2shp: Difference between revisions

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-[[Image:2shp.gif|left|200px]]<br /><applet load="2shp" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2shp, resolution 2.00&Aring;" />
-'''TYROSINE PHOSPHATASE SHP-2'''<br />
-==Overview==
+==TYROSINE PHOSPHATASE SHP-2==
-The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation.
+<StructureSection load='2shp' size='340' side='right'caption='[[2shp]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2shp]] is a 2 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=2SHP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SHP 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]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAT:DODECANE-TRIMETHYLAMINE'>CAT</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=2shp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2shp OCA], [https://pdbe.org/2shp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2shp RCSB], [https://www.ebi.ac.uk/pdbsum/2shp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2shp ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[https://omim.org/entry/151100 151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref>   Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[https://omim.org/entry/163950 163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref>   Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref>   Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[https://omim.org/entry/156250 156250]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sh/2shp_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=2shp ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Leopard syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]], Leukemia, juvenile myelomonocytic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]], Noonan syndrome 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]]
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-SHP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CAT:'>CAT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SHP OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Crystal structure of the tyrosine phosphatase SHP-2., Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE, Cell. 1998 Feb 20;92(4):441-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9491886 9491886]
 [[Category: Homo sapiens]]
-[[Category: Protein-tyrosine-phosphatase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Dhe-Paganon S]]
-[[Category: Dhe-Paganon, S.]]
+[[Category: Eck MJ]]
-[[Category: Eck, M J.]]
+[[Category: Hof P]]
-[[Category: Hof, P.]]
+[[Category: Pluskey S]]
-[[Category: Pluskey, S.]]
+[[Category: Shoelson SE]]
-[[Category: Shoelson, S E.]]
-[[Category: CAT]]
-[[Category: insulin signaling]]
-[[Category: sh2 protein]]
-[[Category: tyrosine phosphatase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:49:11 2008''