1mjs: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1mjs.gif|left|200px]]
- {{Structure
+==MH2 domain of transcriptional factor SMAD3==
-|PDB= 1mjs |SIZE=350|CAPTION= <scene name='initialview01'>1mjs</scene>, resolution 1.91&Aring;
+<StructureSection load='1mjs' size='340' side='right'caption='[[1mjs]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND=
+<table><tr><td colspan='2'>[[1mjs]] is a 1 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=1MJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MJS FirstGlance]. <br>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91&#8491;</td></tr>
-|GENE= SMAD3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mjs OCA], [https://pdbe.org/1mjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mjs RCSB], [https://www.ebi.ac.uk/pdbsum/1mjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mjs ProSAT]</span></td></tr>
-}}
+</table>
+== Disease ==
-'''MH2 domain of transcriptional factor SMAD3'''
+[https://www.uniprot.org/uniprot/SMAD3_HUMAN SMAD3_HUMAN] Defects in SMAD3 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].  Defects in SMAD3 are the cause of Loeys-Dietz syndrome 3 (LDS3) [MIM:[https://omim.org/entry/613795 613795]. An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation. Note=SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (PubMed:21778426), they have been classified as LDS3 by the OMIM resource.<ref>PMID:21778426</ref> <ref>PMID:21217753</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/SMAD3_HUMAN SMAD3_HUMAN] Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.<ref>PMID:9732876</ref> <ref>PMID:9892009</ref> <ref>PMID:10995748</ref> <ref>PMID:15241418</ref> <ref>PMID:15588252</ref> <ref>PMID:16156666</ref> <ref>PMID:16751101</ref> <ref>PMID:17327236</ref> <ref>PMID:16862174</ref> <ref>PMID:19289081</ref> <ref>PMID:19218245</ref>
-==Overview==
+== Evolutionary Conservation ==
-Smad3 transduces the signals of TGF-betas, coupling transmembrane receptor kinase activation to transcriptional control. The membrane-associated molecule SARA (Smad Anchor for Receptor Activation) recruits Smad3 for phosphorylation by the receptor kinase. Upon phosphorylation, Smad3 dissociates from SARA and enters the nucleus, in which its transcriptional activity can be repressed by Ski. Here, we show that SARA and Ski recognize specifically the monomeric and trimeric forms of Smad3, respectively. Thus, trimerization of Smad3, induced by phosphorylation, simultaneously activates the TGF-beta signal by driving Smad3 dissociation from SARA and sets up the negative feedback mechanism by Ski. Structural models of the Smad3/SARA/receptor kinase complex and Smad3/Ski complex provide insights into the molecular basis of regulation.
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
-==About this Structure==
+  <jmolCheckbox>
-MJS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MJS OCA].
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mj/1mjs_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
-==Reference==
+    <text>to colour the structure by Evolutionary Conservation</text>
-Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control., Qin BY, Lam SS, Correia JJ, Lin K, Genes Dev. 2002 Aug 1;16(15):1950-63. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12154125 12154125]
+  </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=1mjs ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Correia, J J.]]
+[[Category: Correia JJ]]
-[[Category: Lam, S S.]]
+[[Category: Lam SS]]
-[[Category: Lin, K.]]
+[[Category: Lin K]]
-[[Category: Qin, B Y.]]
+[[Category: Qin BY]]
-[[Category: beta sandwich]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:44:19 2008''