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| <StructureSection load='2wc0' size='340' side='right'caption='[[2wc0]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='2wc0' size='340' side='right'caption='[[2wc0]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2wc0]] is a 6 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=2WC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WC0 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2wc0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WC0 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.8Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hit|1hit]], [[2jbu|2jbu]], [[2hho|2hho]], [[2c8q|2c8q]], [[1tyl|1tyl]], [[2c8r|2c8r]], [[1t1k|1t1k]], [[1aiy|1aiy]], [[1xda|1xda]], [[1htv|1htv]], [[1mso|1mso]], [[1uz9|1uz9]], [[1fub|1fub]], [[1tym|1tym]], [[1hui|1hui]], [[1vkt|1vkt]], [[2vk0|2vk0]], [[1t1q|1t1q]], [[2ceu|2ceu]], [[1hls|1hls]], [[1qj0|1qj0]], [[1fu2|1fu2]], [[1mhj|1mhj]], [[1sjt|1sjt]], [[1qiy|1qiy]], [[1iog|1iog]], [[2vjz|2vjz]], [[1ioh|1ioh]], [[1trz|1trz]], [[1evr|1evr]], [[1ev3|1ev3]], [[1rwe|1rwe]], [[1os4|1os4]], [[1guj|1guj]], [[1ai0|1ai0]], [[1jco|1jco]], [[1sf1|1sf1]], [[1jca|1jca]], [[1zeg|1zeg]], [[1os3|1os3]], [[1xgl|1xgl]], [[1qiz|1qiz]], [[1t0c|1t0c]], [[1g7b|1g7b]], [[2wby|2wby]], [[2aiy|2aiy]], [[1ev6|1ev6]], [[1q4v|1q4v]], [[2hh4|2hh4]], [[2h67|2h67]], [[4aiy|4aiy]], [[1j73|1j73]], [[1k3m|1k3m]], [[1mhi|1mhi]], [[2hiu|2hiu]], [[1kmf|1kmf]], [[1xw7|1xw7]], [[5aiy|5aiy]], [[1g7a|1g7a]], [[1znj|1znj]], [[1zeh|1zeh]], [[1his|1his]], [[1b9e|1b9e]], [[1w8p|1w8p]], [[3aiy|3aiy]], [[1hiq|1hiq]], [[1lph|1lph]], [[1efe|1efe]], [[1a7f|1a7f]], [[1t1p|1t1p]], [[1ben|1ben]], [[1lkq|1lkq]], [[2jg4|2jg4]]</div></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </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=2wc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wc0 OCA], [https://pdbe.org/2wc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wc0 RCSB], [https://www.ebi.ac.uk/pdbsum/2wc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wc0 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=2wc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wc0 OCA], [https://pdbe.org/2wc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wc0 RCSB], [https://www.ebi.ac.uk/pdbsum/2wc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wc0 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
| |
| [[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[https://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[https://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[https://omim.org/entry/613370 613370]]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
| |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
| | [https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Insulysin]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Guo, Q]] | | [[Category: Guo Q]] |
| [[Category: Malito, E]] | | [[Category: Malito E]] |
| [[Category: Manolopoulou, M]] | | [[Category: Manolopoulou M]] |
| [[Category: Schilling, A B]] | | [[Category: Schilling AB]] |
| [[Category: Tang, W J]] | | [[Category: Tang WJ]] |
| [[Category: Carbohydrate metabolism]]
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| [[Category: Cleavage on pair of basic residue]]
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| [[Category: Cytoplasm]]
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| [[Category: Dioxane]]
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| [[Category: Disulfide bond]]
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| [[Category: Glucose metabolism]]
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| [[Category: Hormone]]
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| [[Category: Human insulin-degrading enzyme]]
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| [[Category: Hydrolase]]
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| [[Category: Hydrolase-hormone complex]]
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| [[Category: Hydrolase/hormone]]
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| [[Category: Insulin]]
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| [[Category: Metal-binding]]
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| [[Category: Metalloprotease]]
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| [[Category: Polymorphism]]
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| [[Category: Protease]]
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| [[Category: Secreted]]
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| [[Category: Zinc]]
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