; 4CZ5; -.
DR PDBsum; 4CZ6; -.
DR PDBsum; 4CZ7; -.
DR AlphaFoldDB; P79734; -.
DR SMR; P79734; -.
DR BioGRID; 78756; 2.
DR STRING; 7955.ENSDARP00000051548; -.
DR PaxDb; P79734; -.
DR Ensembl; ENSDART00000177458; ENSDARP00000144168; ENSDARG00000035559.
DR GeneID; 30590; -.
DR KEGG; dre:30590; -.
DR CTD; 7157; -.
DR ZFIN; ZDB-GENE-990415-270; tp53.
DR eggNOG; ENOG502QVY3; Eukaryota.
DR GeneTree; ENSGT00950000183153; -.
DR InParanoid; P79734; -.
DR Reactome; R-DRE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-DRE-2559584; Formation of Senescence-Associated Heterochromatin Foci (SAHF).
DR Reactome; R-DRE-2559585; Oncogene Induced Senescence.
DR Reactome; R-DRE-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-DRE-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-5689896; Ovarian tumor domain proteases.
DR Reactome; R-DRE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-DRE-6804754; Regulation of TP53 Expression.
DR Reactome; R-DRE-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-DRE-6804757; Regulation of TP53 Degradation.
DR Reactome; R-DRE-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-DRE-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-DRE-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-DRE-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-DRE-69473; G2/M DNA damage checkpoint.
DR Reactome; R-DRE-69481; G2/M Checkpoints.
DR Reactome; R-DRE-69541; Stabilization of p53.
DR Reactome; R-DRE-69895; Transcriptional activation of cell cycle inhibitor p21.
DR Reactome; R-DRE-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-DRE-8941855; RUNX3 regulates CDKN1A transcription.
DR PRO; PR:P79734; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000035559; Expressed in cleaving embryo and 25 other tissues.
DR ExpressionAtlas; P79734; baseline and differential.
DR GO; GO:0000785; C:chromatin; IDA:ZFIN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ZFIN.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN.
DR GO; GO:0006915; P:apoptotic process; IMP:ZFIN.
DR GO; GO:1902262; P:apoptotic process involved in blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0006914; P:autophagy; IGI:ZFIN.
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:0071456; P:cellular response to hypoxia; IMP:ZFIN.
DR GO; GO:0090398; P:cellular senescence; IGI:ZFIN.
DR GO; GO:0060216; P:definitive hemopoiesis; IGI:ZFIN.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:ZFIN.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IMP:ZFIN.
DR GO; GO:0048730; P:epidermis morphogenesis; IMP:ZFIN.
DR GO; GO:0048821; P:erythrocyte development; IGI:ZFIN.
DR GO; GO:0043249; P:erythrocyte maturation; IGI:ZFIN.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IGI:ZFIN.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IGI:ZFIN.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:ZFIN.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IGI:ZFIN.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:ZFIN.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:ZFIN.
DR GO; GO:0010526; P:negative regulation of transposition, RNA-mediated; IMP:ZFIN.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:ZFIN.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:ZFIN.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IGI:ZFIN.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:ZFIN.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:2000779; P:regulation of double-strand break repair; IMP:ZFIN.
DR GO; GO:0031647; P:regulation of protein stability; IGI:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:ZFIN.
DR GO; GO:0051597; P:response to methylmercury; IDA:ZFIN.
DR GO; GO:0009411; P:response to UV; IMP:ZFIN.
DR GO; GO:0010165; P:response to X-ray; IMP:ZFIN.
DR GO; GO:0007283; P:spermatogenesis; IGI:ZFIN.
DR CDD; cd08367; P53; 1.
DR Gene3D; 2.60.40.720; -; 1.
DR Gene3D; 4.10.170.10; -; 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; IPR036674; p53_tetramer_sf.
DR InterPro; IPR010991; p53_tetrameristn.
DR InterPro; IPR002117; p53_tumour_suppressor.
DR PANTHER; PTHR11447; PTHR11447; 1.
DR Pfam; PF00870; P53; 1.
DR Pfam; PF07710; P53_tetramer; 1.
DR PRINTS; PR00386; P53SUPPRESSR.
DR SUPFAM; SSF47719; SSF47719; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS00348; P53; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Apoptosis; Cell cycle; Cytoplasm; DNA-binding;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Tumor suppressor; Zinc.
FT CHAIN 1..373
FT /note="Cellular tumor antigen p53"
FT /id="PRO_0000185718"
FT DNA_BIND 70..260
FT /evidence="ECO:0000250"
FT REGION 1..31
FT /note="Transcription activation (acidic)"
FT REGION 52..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..248
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 250..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..332
FT /note="Oligomerization"
FT REGION 329..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..366
FT /note="Basic (repression of DNA-binding)"
FT MOTIF 274..296
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 315..326
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 52..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..265
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 88
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT MUTAGEN 26
FT /note="S->F: No effect on transactivation activity."
FT /evidence="ECO:0000269|PubMed:15630097"
FT MUTAGEN 168
FT /note="N->K: Loss of transactivation activity. Temperature-
FT sensitive suppression of irradiation-induced apoptosis. No
FT effect on embryonic development."
FT /evidence="ECO:0000269|PubMed:15630097"
FT MUTAGEN 214
FT /note="M->K: Loss of transactivation activity. Suppression
FT of irradiation-induced apoptosis. Defective G1-phase but
FT not G2-phase checkpoint response. Development of malignant
FT peripheral nerve sheath tumors. No effect on embryonic
FT development."
FT /evidence="ECO:0000269|PubMed:15630097"
FT CONFLICT 276..280
FT /note="SLVKE -> K (in Ref. 2; AAO85406)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="L -> S (in Ref. 2; AAO85406)"
FT /evidence="ECO:0000305"
FT STRAND 303..310
FT /evidence="ECO:0007829|PDB:4CZ5"
FT HELIX 311..326
FT /evidence="ECO:0007829|PDB:4CZ5"
SQ SEQUENCE 373 AA; 41899 MW; AC7AB724FA6B61FF CRC64;
MAQNDSQEFA ELWEKNLIIQ PPGGGSCWDI INDEEYLPGS FDPNFFENVL EEQPQPSTLP
PTSTVPETSD YPGDHGFRLR FPQSGTAKSV TCTYSPDLNK LFCQLAKTCP VQMVVDVAPP
QGSVVRATAI YKKSEHVAEV VRRCPHHERT PDGDNLAPAG HLIRVEGNQR ANYREDNITL
RHSVFVPYEA PQLGAEWTTV LLNYMCNSSC MGGMNRRPIL TIITLETQEG QLLGRRSFEV
RVCACPGRDR KTEESNFKKD QETKTMAKTT TGTKRSLVKE SSSATLRPEG SKKAKGSSSD
EEIFTLQVRG RERYEILKKL NDSLELSDVV PASDAEKYRQ KFMTKNKKEN RESSEPKQGK
KLMVKDEGRS DSD
