4u4a - Revision history

OCA at 08:01, 22 March 2023

OCA — Wed, 22 Mar 2023 08:01:12 GMT

←Older revision		Revision as of 08:01, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='4u4a' size='340' side='right'caption='[[4u4a]], [[Resolution\|resolution]] 3.51Å' scene=''>		<StructureSection load='4u4a' size='340' side='right'caption='[[4u4a]], [[Resolution\|resolution]] 3.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4u4a]] is a 6 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=4U4A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4U4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4u4a]] is a 6 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=4U4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U4A FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlu\|4jlu]]</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=4u4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u4a OCA], [https://pdbe.org/4u4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u4a RCSB], [https://www.ebi.ac.uk/pdbsum/4u4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u4a ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRCA1, RNF53 ([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=4u4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u4a OCA], [~~http~~://pdbe.org/4u4a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4u4a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4u4a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4u4a ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] Defects in BRCA1 are a cause of susceptibility to breast cancer (BC) [MIM:[~~http~~://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.<ref>PMID:11301010</ref> <ref>PMID:15133502</ref> <ref>PMID:7545954</ref> <ref>PMID:12427738</ref> <ref>PMID:18285836</ref> <ref>PMID:7939630</ref> <ref>PMID:7894491</ref> <ref>PMID:7894493</ref> <ref>PMID:8554067</ref> <ref>PMID:8776600</ref> <ref>PMID:8723683</ref> <ref>PMID:9760198</ref> <ref>PMID:9482581</ref> <ref>PMID:9609997</ref> <ref>PMID:10323242</ref> <ref>PMID:12442275</ref> <ref>PMID:12938098</ref> <ref>PMID:14722926</ref> Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:[~~http~~://omim.org/entry/604370 604370]]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. Defects in BRCA1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[~~http~~://omim.org/entry/167000 167000]]. The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in BRCA1 are a cause of susceptibility to pancreatic cancer type 4 (PNCA4) [MIM:[~~http~~://omim.org/entry/614320 614320]]. A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.	+	[https://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN] Defects in BRCA1 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.<ref>PMID:11301010</ref> <ref>PMID:15133502</ref> <ref>PMID:7545954</ref> <ref>PMID:12427738</ref> <ref>PMID:18285836</ref> <ref>PMID:7939630</ref> <ref>PMID:7894491</ref> <ref>PMID:7894493</ref> <ref>PMID:8554067</ref> <ref>PMID:8776600</ref> <ref>PMID:8723683</ref> <ref>PMID:9760198</ref> <ref>PMID:9482581</ref> <ref>PMID:9609997</ref> <ref>PMID:10323242</ref> <ref>PMID:12442275</ref> <ref>PMID:12938098</ref> <ref>PMID:14722926</ref> Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:[https://omim.org/entry/604370 604370]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. Defects in BRCA1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in BRCA1 are a cause of susceptibility to pancreatic cancer type 4 (PNCA4) [MIM:[https://omim.org/entry/614320 614320]. A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> [[http://www.uniprot.org/uniprot/F175A_HUMAN F175A_HUMAN]] Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as a central scaffold protein that assembles the various components of the BRCA1-A complex and mediates the recruitment of BRCA1.<ref>PMID:17525340</ref> <ref>PMID:17643121</ref> <ref>PMID:17643122</ref> <ref>PMID:18077395</ref> <ref>PMID:19261748</ref>	+	[https://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref>

	==See Also==		==See Also==
Line 20:		Line 18:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Badgujar, D]]	+	[[Category: Badgujar D]]
-	[[Category: Hosur~~, M V~~]]	+	[[Category: Hosur MV]]
-	[[Category: Varma~~, A K]]~~	+	[[Category: Varma AK]]
-	~~[[Category: Antitumor protein-signaling protein complex]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Phosphospecific~~]]	+

OCA at 14:18, 10 May 2019

OCA — Fri, 10 May 2019 14:18:07 GMT

←Older revision		Revision as of 14:18, 10 May 2019
Line 1:		Line 1:
		+
	==Complex Structure of BRCA1 BRCT with singly phospho Abraxas==		==Complex Structure of BRCA1 BRCT with singly phospho Abraxas==
-	<StructureSection load='4u4a' size='340' side='right' caption='[[4u4a]], [[Resolution\|resolution]] 3.51Å' scene=''>	+	<StructureSection load='4u4a' size='340' side='right'caption='[[4u4a]], [[Resolution\|resolution]] 3.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4u4a]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4u4a]] is a 6 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=4U4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U4A FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlu\|4jlu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlu\|4jlu]]</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=4u4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u4a RCSB], [http://www.ebi.ac.uk/pdbsum/4u4a PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRCA1, RNF53 ([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=4u4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u4a OCA], [http://pdbe.org/4u4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u4a RCSB], [http://www.ebi.ac.uk/pdbsum/4u4a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u4a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 11:		Line 13:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> [[http://www.uniprot.org/uniprot/F175A_HUMAN F175A_HUMAN]] Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as a central scaffold protein that assembles the various components of the BRCA1-A complex and mediates the recruitment of BRCA1.<ref>PMID:17525340</ref> <ref>PMID:17643121</ref> <ref>PMID:17643122</ref> <ref>PMID:18077395</ref> <ref>PMID:19261748</ref>		[[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> [[http://www.uniprot.org/uniprot/F175A_HUMAN F175A_HUMAN]] Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as a central scaffold protein that assembles the various components of the BRCA1-A complex and mediates the recruitment of BRCA1.<ref>PMID:17525340</ref> <ref>PMID:17643121</ref> <ref>PMID:17643122</ref> <ref>PMID:18077395</ref> <ref>PMID:19261748</ref>
		+
		+	==See Also==
		+	*[[BRCA 3D structures\|BRCA 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Badgujar, D]]		[[Category: Badgujar, D]]
	[[Category: Hosur, M V]]		[[Category: Hosur, M V]]

OCA at 13:33, 26 August 2015

OCA — Wed, 26 Aug 2015 13:33:25 GMT

←Older revision		Revision as of 13:33, 26 August 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Complex Structure of BRCA1 BRCT with singly phospho Abraxas==
-		+	<StructureSection load='4u4a' size='340' side='right' caption='[[4u4a]], [[Resolution\|resolution]] 3.51Å' scene=''>
-	~~The entry~~ 4u4a is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4u4a]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U4A FirstGlance]. <br>
-	~~Authors~~: ~~Badgujar, D~~., ~~Hosur~~, M.V., ~~Varma, A~~.K.	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jlu\|4jlu]]</td></tr>
-	~~Description~~: ~~Complex Structure~~ of BRCA1 ~~BRCT~~ with ~~singly phospho Abraxas~~	+	<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=4u4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u4a RCSB], [http://www.ebi.ac.uk/pdbsum/4u4a PDBsum]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Varma~~, A.K]]	+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] Defects in BRCA1 are a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.<ref>PMID:11301010</ref> <ref>PMID:15133502</ref> <ref>PMID:7545954</ref> <ref>PMID:12427738</ref> <ref>PMID:18285836</ref> <ref>PMID:7939630</ref> <ref>PMID:7894491</ref> <ref>PMID:7894493</ref> <ref>PMID:8554067</ref> <ref>PMID:8776600</ref> <ref>PMID:8723683</ref> <ref>PMID:9760198</ref> <ref>PMID:9482581</ref> <ref>PMID:9609997</ref> <ref>PMID:10323242</ref> <ref>PMID:12442275</ref> <ref>PMID:12938098</ref> <ref>PMID:14722926</ref> Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:[http://omim.org/entry/604370 604370]]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. Defects in BRCA1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in BRCA1 are a cause of susceptibility to pancreatic cancer type 4 (PNCA4) [MIM:[http://omim.org/entry/614320 614320]]. A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> [[http://www.uniprot.org/uniprot/F175A_HUMAN F175A_HUMAN]] Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as a central scaffold protein that assembles the various components of the BRCA1-A complex and mediates the recruitment of BRCA1.<ref>PMID:17525340</ref> <ref>PMID:17643121</ref> <ref>PMID:17643122</ref> <ref>PMID:18077395</ref> <ref>PMID:19261748</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Badgujar, D]]		[[Category: Badgujar, D]]
-	[[Category: Hosur, M.V]]	+	[[Category: Hosur, M V]]
		+	[[Category: Varma, A K]]
		+	[[Category: Antitumor protein-signaling protein complex]]
		+	[[Category: Complex]]
		+	[[Category: Phosphospecific]]

OCA at 18:07, 24 December 2014

OCA — Wed, 24 Dec 2014 18:07:55 GMT

←Older revision		Revision as of 18:07, 24 December 2014
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	Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas		Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas
		+	[[Category: Unreleased Structures]]
		+	[[Category: Varma, A.K]]
		+	[[Category: Badgujar, D]]
		+	[[Category: Hosur, M.V]]

OCA at 08:46, 24 September 2014

OCA — Wed, 24 Sep 2014 08:46:33 GMT

←Older revision		Revision as of 08:46, 24 September 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4u4a is ON HOLD	+	The entry 4u4a is ON HOLD until Paper Publication

	Authors: Badgujar, D., Hosur, M.V., Varma, A.K.		Authors: Badgujar, D., Hosur, M.V., Varma, A.K.

	Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas		Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas

OCA: Protected "4u4a" [edit=sysop:move=sysop]

OCA — Wed, 30 Jul 2014 07:16:03 GMT

Protected "4u4a" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:16, 30 July 2014

OCA: New page: '''Unreleased structure''' The entry 4u4a is ON HOLD Authors: Badgujar, D., Hosur, M.V., Varma, A.K. Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas

OCA — Wed, 30 Jul 2014 07:16:03 GMT

New page: '''Unreleased structure''' The entry 4u4a is ON HOLD Authors: Badgujar, D., Hosur, M.V., Varma, A.K. Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas

New page

'''Unreleased structure'''

The entry 4u4a is ON HOLD

Authors: Badgujar, D., Hosur, M.V., Varma, A.K.

Description: Complex Structure of BRCA1 BRCT with singly phospho Abraxas