2j1z - Revision history

OCA at 14:32, 13 December 2023

OCA — Wed, 13 Dec 2023 14:32:16 GMT

←Older revision		Revision as of 14:32, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2j1z' size='340' side='right'caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2j1z' size='340' side='right'caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.8Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [https://pdbe.org/2j1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [https://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [https://pdbe.org/2j1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [https://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[https://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[https://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[https://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[https://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[https://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>	+	[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[https://omim.org/entry/133239 133239]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[https://omim.org/entry/151623 151623]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[https://omim.org/entry/260500 260500]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[https://omim.org/entry/202300 202300]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[https://omim.org/entry/614740 614740]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>	+	[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fersht~~, A R~~]]	+	[[Category: Fersht AR]]
-	[[Category: Joerger~~, A C]]~~	+	[[Category: Joerger AC]]
-	~~[[Category: Acetylation]]~~	+
-	~~[[Category: Activator]]~~	+
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Anti-oncogene]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Dna-binding protein]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Host-virus interaction]]~~	+
-	~~[[Category: Li- fraumeni syndrome]]~~	+
-	~~[[Category: Li-fraumeni syndrome]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Nuclear protein]]~~	+
-	~~[[Category: P53 dna-binding domain]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Second-site suppressor mutation]]~~	+
-	~~[[Category: Superstable mutant]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription regulation]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Tumor suppressor]]~~	+
-	~~[[Category: Zinc~~]]	+

OCA at 07:59, 19 January 2022

OCA — Wed, 19 Jan 2022 07:59:23 GMT

OCA at 07:37, 15 April 2020

OCA — Wed, 15 Apr 2020 07:37:09 GMT

←Older revision		Revision as of 07:37, 15 April 2020
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	==Human p53 core domain mutant M133L-V203A-N239Y-N268D-F270L==		==Human p53 core domain mutant M133L-V203A-N239Y-N268D-F270L==
-	<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='2j1z' size='340' side='right'caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://pdbe.org/2j1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://pdbe.org/2j1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[P53\|P53]]	+	*[[P53 3D structures\|P53 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Fersht, A R]]		[[Category: Fersht, A R]]
	[[Category: Joerger, A C]]		[[Category: Joerger, A C]]

OCA at 06:35, 11 July 2018

OCA — Wed, 11 Jul 2018 06:35:51 GMT

←Older revision		Revision as of 06:35, 11 July 2018
Line 1:		Line 1:
-	==~~HUMAN P53 CORE DOMAIN MUTANT~~ M133L-V203A-N239Y-N268D-F270L==	+
		+	==Human p53 core domain mutant M133L-V203A-N239Y-N268D-F270L==
	<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://pdbe.org/2j1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://pdbe.org/2j1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j1/2j1z_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j1/2j1z_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 40:		Line 41:
	[[Category: Fersht, A R]]		[[Category: Fersht, A R]]
	[[Category: Joerger, A C]]		[[Category: Joerger, A C]]
		+	[[Category: Acetylation]]
	[[Category: Activator]]		[[Category: Activator]]
		+	[[Category: Alternative splicing]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
Line 55:		Line 58:
	[[Category: P53 dna-binding domain]]		[[Category: P53 dna-binding domain]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
		+	[[Category: Polymorphism]]
	[[Category: Second-site suppressor mutation]]		[[Category: Second-site suppressor mutation]]
	[[Category: Superstable mutant]]		[[Category: Superstable mutant]]
Line 61:		Line 65:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Tumor suppressor]]		[[Category: Tumor suppressor]]
		+	[[Category: Zinc]]

OCA at 07:25, 9 February 2016

OCA — Tue, 09 Feb 2016 07:25:33 GMT

←Older revision		Revision as of 07:25, 9 February 2016
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j1z ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 19:57, 10 September 2015

OCA — Thu, 10 Sep 2015 19:57:09 GMT

←Older revision		Revision as of 19:57, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://pdbe.org/2j1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2j1z" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Fersht, A R]]		[[Category: Fersht, A R]]
	[[Category: Joerger, A C]]		[[Category: Joerger, A C]]

OCA at 15:01, 19 January 2015

OCA — Mon, 19 Jan 2015 15:01:44 GMT

←Older revision		Revision as of 15:01, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>		<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[http://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[http://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[http://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>		[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[http://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[http://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[http://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Fersht, A R.]]	+	[[Category: Fersht, A R]]
-	[[Category: Joerger, A C.]]	+	[[Category: Joerger, A C]]
	[[Category: Activator]]		[[Category: Activator]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]

OCA at 08:32, 30 September 2014

OCA — Tue, 30 Sep 2014 08:32:00 GMT

←Older revision		Revision as of 08:32, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2j1z\| PDB=2j1z \| SCENE= }}~~	+	==HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-F270L==
-	===HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-F270L===	+	<StructureSection load='2j1z' size='340' side='right' caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	~~{{ABSTRACT_PUBMED_17015838}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [http://www.ebi.ac.uk/pdbsum/2j1z PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[http://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[http://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[http://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j1/2j1z_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. We have solved high-resolution crystal structures of several oncogenic mutants to investigate the structural basis of inactivation and provide information for designing drugs that may rescue inactivated mutants. We found a variety of structural consequences upon mutation: (i) the removal of an essential contact with DNA, (ii) creation of large, water-accessible crevices or hydrophobic internal cavities with no other structural changes but with a large loss of thermodynamic stability, (iii) distortion of the DNA-binding surface, and (iv) alterations to surfaces not directly involved in DNA binding but involved in domain-domain interactions on binding as a tetramer. These findings explain differences in functional properties and associated phenotypes (e.g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug.

-	~~==Disease==~~	+	Structural basis for understanding oncogenic p53 mutations and designing rescue drugs.,Joerger AC, Ang HC, Fersht AR Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:17015838<ref>PMID:17015838</ref>
-	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for ~~LFS have been proposed (PubMed:8118819~~ and ~~PubMed:8718514) and called Li-Fraumeni like syndrome (LFL)~~. In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, ~~soft tissue and bone sarcomas~~, ~~brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15~~, ~~rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers~~.<ref>PMID:10570149</ref><ref>PMID:1933902</ref><ref>PMID:1978757</ref><ref>PMID:2259385</ref><ref>PMID:1737852</ref><ref>PMID:1565144</ref><ref>PMID:7887414</ref><ref>PMID:8825920</ref><ref>PMID:9452042</ref><ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; ~~also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer~~ (~~LNCR~~) ~~[MIM~~:~~[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non~~-~~small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer~~. ~~NSCLC is often diagnosed at an advanced stage and has a poor prognosis~~. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[http://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[http://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[http://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:~~21946351~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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~~. ~~In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent~~ of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<~~ref~~>~~PMID:9840937~~</~~ref~~><ref>PMID:11025664</ref><ref>PMID:12810724</ref><ref>PMID:15186775</ref><ref>PMID:15340061</ref><ref>PMID:17317671</ref><ref>PMID:17349958</ref><ref>PMID:19556538</ref><ref>PMID:20673990</ref><ref>PMID:20959462</ref><ref>PMID:22726440</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA].	+

	==See Also==		==See Also==
	*[[P53\|P53]]		*[[P53\|P53]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017015838</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:015703170</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fersht, A R.]]		[[Category: Fersht, A R.]]

OCA at 04:22, 25 March 2013

OCA — Mon, 25 Mar 2013 04:22:53 GMT

←Older revision		Revision as of 04:22, 25 March 2013
Line 1:		Line 1:
-	[[Image:2j1z.png\|left\|200px]]
-
	{{STRUCTURE_2j1z\| PDB=2j1z \| SCENE= }}		{{STRUCTURE_2j1z\| PDB=2j1z \| SCENE= }}
-
	===HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-F270L===		===HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-F270L===
		+	{{ABSTRACT_PUBMED_17015838}}

-	~~{{ABSTRACT_PUBMED_17015838}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref><ref>PMID:1933902</ref><ref>PMID:1978757</ref><ref>PMID:2259385</ref><ref>PMID:1737852</ref><ref>PMID:1565144</ref><ref>PMID:7887414</ref><ref>PMID:8825920</ref><ref>PMID:9452042</ref><ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[http://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[http://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[http://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref><ref>PMID:11025664</ref><ref>PMID:12810724</ref><ref>PMID:15186775</ref><ref>PMID:15340061</ref><ref>PMID:17317671</ref><ref>PMID:17349958</ref><ref>PMID:19556538</ref><ref>PMID:20673990</ref><ref>PMID:20959462</ref><ref>PMID:22726440</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017015838</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:015703170</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017015838</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:015703170</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fersht, A R.]]		[[Category: Fersht, A R.]]

OCA at 13:06, 20 October 2012

OCA — Sat, 20 Oct 2012 13:06:36 GMT

←Older revision		Revision as of 13:06, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2j1z]] is a 2 chain structure ~~of [[P53]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA].	+	[[2j1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA].

	==See Also==		==See Also==

←Older revision		Revision as of 07:59, 19 January 2022
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	<StructureSection load='2j1z' size='340' side='right'caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2j1z' size='340' side='right'caption='[[2j1z]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j1z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J1Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a1u\|1a1u]], [[1aie\|1aie]], [[1c26\|1c26]], [[1dt7\|1dt7]], [[1gzh\|1gzh]], [[1h26\|1h26]], [[1hs5\|1hs5]], [[1jsp\|1jsp]], [[1kzy\|1kzy]], [[1ma3\|1ma3]], [[1olg\|1olg]], [[1olh\|1olh]], [[1pes\|1pes]], [[1pet\|1pet]], [[1sae\|1sae]], [[1saf\|1saf]], [[1sag\|1sag]], [[1sah\|1sah]], [[1sai\|1sai]], [[1saj\|1saj]], [[1sak\|1sak]], [[1sal\|1sal]], [[1tsr\|1tsr]], [[1tup\|1tup]], [[1uol\|1uol]], [[1xqh\|1xqh]], [[1ycq\|1ycq]], [[1ycr\|1ycr]], [[1ycs\|1ycs]], [[2ac0\|2ac0]], [[2ady\|2ady]], [[2ahi\|2ahi]], [[2ata\|2ata]], [[2b3g\|2b3g]], [[2bim\|2bim]], [[2bin\|2bin]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]], [[2f1x\|2f1x]], [[2fej\|2fej]], [[2j0z\|2j0z]], [[2j10\|2j10]], [[2j11\|2j11]], [[2j1w\|2j1w]], [[2j1x\|2j1x]], [[2j1y\|2j1y]], [[2j20\|2j20]], [[2j21\|2j21]], [[3sak\|3sak]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [~~http~~://pdbe.org/2j1z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j1z OCA], [https://pdbe.org/2j1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j1z RCSB], [https://www.ebi.ac.uk/pdbsum/2j1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j1z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[~~http~~://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[~~http~~://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[~~http~~://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[~~http~~://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[~~http~~://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[~~http~~://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[~~http~~://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>	+	[[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[https://omim.org/entry/133239 133239]]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[https://omim.org/entry/151623 151623]]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[https://omim.org/entry/260500 260500]]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[https://omim.org/entry/202300 202300]]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[https://omim.org/entry/614740 614740]]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>	+	[[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN]] 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. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. 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 seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]