4ell - Revision history

OCA at 11:04, 1 March 2024

OCA — Fri, 01 Mar 2024 11:04:08 GMT

←Older revision		Revision as of 11:04, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELL FirstGlance]. <br>
-	</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [https://pdbe.org/4ell PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [https://www.ebi.ac.uk/pdbsum/4ell PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ell ProSAT]</span></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]] 1.98Å</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [https://pdbe.org/4ell PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [https://www.ebi.ac.uk/pdbsum/4ell PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ell ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[https://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500]].	+	[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[https://omim.org/entry/180200 180200]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500].
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>	+	[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins. We present the first structures of phosphorylated Rb that reveal the mechanism of its inactivation. S608 phosphorylation orders a flexible "pocket" domain loop such that it mimics and directly blocks E2F transactivation domain (E2F(TD)) binding. T373 phosphorylation induces a global conformational change that associates the pocket and N-terminal domains (RbN). This first multidomain Rb structure demonstrates a novel role for RbN in allosterically inhibiting the E2F(TD)-pocket association and protein binding to the pocket "LxCxE" site. Together, these structures detail the regulatory mechanism for a canonical growth-repressive complex and provide a novel example of how multisite Cdk phosphorylation induces diverse structural changes to influence cell cycle signaling.	+
-		+
-	~~Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control.,Burke JR, Hura GL, Rubin SM Genes Dev. 2012 May 8. PMID:22569856<ref>PMID:22569856</ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4ell" style="background-color:#fffaf0;"></div~~>	+

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

OCA at 07:17, 28 September 2022

OCA — Wed, 28 Sep 2022 07:17:06 GMT

←Older revision		Revision as of 07:17, 28 September 2022
Line 1:		Line 1:

	==Structure of the inactive retinoblastoma protein pocket domain==		==Structure of the inactive retinoblastoma protein pocket domain==
-	<StructureSection load='4ell' size='340' side='right' caption='[[4ell]], [[Resolution\|resolution]] 1.98Å' scene=''>	+	<StructureSection load='4ell' size='340' side='right'caption='[[4ell]], [[Resolution\|resolution]] 1.98Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ELL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELL FirstGlance]. <br>
-	</td></tr>~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4elj\|4elj]]</td></tr>~~	+	</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [https://pdbe.org/4ell PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [https://www.ebi.ac.uk/pdbsum/4ell PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ell ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [~~http~~://pdbe.org/4ell PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ell PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ell ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[~~http~~://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[~~http~~://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[~~http~~://omim.org/entry/259500 259500]].	+	[[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[https://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500]].
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>	+	[[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4ell" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ell" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Retinoblastoma protein\|Retinoblastoma protein]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Burke, J R~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Rubin, S M~~]]	+	[[Category: Burke JR]]
-	[[Category: ~~Cell cycle]]~~	+	[[Category: Rubin SM]]
-	~~[[Category: Cyclin fold]]~~	+
-	~~[[Category: Tumor suppressor~~]]	+

OCA at 03:05, 5 August 2016

OCA — Fri, 05 Aug 2016 03:05:42 GMT

←Older revision		Revision as of 03:05, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of the inactive retinoblastoma protein pocket domain==		==Structure of the inactive retinoblastoma protein pocket domain==
	<StructureSection load='4ell' size='340' side='right' caption='[[4ell]], [[Resolution\|resolution]] 1.98Å' scene=''>		<StructureSection load='4ell' size='340' side='right' caption='[[4ell]], [[Resolution\|resolution]] 1.98Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELL FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4elj\|4elj]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4elj\|4elj]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [http://www.ebi.ac.uk/pdbsum/4ell 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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [http://pdbe.org/4ell PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [http://www.ebi.ac.uk/pdbsum/4ell PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ell ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4ell" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Burke, J R]]		[[Category: Burke, J R]]
	[[Category: Rubin, S M]]		[[Category: Rubin, S M]]

OCA at 11:14, 21 December 2014

OCA — Sun, 21 Dec 2014 11:14:02 GMT

←Older revision		Revision as of 11:14, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ell~~\| ~~PDB~~=4ell \| ~~SCENE~~= }}	+	==Structure of the inactive retinoblastoma protein pocket domain==
-	===~~Structure~~ of the ~~inactive retinoblastoma~~ protein ~~pocket domain~~===	+	<StructureSection load='4ell' size='340' side='right' caption='[[4ell]], [[Resolution\|resolution]] 1.98Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22569856}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ell]] 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=4ELL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELL FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4elj\|4elj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4ell FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ell OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ell RCSB], [http://www.ebi.ac.uk/pdbsum/4ell PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[http://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[http://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[http://omim.org/entry/259500 259500]].
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins. We present the first structures of phosphorylated Rb that reveal the mechanism of its inactivation. S608 phosphorylation orders a flexible "pocket" domain loop such that it mimics and directly blocks E2F transactivation domain (E2F(TD)) binding. T373 phosphorylation induces a global conformational change that associates the pocket and N-terminal domains (RbN). This first multidomain Rb structure demonstrates a novel role for RbN in allosterically inhibiting the E2F(TD)-pocket association and protein binding to the pocket "LxCxE" site. Together, these structures detail the regulatory mechanism for a canonical growth-repressive complex and provide a novel example of how multisite Cdk phosphorylation induces diverse structural changes to influence cell cycle signaling.

-	~~==Disease==~~	+	Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control.,Burke JR, Hura GL, Rubin SM Genes Dev. 2012 May 8. PMID:22569856<ref>PMID:22569856</ref>
-	~~[[http://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause~~ of ~~childhood cancer~~ retinoblastoma (RB) [MIM:[http://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. ~~Although most RB appear sporadically~~, ~~about 20% are transmitted as an autosomal dominant trait with incomplete penetrance~~. ~~The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated~~.~~<ref>~~PMID:~~2594029</ref>~~<ref>PMID:~~1352883~~</ref><ref>PMID:8346255</ref><ref>PMID:7704558</ref><ref>PMID:7927327</ref><ref>PMID:8605116</ref><ref>PMID:7795591</ref><ref>PMID:8776589</ref><ref>PMID:9311732</ref><ref>PMID:9140452</ref><ref>PMID:10671068</ref><ref>PMID:9973307</ref><ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[http://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[http://omim.org/entry/259500 259500]].	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~//www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a ~~histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription~~ of the ~~c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex~~. ~~Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity)~~. ~~In case~~ of ~~viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity~~.<~~ref~~>~~PMID:15084261~~</~~ref~~>	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[4ell]] 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=4ELL OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:022569856</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Burke, J R.]]	+	[[Category: Burke, J R]]
-	[[Category: Rubin, S M.]]	+	[[Category: Rubin, S M]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Cyclin fold]]		[[Category: Cyclin fold]]
	[[Category: Tumor suppressor]]		[[Category: Tumor suppressor]]

OCA at 09:35, 24 March 2013

OCA — Sun, 24 Mar 2013 09:35:20 GMT

←Older revision		Revision as of 09:35, 24 March 2013
Line 1:		Line 1:
-	[[Image:4ell.png\|left\|200px]]
-
	{{STRUCTURE_4ell\| PDB=4ell \| SCENE= }}		{{STRUCTURE_4ell\| PDB=4ell \| SCENE= }}
-
	===Structure of the inactive retinoblastoma protein pocket domain===		===Structure of the inactive retinoblastoma protein pocket domain===
		+	{{ABSTRACT_PUBMED_22569856}}

-	~~{{ABSTRACT_PUBMED_22569856}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[http://omim.org/entry/180200 180200]]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref><ref>PMID:1352883</ref><ref>PMID:8346255</ref><ref>PMID:7704558</ref><ref>PMID:7927327</ref><ref>PMID:8605116</ref><ref>PMID:7795591</ref><ref>PMID:8776589</ref><ref>PMID:9311732</ref><ref>PMID:9140452</ref><ref>PMID:10671068</ref><ref>PMID:9973307</ref><ref>PMID:11524739</ref> Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[http://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[http://omim.org/entry/259500 259500]].
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN]] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022569856</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022569856</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Burke, J R.]]		[[Category: Burke, J R.]]

OCA at 04:58, 15 August 2012

OCA — Wed, 15 Aug 2012 04:58:49 GMT

←Older revision		Revision as of 04:58, 15 August 2012
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-	[[Image:4ell.~~jpg~~\|left\|200px]]	+	[[Image:4ell.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4ell", 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_4ell\| PDB=4ell \| SCENE= }}		{{STRUCTURE_4ell\| PDB=4ell \| SCENE= }}

	===Structure of the inactive retinoblastoma protein pocket domain===		===Structure of the inactive retinoblastoma protein pocket domain===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22569856}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22569856 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22569856}}		{{ABSTRACT_PUBMED_22569856}}

OCA at 06:05, 23 May 2012

OCA — Wed, 23 May 2012 06:05:53 GMT

←Older revision		Revision as of 06:05, 23 May 2012
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-	~~'''Unreleased structure'''~~	+	[[Image:4ell.jpg\|left\|200px]]

-	The ~~entry 4ell~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4ell", 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_4ell\| PDB=4ell \| SCENE= }}

-	~~Authors: Burke, J.R., Rubin, S.M.~~	+	===Structure of the inactive retinoblastoma protein pocket domain===

-	~~Description~~: ~~Structure of~~ the ~~inactive retinoblastoma protein pocket domain~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22569856}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22569856 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22569856}}
		+
		+	==About this Structure==
		+	[[4ell]] 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=4ELL OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022569856</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Burke, J R.]]
		+	[[Category: Rubin, S M.]]
		+	[[Category: Cell cycle]]
		+	[[Category: Cyclin fold]]
		+	[[Category: Tumor suppressor]]

OCA at 08:48, 16 May 2012

OCA — Wed, 16 May 2012 08:48:26 GMT

←Older revision		Revision as of 08:48, 16 May 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ell is ON HOLD until ~~sometime in the future~~	+	The entry 4ell is ON HOLD until Paper Publication

-	Authors: ~~BURKE~~, J.R., ~~RUBIN~~, S.M.	+	Authors: Burke, J.R., Rubin, S.M.

-	Description: ~~STRUCTURE OF THE INACTIVE RETINOBLASTOMA PROTEIN POCKET DOMAIN~~	+	Description: Structure of the inactive retinoblastoma protein pocket domain

OCA at 08:47, 9 May 2012

OCA — Wed, 09 May 2012 08:47:44 GMT

←Older revision		Revision as of 08:47, 9 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ell is ON HOLD	+	The entry 4ell is ON HOLD until sometime in the future

	Authors: BURKE, J.R., RUBIN, S.M.		Authors: BURKE, J.R., RUBIN, S.M.

	Description: STRUCTURE OF THE INACTIVE RETINOBLASTOMA PROTEIN POCKET DOMAIN		Description: STRUCTURE OF THE INACTIVE RETINOBLASTOMA PROTEIN POCKET DOMAIN

OCA: Protected "4ell" [edit=sysop:move=sysop]

OCA — Wed, 18 Apr 2012 07:34:48 GMT

Protected "4ell" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 18 April 2012