View source for 8se8


==HTRA-1 PD/SA bound to CKP 1G10==
<StructureSection load='8se8' size='340' side='right'caption='[[8se8]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8se8]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecballium_elaterium Ecballium elaterium] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SE8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8se8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8se8 OCA], [https://pdbe.org/8se8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8se8 RCSB], [https://www.ebi.ac.uk/pdbsum/8se8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8se8 ProSAT]</span></td></tr>
</table>
== 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> 
== 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> 
== References ==
<references/>
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</StructureSection>
[[Category: Ecballium elaterium]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ultsch MH]]