5whe - Revision history

OCA at 14:12, 4 October 2023

OCA — Wed, 04 Oct 2023 14:12:56 GMT

←Older revision		Revision as of 14:12, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5whe' size='340' side='right'caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='5whe' size='340' side='right'caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Synthetic_construct_sequences~~ Synthetic construct ~~sequences~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WHE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WHE FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=CA:CALCIUM+ION'~~>~~CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID~~-~~GUANYLATE+ESTER'>GNP</scene>~~, ~~<scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.91Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5kno\|5kno]], [[5klj\|5klj]], [[5kme\|5kme]], [[5kn6\|5kn6]]~~<~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<~~tr id~~='~~gene~~'><~~td class="sblockLbl"~~><~~b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">KRAS, KRAS2, RASK2 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whe OCA], [https://pdbe.org/5whe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5whe RCSB], [https://www.ebi.ac.uk/pdbsum/5whe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5whe 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=5whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whe OCA], [~~http~~://pdbe.org/5whe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5whe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5whe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5whe ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:[~~http~~://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.<ref>PMID:8955068</ref> Defects in KRAS 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. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[~~http~~://omim.org/entry/609942 609942]]. Noonan syndrome (NS) [MIM:[~~http~~://omim.org/entry/163950 163950]] 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. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[~~http~~://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[~~http~~://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.	+	[https://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN] Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:[https://omim.org/entry/601626 601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.<ref>PMID:8955068</ref> Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://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. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[https://omim.org/entry/609942 609942]. Noonan syndrome (NS) [MIM:[https://omim.org/entry/163950 163950] 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. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[https://omim.org/entry/613659 613659]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.	+	[https://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Synthetic construct ~~sequences~~]]	+	[[Category: Synthetic construct]]
-	[[Category: Lee, S J]]	+	[[Category: Lee S-J]]
-	[[Category: McGee~~, J H~~]]	+	[[Category: McGee JH]]
-	[[Category: Shim~~, S Y~~]]	+	[[Category: Shim SY]]
-	[[Category: Verdine~~, G L]]~~	+	[[Category: Verdine GL]]
-	~~[[Category: Gtp binding protein]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Ras binder~~]]	+

OCA at 16:03, 29 January 2020

OCA — Wed, 29 Jan 2020 16:03:53 GMT

←Older revision		Revision as of 16:03, 29 January 2020
Line 1:		Line 1:

	==KRas G12V/D38P, bound to GppNHp and miniprotein 225-11==		==KRas G12V/D38P, bound to GppNHp and miniprotein 225-11==
-	<StructureSection load='5whe' size='340' side='right' caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>	+	<StructureSection load='5whe' size='340' side='right'caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHE FirstGlance]. <br>		<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHE FirstGlance]. <br>
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[GTPase KRas\|GTPase KRas]]	+	*[[GTPase KRas 3D structures\|GTPase KRas 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Synthetic construct sequences]]		[[Category: Synthetic construct sequences]]
	[[Category: Lee, S J]]		[[Category: Lee, S J]]

OCA at 06:54, 14 March 2018

OCA — Wed, 14 Mar 2018 06:54:48 GMT

←Older revision		Revision as of 06:54, 14 March 2018
Line 3:		Line 3:
	<StructureSection load='5whe' size='340' side='right' caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='5whe' size='340' side='right' caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5kno\|5kno]], [[5klj\|5klj]], [[5kme\|5kme]], [[5kn6\|5kn6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5kno\|5kno]], [[5klj\|5klj]], [[5kme\|5kme]], [[5kn6\|5kn6]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS2, RASK2 ([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=5whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whe OCA], [http://pdbe.org/5whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whe RCSB], [http://www.ebi.ac.uk/pdbsum/5whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whe 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=5whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whe OCA], [http://pdbe.org/5whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whe RCSB], [http://www.ebi.ac.uk/pdbsum/5whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whe ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5whe" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5whe" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GTPase KRas\|GTPase KRas]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Synthetic construct sequences]]
	[[Category: Lee, S J]]		[[Category: Lee, S J]]
	[[Category: McGee, J H]]		[[Category: McGee, J H]]

OCA at 08:40, 10 January 2018

OCA — Wed, 10 Jan 2018 08:40:51 GMT

←Older revision		Revision as of 08:40, 10 January 2018
Line 12:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.		[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Ras proteins are aberrantly activated in a wide range of human cancers, often endowing tumors with aggressive properties and resistance to therapy. Decades of effort to develop direct Ras inhibitors for clinical use have thus far failed, largely because of a lack of adequate small-molecule binding pockets on the Ras surface. Here, we report the discovery of Ras-binding miniproteins from a naive library, and their evolution to afford versions with mid-picomolar affinity to Ras. A series of biochemical experiments indicated that these miniproteins bind to the Ras effector domain as dimers, and high-resolution crystal structures revealed that these miniprotein dimers bind Ras in an unprecedented mode, in which the Ras effector domain is remodeled to expose an extended pocket that connects two isolated pockets previously found to engage small-molecule ligands. We also report a Ras point mutant that stabilizes the protein in the open conformation trapped by these miniproteins. These findings provide new tools for studying Ras structure and function, and present opportunities for the development of both miniprotein and small-molecule inhibitors that directly target the Ras proteins.
		+
		+	Exceptionally high-affinity Ras binders that remodel its effector domain.,McGee JH, Shim SY, Lee SJ, Swanson PK, Jiang Y, Durney MA, Verdine GL J Biol Chem. 2017 Dec 27. pii: M117.816348. doi: 10.1074/jbc.M117.816348. PMID:29282294<ref>PMID:29282294</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5whe" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:49, 3 January 2018

OCA — Wed, 03 Jan 2018 05:49:05 GMT

←Older revision		Revision as of 05:49, 3 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5whe~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==KRas G12V/D38P, bound to GppNHp and miniprotein 225-11==
-		+	<StructureSection load='5whe' size='340' side='right' caption='[[5whe]], [[Resolution\|resolution]] 1.91Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5whe]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHE FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5kno\|5kno]], [[5klj\|5klj]], [[5kme\|5kme]], [[5kn6\|5kn6]]</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=5whe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whe OCA], [http://pdbe.org/5whe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whe RCSB], [http://www.ebi.ac.uk/pdbsum/5whe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whe ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:[http://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.<ref>PMID:8955068</ref> Defects in KRAS 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. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[http://omim.org/entry/609942 609942]]. Noonan syndrome (NS) [MIM:[http://omim.org/entry/163950 163950]] 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. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Lee, S J]]
		+	[[Category: McGee, J H]]
		+	[[Category: Shim, S Y]]
		+	[[Category: Verdine, G L]]
		+	[[Category: Gtp binding protein]]
		+	[[Category: Protein binding]]
		+	[[Category: Ras binder]]

OCA: Protected "5whe" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:49:27 GMT

Protected "5whe" [edit=sysop:move=sysop]

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Revision as of 14:49, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5whe is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 14:49:26 GMT

New page: '''Unreleased structure''' The entry 5whe is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

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'''Unreleased structure'''

The entry 5whe is ON HOLD until Paper Publication

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Description:
[[Category: Unreleased Structures]]