1qty - Revision history

OCA at 10:05, 16 August 2023

OCA — Wed, 16 Aug 2023 10:05:26 GMT

←Older revision		Revision as of 10:05, 16 August 2023
Line 3:		Line 3:
	<StructureSection load='1qty' size='340' side='right'caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='1qty' size='340' side='right'caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1qty]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QTY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~<div style='overflow: auto; max~~-~~height: 3em;'>[[1flt\|1flt]]~~, [[~~1qsv~~\|~~1qsv~~]]~~, [[1qsz\|1qsz]]</div>~~</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]] 2.7Å</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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [https://pdbe.org/1qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [https://www.ebi.ac.uk/pdbsum/1qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qty 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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [https://pdbe.org/1qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [https://www.ebi.ac.uk/pdbsum/1qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qty ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[https://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.	+	[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[https://omim.org/entry/603933 603933]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref> [[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref> <ref>PMID:18593464</ref> <ref>PMID:18515749</ref> <ref>PMID:20512933</ref> <ref>PMID:7824266</ref> <ref>PMID:8605350</ref> <ref>PMID:9299537</ref> <ref>PMID:11141500</ref> <ref>PMID:11811792</ref> <ref>PMID:11312102</ref> <ref>PMID:14633857</ref> <ref>PMID:12796773</ref> <ref>PMID:15735759</ref> <ref>PMID:16685275</ref> <ref>PMID:18079407</ref> <ref>PMID:18583712</ref> <ref>PMID:20551949</ref> <ref>PMID:21752276</ref>	+	[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Vos, A M.de]]~~	+	[[Category: Wiesmann C]]
-	[[Category: Wiesmann, C]]	+	[[Category: De Vos AM]]
-	[[Category: ~~Cystine knot]]~~	+
-	~~[[Category: Flt-1]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Hormone-growth factor receptor complex]]~~	+
-	~~[[Category: Hormone/growth factor receptor]]~~	+
-	~~[[Category: I-set]]~~	+
-	~~[[Category: Immunoglobulin-like domain]]~~	+
-	~~[[Category: Receptor tyrosine kinase]]~~	+
-	~~[[Category: Vegf receptor~~]]	+

OCA at 10:04, 15 September 2021

OCA — Wed, 15 Sep 2021 10:04:18 GMT

←Older revision		Revision as of 10:04, 15 September 2021
Line 3:		Line 3:
	<StructureSection load='1qty' size='340' side='right'caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='1qty' size='340' side='right'caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1QTY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1qty]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</div></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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [~~http~~://pdbe.org/1qty PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1qty PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1qty 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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [https://pdbe.org/1qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [https://www.ebi.ac.uk/pdbsum/1qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qty ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[~~http~~://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[~~http~~://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.	+	[[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[https://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref> [[~~http~~://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref> <ref>PMID:18593464</ref> <ref>PMID:18515749</ref> <ref>PMID:20512933</ref> <ref>PMID:7824266</ref> <ref>PMID:8605350</ref> <ref>PMID:9299537</ref> <ref>PMID:11141500</ref> <ref>PMID:11811792</ref> <ref>PMID:11312102</ref> <ref>PMID:14633857</ref> <ref>PMID:12796773</ref> <ref>PMID:15735759</ref> <ref>PMID:16685275</ref> <ref>PMID:18079407</ref> <ref>PMID:18583712</ref> <ref>PMID:20551949</ref> <ref>PMID:21752276</ref>	+	[[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref> [[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref> <ref>PMID:18593464</ref> <ref>PMID:18515749</ref> <ref>PMID:20512933</ref> <ref>PMID:7824266</ref> <ref>PMID:8605350</ref> <ref>PMID:9299537</ref> <ref>PMID:11141500</ref> <ref>PMID:11811792</ref> <ref>PMID:11312102</ref> <ref>PMID:14633857</ref> <ref>PMID:12796773</ref> <ref>PMID:15735759</ref> <ref>PMID:16685275</ref> <ref>PMID:18079407</ref> <ref>PMID:18583712</ref> <ref>PMID:20551949</ref> <ref>PMID:21752276</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[~~Colony-stimulating factor receptor~~ 3D ~~structures~~\|~~Colony-stimulating factor receptor~~ 3D ~~structures]]~~	+	*[[VEGF 3D Structures\|VEGF 3D Structures]]
-	*[[Vascular Endothelial Growth Factor\|Vascular Endothelial Growth Factor]]	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:52, 4 December 2019

OCA — Wed, 04 Dec 2019 11:52:14 GMT

←Older revision		Revision as of 11:52, 4 December 2019
Line 1:		Line 1:

	==VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR==		==VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR==
-	<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='1qty' size='340' side='right'caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[~~Tyrosine kinase~~\|~~Tyrosine kinase~~]]	+	*[[Colony-stimulating factor receptor 3D structures\|Colony-stimulating factor receptor 3D structures]]
	*[[Vascular Endothelial Growth Factor\|Vascular Endothelial Growth Factor]]		*[[Vascular Endothelial Growth Factor\|Vascular Endothelial Growth Factor]]
	== References ==		== References ==
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Vos, A M.de]]		[[Category: Vos, A M.de]]
	[[Category: Wiesmann, C]]		[[Category: Wiesmann, C]]

OCA at 08:16, 28 February 2018

OCA — Wed, 28 Feb 2018 08:16:15 GMT

←Older revision		Revision as of 08:16, 28 February 2018
Line 1:		Line 1:
		+
	==VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR==		==VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR==
	<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://pdbe.org/1qty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty 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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://pdbe.org/1qty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1qty ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qt/1qty_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qt/1qty_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 12:20, 8 February 2016

OCA — Mon, 08 Feb 2016 12:20:09 GMT

←Older revision		Revision as of 12:20, 8 February 2016
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qty ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 11:30, 10 September 2015

OCA — Thu, 10 Sep 2015 11:30:41 GMT

←Older revision		Revision as of 11:30, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty 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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://pdbe.org/1qty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 28:		Line 28:
	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 1qty" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Vos, A M.de]]		[[Category: Vos, A M.de]]
	[[Category: Wiesmann, C]]		[[Category: Wiesmann, C]]

OCA at 08:31, 6 January 2015

OCA — Tue, 06 Jan 2015 08:31:32 GMT

←Older revision		Revision as of 08:31, 6 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty 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=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.		[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Vos, A M.de.]]	+	[[Category: Vos, A M.de]]
-	[[Category: Wiesmann, C.]]	+	[[Category: Wiesmann, C]]
	[[Category: Cystine knot]]		[[Category: Cystine knot]]
	[[Category: Flt-1]]		[[Category: Flt-1]]

OCA at 14:50, 29 September 2014

OCA — Mon, 29 Sep 2014 14:50:59 GMT

←Older revision		Revision as of 14:50, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1qty\| PDB=1qty \| SCENE= }}~~	+	==VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR==
-	===VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR===	+	<StructureSection load='1qty' size='340' side='right' caption='[[1qty]], [[Resolution\|resolution]] 2.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_10543948}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[1qty]] is a 8 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=1QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QTY FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1flt\|1flt]], [[1qsv\|1qsv]], [[1qsz\|1qsz]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qty RCSB], [http://www.ebi.ac.uk/pdbsum/1qty PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.		[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref> [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref> <ref>PMID:18593464</ref> <ref>PMID:18515749</ref> <ref>PMID:20512933</ref> <ref>PMID:7824266</ref> <ref>PMID:8605350</ref> <ref>PMID:9299537</ref> <ref>PMID:11141500</ref> <ref>PMID:11811792</ref> <ref>PMID:11312102</ref> <ref>PMID:14633857</ref> <ref>PMID:12796773</ref> <ref>PMID:15735759</ref> <ref>PMID:16685275</ref> <ref>PMID:18079407</ref> <ref>PMID:18583712</ref> <ref>PMID:20551949</ref> <ref>PMID:21752276</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qt/1qty_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The extracellular portion of the VEGF and PlGF receptor, Flt-1 (or VEGFR-1), consists of seven immunoglobulin-like domains. The second domain from the N terminus (Flt-1D2) is necessary and sufficient for high affinity VEGF binding. The 1.7 A resolution crystal structure of Flt-1D2 bound to VEGF revealed that this domain is a member of the I-set of the immunoglobulin superfamily, but has several unusual features including a region near the N terminus that bulges away from the domain rather than pairing with the neighboring beta-strand. Some of the residues in this region make contact with VEGF, raising the possibility that this bulge could be a consequence of VEGF binding and might not be present in the absence of ligand. Here we report the three-dimensional structure of Flt-1D2 in its uncomplexed form determined by NMR spectroscopy. A semi-automated method for NOE assignment that takes advantage of the previously solved crystal structure was used to facilitate rapid analysis of the 3D NOESY spectra. The solution structure is very similar to the previously reported VEGF-bound crystal structure; the N-terminal bulge is present, albeit in a different conformation. We also report the 2.7 A crystal structure of Flt-1D2 in complex with VEGF solved in a different crystal form that reveals yet another conformation for the N-terminal bulge region. (1)H-(15)N heteronuclear NOEs indicate this region is flexible in solution; the crystal structures show that this region is able to adopt more than one conformation even when bound to VEGF. Thus, VEGF-binding is not accompanied by significant structural change in Flt-1D2, and the unusual structural features of Flt-1D2 are an intrinsic property of this domain.

-	~~==Function==~~	+	Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states.,Starovasnik MA, Christinger HW, Wiesmann C, Champe MA, de Vos AM, Skelton NJ J Mol Biol. 1999 Oct 29;293(3):531-44. PMID:10543948<ref>PMID:10543948</ref>
-	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of ~~blood vessels. Binds to~~ the ~~FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms~~ VEGF-~~165 and VEGF~~-~~145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID~~:11427521</ref><ref>PMID:15520188</ref><ref>PMID:16489009</ref> [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free ~~VEGFA~~ and ~~preventing its binding to KDR~~. ~~Likewise~~, ~~isoforms lacking a transmembrane domain~~, ~~such as isoform 2~~, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C~~. Mediates phosphorylation of PIK3R1~~, ~~the regulatory subunit of phosphatidylinositol 3-kinase~~, ~~leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2~~, ~~MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway~~. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; ~~it increases phosphorylation of SRC at 'Tyr~~-~~418' by unknown means and promotes tumor cell invasion~~.~~<ref>~~PMID:8248162</ref><ref>PMID:18593464</ref><ref>PMID:18515749</ref><ref>PMID:20512933</ref><ref>PMID:7824266</ref><ref>PMID:8605350</ref><ref>PMID:9299537</ref><ref>PMID:11141500</ref><ref>PMID:11811792</ref><ref>PMID:11312102</ref><ref>PMID:14633857</ref><ref>PMID:12796773</ref><ref>PMID:15735759</ref><ref>PMID:16685275</ref><ref>PMID:18079407</ref><ref>PMID:18583712</ref><ref>PMID:20551949</ref><ref>PMID:~~21752276~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[1qty]] is~~ a ~~8 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=1QTY OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase\|Tyrosine kinase]]
	*[[Vascular Endothelial Growth Factor\|Vascular Endothelial Growth Factor]]		*[[Vascular Endothelial Growth Factor\|Vascular Endothelial Growth Factor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:010543948</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Vos, A M.de.]]		[[Category: Vos, A M.de.]]

OCA at 11:54, 24 March 2013

OCA — Sun, 24 Mar 2013 11:54:09 GMT

←Older revision		Revision as of 11:54, 24 March 2013
Line 1:		Line 1:
-	[[Image:1qty.png\|left\|200px]]
-
	{{STRUCTURE_1qty\| PDB=1qty \| SCENE= }}		{{STRUCTURE_1qty\| PDB=1qty \| SCENE= }}
-
	===VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR===		===VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR===
		+	{{ABSTRACT_PUBMED_10543948}}

-	~~{{ABSTRACT_PUBMED_10543948}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref><ref>PMID:15520188</ref><ref>PMID:16489009</ref> [[http://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref><ref>PMID:18593464</ref><ref>PMID:18515749</ref><ref>PMID:20512933</ref><ref>PMID:7824266</ref><ref>PMID:8605350</ref><ref>PMID:9299537</ref><ref>PMID:11141500</ref><ref>PMID:11811792</ref><ref>PMID:11312102</ref><ref>PMID:14633857</ref><ref>PMID:12796773</ref><ref>PMID:15735759</ref><ref>PMID:16685275</ref><ref>PMID:18079407</ref><ref>PMID:18583712</ref><ref>PMID:20551949</ref><ref>PMID:21752276</ref>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:010543948</ref><references group="xtra"/>	+	<ref group="xtra">PMID:010543948</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Vos, A M.de.]]		[[Category: Vos, A M.de.]]

OCA at 10:07, 20 October 2012

OCA — Sat, 20 Oct 2012 10:07:01 GMT

←Older revision		Revision as of 10:07, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[1qty]] is a 8 chain structure ~~of [[Tyrosine kinase]] and [[Vascular Endothelial Growth Factor]]~~ 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=1QTY OCA].	+	[[1qty]] is a 8 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=1QTY OCA].

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