4tye - Revision history

OCA at 07:19, 1 May 2024

2024-05-01T07:19:25Z

←Older revision		Revision as of 07:19, 1 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4tye]] is a 1 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=4TYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TYE FirstGlance]. <br>		<table><tr><td colspan='2'>[[4tye]] is a 1 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=4TYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TYE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [https://pdbe.org/4tye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [https://www.ebi.ac.uk/pdbsum/4tye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye 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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [https://pdbe.org/4tye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [https://www.ebi.ac.uk/pdbsum/4tye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>		[https://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The family of Fibroblast Growth Factor Receptors (FGFRs) plays an important and well characterized role in a variety of pathological disorders. FGFR4 is involved in myogenesis and muscle regeneration. Mutations affecting the kinase domain of FGFR4 may cause cancer e.g. breast cancer or rhabdomyosarcoma. Whereas FGFRs 1-3 have been structurally characterized, the structure of the FGFR4 kinase domain has not yet been reported. In this study we present four structures of the kinase domain of FGFR4, in its apo-form and in complex with different types of small-molecule inhibitors. The two apo-FGFR4 kinase domain structures show an activation segment similar in conformation to an autoinhibitory segment observed in the hepatocyte growth factor receptor kinase but different from the known structures of other FGFR kinases. The structures of FGFR4 in complex with the type I-inhibitor Dovitinib and the type II-inhibitor Ponatinib reveal the molecular interactions with different types of kinase inhibitors and may assist in the design and development of FGFR4-inhibitors.
-
-	Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase.,Lesca E, Lammens A, Huber R, Augustin M J Mol Biol. 2014 Sep 11. pii: S0022-2836(14)00474-4. doi:, 10.1016/j.jmb.2014.09.004. PMID:25219510<ref>PMID:25219510</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4tye" style="background-color:#fffaf0;"></div>

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

OCA at 07:51, 22 March 2023

2023-03-22T07:51:49Z

←Older revision		Revision as of 07:51, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='4tye' size='340' side='right'caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4tye' size='340' side='right'caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4tye]] is a 1 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=4TYE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4TYE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4tye]] is a 1 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=4TYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TYE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [https://pdbe.org/4tye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [https://www.ebi.ac.uk/pdbsum/4tye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGFR4, JTK2, TKF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [~~http~~://pdbe.org/4tye PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4tye PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>	+	[https://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]	+	*[[Fibroblast growth factor receptor 3D receptor\|Fibroblast growth factor receptor 3D receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Augustin M]]
-	[[Category: Augustin, M]]	+	[[Category: Huber R]]
-	[[Category: Huber, R]]	+	[[Category: Lammens A]]
-	[[Category: Lammens, A]]	+	[[Category: Lesca E]]
-	[[Category: Lesca, E]]	+
-	~~[[Category: Dovitinib]]~~	+
-	~~[[Category: Fibroblast growth factor receptor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Ponatinb]]~~	+
-	~~[[Category: Proteros biostructures gmbh]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 14:59, 10 May 2019

2019-05-10T14:59:36Z

←Older revision		Revision as of 14:59, 10 May 2019
Line 1:		Line 1:

	==Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase==		==Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase==
-	<StructureSection load='4tye' size='340' side='right' caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='4tye' size='340' side='right'caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4tye]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4tye]] is a 1 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=4TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGFR4, JTK2, TKF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://pdbe.org/4tye PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye 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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://pdbe.org/4tye PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Augustin, M]]		[[Category: Augustin, M]]

OCA at 19:52, 4 August 2016

2016-08-04T19:52:07Z

←Older revision		Revision as of 19:52, 4 August 2016
Line 1:		Line 1:
		+
	==Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase==		==Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase==
	<StructureSection load='4tye' size='340' side='right' caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4tye' size='340' side='right' caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye 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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://pdbe.org/4tye PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tye ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4tye" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:35, 25 December 2014

2014-12-25T12:35:07Z

←Older revision		Revision as of 12:35, 25 December 2014
Line 8:		Line 8:
	<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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye 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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:44, 10 December 2014

2014-12-10T11:44:35Z

←Older revision		Revision as of 11:44, 10 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4tye]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYE FirstGlance]. <br>		<table><tr><td colspan='2'>[[4tye]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYE FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye 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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Augustin, M.]]	+	[[Category: Augustin, M]]
-	[[Category: Huber, R.]]	+	[[Category: Huber, R]]
-	[[Category: Lammens, A.]]	+	[[Category: Lammens, A]]
-	[[Category: Lesca, E.]]	+	[[Category: Lesca, E]]
	[[Category: Dovitinib]]		[[Category: Dovitinib]]
	[[Category: Fibroblast growth factor receptor]]		[[Category: Fibroblast growth factor receptor]]

OCA at 10:29, 24 September 2014

2014-09-24T10:29:56Z

←Older revision		Revision as of 10:29, 24 September 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase==
		+	<StructureSection load='4tye' size='340' side='right' caption='[[4tye]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4tye]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYE FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tyg\|4tyg]], [[4tyi\|4tyi]], [[4tyj\|4tyj]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=4tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tye RCSB], [http://www.ebi.ac.uk/pdbsum/4tye PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The family of Fibroblast Growth Factor Receptors (FGFRs) plays an important and well characterized role in a variety of pathological disorders. FGFR4 is involved in myogenesis and muscle regeneration. Mutations affecting the kinase domain of FGFR4 may cause cancer e.g. breast cancer or rhabdomyosarcoma. Whereas FGFRs 1-3 have been structurally characterized, the structure of the FGFR4 kinase domain has not yet been reported. In this study we present four structures of the kinase domain of FGFR4, in its apo-form and in complex with different types of small-molecule inhibitors. The two apo-FGFR4 kinase domain structures show an activation segment similar in conformation to an autoinhibitory segment observed in the hepatocyte growth factor receptor kinase but different from the known structures of other FGFR kinases. The structures of FGFR4 in complex with the type I-inhibitor Dovitinib and the type II-inhibitor Ponatinib reveal the molecular interactions with different types of kinase inhibitors and may assist in the design and development of FGFR4-inhibitors.

-	~~The entry 4tye is ON HOLD until Paper Publication~~	+	Structural analysis of the human Fibroblast Growth Factor Receptor 4 Kinase.,Lesca E, Lammens A, Huber R, Augustin M J Mol Biol. 2014 Sep 11. pii: S0022-2836(14)00474-4. doi:, 10.1016/j.jmb.2014.09.004. PMID:25219510<ref>PMID:25219510</ref>

-	~~Authors: Lesca~~, E.~~, Lammens, A~~., Huber, R., ~~Augustin~~, M.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structural analysis of the human~~ Fibroblast ~~Growth Factor Receptor 4~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Augustin, M.]]
		+	[[Category: Huber, R.]]
		+	[[Category: Lammens, A.]]
		+	[[Category: Lesca, E.]]
		+	[[Category: Dovitinib]]
		+	[[Category: Fibroblast growth factor receptor]]
		+	[[Category: Kinase]]
		+	[[Category: Ponatinb]]
		+	[[Category: Proteros biostructures gmbh]]
		+	[[Category: Transferase]]

OCA at 01:23, 7 August 2014

2014-08-07T01:23:41Z

←Older revision		Revision as of 01:23, 7 August 2014
Line 3:		Line 3:
	The entry 4tye is ON HOLD until Paper Publication		The entry 4tye is ON HOLD until Paper Publication

-	Authors: Lesca, E., Lammens, A, Huber, R., Augustin, M.	+	Authors: Lesca, E., Lammens, A., Huber, R., Augustin, M.

	Description: Structural analysis of the human Fibroblast Growth Factor Receptor 4		Description: Structural analysis of the human Fibroblast Growth Factor Receptor 4

OCA at 07:22, 23 July 2014

2014-07-23T07:22:37Z

←Older revision		Revision as of 07:22, 23 July 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lesca, E., Lammens, A, Huber, R., Augustin, M.		Authors: Lesca, E., Lammens, A, Huber, R., Augustin, M.

	Description: Structural analysis of the human Fibroblast Growth Factor Receptor 4		Description: Structural analysis of the human Fibroblast Growth Factor Receptor 4

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

2014-07-16T09:57:12Z

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

←Older revision

Revision as of 09:57, 16 July 2014