2bin - Revision history

OCA at 13:39, 13 December 2023

2023-12-13T13:39:16Z

← Older revision		Revision as of 13:39, 13 December 2023
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	<StructureSection load='2bin' size='340' side='right'caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2bin' size='340' side='right'caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BIN FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BIN 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]] 1.9Å</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</~~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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [https://pdbe.org/2bin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [https://www.ebi.ac.uk/pdbsum/2bin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bin 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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [https://pdbe.org/2bin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [https://www.ebi.ac.uk/pdbsum/2bin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bin 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: Activator]]~~
	~~[[Category: Anti-oncogene]]~~
	~~[[Category: Apoptosis]]~~
	~~[[Category: Disease mutation]]~~
	~~[[Category: Dna binding protein]]~~
	~~[[Category: Dna-binding]]~~
	~~[[Category: Dna-binding protein]]~~
	~~[[Category: Li-fraumeni syndrome]]~~
	~~[[Category: Nuclear protein]]~~
	~~[[Category: P53 dna-binding domain]]~~
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Polymorphism]]~~
	~~[[Category: Second-site suppressor mutation]]~~
	~~[[Category: Superstable mutant]]~~
	~~[[Category: Transcription regulation]]~~
	~~[[Category: Transferase]]~~
	~~[[Category: Tumor suppressor~~]]

OCA at 13:10, 24 November 2021

2021-11-24T13:10:43Z

OCA at 08:21, 19 February 2020

2020-02-19T08:21:54Z

← Older revision		Revision as of 08:21, 19 February 2020
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	==human p53 core domain mutant M133L-H168R-V203A-N239Y-N268D==		==human p53 core domain mutant M133L-H168R-V203A-N239Y-N268D==
	<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2bin' size='340' side='right'caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN FirstGlance]. <br>
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	==See Also==		==See Also==
	*[[P53\|P53]]		*[[P53 3D structures\|P53 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</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 06:55, 16 May 2018

2018-05-16T06:55:22Z

← Older revision		Revision as of 06:55, 16 May 2018
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	==~~HUMAN P53 CORE DOMAIN MUTANT~~ M133L-H168R-V203A-N239Y-N268D==
			==human p53 core domain mutant M133L-H168R-V203A-N239Y-N268D==
	<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
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	</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://pdbe.org/2bin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://pdbe.org/2bin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bin ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bi/2bin_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bi/2bin_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>
	</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=2bin ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Disease mutation]]		[[Category: Disease mutation]]
			[[Category: Dna binding protein]]
	[[Category: Dna-binding]]		[[Category: Dna-binding]]
	[[Category: Dna-binding protein]]		[[Category: Dna-binding protein]]
Line 50:		Line 52:
	[[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]]

OCA at 10:21, 11 September 2015

2015-09-11T10:21:16Z

← Older revision		Revision as of 10:21, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN 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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://pdbe.org/2bin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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 2bin" 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 10:45, 8 January 2015

2015-01-08T10:45:03Z

← Older revision		Revision as of 10:45, 8 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN 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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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 03:07, 30 September 2014

2014-09-30T03:07:12Z

← Older revision		Revision as of 03:07, 30 September 2014
Line 1:		Line 1:
	~~{{STRUCTURE_2bin\| PDB=2bin \| SCENE= }}~~		==HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-N268D==
	===HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-N268D===		<StructureSection load='2bin' size='340' side='right' caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	~~{{ABSTRACT_PUBMED_15703170}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BIN 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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [http://www.ebi.ac.uk/pdbsum/2bin 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/bi/2bin_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 ==
			We have solved the crystal structures of three oncogenic mutants of the core domain of the human tumor suppressor p53. The mutations were introduced into a stabilized variant. The cancer hot spot mutation R273H simply removes an arginine involved in DNA binding without causing structural distortions in neighboring residues. In contrast, the "structural" oncogenic mutations H168R and R249S induce substantial structural perturbation around the mutation site in the L2 and L3 loops, respectively. H168R is a specific intragenic suppressor mutation for R249S. When both cancer mutations are combined in the same molecule, Arg(168) mimics the role of Arg(249) in wild type, and the wild type conformation is largely restored in both loops. Our structural and biophysical data provide compelling evidence for the mechanism of rescue of mutant p53 by intragenic suppressor mutations and reveal features by which proteins can adapt to deleterious mutations.

	~~==Disease==~~		Structures of p53 cancer mutants and mechanism of rescue by second-site suppressor mutations.,Joerger AC, Ang HC, Veprintsev DB, Blair CM, Fersht AR J Biol Chem. 2005 Apr 22;280(16):16030-7. Epub 2005 Feb 9. PMID:15703170<ref>PMID:15703170</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==~~
	[[2bin]] is a 1 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=2BIN OCA].

	==See Also==		==See Also==
	*[[P53\|P53]]		*[[P53\|P53]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:015703170</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:008023157</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fersht, A R.]]		[[Category: Fersht, A R.]]

OCA at 07:22, 25 March 2013

2013-03-25T07:22:42Z

← Older revision		Revision as of 07:22, 25 March 2013
Line 1:		Line 1:
	~~[[Image:2bin.png\|left\|200px]]~~

	{{STRUCTURE_2bin\| PDB=2bin \| SCENE= }}		{{STRUCTURE_2bin\| PDB=2bin \| SCENE= }}
			===HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-N268D===
			{{ABSTRACT_PUBMED_15703170}}

	===~~HUMAN P53 CORE DOMAIN MUTANT M133L~~-~~H168R~~-~~V203A~~-~~N239Y~~-~~N268D===~~		==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>

	~~{{ABSTRACT_PUBMED_15703170}}~~		==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:015703170</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:008023157</ref><references group="xtra"/>		<ref group="xtra">PMID:015703170</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:008023157</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fersht, A R.]]		[[Category: Fersht, A R.]]

OCA at 18:08, 20 October 2012

2012-10-20T18:08:44Z

← Older revision		Revision as of 18:08, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[2bin]] is a 1 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=2BIN OCA].		[[2bin]] is a 1 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=2BIN OCA].

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

OCA at 03:09, 27 July 2012

2012-07-27T03:09:48Z

← Older revision		Revision as of 03:09, 27 July 2012
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	[[Image:2bin.png\|left\|200px]]		[[Image:2bin.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2bin", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_2bin\| PDB=2bin \| SCENE= }}		{{STRUCTURE_2bin\| PDB=2bin \| SCENE= }}

	===HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-N268D===		===HUMAN P53 CORE DOMAIN MUTANT M133L-H168R-V203A-N239Y-N268D===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_15703170}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 15703170 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_15703170}}		{{ABSTRACT_PUBMED_15703170}}

	==About this Structure==		==About this Structure==
	[[2bin]] is a 1 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=2BIN OCA].		[[2bin]] is a 1 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=2BIN OCA].

			==See Also==
			*[[P53\|P53]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~15703170~~</ref><ref group="xtra">PMID:~~14534297~~</ref><ref group="xtra">PMID:~~8023157~~</ref><references group="xtra"/>		<ref group="xtra">PMID:015703170</ref><ref group="xtra">PMID:014534297</ref><ref group="xtra">PMID:008023157</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fersht, A R.]]		[[Category: Fersht, A R.]]
	[[Category: Joerger, A C.]]		[[Category: Joerger, A C.]]
	~~[[Category: 3d-structure]]~~
	[[Category: Activator]]		[[Category: Activator]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]
Line 37:		Line 28:
	[[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]]

← Older revision		Revision as of 13:10, 24 November 2021
Line 3:		Line 3:
	<StructureSection load='2bin' size='340' side='right'caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2bin' size='340' side='right'caption='[[2bin]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2BIN FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bin]] is a 1 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=2BIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BIN 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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</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]], [[2bim\|2bim]], [[3sak\|3sak]], [[2bio\|2bio]], [[2bip\|2bip]], [[2biq\|2biq]]</div></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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [~~http~~://pdbe.org/2bin PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2bin PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2bin 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=2bin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bin OCA], [https://pdbe.org/2bin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bin RCSB], [https://www.ebi.ac.uk/pdbsum/2bin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bin 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]]