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==STRUCTURE OF THE HUMAN RECEPTOR TYROSINE KINASE MET IN COMPLEX WITH THE LISTERIA MONOCYTOGENES INVASION PROTEIN INLB: CRYSTAL FORM I==
 
<StructureSection load='2uzx' size='340' side='right' caption='[[2uzx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
==Structure of the human receptor tyrosine kinase Met in complex with the Listeria monocytogenes invasion protein InlB: Crystal form I==
<StructureSection load='2uzx' size='340' side='right'caption='[[2uzx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Listeria_monocytogenes Listeria monocytogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZX FirstGlance]. <br>
<table><tr><td colspan='2'>[[2uzx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Listeria_monocytogenes_EGD-e Listeria monocytogenes EGD-e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZX FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d0b|1d0b]], [[1fyr|1fyr]], [[1h6t|1h6t]], [[1m9s|1m9s]], [[1otm|1otm]], [[1otn|1otn]], [[1oto|1oto]], [[1r0p|1r0p]], [[1r1w|1r1w]], [[1shy|1shy]], [[1ssl|1ssl]], [[1ux3|1ux3]], [[2cew|2cew]], [[2g15|2g15]], [[2uzy|2uzy]]</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]] 2.8&#8491;</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=2uzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2uzx RCSB], [http://www.ebi.ac.uk/pdbsum/2uzx PDBsum]</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=2uzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzx OCA], [https://pdbe.org/2uzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzx RCSB], [https://www.ebi.ac.uk/pdbsum/2uzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzx ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.  Note=Defects in MET may be associated with gastric cancer.  Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref>  Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[http://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref>  Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes.  Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>  Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> 
[https://www.uniprot.org/uniprot/INLB_LISMO INLB_LISMO] Mediates the entry of Listeria monocytogenes into cells.
== 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/uz/2uzx_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uz/2uzx_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=2uzx 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 2uzx" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Hepatocyte growth factor receptor|Hepatocyte growth factor receptor]]
*[[Hepatocyte growth factor receptor 3D structures|Hepatocyte growth factor receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Listeria monocytogenes]]
[[Category: Large Structures]]
[[Category: Butler, P J.G]]
[[Category: Listeria monocytogenes EGD-e]]
[[Category: Ferraris, D]]
[[Category: Butler PJG]]
[[Category: Gherardi, E]]
[[Category: Ferraris D]]
[[Category: Heinz, D W]]
[[Category: Gherardi E]]
[[Category: Heuvel, J Van Den]]
[[Category: Heinz DW]]
[[Category: Jager, V]]
[[Category: Jager V]]
[[Category: Niemann, H H]]
[[Category: Niemann HH]]
[[Category: Schmidt, S]]
[[Category: Schmidt S]]
[[Category: Atp-binding]]
[[Category: Van Den Heuvel J]]
[[Category: Disease mutation]]
[[Category: Glycoprotein]]
[[Category: Hepatocyte growth factor receptor]]
[[Category: Hgfr]]
[[Category: Internalin]]
[[Category: Kinase]]
[[Category: Leucine rich repeat]]
[[Category: Leucine-rich repeat]]
[[Category: Lrr]]
[[Category: Membrane]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Proto-oncogene]]
[[Category: Receptor]]
[[Category: Receptor ectodomain]]
[[Category: Signaling protein]]
[[Category: Signaling protein-receptor complex]]
[[Category: Signaling protein/receptor]]
[[Category: Transferase]]
[[Category: Transmembrane]]
[[Category: Tyrosine-protein kinase]]
[[Category: Virulence factor]]

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