3cu8 - Revision history

OCA at 07:45, 2 February 2022

2022-02-02T07:45:15Z

←Older revision		Revision as of 07:45, 2 February 2022
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	==Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome==		==Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome==
-	<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='3cu8' size='340' side='right'caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [~~http~~://pdbe.org/3cu8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3cu8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3cu8 ProSAT]</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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [https://pdbe.org/3cu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [https://www.ebi.ac.uk/pdbsum/3cu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cu8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN]] Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:[~~http~~://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:[~~http~~://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>	+	[[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 ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[~~http~~://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>	+	[[https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[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 ==		== 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/cu/3cu8_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cu/3cu8_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>
Line 35:		Line 35:

	==See Also==		==See Also==
-	*[[14-3-3 protein\|14-3-3 protein]]	+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 41:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kuhlmann, J]]		[[Category: Kuhlmann, J]]

OCA at 06:56, 25 October 2017

2017-10-25T06:56:12Z

←Older revision		Revision as of 06:56, 25 October 2017
Line 3:		Line 3:
	<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://pdbe.org/3cu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cu8 ProSAT]</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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://pdbe.org/3cu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cu8 ProSAT]</span></td></tr>
Line 39:		Line 40:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kuhlmann, J]]		[[Category: Kuhlmann, J]]

OCA at 11:38, 3 August 2017

2017-08-03T11:38:39Z

←Older revision		Revision as of 11:38, 3 August 2017
Line 1:		Line 1:
		+
	==Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome==		==Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome==
	<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Human Human]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://pdbe.org/3cu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://pdbe.org/3cu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cu8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 23:
	</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=3cu8 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=3cu8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Ras-RAF-MAPK pathway is overactive in many cancers and in some developmental disorders. In one of the latter, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization by promoting Ras-mediated plasma membrane recruitment of C-RAF. By providing biophysical binding data, the 14-3-3/C-RAFpS(259) crystal structure, and cellular analyses we present a mechanistic link between a well-described human developmental disorder and the impairment of a 14-3-3/target protein interaction. As a broader implication of these findings, modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for diseases resulting from an overactive Ras-RAF-MAPK pathway.
		+
		+	Impaired binding of 14-3-3 to C-RAF in Noonan Syndrome implies new approaches in diseases with increased Ras signaling.,Molzan M, Schumacher B, Ottmann C, Baljuls A, Polzien L, Weyand M, Thiel P, Rose R, Rose M, Kuhenne P, Kaiser M, Rapp UR, Kuhlmann J, Ottmann C Mol Cell Biol. 2010 Aug 2. PMID:20679480<ref>PMID:20679480</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 3cu8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 30:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kuhlmann, J]]		[[Category: Kuhlmann, J]]

OCA at 08:28, 9 February 2016

2016-02-09T08:28:34Z

←Older revision		Revision as of 08:28, 9 February 2016
Line 2:		Line 2:
	<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with 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=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://pdbe.org/3cu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	<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=3cu8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>

Line 30:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kuhlmann, J]]		[[Category: Kuhlmann, J]]

OCA at 09:44, 20 January 2015

2015-01-20T09:44:01Z

←Older revision		Revision as of 09:44, 20 January 2015
Line 32:		Line 32:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Kuhlmann, J.]]	+	[[Category: Kuhlmann, J]]
-	[[Category: Ottmann, C.]]	+	[[Category: Ottmann, C]]
-	[[Category: Schumacher, B.]]	+	[[Category: Schumacher, B]]
-	[[Category: Weyand, M.]]	+	[[Category: Weyand, M]]
	[[Category: 14-3-3]]		[[Category: 14-3-3]]
	[[Category: Adapter protein]]		[[Category: Adapter protein]]

OCA at 06:49, 10 October 2014

2014-10-10T06:49:39Z

←Older revision		Revision as of 06:49, 10 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}~~	+	==Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome==
-	===Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome===	+	<StructureSection load='3cu8' size='340' side='right' caption='[[3cu8]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3cu8]] is a 4 chain structure with 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=3CU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CU8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3cu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cu8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3cu8 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN]] Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:[http://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:[http://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 ==
		+	[[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[http://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/cu/3cu8_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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>

-	==~~Disease~~==	+	==See Also==
-	[[http://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN]] Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:[http://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:[http://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>	+	*[[14-3-3 protein\|14-3-3 protein]]
-		+	== References ==
-	~~==Function==~~	+	<references/>
-	[[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref><ref>PMID:14578935</ref><ref>PMID:15071501</ref><ref>PMID:15644438</ref><ref>PMID:16376338</ref> [[http://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>	+	__TOC__
-		+	</StructureSection>
-	~~==About this Structure==~~	+
-	~~[[3cu8~~]] is a 4 chain structure with 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=3CU8 OCA].	+
-		+
-	==~~Reference~~==	+
-	<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 05:03, 25 March 2013

2013-03-25T05:03:55Z

←Older revision		Revision as of 05:03, 25 March 2013
Line 1:		Line 1:
-	[[Image:3cu8.png\|left\|200px]]
-
	{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}		{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}
-
	===Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome===		===Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome===

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/RAF1_HUMAN RAF1_HUMAN]] Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:[http://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:[http://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==
		+	[[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref><ref>PMID:14578935</ref><ref>PMID:15071501</ref><ref>PMID:15644438</ref><ref>PMID:16376338</ref> [[http://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>

	==About this Structure==		==About this Structure==
	[[3cu8]] is a 4 chain structure with 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=3CU8 OCA].		[[3cu8]] is a 4 chain structure with 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=3CU8 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA: Protected "3cu8" [edit=sysop:move=sysop]

2013-01-07T21:43:13Z

Protected "3cu8" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:43, 7 January 2013

OCA at 21:43, 7 January 2013

2013-01-07T21:43:10Z

←Older revision		Revision as of 21:43, 7 January 2013
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3cu8.png\|left\|200px]]
-	[[Image:3cu8.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3cu8", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}		{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}

Line 14:		Line 7:

	==About this Structure==		==About this Structure==
-	~~3CU8~~ is a 4 ~~chains~~ structure ~~of sequences~~ 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=3CU8 OCA].	+	[[3cu8]] is a 4 chain structure with 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=3CU8 OCA].
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 22:		Line 15:
	[[Category: Weyand, M.]]		[[Category: Weyand, M.]]
	[[Category: 14-3-3]]		[[Category: 14-3-3]]
-	[[Category: Acetylation]]
	[[Category: Adapter protein]]		[[Category: Adapter protein]]
	[[Category: Craf1]]		[[Category: Craf1]]
-	[[Category: Cytoplasm]]
	[[Category: Leopard syndrome]]		[[Category: Leopard syndrome]]
	[[Category: Noonan syndrome]]		[[Category: Noonan syndrome]]
Line 32:		Line 23:
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
	[[Category: Zeta]]		[[Category: Zeta]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 6 11:25:37 2009''

OCA at 08:25, 6 May 2009

2009-05-06T08:25:39Z

←Older revision		Revision as of 08:25, 6 May 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3cu8.jpg\|left\|200px]]

-	The ~~entry 3cu8~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3cu8", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3cu8\| PDB=3cu8 \| SCENE= }}

-	~~Authors: Schumacher, B., Weyand, M., Kuhlmann, J., Ottmann, C.~~	+	===Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome===

-	Description: Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome

		+	==About this Structure==
		+	3CU8 is a 4 chains structure of sequences 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=3CU8 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Kuhlmann, J.]]
		+	[[Category: Ottmann, C.]]
		+	[[Category: Schumacher, B.]]
		+	[[Category: Weyand, M.]]
		+	[[Category: 14-3-3]]
		+	[[Category: Acetylation]]
		+	[[Category: Adapter protein]]
		+	[[Category: Craf1]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Leopard syndrome]]
		+	[[Category: Noonan syndrome]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Protein binding]]
		+	[[Category: Signaling protein]]
		+	[[Category: Zeta]]

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