4iea - Revision history

OCA at 15:21, 20 September 2023

2023-09-20T15:21:03Z

←Older revision		Revision as of 15:21, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4iea]] 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4iea]] 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [https://pdbe.org/4iea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [https://www.ebi.ac.uk/pdbsum/4iea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iea 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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [https://pdbe.org/4iea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [https://www.ebi.ac.uk/pdbsum/4iea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iea ProSAT]</span></td></tr>
	</table>		</table>

OCA at 09:04, 9 November 2022

2022-11-09T09:04:27Z

←Older revision		Revision as of 09:04, 9 November 2022
Line 1:		Line 1:

	==14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide==		==14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide==
-	<StructureSection load='4iea' size='340' side='right' caption='[[4iea]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='4iea' size='340' side='right'caption='[[4iea]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4iea]] is a 2 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IEA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4iea]] 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEA FirstGlance]. <br>
-	</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>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4fj3\|4fj3]], [[1yz5\|1yz5]], [[1ywt\|1ywt]], [[3iqj\|3iqj]], [[3iqu\|3iqu]], [[1a37\|1a37]], [[4ihl\|4ihl]]</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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [https://pdbe.org/4iea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [https://www.ebi.ac.uk/pdbsum/4iea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iea ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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='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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [~~http~~://pdbe.org/4iea PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4iea PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4iea ProSAT]</span></td></tr>	+
	</table>		</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 ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/1433S_HUMAN 1433S_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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[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/1433S_HUMAN 1433S_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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 20:

	==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/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Molzan, M]]	+	[[Category: Molzan M]]
-	[[Category: Ottmann, C]]	+	[[Category: Ottmann C]]
-	~~[[Category: 14-3-3 fold]]~~	+
-	~~[[Category: Adapter protein]]~~	+
-	~~[[Category: All alpha-helical]]~~	+
-	~~[[Category: Peptide binding protein]]~~	+
-	~~[[Category: Protein-protein interaction]]~~	+
-	~~[[Category: Raf~~]]	+

OCA at 10:49, 11 August 2016

2016-08-11T10:49:00Z

←Older revision		Revision as of 10:49, 11 August 2016
Line 1:		Line 1:
		+
	==14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide==		==14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide==
	<StructureSection load='4iea' size='340' side='right' caption='[[4iea]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='4iea' size='340' side='right' caption='[[4iea]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4iea]] is a 2 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4iea]] is a 2 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEA FirstGlance]. <br>
	</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>		</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4fj3\|4fj3]], [[1yz5\|1yz5]], [[1ywt\|1ywt]], [[3iqj\|3iqj]], [[3iqu\|3iqu]], [[1a37\|1a37]], [[4ihl\|4ihl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4fj3\|4fj3]], [[1yz5\|1yz5]], [[1ywt\|1ywt]], [[3iqj\|3iqj]], [[3iqu\|3iqu]], [[1a37\|1a37]], [[4ihl\|4ihl]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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">SFN, HME1 ([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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [http://www.ebi.ac.uk/pdbsum/4iea 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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [http://pdbe.org/4iea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [http://www.ebi.ac.uk/pdbsum/4iea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iea ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4iea" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		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: Molzan, M]]		[[Category: Molzan, M]]

OCA at 12:25, 4 January 2015

2015-01-04T12:25:59Z

←Older revision		Revision as of 12:25, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4iea\| PDB=4iea \| SCENE= }}~~	+	==14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide==
-	===14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide===	+	<StructureSection load='4iea' size='340' side='right' caption='[[4iea]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23808890}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4iea]] is a 2 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=4IEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEA FirstGlance]. <br>
-	==Disease==	+	</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4fj3\|4fj3]], [[1yz5\|1yz5]], [[1ywt\|1ywt]], [[3iqj\|3iqj]], [[3iqu\|3iqu]], [[1a37\|1a37]], [[4ihl\|4ihl]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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=4iea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iea OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iea RCSB], [http://www.ebi.ac.uk/pdbsum/4iea 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>		[[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/1433S_HUMAN 1433S_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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of RAS mutant cancers.

-	~~==Function==~~	+	Stabilization of Physical RAF/14-3-3 Interaction by Cotylenin A as Treatment Strategy for RAS Mutant Cancers.,Molzan M, Kasper S, Roglin L, Skwarczynska M, Sassa T, Inoue T, Breitenbuecher F, Ohkanda J, Kato N, Schuler M, Ottmann C ACS Chem Biol. 2013 Sep 20;8(9):1869-75. doi: 10.1021/cb4003464. Epub 2013 Jul 5. PMID:23808890<ref>PMID:23808890</ref>
-	~~[[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/~~mTOR pathway (By similarity). p53~~-~~regulated inhibitor of G2/M progression. [[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4iea]] is~~ a ~~2 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=4IEA OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023808890</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[14-3-3 protein\|14-3-3 protein]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Molzan, M.]]	+	[[Category: Molzan, M]]
-	[[Category: Ottmann, C.]]	+	[[Category: Ottmann, C]]
	[[Category: 14-3-3 fold]]		[[Category: 14-3-3 fold]]
	[[Category: Adapter protein]]		[[Category: Adapter protein]]

OCA at 08:09, 29 September 2013

2013-09-29T08:09:12Z

←Older revision		Revision as of 08:09, 29 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4iea\| PDB=4iea \| SCENE= }}
		+	===14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide===
		+	{{ABSTRACT_PUBMED_23808890}}

-	~~The~~ entry ~~4iea~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Molzan~~, M., ~~Ottmann~~, C.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_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. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[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>

-	~~Description~~: 14-3-3 ~~isoform sigma in complex with a phosphorylated C~~-~~RAF peptide~~	+	==About this Structure==
		+	[[4iea]] is a 2 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=4IEA OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023808890</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Molzan, M.]]
		+	[[Category: Ottmann, C.]]
		+	[[Category: 14-3-3 fold]]
		+	[[Category: Adapter protein]]
		+	[[Category: All alpha-helical]]
		+	[[Category: Peptide binding protein]]
		+	[[Category: Protein-protein interaction]]
		+	[[Category: Raf]]

OCA at 12:25, 6 February 2013

2013-02-06T12:25:37Z

←Older revision		Revision as of 12:25, 6 February 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4iea is ON HOLD	+	The entry 4iea is ON HOLD until Paper Publication

	Authors: Molzan, M., Ottmann, C.		Authors: Molzan, M., Ottmann, C.

	Description: 14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide		Description: 14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide

OCA: Protected "4iea" [edit=sysop:move=sysop]

2012-12-19T11:09:05Z

Protected "4iea" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:09, 19 December 2012

OCA: New page: '''Unreleased structure''' The entry 4iea is ON HOLD Authors: Molzan, M., Ottmann, C. Description: 14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide

2012-12-19T11:09:04Z

New page: '''Unreleased structure''' The entry 4iea is ON HOLD Authors: Molzan, M., Ottmann, C. Description: 14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide

New page

'''Unreleased structure'''

The entry 4iea is ON HOLD

Authors: Molzan, M., Ottmann, C.

Description: 14-3-3 isoform sigma in complex with a phosphorylated C-RAF peptide