TP53

TP53
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 4QO1, 1A1U, 1AIE, 1C26, 1DT7, 1GZH, 1H26, 1HS5, 1KZY, 1MA3, 1OLG, 1OLH, 1PES, 1PET, 1SAE, 1SAF, 1SAK, 1SAL, 1TSR, 1TUP, 1UOL, 1XQH, 1YC5, 1YCQ, 1YCR, 1YCS, 2AC0, 2ADY, 2AHI, 2ATA, 2B3G, 2BIM, 2BIN, 2BIO, 2BIP, 2BIQ, 2FEJ, 2FOJ, 2FOO, 2GS0, 2H1L, 2H2D, 2H2F, 2H4F, 2H4H, 2H4J, 2H59, 2J0Z, 2J10, 2J11, 2J1W, 2J1X, 2J1Y, 2J1Z, 2J20, 2J21, 2K8F, 2L14, 2LY4, 2MEJ, 2MWO, 2MWP, 2MZD, 2OCJ, 2PCX, 2RUK, 2VUK, 2WGX, 2X0U, 2X0V, 2X0W, 2XWR, 2YBG, 2YDR, 2Z5S, 2Z5T, 3D05, 3D06, 3D07, 3D08, 3D09, 3D0A, 3DAB, 3DAC, 3IGK, 3IGL, 3KMD, 3KZ8, 3LW1, 3OQ5, 3PDH, 3Q01, 3Q05, 3Q06, 3SAK, 3TG5, 3TS8, 3ZME, 4AGL, 4AGM, 4AGN, 4AGO, 4AGP, 4AGQ, 4BUZ, 4BV2, 4HFZ, 4HJE, 4IBQ, 4IBS, 4IBT, 4IBU, 4IBV, 4IBW, 4IBY, 4IBZ, 4IJT, 4KVP, 4LO9, 4LOE, 4LOF, 4MZI, 4MZR, 4X34, 4ZZJ, 5AOL, 5ABA, 5AOK, 2MWY, 5A7B, 5AOJ, 5AOI, 5ECG, 5AB9, 4FZ3, 4RP6, 4XR8, 5AOM, 4RP7, 5HOU, 5HP0, 5HPD, 5LGY, 5G4M, 5G4O, 5G4N, 5BUA
Identifikatori
Aliasi	TP53
Vanjski ID-jevi	OMIM: 191170 MGI: 98834 HomoloGene: 460 GeneCards: TP53
Lokacija gena (čovjek) Hrom. Hromosom 17 (čovjek)[1] Bend 17p13.1 Početak 7,661,779 bp[1] Kraj 7,687,538 bp[1]
Lokacija gena (miš) Hrom. Hromosom 11 (miš)[2] Bend 11 B3|11 42.83 cM Početak 69,471,185 bp[2] Kraj 69,482,699 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • protein N-terminus binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • protein self-association • core promoter sequence-specific DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • protein phosphatase binding • ATP binding • transcription factor binding • vezivanje iona metala • protein phosphatase 2A binding • vezivanje enzima • vezivanje iona cinka • chromatin binding • protease binding • oštećeno vezivanje sa DNK • GO:0001948, GO:0016582 vezivanje za proteine • histone acetyltransferase binding • copper ion binding • protein kinase binding • chaperone binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • receptor tyrosine kinase binding • p53 binding • vezivanje identičnih proteina • protein heterodimerization activity • ubiquitin protein ligase binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding • vezivanje sa DNK • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • TFIID-class transcription factor complex binding • mRNA 3'-UTR binding • histone deacetylase binding • disordered domain specific binding • promoter-specific chromatin binding • histone deacetylase regulator activity • protein homodimerization activity • MDM2/MDM4 family protein binding Ćelijska komponenta • citoplazma • mitohondrija • jedro • nuclear body • transcription factor TFIID complex • nuclear matrix • replication fork • Jedarce • Endoplazmatski retikulum • nukleoplazma • mitochondrial matrix • PML body • citosol • intracellular anatomical structure • transcription regulator complex • GO:0009327 makromolekulani kompleks • site of double-strand break Biološki proces • positive regulation of histone deacetylation • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest • rhythmic process • replicative senescence • negative regulation of telomerase activity • oligodendrocyte apoptotic process • cellular response to DNA damage stimulus • intrinsic apoptotic signaling pathway • positive regulation of neuron apoptotic process • regulation of mitochondrial membrane permeability • positive regulation of reactive oxygen species metabolic process • cellular response to ionizing radiation • positive regulation of thymocyte apoptotic process • negative regulation of helicase activity • ćelijski ciklus • Ras protein signal transduction • Ćelijska proliferacija • cellular response to hypoxia • negative regulation of cell population proliferation • Popravak ekscizijom nukleotida • cellular response to glucose starvation • GO:0009373 regulation of transcription, DNA-templated • GO:1904576 response to antibiotic • transcription, DNA-templated • ER overload response • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • negative regulation of cell growth • intrinsic apoptotic signaling pathway by p53 class mediator • positive regulation of peptidyl-tyrosine phosphorylation • GO:0022415 viral process • response to gamma radiation • negative regulation of fibroblast proliferation • positive regulation of intrinsic apoptotic signaling pathway • Ćelijska diferencijacija • determination of adult lifespan • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • cellular response to UV • DNA damage response, signal transduction by p53 class mediator • negative regulation of apoptotic process • protein tetramerization • oxidative stress-induced premature senescence • positive regulation of release of cytochrome c from mitochondria • circadian behavior • GO:0045996 negative regulation of transcription, DNA-templated • GO:0034613 protein localization • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • positive regulation of execution phase of apoptosis • multicellular organism development • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • GO:1901313 positive regulation of gene expression • mitotic G1 DNA damage checkpoint signaling • positive regulation of protein oligomerization • positive regulation of apoptotic process • entrainment of circadian clock by photoperiod • response to X-ray • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • base-excision repair • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • regulation of cell cycle G2/M phase transition • proteasome-mediated ubiquitin-dependent protein catabolic process • regulation of signal transduction by p53 class mediator • GO:0097285 apoptoza • transcription by RNA polymerase II • positive regulation of protein export from nucleus • GO:0010703, GO:0010702 programirana ćelijska smrt • regulation of apoptotic process • protein deubiquitination • phosphatidylinositol-mediated signaling • GO:1901227 negative regulation of transcription by RNA polymerase II • Autofagija • mRNA transcription • cytokine-mediated signaling pathway • positive regulation of RNA polymerase II transcription preinitiation complex assembly • RNA polymerase II preinitiation complex assembly • protein homotetramerization • GO:0034622 protein-containing complex assembly • cellular response to gamma radiation • signal transduction by p53 class mediator • cellular response to actinomycin D • positive regulation of pri-miRNA transcription by RNA polymerase II • positive regulation of production of miRNAs involved in gene silencing by miRNA • in utero embryonic development • somitogenesis • release of cytochrome c from mitochondria • hematopoietic progenitor cell differentiation • T cell proliferation involved in immune response • B cell lineage commitment • T cell lineage commitment • response to ischemia • double-strand break repair • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • protein import into nucleus • GO:0001306 response to oxidative stress • transforming growth factor beta receptor signaling pathway • Gastrulacija • negative regulation of neuroblast proliferation • central nervous system development • heart development • Jednodnevni biološki ritam • negative regulation of DNA replication • rRNA transcription • response to UV • response to salt stress • embryo development ending in birth or egg hatching • negative regulation of gene expression • positive regulation of cardiac muscle cell apoptotic process • cerebellum development • negative regulation of transforming growth factor beta receptor signaling pathway • T cell differentiation in thymus • regulation of tissue remodeling • multicellular organism growth • positive regulation of mitochondrial membrane permeability • positive regulation of transcription from RNA polymerase II promoter in response to stress • regulation of cell population proliferation • mitochondrial DNA repair • regulation of DNA damage response, signal transduction by p53 class mediator • regulation of neuron apoptotic process • negative regulation of proteolysis • negative regulation of mitotic cell cycle • bone marrow development • embryonic organ development • protein stabilization • GO:0051312, GO:0007083 chromosome organization • neuron apoptotic process • regulation of cell cycle • hematopoietic stem cell differentiation • interferon-gamma-mediated signaling pathway • cardiac septum morphogenesis • positive regulation of transcription from RNA polymerase II promoter in response to hypoxia • positive regulation of programmed necrotic cell death • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • regulation of thymocyte apoptotic process • GO:0060554, GO:0060555 necroptosis • cellular response to UV-C • negative regulation of mitophagy • regulation of mitochondrial membrane permeability involved in apoptotic process • regulation of intrinsic apoptotic signaling pathway by p53 class mediator • negative regulation of production of miRNAs involved in gene silencing by miRNA • negative regulation of glucose catabolic process to lactate via pyruvate • intrinsic apoptotic signaling pathway in response to hypoxia • regulation of fibroblast apoptotic process • negative regulation of reactive oxygen species metabolic process • regulation of cellular senescence Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	7157	22059
Ensembl	ENSG00000141510	ENSMUSG00000059552
UniProt	P04637	P02340
RefSeq (mRNK)	NM_001276761 NM_000546 NM_001126112 NM_001126113 NM_001126114 NM_001126115 NM_001126116 NM_001126117 NM_001126118 NM_001276695 NM_001276696 NM_001276697 NM_001276698 NM_001276699 NM_001276760	NM_001127233 NM_011640
RefSeq (bjelančevina)	NP_000537 NP_001119584 NP_001119585 NP_001119586 NP_001119587 NP_001119588 NP_001119589 NP_001119590 NP_001263624 NP_001263625 NP_001263626 NP_001263627 NP_001263628 NP_001263689 NP_001263690	NP_001120705 NP_035770
Lokacija (UCSC)	Chr 17: 7.66 – 7.69 Mb	Chr 11: 69.47 – 69.48 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Tumorski protein P53, znan i kao p53, ćelijski tumorski-antigen p53 (UniProt ime), domaćinski gen,^[5] fosfoprotein p53, tumorski supresor p53, antigen NY-CO-13 ili transformacijski vezani protein 53 (TRP53), je bilo koja proteinska izoforma proteina kodiranog homolognim genom u različitim organizmima, kao što su TP53 (ljudi) i Trp53 (miševi). Ovaj homolog (za koji se prvobitno mislilo da je, i o njemu se često govori, kao jedan protein) presudan je u višim kičmenjacima, gdje sprečava stvaranje karcinoma, te stoga funkcionira kao supresor tumora.^[6] Kao takav, p53 je opisan kao "čuvar genoma" zbog svoje uloge u očuvanju stabilnosti, sprečavanjem mutacije genoma.^[7] Stoga se TP53 koriste za označavanje imena gena TP53 i razlikovanje od proteina koje kodiraju (klasificiran je kao gen za supresiju tumora).^{[8][9][10][11][12]}

Naziv 'p53' dobio je 1979. godine opisujući prividnu molekulskuu masu. Analiza SDS-PAGE pokazuje da je riječ o proteinu od 53-kilodaltona (kDa). Međutim, stvarna masa proteina p53 pune dužine (p53α) na osnovu zbroja mase aminokiselinskih ostataka iznosi samo 43,7 kDa. Ova razlika je zbog velikog broja prolinskih ostataka u proteinu, koji usporavaju njegovu migraciju na SDS-PAGE, čineći ga tako težim nego što zapravo jeste.^[13] Pored proteina pune dužine, ljudski gen TP53 kodira najmanje 15 izoformnih proteina, veličine od 3,5 do 43,7 kDa. Svi ovi proteini p53 nazivaju se izoformama p53.^[6] Gen TP53 je najčešće mutirani gen (> 50%) u karcinomu čovjeka, što ukazuje da TP53 ima presudnu ulogu u sprečavanju stvaranja karcinoma. Gen TP53 kodira proteine koji se vežu za DNK i regulišu ekspresiju, kako bi se spriječile mutacije genoma.^[14]

1. ^ ^{a b c} GRCh38: Ensembl release 89: ENSG00000141510 - Ensembl, maj 2017
2. ^ ^{a b c} GRCm38: Ensembl release 89: ENSMUSG00000059552 - Ensembl, maj 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Toufektchan, E.; Toledo, F. (2018). "The Guardian of the Genome Revisited: P53 Downregulates Genes Required for Telomere Maintenance, DNA Repair, and Centromere Structure". Cancers. 10 (5): 135. doi:10.3390/cancers10050135. PMC 5977108. PMID 29734785.
6. ^ ^{a b} Surget S, Khoury MP, Bourdon JC (decembar 2013). "Uncovering the role of p53 splice variants in human malignancy: a clinical perspective". OncoTargets and Therapy. 7: 57–68. doi:10.2147/OTT.S53876. PMC 3872270. PMID 24379683.
7. ^ Read AP, Strachan T (1999). "Chapter 18: Cancer Genetics". Human molecular genetics 2. New York: Wiley. ISBN 978-0-471-33061-5.
8. ^ Matlashewski G, Lamb P, Pim D, Peacock J, Crawford L, Benchimol S (decembar 1984). "Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene". The EMBO Journal. 3 (13): 3257–62. doi:10.1002/j.1460-2075.1984.tb02287.x. PMC 557846. PMID 6396087.
9. ^ Isobe M, Emanuel BS, Givol D, Oren M, Croce CM (1986). "Localization of gene for human p53 tumour antigen to band 17p13". Nature. 320 (6057): 84–5. Bibcode:1986Natur.320...84I. doi:10.1038/320084a0. PMID 3456488. S2CID 4310476.
10. ^ Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B (juni 1991). "Identification of p53 as a sequence-specific DNA-binding protein". Science. 252 (5013): 1708–11. Bibcode:1991Sci...252.1708K. doi:10.1126/science.2047879. PMID 2047879. S2CID 19647885.
11. ^ McBride OW, Merry D, Givol D (januar 1986). "The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13)". Proceedings of the National Academy of Sciences of the United States of America. 83 (1): 130–4. Bibcode:1986PNAS...83..130M. doi:10.1073/pnas.83.1.130. PMC 322805. PMID 3001719.
12. ^ Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom Bourdon
13. ^ Ziemer MA, Mason A, Carlson DM (septembar 1982). "Cell-free translations of proline-rich protein mRNAs". The Journal of Biological Chemistry. 257 (18): 11176–80. doi:10.1016/S0021-9258(18)33948-6. PMID 7107651.
14. ^ Levine AJ, Lane DP, ured. (2010). The p53 family. Cold Spring Harbor Perspectives in Biology. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press. ISBN 978-0-87969-830-0.