1rfa: Difference between revisions

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-[[Image:1rfa.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1rfa", creates the "Structure Box" on the page.
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-{{STRUCTURE_1rfa|  PDB=1rfa  |  SCENE=  }}
-'''NMR SOLUTION STRUCTURE OF THE RAS-BINDING DOMAIN OF C-RAF-1'''
+==NMR SOLUTION STRUCTURE OF THE RAS-BINDING DOMAIN OF C-RAF-1==
+<StructureSection load='1rfa' size='340' side='right'caption='[[1rfa]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1rfa]] 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=1RFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RFA FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1rfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rfa OCA], [https://pdbe.org/1rfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rfa RCSB], [https://www.ebi.ac.uk/pdbsum/1rfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rfa ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN] Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:[https://omim.org/entry/611553 611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births.<ref>PMID:17603483</ref> <ref>PMID:17603482</ref> <ref>PMID:20683980</ref>   Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD2) [MIM:[https://omim.org/entry/611554 611554]. LEOPARD syndrome 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:17603483</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN] Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.<ref>PMID:9360956</ref> <ref>PMID:11427728</ref> <ref>PMID:11719507</ref> <ref>PMID:15385642</ref> <ref>PMID:15618521</ref> <ref>PMID:15849194</ref> <ref>PMID:16924233</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/rf/1rfa_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=1rfa ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The structure of the Ras-binding domain of human c-Raf-1 (residues 55-132) has been determined in solution by nuclear magnetic resonance (NMR) spectroscopy. Following complete assignment of the backbone and side-chain 1H, 15N, and 13C resonances, the structure was calculated using the program CHARMM. Over 1300 NOE-derived constraints were applied, resulting in a detailed structure. The fold of Raf55-132 consists of a five-stranded beta-sheet, a 12-residue alpha-helix, and an additional one-turn helix. It is similar to those of ubiquitin and the IgG-binding domain of protein G, although the three proteins share very little sequence identity. The surface of Raf55-132 that interacts with Ras has been identified by monitoring perturbation of line widths and chemical shifts of 15N-labeled Raf55-132 resonances during titration with unlabeled Ras-GMPPNP. The Ras-binding site is contained within a spatially contiguous patch comprised of the N-terminal beta-hairpin and the C-terminal end of the alpha-helix.
-==Overview==
+Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface.,Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC Biochemistry. 1995 May 30;34(21):6911-8. PMID:7766599<ref>PMID:7766599</ref>
-The structure of the Ras-binding domain of human c-Raf-1 (residues 55-132) has been determined in solution by nuclear magnetic resonance (NMR) spectroscopy. Following complete assignment of the backbone and side-chain 1H, 15N, and 13C resonances, the structure was calculated using the program CHARMM. Over 1300 NOE-derived constraints were applied, resulting in a detailed structure. The fold of Raf55-132 consists of a five-stranded beta-sheet, a 12-residue alpha-helix, and an additional one-turn helix. It is similar to those of ubiquitin and the IgG-binding domain of protein G, although the three proteins share very little sequence identity. The surface of Raf55-132 that interacts with Ras has been identified by monitoring perturbation of line widths and chemical shifts of 15N-labeled Raf55-132 resonances during titration with unlabeled Ras-GMPPNP. The Ras-binding site is contained within a spatially contiguous patch comprised of the N-terminal beta-hairpin and the C-terminal end of the alpha-helix.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-RFA 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=1RFA OCA].
+</div>
+<div class="pdbe-citations 1rfa" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface., Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC, Biochemistry. 1995 May 30;34(21):6911-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7766599 7766599]
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Emerson, S D.]]
+[[Category: Emerson SD]]
-[[Category: Fry, D C.]]
+[[Category: Fry DC]]
-[[Category: Kiefer, S E.]]
+[[Category: Kiefer SE]]
-[[Category: Liu, S P.]]
+[[Category: Liu SP]]
-[[Category: Madison, V S.]]
+[[Category: Madison VS]]
-[[Category: Palermo, R E.]]
+[[Category: Palermo RE]]
-[[Category: Scheffler, J E.]]
+[[Category: Scheffler JE]]
-[[Category: Tsao, K L.]]
+[[Category: Tsao K-L]]
-[[Category: Waugh, D S.]]
+[[Category: Waugh DS]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Signal transduction protein]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 07:25:32 2008''