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==STRUCTURE OF THE HUMAN RECEPTOR TYROSINE KINASE MET IN COMPLEX WITH THE LISTERIA MONOCYTOGENES INVASION PROTEIN INLB: LOW RESOLUTION, CRYSTAL FORM II==
 
==Structure of the human receptor tyrosine kinase Met in complex with the Listeria monocytogenes invasion protein inlb: low resolution, Crystal form II==
<StructureSection load='2uzy' size='340' side='right' caption='[[2uzy]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
<StructureSection load='2uzy' size='340' side='right' caption='[[2uzy]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZY FirstGlance]. <br>
<table><tr><td colspan='2'>[[2uzy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZY 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]], [[2uzx|2uzx]]</td></tr>
</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]], [[2uzx|2uzx]]</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=2uzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzy OCA], [http://pdbe.org/2uzy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uzy RCSB], [http://www.ebi.ac.uk/pdbsum/2uzy 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=2uzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzy OCA], [http://pdbe.org/2uzy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uzy RCSB], [http://www.ebi.ac.uk/pdbsum/2uzy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzy 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 ==
[[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> 
== 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/2uzy_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uz/2uzy_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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[[Category: Gherardi, E]]
[[Category: Gherardi, E]]
[[Category: Heinz, D W]]
[[Category: Heinz, D W]]
[[Category: Heuvel, J Van Den]]
[[Category: Heuvel, J van den]]
[[Category: Jager, V]]
[[Category: Jager, V]]
[[Category: Niemann, H H]]
[[Category: Niemann, H H]]
[[Category: Schmidt, S]]
[[Category: Schmidt, S]]
[[Category: Alternative splicing]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Chromosomal rearrangement]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]
[[Category: Glycoprotein]]
[[Category: Glycoprotein]]
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[[Category: Nucleotide-binding]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Phosphorylation]]
[[Category: Polymorphism]]
[[Category: Proto-oncogene]]
[[Category: Proto-oncogene]]
[[Category: Receptor]]
[[Category: Receptor]]

Revision as of 08:38, 12 September 2018

Structure of the human receptor tyrosine kinase Met in complex with the Listeria monocytogenes invasion protein inlb: low resolution, Crystal form II

2uzy, resolution 4.00Å

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