3ztc - Revision history

OCA at 18:07, 5 August 2016

OCA — Fri, 05 Aug 2016 18:07:01 GMT

←Older revision		Revision as of 18:07, 5 August 2016
Line 1:		Line 1:
		+
	==pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide==		==pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide==
	<StructureSection load='3ztc' size='340' side='right' caption='[[3ztc]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='3ztc' size='340' side='right' caption='[[3ztc]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ztc]] is a 12 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=3ZTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZTC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ztc]] is a 12 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=3ZTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZTC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TR0:(4R)-N-(BIPHENYL-4-YLMETHYL)-4-HYDROXY-1-[(3-METHYLISOXAZOL-5-YL)ACETYL]-L-PROLINAMIDE'>TR0</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TR0:(4R)-N-(BIPHENYL-4-YLMETHYL)-4-HYDROXY-1-[(3-METHYLISOXAZOL-5-YL)ACETYL]-L-PROLINAMIDE'>TR0</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2c9w\|2c9w]], [[1lqb\|1lqb]], [[3zrf\|3zrf]], [[1vcb\|1vcb]], [[1lm8\|1lm8]], [[2izv\|2izv]], [[2xai\|2xai]], [[3zrc\|3zrc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2c9w\|2c9w]], [[1lqb\|1lqb]], [[3zrf\|3zrf]], [[1vcb\|1vcb]], [[1lm8\|1lm8]], [[2izv\|2izv]], [[2xai\|2xai]], [[3zrc\|3zrc]]</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=3ztc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ztc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ztc RCSB], [http://www.ebi.ac.uk/pdbsum/3ztc 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=3ztc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ztc OCA], [http://pdbe.org/3ztc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ztc RCSB], [http://www.ebi.ac.uk/pdbsum/3ztc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ztc 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 3ztc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
		+	*[[Elongation factor\|Elongation factor]]
	*[[Transcription factor SIII\|Transcription factor SIII]]		*[[Transcription factor SIII\|Transcription factor SIII]]
	== References ==		== References ==
Line 26:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Buckley, D L]]		[[Category: Buckley, D L]]
	[[Category: Ciulli, A]]		[[Category: Ciulli, A]]

OCA at 10:05, 21 December 2014

OCA — Sun, 21 Dec 2014 10:05:53 GMT

←Older revision		Revision as of 10:05, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}~~	+	==pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide==
-	===pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide===	+	<StructureSection load='3ztc' size='340' side='right' caption='[[3ztc]], [[Resolution\|resolution]] 2.65Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23102223}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ztc]] is a 12 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=3ZTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZTC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TR0:(4R)-N-(BIPHENYL-4-YLMETHYL)-4-HYDROXY-1-[(3-METHYLISOXAZOL-5-YL)ACETYL]-L-PROLINAMIDE'>TR0</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2c9w\|2c9w]], [[1lqb\|1lqb]], [[3zrf\|3zrf]], [[1vcb\|1vcb]], [[1lm8\|1lm8]], [[2izv\|2izv]], [[2xai\|2xai]], [[3zrc\|3zrc]]</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=3ztc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ztc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ztc RCSB], [http://www.ebi.ac.uk/pdbsum/3ztc PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref> <ref>PMID:8493574</ref> <ref>PMID:7987306</ref> <ref>PMID:7728151</ref> <ref>PMID:8634692</ref> <ref>PMID:8592333</ref> <ref>PMID:8825918</ref> <ref>PMID:8730290</ref> <ref>PMID:8956040</ref> <ref>PMID:9452032</ref> <ref>PMID:9452106</ref> <ref>PMID:10627136</ref> <ref>PMID:9829911</ref> <ref>PMID:9829912</ref> [:]<ref>PMID:10533030</ref> <ref>PMID:10408776</ref> <ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref> <ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> [[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.<ref>PMID:9751722</ref> <ref>PMID:10944113</ref> <ref>PMID:19584355</ref> [[http://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1alpha interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed.

-	~~==Disease==~~	+	Dissecting fragment-based lead discovery at the von hippel-lindau protein:hypoxia inducible factor 1alpha protein-protein interface.,Van Molle I, Thomann A, Buckley DL, So EC, Lang S, Crews CM, Ciulli A Chem Biol. 2012 Oct 26;19(10):1300-12. doi: 10.1016/j.chembiol.2012.08.015. PMID:23102223<ref>PMID:23102223</ref>
-	~~[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine~~-~~producing tumor of chromaffin tissue of~~ the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von ~~Hippel~~-~~Lindau disease (VHLD) [MIM~~:~~[http://omim~~.~~org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis~~, ~~cerebellar and spinal hemangioblastoma~~, ~~renal cell carcinoma (RCC)~~, ~~phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma~~, ~~type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma~~, ~~retinal angioma~~, ~~and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma~~, ~~retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst)~~. VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref><ref>PMID:8493574</ref><ref>PMID:7987306</ref><ref>PMID:7728151</ref><ref>PMID:8634692</ref><ref>PMID:8592333</ref><ref>PMID:8825918</ref><ref>PMID:8730290</ref><ref>PMID:8956040</ref><ref>PMID:9452032</ref><ref>PMID:9452106</ref><ref>PMID:10627136</ref><ref>PMID:9829911</ref><ref>PMID:9829912</ref>[:]<ref>PMID:10533030</ref><ref>PMID:10408776</ref><ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (~~ECYT2~~) ~~[MIM~~:~~[http~~:~~//omim~~.~~org~~/~~entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia~~. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. ~~Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events~~.~~<ref>~~PMID:12844285</ref><ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:~~11986208~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http://www.uniprot.org/uniprot~~/~~ELOB_HUMAN ELOB_HUMAN]] SIII~~, ~~also known as elongin, is~~ a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the ~~SIII regulatory subunits B and C (elongin BC complex)~~.<ref>PMID:7638163</ref><ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). ~~By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members~~ of ~~the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes~~.<~~ref~~>~~PMID:7638163~~</~~ref~~><ref>PMID:15590694</ref> [[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.<ref>PMID:9751722</ref><ref>PMID:10944113</ref><ref>PMID:19584355</ref> [[http://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[3ztc]] is a 12 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=3ZTC OCA].	+

	==See Also==		==See Also==
-	*[[~~Elongation~~ factor\|~~Elongation~~ factor]]	+	*[[Transcription factor SIII\|Transcription factor SIII]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Buckley, D L.]]	+	[[Category: Buckley, D L]]
-	[[Category: Ciulli, A.]]	+	[[Category: Ciulli, A]]
-	[[Category: Crews, C M.]]	+	[[Category: Crews, C M]]
-	[[Category: Vanmolle, I.]]	+	[[Category: Vanmolle, I]]
	[[Category: Chronic aneamia treatment]]		[[Category: Chronic aneamia treatment]]
	[[Category: E3 ubiquitin ligase]]		[[Category: E3 ubiquitin ligase]]
	[[Category: Transcription]]		[[Category: Transcription]]
	[[Category: Tumour supressor protein]]		[[Category: Tumour supressor protein]]

OCA at 03:02, 25 March 2013

OCA — Mon, 25 Mar 2013 03:02:12 GMT

←Older revision		Revision as of 03:02, 25 March 2013
Line 1:		Line 1:
-	[[Image:3ztc.png\|left\|200px]]
-
	{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}		{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}
-
	===pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide===		===pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide===
		+	{{ABSTRACT_PUBMED_23102223}}

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref><ref>PMID:8493574</ref><ref>PMID:7987306</ref><ref>PMID:7728151</ref><ref>PMID:8634692</ref><ref>PMID:8592333</ref><ref>PMID:8825918</ref><ref>PMID:8730290</ref><ref>PMID:8956040</ref><ref>PMID:9452032</ref><ref>PMID:9452106</ref><ref>PMID:10627136</ref><ref>PMID:9829911</ref><ref>PMID:9829912</ref>[:]<ref>PMID:10533030</ref><ref>PMID:10408776</ref><ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref><ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref><ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref><ref>PMID:15590694</ref> [[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.<ref>PMID:9751722</ref><ref>PMID:10944113</ref><ref>PMID:19584355</ref> [[http://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 14:
	==See Also==		==See Also==
	*[[Elongation factor\|Elongation factor]]		*[[Elongation factor\|Elongation factor]]
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Buckley, D L.]]		[[Category: Buckley, D L.]]

OCA at 06:44, 14 November 2012

OCA — Wed, 14 Nov 2012 06:44:58 GMT

←Older revision		Revision as of 06:44, 14 November 2012
Line 12:		Line 12:
	*[[Elongation factor\|Elongation factor]]		*[[Elongation factor\|Elongation factor]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Buckley, D.]]	+	[[Category: Buckley, D L.]]
	[[Category: Ciulli, A.]]		[[Category: Ciulli, A.]]
	[[Category: Crews, C M.]]		[[Category: Crews, C M.]]

OCA at 12:46, 20 October 2012

OCA — Sat, 20 Oct 2012 12:46:04 GMT

←Older revision		Revision as of 12:46, 20 October 2012
Line 1:		Line 1:
-	[[Image:3ztc.~~jpg~~\|left\|200px]]	+	[[Image:3ztc.png\|left\|200px]]

	{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}		{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}
Line 8:		Line 8:
	==About this Structure==		==About this Structure==
	[[3ztc]] is a 12 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=3ZTC OCA].		[[3ztc]] is a 12 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=3ZTC OCA].
		+
		+	==See Also==
		+	*[[Elongation factor\|Elongation factor]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Buckley, D.]]		[[Category: Buckley, D.]]

OCA at 07:17, 25 July 2012

OCA — Wed, 25 Jul 2012 07:17:10 GMT

←Older revision		Revision as of 07:17, 25 July 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3ztc.jpg\|left\|200px]]

-	~~The entry~~ 3ztc ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3ztc\| PDB=3ztc \| SCENE= }}

-	~~Authors: VanMolle~~, I., ~~Buckley, D., Crews, C.M., Ciulli, A.~~	+	===pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide===

-	~~Description~~:	+
		+	==About this Structure==
		+	[[3ztc]] is a 12 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=3ZTC OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Buckley, D.]]
		+	[[Category: Ciulli, A.]]
		+	[[Category: Crews, C M.]]
		+	[[Category: Vanmolle, I.]]
		+	[[Category: Chronic aneamia treatment]]
		+	[[Category: E3 ubiquitin ligase]]
		+	[[Category: Transcription]]
		+	[[Category: Tumour supressor protein]]

OCA at 06:16, 15 February 2012

OCA — Wed, 15 Feb 2012 06:16:22 GMT

←Older revision		Revision as of 06:16, 15 February 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ztc is ON HOLD	+	The entry 3ztc is ON HOLD until Paper Publication

	Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.		Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.

	Description:		Description:

OCA at 06:07, 8 February 2012

OCA — Wed, 08 Feb 2012 06:07:00 GMT

←Older revision		Revision as of 06:07, 8 February 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ztc is ON HOLD ~~until Paper Publication~~	+	The entry 3ztc is ON HOLD

	Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.		Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.

	Description:		Description:

OCA at 06:29, 31 August 2011

OCA — Wed, 31 Aug 2011 06:29:01 GMT

←Older revision		Revision as of 06:29, 31 August 2011
Line 5:		Line 5:
	Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.		Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.

-	Description: ~~pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)-4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2-carboxamide~~	+	Description:

OCA at 05:40, 10 August 2011

OCA — Wed, 10 Aug 2011 05:40:31 GMT

←Older revision		Revision as of 05:40, 10 August 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ztc is ON HOLD	+	The entry 3ztc is ON HOLD until Paper Publication

	Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.		Authors: VanMolle, I., Buckley, D., Crews, C.M., Ciulli, A.

	Description: pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)-4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2-carboxamide		Description: pVHL54-213-EloB-EloC complex _ (2S,4R)-N-((1,1'-biphenyl)-4-ylmethyl)-4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2-carboxamide