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==The Third Fibronectin Type II Module from Human Matrix Metalloproteinase 2==
==The Third Fibronectin Type II Module from Human Matrix Metalloproteinase 2==
<StructureSection load='1j7m' size='340' side='right' caption='[[1j7m]], [[NMR_Ensembles_of_Models | 50 NMR models]]' scene=''>
<StructureSection load='1j7m' size='340' side='right'caption='[[1j7m]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1j7m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J7M FirstGlance]. <br>
<table><tr><td colspan='2'>[[1j7m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J7M FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cxw|1cxw]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 50 models</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] </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=1j7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7m OCA], [https://pdbe.org/1j7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j7m RCSB], [https://www.ebi.ac.uk/pdbsum/1j7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j7m ProSAT]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j7m RCSB], [http://www.ebi.ac.uk/pdbsum/1j7m PDBsum]</span></td></tr>
</table>
<table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN]] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:[http://omim.org/entry/259600 259600]]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.<ref>PMID:11431697</ref> <ref>PMID:15691365</ref> <ref>PMID:16542393</ref>
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:[https://omim.org/entry/259600 259600]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.<ref>PMID:11431697</ref> <ref>PMID:15691365</ref> <ref>PMID:16542393</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN]] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j7/1j7m_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j7/1j7m_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1j7m ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 1j7m" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Matrix metalloproteinase|Matrix metalloproteinase]]
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Gelatinase A]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Banyai, L.]]
[[Category: Large Structures]]
[[Category: Briknarova, K.]]
[[Category: Banyai L]]
[[Category: Gehrmann, M.]]
[[Category: Briknarova K]]
[[Category: Llinas, M.]]
[[Category: Gehrmann M]]
[[Category: Patthy, L.]]
[[Category: Llinas M]]
[[Category: Tordai, H.]]
[[Category: Patthy L]]
[[Category: Alpha helix]]
[[Category: Tordai H]]
[[Category: Beta sheet]]
[[Category: Hydrolase]]

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