3tjn - Revision history

OCA at 13:31, 14 March 2024

OCA — Thu, 14 Mar 2024 13:31:09 GMT

←Older revision		Revision as of 13:31, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tjn' size='340' side='right'caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='3tjn' size='340' side='right'caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjn]] is a 3 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=3TJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJN FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[3tjo\|3tjo]], [[3tjq\|3tjq]]</div></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]] 3Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [https://pdbe.org/3tjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [https://www.ebi.ac.uk/pdbsum/3tjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjn 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=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [https://pdbe.org/3tjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [https://www.ebi.ac.uk/pdbsum/3tjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[https://omim.org/entry/610149 610149]]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref> <ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[https://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>	+	[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[https://omim.org/entry/610149 610149]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref> <ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[https://omim.org/entry/600142 600142]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref> <ref>PMID:16377621</ref> <ref>PMID:20671064</ref>	+	[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref> <ref>PMID:16377621</ref> <ref>PMID:20671064</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology. The crystal structures and SAXS analysis presented herein reveal the rare tandem of IGFBP- and Kazal-like modules, a protease active site that adopts a competent conformation in the absence of substrate or inhibitor and a model for the intact protein in solution. Highly sensitive enzymatic assays and binding studies demonstrate that the N-terminal tandem has no apparent effect on protease activity, and in accordance with the structure-based predictions, neither the IGFBP- nor Kazal-like module retains the function of their prototype proteins. Our structures of the unliganded HtrA1 active site suggest two-state equilibrium and a "conformational selection" model, in which substrate binds to the active conformer.	+
-		+
-	Structural and Functional Analysis of HtrA1 and Its Subdomains.,Eigenbrot C, Ultsch M, Lipari MT, Moran P, Lin SJ, Ganesan R, Quan C, Tom J, Sandoval W, van Lookeren Campagne M, Kirchhofer D Structure. 2012 Jun 6;20(6):1040-50. Epub 2012 May 10. PMID:22578544<ref>PMID:22578544</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tjn" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Eigenbrot, C]]	+	[[Category: Eigenbrot C]]
-	[[Category: Ultsch, M]]	+	[[Category: Ultsch M]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 17:01, 6 July 2022

OCA — Wed, 06 Jul 2022 17:01:10 GMT

←Older revision		Revision as of 17:01, 6 July 2022
Line 1:		Line 1:

	==HtrA1 catalytic domain, apo form==		==HtrA1 catalytic domain, apo form==
-	<StructureSection load='3tjn' size='340' side='right' caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='3tjn' size='340' side='right'caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjn]] is a 3 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=3TJN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TJN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJN FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3tjo\|3tjo]], [[3tjq\|3tjq]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3tjo\|3tjo]], [[3tjq\|3tjq]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([https://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=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [~~http~~://pdbe.org/3tjn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tjn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjn 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=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [https://pdbe.org/3tjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [https://www.ebi.ac.uk/pdbsum/3tjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[~~http~~://omim.org/entry/610149 610149]]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref> <ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[~~http~~://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>	+	[[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[https://omim.org/entry/610149 610149]]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref> <ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[https://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref> <ref>PMID:16377621</ref> <ref>PMID:20671064</ref>	+	[[https://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref> <ref>PMID:16377621</ref> <ref>PMID:20671064</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]
	[[Category: Ultsch, M]]		[[Category: Ultsch, M]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease]]		[[Category: Protease]]

OCA at 11:24, 5 August 2016

OCA — Fri, 05 Aug 2016 11:24:30 GMT

←Older revision		Revision as of 11:24, 5 August 2016
Line 1:		Line 1:
		+
	==HtrA1 catalytic domain, apo form==		==HtrA1 catalytic domain, apo form==
	<StructureSection load='3tjn' size='340' side='right' caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='3tjn' size='340' side='right' caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjn]] is a 3 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=3TJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjn]] is a 3 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=3TJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJN FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3tjo\|3tjo]], [[3tjq\|3tjq]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3tjo\|3tjo]], [[3tjq\|3tjq]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([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=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [http://www.ebi.ac.uk/pdbsum/3tjn 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=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [http://pdbe.org/3tjn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [http://www.ebi.ac.uk/pdbsum/3tjn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjn 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 3tjn" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]
	[[Category: Ultsch, M]]		[[Category: Ultsch, M]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease]]		[[Category: Protease]]

OCA at 07:19, 21 December 2014

OCA — Sun, 21 Dec 2014 07:19:16 GMT

←Older revision		Revision as of 07:19, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3tjn~~\| ~~PDB~~=3tjn \| ~~SCENE~~= }}	+	==HtrA1 catalytic domain, apo form==
-	===~~HtrA1~~ catalytic ~~domain~~, ~~apo form~~===	+	<StructureSection load='3tjn' size='340' side='right' caption='[[3tjn]], [[Resolution\|resolution]] 3.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22578544}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tjn]] is a 3 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=3TJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJN FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3tjo\|3tjo]], [[3tjq\|3tjq]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA, HTRA1, PRSS11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjn RCSB], [http://www.ebi.ac.uk/pdbsum/3tjn PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[http://omim.org/entry/610149 610149]]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref> <ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[http://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref> <ref>PMID:16377621</ref> <ref>PMID:20671064</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology. The crystal structures and SAXS analysis presented herein reveal the rare tandem of IGFBP- and Kazal-like modules, a protease active site that adopts a competent conformation in the absence of substrate or inhibitor and a model for the intact protein in solution. Highly sensitive enzymatic assays and binding studies demonstrate that the N-terminal tandem has no apparent effect on protease activity, and in accordance with the structure-based predictions, neither the IGFBP- nor Kazal-like module retains the function of their prototype proteins. Our structures of the unliganded HtrA1 active site suggest two-state equilibrium and a "conformational selection" model, in which substrate binds to the active conformer.

-	~~==Disease==~~	+	Structural and Functional Analysis of HtrA1 and Its Subdomains.,Eigenbrot C, Ultsch M, Lipari MT, Moran P, Lin SJ, Ganesan R, Quan C, Tom J, Sandoval W, van Lookeren Campagne M, Kirchhofer D Structure. 2012 Jun 6;20(6):1040-50. Epub 2012 May 10. PMID:22578544<ref>PMID:22578544</ref>
-	[[http://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[http://omim.org/entry/610149 610149]]. ARMD is the leading cause of ~~vision loss~~ and ~~blindness among older individuals in the developed word~~. ~~It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form~~, ~~in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue~~, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref><ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[http://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, ~~alopecia~~, ~~and spondylosis~~, ~~with an onset in early adulthood. On neuropathological examination~~, ~~atherosclerosis associated with intimal thickening and dense collagen fibers~~, ~~loss of vascular smooth-muscle cells~~, ~~and hyaline degeneration of the tunica media has been observed in cerebral small arteries~~.<ref>PMID:~~19387015~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with~~ a ~~variety~~ of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the ~~range and intensity of FGF signals in the extracellular space~~. ~~Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins~~. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of ~~TSC2 downstream targets~~.<~~ref~~>~~PMID:9852107~~</~~ref~~>~~<ref>PMID:16377621</ref><ref>PMID:20671064</ref>~~	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[3tjn]] is a 3 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=3TJN OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:022578544</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Eigenbrot, C.]]	+	[[Category: Eigenbrot, C]]
-	[[Category: Ultsch, M.]]	+	[[Category: Ultsch, M]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease]]		[[Category: Protease]]

OCA at 21:15, 24 March 2013

OCA — Sun, 24 Mar 2013 21:15:00 GMT

←Older revision		Revision as of 21:15, 24 March 2013
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-	[[Image:3tjn.png\|left\|200px]]
-
	{{STRUCTURE_3tjn\| PDB=3tjn \| SCENE= }}		{{STRUCTURE_3tjn\| PDB=3tjn \| SCENE= }}
-
	===HtrA1 catalytic domain, apo form===		===HtrA1 catalytic domain, apo form===
		+	{{ABSTRACT_PUBMED_22578544}}

-	~~{{ABSTRACT_PUBMED_22578544}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Variations in the promoter region of HTRA1 are the cause of susceptibility to age-related macular degeneration type 7 (ARMD7) [MIM:[http://omim.org/entry/610149 610149]]. ARMD is the leading cause of vision loss and blindness among older individuals in the developed word. It is classified as either dry (nonneovascular) or wet (neovascular). ARMD7 is a wet form, in which new blood vessels form and break beneath the retina. This leakage causes permanent damage to surrounding retinal tissue, distorting and destroying central vision. Wet ARMD is more prevalent among Asians than Caucasians.<ref>PMID:17053108</ref><ref>PMID:17053109</ref> Defects in HTRA1 are the cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:[http://omim.org/entry/600142 600142]]. CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with subcortical infarcts, alopecia, and spondylosis, with an onset in early adulthood. On neuropathological examination, atherosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media has been observed in cerebral small arteries.<ref>PMID:19387015</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/HTRA1_HUMAN HTRA1_HUMAN]] Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.<ref>PMID:9852107</ref><ref>PMID:16377621</ref><ref>PMID:20671064</ref>

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022578544</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022578544</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Eigenbrot, C.]]		[[Category: Eigenbrot, C.]]

OCA at 05:01, 27 June 2012

OCA — Wed, 27 Jun 2012 05:01:05 GMT

←Older revision		Revision as of 05:01, 27 June 2012
Line 1:		Line 1:
	[[Image:3tjn.png\|left\|200px]]		[[Image:3tjn.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3tjn", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3tjn\| PDB=3tjn \| SCENE= }}		{{STRUCTURE_3tjn\| PDB=3tjn \| SCENE= }}

	===HtrA1 catalytic domain, apo form===		===HtrA1 catalytic domain, apo form===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22578544}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22578544 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22578544}}		{{ABSTRACT_PUBMED_22578544}}

OCA at 05:26, 13 June 2012

OCA — Wed, 13 Jun 2012 05:26:22 GMT

←Older revision		Revision as of 05:26, 13 June 2012
Line 1:		Line 1:
-	[[Image:3tjn.~~jpg~~\|left\|200px]]	+	[[Image:3tjn.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===HtrA1 catalytic domain, apo form===		===HtrA1 catalytic domain, apo form===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22578544}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22578544 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22578544}}

	==About this Structure==		==About this Structure==
	[[3tjn]] is a 3 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=3TJN OCA].		[[3tjn]] is a 3 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=3TJN OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022578544</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Eigenbrot, C.]]		[[Category: Eigenbrot, C.]]

OCA at 09:19, 16 May 2012

OCA — Wed, 16 May 2012 09:19:19 GMT

←Older revision		Revision as of 09:19, 16 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3tjn.jpg\|left\|200px]]

-	The ~~entry 3tjn~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tjn", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3tjn\| PDB=3tjn \| SCENE= }}

-	~~Authors: Eigenbrot~~, ~~C., Ultsch, M.~~	+	===HtrA1 catalytic domain, apo form===

-	~~Description~~: ~~HtrA1 catalytic domain~~, ~~apo form~~	+
		+	==About this Structure==
		+	[[3tjn]] is a 3 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=3TJN OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Eigenbrot, C.]]
		+	[[Category: Ultsch, M.]]
		+	[[Category: Hydrolase]]
		+	[[Category: Protease]]

OCA at 08:36, 25 April 2012

OCA — Wed, 25 Apr 2012 08:36:44 GMT

←Older revision		Revision as of 08:36, 25 April 2012
Line 5:		Line 5:
	Authors: Eigenbrot, C., Ultsch, M.		Authors: Eigenbrot, C., Ultsch, M.

-	Description: ~~Serine peptidase fragment~~	+	Description: HtrA1 catalytic domain, apo form

OCA at 05:15, 28 September 2011

OCA — Wed, 28 Sep 2011 05:15:15 GMT

←Older revision		Revision as of 05:15, 28 September 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Eigenbrot, C., Ultsch, M.		Authors: Eigenbrot, C., Ultsch, M.

	Description: Serine peptidase fragment		Description: Serine peptidase fragment