4p7u - Revision history

OCA at 07:12, 27 September 2023

2023-09-27T07:12:56Z

←Older revision		Revision as of 07:12, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P7U FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P7U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.502Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [https://pdbe.org/4p7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [https://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [https://pdbe.org/4p7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [https://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>
	</table>		</table>

OCA at 03:45, 2 October 2022

2022-10-02T03:45:19Z

←Older revision		Revision as of 03:45, 2 October 2022
Line 3:		Line 3:
	<StructureSection load='4p7u' size='340' side='right'caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='4p7u' size='340' side='right'caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4P7U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P7U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [https://pdbe.org/4p7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [https://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [~~http~~://pdbe.org/4p7u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN]] Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:[~~http~~://omim.org/entry/614331 614331]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases.<ref>PMID:9590282</ref> Defects in TGFBR2 are a cause of esophageal cancer (ESCR) [MIM:[~~http~~://omim.org/entry/133239 133239]]. Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:[~~http~~://omim.org/entry/610168 610168]]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16251899</ref> <ref>PMID:20101701</ref> <ref>PMID:20358619</ref> <ref>PMID:22113417</ref> <ref>PMID:21949523</ref> Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:[~~http~~://omim.org/entry/610380 610380]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2B by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2B by the OMIM resource.	+	[https://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN] Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:[https://omim.org/entry/614331 614331]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases.<ref>PMID:9590282</ref> Defects in TGFBR2 are a cause of esophageal cancer (ESCR) [MIM:[https://omim.org/entry/133239 133239]. Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:[https://omim.org/entry/610168 610168]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16251899</ref> <ref>PMID:20101701</ref> <ref>PMID:20358619</ref> <ref>PMID:22113417</ref> <ref>PMID:21949523</ref> Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:[https://omim.org/entry/610380 610380]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2B by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2B by the OMIM resource.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.<ref>PMID:7774578</ref>	+	[https://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN] Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.<ref>PMID:7774578</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[TGF-beta receptor\|TGF-beta receptor]]	+	*[[TGF-beta receptor 3D structures\|TGF-beta receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein serine/threonine kinase]]~~	+	[[Category: Forest KT]]
-	[[Category: Forest~~, K T~~]]	+	[[Category: Wangkanont K]]
-	[[Category: Wangkanont, K]]	+
-	~~[[Category: Ndsb-201]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Type ii transforming growth factor beta receptor~~]]	+

OCA at 10:10, 25 December 2019

2019-12-25T10:10:03Z

←Older revision		Revision as of 10:10, 25 December 2019
Line 3:		Line 3:
	<StructureSection load='4p7u' size='340' side='right'caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='4p7u' size='340' side='right'caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P7U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P7U FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://pdbe.org/4p7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://pdbe.org/4p7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>
Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]

OCA at 07:24, 10 July 2019

2019-07-10T07:24:58Z

←Older revision		Revision as of 07:24, 10 July 2019
Line 1:		Line 1:

	==Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201==		==Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201==
-	<StructureSection load='4p7u' size='340' side='right' caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='4p7u' size='340' side='right'caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P7U FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P7U FirstGlance]. <br>
Line 29:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
	[[Category: Forest, K T]]		[[Category: Forest, K T]]

OCA at 05:46, 6 October 2017

2017-10-06T05:46:25Z

←Older revision		Revision as of 05:46, 6 October 2017
Line 1:		Line 1:
		+
	==Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201==		==Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201==
	<StructureSection load='4p7u' size='340' side='right' caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='4p7u' size='340' side='right' caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://pdbe.org/4p7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u 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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://pdbe.org/4p7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 08:01, 30 September 2015

2015-09-30T08:01:53Z

←Older revision		Revision as of 08:01, 30 September 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u 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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://pdbe.org/4p7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		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 4p7u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[TGF-beta receptor\|TGF-beta receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:53, 24 June 2015

2015-06-24T12:53:11Z

←Older revision		Revision as of 12:53, 24 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201==
		+	<StructureSection load='4p7u' size='340' side='right' caption='[[4p7u]], [[Resolution\|resolution]] 1.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4p7u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P7U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1m9z\|1m9z]], [[1plo\|1plo]], [[4xjj\|4xjj]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=4p7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p7u RCSB], [http://www.ebi.ac.uk/pdbsum/4p7u PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN]] Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:[http://omim.org/entry/614331 614331]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases.<ref>PMID:9590282</ref> Defects in TGFBR2 are a cause of esophageal cancer (ESCR) [MIM:[http://omim.org/entry/133239 133239]]. Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:[http://omim.org/entry/610168 610168]]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16251899</ref> <ref>PMID:20101701</ref> <ref>PMID:20358619</ref> <ref>PMID:22113417</ref> <ref>PMID:21949523</ref> Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:[http://omim.org/entry/610380 610380]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2B by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2B by the OMIM resource.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TGFR2_HUMAN TGFR2_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.<ref>PMID:7774578</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The roles of the extracellular domain of type II TGF-beta receptor (TBRII-ECD) in physiological processes ranging from development to cancer to wound healing render it an attractive target for exploration with chemical tools. For such applications, large amounts of active soluble protein are needed, but the yields of TBRII-ECD we obtained with current folding protocols were variable. To expedite the identification of alternative folding conditions, we developed an on-plate screen. This assay indicated that effective folding additives included the non-detergent sulfobetaine-201 (NDSB-201). Although NDSB-201 can facilitate protein folding, the mode by which it does so is poorly understood. We postulated that specific interactions between NDSB-201 and TBRII-ECD might be responsible. Analysis by X-ray crystallography indicates that the TBRII-ECD possesses a binding pocket for NDSB-201. The pyridinium group of the additive stacks with a phenylalanine side chain in the binding site. The ability of NDSB-201 to occupy a pocket on the protein provides a molecular mechanism for the additive's ability to minimize TBRII-ECD aggregation and stabilize the folded state. NDSB-201 also accelerates TBRII-ECD crystallization, suggesting it may serve as a useful crystallization additive for proteins refolded with it. Our results also suggest there is a site on TBRII-ECD that could be targeted by small-molecule modulators.

-	The ~~entry 4p7u is ON HOLD until Paper Publication~~	+	The non-detergent sulfobetaine-201 acts as a pharmacological chaperone to promote folding and crystallization of the type II TGF-beta receptor extracellular domain.,Wangkanont K, Forest KT, Kiessling LL Protein Expr Purif. 2015 Jun 11. pii: S1046-5928(15)00140-0. doi:, 10.1016/j.pep.2015.06.001. PMID:26073093<ref>PMID:26073093</ref>

-	~~Authors: Wangkanont~~, K.~~, Forest, K~~.T.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Forest, K.T]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein serine/threonine kinase]]
		+	[[Category: Forest, K T]]
	[[Category: Wangkanont, K]]		[[Category: Wangkanont, K]]
		+	[[Category: Ndsb-201]]
		+	[[Category: Signaling protein]]
		+	[[Category: Type ii transforming growth factor beta receptor]]

OCA at 14:50, 24 December 2014

2014-12-24T14:50:24Z

←Older revision		Revision as of 14:50, 24 December 2014
Line 6:		Line 6:

	Description: Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201		Description: Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201
		+	[[Category: Unreleased Structures]]
		+	[[Category: Forest, K.T]]
		+	[[Category: Wangkanont, K]]

OCA at 09:39, 16 July 2014

2014-07-16T09:39:56Z

←Older revision		Revision as of 09:39, 16 July 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4p7u is ON HOLD	+	The entry 4p7u is ON HOLD until Paper Publication

	Authors: Wangkanont, K., Forest, K.T.		Authors: Wangkanont, K., Forest, K.T.

	Description: Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201		Description: Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201

OCA: Protected "4p7u" [edit=sysop:move=sysop]

2014-04-02T08:31:46Z

Protected "4p7u" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:31, 2 April 2014