4je4 - Revision history

OCA at 12:03, 1 March 2024

OCA — Fri, 01 Mar 2024 12:03:12 GMT

←Older revision		Revision as of 12:03, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>
-	</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [https://pdbe.org/4je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [https://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></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]] 2.31Å</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [https://pdbe.org/4je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [https://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref> Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>		[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref> Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.
-
-	Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.,Sha F, Gencer EB, Georgeon S, Koide A, Yasui N, Koide S, Hantschel O Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14924-9. doi:, 10.1073/pnas.1303640110. Epub 2013 Aug 26. PMID:23980151<ref>PMID:23980151</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:08, 24 November 2022

OCA — Thu, 24 Nov 2022 11:08:32 GMT

←Older revision		Revision as of 11:08, 24 November 2022
Line 1:		Line 1:

	==Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex==		==Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex==
-	<StructureSection load='4je4' size='340' side='right' caption='[[4je4]], [[Resolution\|resolution]] 2.31Å' scene=''>	+	<StructureSection load='4je4' size='340' side='right'caption='[[4je4]], [[Resolution\|resolution]] 2.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>
-	</td></tr>~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jeg\|4jeg]]</td></tr>~~	+	</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [https://pdbe.org/4je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [https://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTP2C, PTPN11, SHPTP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [~~http~~://pdbe.org/4je4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PTN11_HUMAN PTN11_HUMAN]~~] Defects in ~~PTPN11~~ are the cause of ~~LEOPARD syndrome~~ type 1 (~~LEOPARD1~~) [MIM:[~~http~~://omim.org/entry/~~151100 151100]~~]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by ~~dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness~~, ~~motor delay~~, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to ~~granulocyte~~-~~macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects~~ in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the ~~presence~~ of ~~multiple enchondromas and osteochondroma-like lesions~~.<ref>PMID:~~20577567~~</ref>	+	[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:[https://omim.org/entry/601894 601894]; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.<ref>PMID:18268355</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PTN11_HUMAN PTN11_HUMAN~~]~~] Acts downstream of~~ various ~~receptor~~ and ~~cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus~~. ~~Dephosphorylates ROCK2 at Tyr-722 resulting~~ in ~~stimulatation~~ of ~~its RhoA binding activity~~.<ref>PMID:~~10655584~~</ref> <ref>PMID:~~18829466~~</ref> <ref>PMID:~~18559669~~</ref>	+	[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref> Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine phosphatase 3D structures\|Tyrosine phosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Koide, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Sha, F~~]]	+	[[Category: Koide S]]
-	[[Category: ~~Engineered binding protein]]~~	+	[[Category: Sha F]]
-	~~[[Category: Phosphatase]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Phosphotyrosine binding]]~~	+
-	~~[[Category: Shp2 sh2-monobody complex]]~~	+
-	~~[[Category: Signaling protein-protein binding complex~~]]	+

OCA at 15:03, 15 November 2017

OCA — Wed, 15 Nov 2017 15:03:41 GMT

←Older revision		Revision as of 15:03, 15 November 2017
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	</div>		</div>
	<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:08, 11 August 2016

OCA — Thu, 11 Aug 2016 14:08:27 GMT

←Older revision		Revision as of 14:08, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex==		==Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex==
	<StructureSection load='4je4' size='340' side='right' caption='[[4je4]], [[Resolution\|resolution]] 2.31Å' scene=''>		<StructureSection load='4je4' size='340' side='right' caption='[[4je4]], [[Resolution\|resolution]] 2.31Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jeg\|4jeg]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jeg\|4jeg]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTP2C, PTPN11, SHPTP2 ([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">PTP2C, PTPN11, SHPTP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [http://www.ebi.ac.uk/pdbsum/4je4 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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [http://pdbe.org/4je4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [http://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4je4" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:35, 4 January 2015

OCA — Sun, 04 Jan 2015 14:35:07 GMT

←Older revision		Revision as of 14:35, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4je4\| PDB=4je4 \| SCENE= }}~~	+	==Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex==
-	===Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex===	+	<StructureSection load='4je4' size='340' side='right' caption='[[4je4]], [[Resolution\|resolution]] 2.31Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23980151}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jeg\|4jeg]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTP2C, PTPN11, SHPTP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [http://www.ebi.ac.uk/pdbsum/4je4 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[http://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>		[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[http://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.

-	~~==Function==~~	+	Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.,Sha F, Gencer EB, Georgeon S, Koide A, Yasui N, Koide S, Hantschel O Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14924-9. doi:, 10.1073/pnas.1303640110. Epub 2013 Aug 26. PMID:23980151<ref>PMID:23980151</ref>
-	~~[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream~~ of ~~various receptor and cytoplasmic protein tyrosine kinases to participate in~~ the ~~signal transduction from the cell surface~~ to the ~~nucleus~~. ~~Dephosphorylates ROCK2 at Tyr~~-~~722 resulting in stimulatation of its RhoA binding activity~~.~~<ref>PMID~~:~~10655584<~~/~~ref> <ref>~~PMID:~~18829466</ref>~~ <ref>PMID:~~18559669~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4je4]] 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=4JE4 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023980151</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Koide, S.]]	+	[[Category: Koide, S]]
-	[[Category: Sha, F.]]	+	[[Category: Sha, F]]
	[[Category: Engineered binding protein]]		[[Category: Engineered binding protein]]
	[[Category: Phosphatase]]		[[Category: Phosphatase]]

OCA at 14:26, 12 March 2014

OCA — Wed, 12 Mar 2014 14:26:23 GMT

←Older revision		Revision as of 14:26, 12 March 2014
Line 10:		Line 10:

	==About this Structure==		==About this Structure==
-	[[4je4]] 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=4JE4 OCA].	+	[[4je4]] 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=4JE4 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:023980151</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:023980151</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
		+	[[Category: Koide, S.]]
	[[Category: Sha, F.]]		[[Category: Sha, F.]]
	[[Category: Engineered binding protein]]		[[Category: Engineered binding protein]]

OCA at 04:22, 12 September 2013

OCA — Thu, 12 Sep 2013 04:22:22 GMT

←Older revision		Revision as of 04:22, 12 September 2013
Line 1:		Line 1:
	{{STRUCTURE_4je4\| PDB=4je4 \| SCENE= }}		{{STRUCTURE_4je4\| PDB=4je4 \| SCENE= }}
	===Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex===		===Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex===
		+	{{ABSTRACT_PUBMED_23980151}}

	==Disease==		==Disease==
Line 12:		Line 13:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023980151</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sha, F.]]		[[Category: Sha, F.]]

OCA at 07:38, 28 August 2013

OCA — Wed, 28 Aug 2013 07:38:22 GMT

←Older revision		Revision as of 07:38, 28 August 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4je4\| PDB=4je4 \| SCENE= }}
		+	===Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex===

-	The entry ~~4je4~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[http://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>

-	~~Authors~~: ~~Sha, F~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>

-	~~Description: Crystal~~ Structure ~~of Monobody NSa1~~/~~SHP2 N~~-~~SH2 Domain Complex~~	+	==About this Structure==
		+	[[4je4]] 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=4JE4 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Sha, F.]]
		+	[[Category: Engineered binding protein]]
		+	[[Category: Phosphatase]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Phosphotyrosine binding]]
		+	[[Category: Shp2 sh2-monobody complex]]
		+	[[Category: Signaling protein-protein binding complex]]

OCA at 19:53, 17 April 2013

OCA — Wed, 17 Apr 2013 19:53:16 GMT

←Older revision		Revision as of 19:53, 17 April 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4je4 is ON HOLD	+	The entry 4je4 is ON HOLD until Paper Publication

	Authors: Sha, F.		Authors: Sha, F.

	Description: Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex		Description: Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex

OCA: Protected "4je4" [edit=sysop:move=sysop]

OCA — Wed, 06 Mar 2013 13:53:26 GMT

Protected "4je4" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:53, 6 March 2013