5flf - Revision history

OCA at 06:56, 19 July 2023

2023-07-19T06:56:06Z

←Older revision		Revision as of 06:56, 19 July 2023
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	<StructureSection load='5flf' size='340' side='right'caption='[[5flf]], [[Resolution\|resolution]] 2.58Å' scene=''>		<StructureSection load='5flf' size='340' side='right'caption='[[5flf]], [[Resolution\|resolution]] 2.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5flf]] is a 5 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=5FLF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5FLF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5flf]] is a 5 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=5FLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FLF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.58Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [~~http~~://pdbe.org/5flf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5flf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5flf 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=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [https://pdbe.org/5flf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [https://www.ebi.ac.uk/pdbsum/5flf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5flf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:[~~http~~://omim.org/entry/101600 101600]]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.<ref>PMID:20139426</ref> <ref>PMID:7874169</ref> Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:[~~http~~://omim.org/entry/147950 147950]]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).<ref>PMID:20139426</ref> <ref>PMID:12627230</ref> <ref>PMID:15001591</ref> <ref>PMID:15605412</ref> <ref>PMID:15845591</ref> <ref>PMID:16882753</ref> <ref>PMID:16764984</ref> <ref>PMID:16757108</ref> <ref>PMID:16606836</ref> <ref>PMID:17154279</ref> Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:[~~http~~://omim.org/entry/166250 166250]]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.<ref>PMID:20139426</ref> <ref>PMID:15625620</ref> <ref>PMID:16470795</ref> Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:[~~http~~://omim.org/entry/190440 190440]]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.<ref>PMID:20139426</ref> <ref>PMID:11173846</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.<ref>PMID:20139426</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.	+	[https://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:[https://omim.org/entry/101600 101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.<ref>PMID:20139426</ref> <ref>PMID:7874169</ref> Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:[https://omim.org/entry/147950 147950]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).<ref>PMID:20139426</ref> <ref>PMID:12627230</ref> <ref>PMID:15001591</ref> <ref>PMID:15605412</ref> <ref>PMID:15845591</ref> <ref>PMID:16882753</ref> <ref>PMID:16764984</ref> <ref>PMID:16757108</ref> <ref>PMID:16606836</ref> <ref>PMID:17154279</ref> Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:[https://omim.org/entry/166250 166250]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.<ref>PMID:20139426</ref> <ref>PMID:15625620</ref> <ref>PMID:16470795</ref> Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:[https://omim.org/entry/190440 190440]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.<ref>PMID:20139426</ref> <ref>PMID:11173846</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.<ref>PMID:20139426</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.<ref>PMID:20139426</ref> <ref>PMID:1379697</ref> <ref>PMID:1379698</ref> <ref>PMID:8622701</ref> <ref>PMID:8663044</ref> <ref>PMID:11353842</ref> <ref>PMID:12181353</ref> <ref>PMID:15117958</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:19261810</ref> <ref>PMID:19224897</ref> <ref>PMID:21765395</ref> <ref>PMID:10830168</ref> <ref>PMID:19665973</ref> <ref>PMID:20133753</ref>	+	[https://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.<ref>PMID:20139426</ref> <ref>PMID:1379697</ref> <ref>PMID:1379698</ref> <ref>PMID:8622701</ref> <ref>PMID:8663044</ref> <ref>PMID:11353842</ref> <ref>PMID:12181353</ref> <ref>PMID:15117958</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:19261810</ref> <ref>PMID:19224897</ref> <ref>PMID:21765395</ref> <ref>PMID:10830168</ref> <ref>PMID:19665973</ref> <ref>PMID:20133753</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Bunney TD]]
-	[[Category: Bunney~~, T D~~]]	+	[[Category: Katan M]]
-	[[Category: Katan, M]]	+	[[Category: Thiyagarajan N]]
-	[[Category: Thiyagarajan, N]]	+
-	~~[[Category: Auto-activating]]~~	+
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Growth factor]]~~	+
-	~~[[Category: Mutation]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:24, 6 May 2020

2020-05-06T07:24:30Z

←Older revision		Revision as of 07:24, 6 May 2020
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	==DISEASE LINKED MUTATION IN FGFR==		==DISEASE LINKED MUTATION IN FGFR==
-	<StructureSection load='5flf' size='340' side='right' caption='[[5flf]], [[Resolution\|resolution]] 2.58Å' scene=''>	+	<StructureSection load='5flf' size='340' side='right'caption='[[5flf]], [[Resolution\|resolution]] 2.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5flf]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FLF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5FLF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5flf]] is a 5 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=5FLF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FLF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [http://pdbe.org/5flf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [http://www.ebi.ac.uk/pdbsum/5flf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5flf ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [http://pdbe.org/5flf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [http://www.ebi.ac.uk/pdbsum/5flf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5flf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5flf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5flf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fibroblast growth factor receptor 3D receptor\|Fibroblast growth factor receptor 3D receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Bunney, T D]]		[[Category: Bunney, T D]]

OCA at 08:25, 10 August 2016

2016-08-10T08:25:33Z

←Older revision		Revision as of 08:25, 10 August 2016
Line 6:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [http://pdbe.org/5flf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [http://www.ebi.ac.uk/pdbsum/5flf 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=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [http://pdbe.org/5flf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [http://www.ebi.ac.uk/pdbsum/5flf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5flf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 20:34, 11 May 2016

2016-05-11T20:34:43Z

←Older revision		Revision as of 20:34, 11 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5flf is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==DISEASE LINKED MUTATION IN FGFR==
		+	<StructureSection load='5flf' size='340' side='right' caption='[[5flf]], [[Resolution\|resolution]] 2.58Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5flf]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FLF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FLF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5flf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5flf OCA], [http://pdbe.org/5flf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5flf RCSB], [http://www.ebi.ac.uk/pdbsum/5flf PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:[http://omim.org/entry/101600 101600]]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.<ref>PMID:20139426</ref> <ref>PMID:7874169</ref> Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:[http://omim.org/entry/147950 147950]]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).<ref>PMID:20139426</ref> <ref>PMID:12627230</ref> <ref>PMID:15001591</ref> <ref>PMID:15605412</ref> <ref>PMID:15845591</ref> <ref>PMID:16882753</ref> <ref>PMID:16764984</ref> <ref>PMID:16757108</ref> <ref>PMID:16606836</ref> <ref>PMID:17154279</ref> Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:[http://omim.org/entry/166250 166250]]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.<ref>PMID:20139426</ref> <ref>PMID:15625620</ref> <ref>PMID:16470795</ref> Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:[http://omim.org/entry/190440 190440]]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.<ref>PMID:20139426</ref> <ref>PMID:11173846</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.<ref>PMID:20139426</ref> Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.<ref>PMID:20139426</ref> <ref>PMID:1379697</ref> <ref>PMID:1379698</ref> <ref>PMID:8622701</ref> <ref>PMID:8663044</ref> <ref>PMID:11353842</ref> <ref>PMID:12181353</ref> <ref>PMID:15117958</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:19261810</ref> <ref>PMID:19224897</ref> <ref>PMID:21765395</ref> <ref>PMID:10830168</ref> <ref>PMID:19665973</ref> <ref>PMID:20133753</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Frequent genetic alterations discovered in FGFRs and evidence implicating some as drivers in diverse tumors has been accompanied by rapid progress in targeting FGFRs for anticancer treatments. Wider assessment of the impact of genetic changes on the activation state and drug responses is needed to better link the genomic data and treatment options. We here apply a direct comparative and comprehensive analysis of FGFR3 kinase domain variants representing the diversity of point-mutations reported in this domain. We reinforce the importance of N540K and K650E and establish that not all highly activating mutations (for example R669G) occur at high-frequency and conversely, that some "hotspots" may not be linked to activation. Further structural characterization consolidates a mechanistic view of FGFR kinase activation and extends insights into drug binding. Importantly, using several inhibitors of particular clinical interest (AZD4547, BGJ-398, TKI258, JNJ42756493 and AP24534), we find that some activating mutations (including different replacements of the same residue) result in distinct changes in their efficacy. Considering that there is no approved inhibitor for anticancer treatments based on FGFR-targeting, this information will be immediately translatable to ongoing clinical trials.

-	~~Authors: Thiyagarajan, N~~., Bunney, T.D., ~~Katan~~, M.	+	Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use.,Patani H, Bunney TD, Thiyagarajan N, Norman RA, Ogg D, Breed J, Ashford P, Potterton A, Edwards M, Williams SV, Thomson GS, Pang CS, Knowles MA, Breeze AL, Orengo C, Phillips C, Katan M Oncotarget. 2016 Mar 16. doi: 10.18632/oncotarget.8132. PMID:26992226<ref>PMID:26992226</ref>

-	~~Description~~: ~~DISEASE LINKED MUTATION IN FGFR~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Bunney, T.D]]	+	<div class="pdbe-citations 5flf" style="background-color:#fffaf0;"></div>
-	~~[[Category: Thiyagarajan, N~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Bunney, T D]]
	[[Category: Katan, M]]		[[Category: Katan, M]]
		+	[[Category: Thiyagarajan, N]]
		+	[[Category: Auto-activating]]
		+	[[Category: Cancer]]
		+	[[Category: Growth factor]]
		+	[[Category: Mutation]]
		+	[[Category: Receptor]]
		+	[[Category: Transferase]]

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

2015-12-01T03:32:44Z

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

←Older revision

Revision as of 03:32, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5flf is ON HOLD until Paper Publication Authors: Thiyagarajan, N., Bunney, T.D., Katan, M. Description: DISEASE LINKED MUTATION IN FGFR [[Category:...

2015-12-01T03:32:43Z

New page: '''Unreleased structure''' The entry 5flf is ON HOLD until Paper Publication Authors: Thiyagarajan, N., Bunney, T.D., Katan, M. Description: DISEASE LINKED MUTATION IN FGFR [[Category:...

New page

'''Unreleased structure'''

The entry 5flf is ON HOLD until Paper Publication

Authors: Thiyagarajan, N., Bunney, T.D., Katan, M.

Description: DISEASE LINKED MUTATION IN FGFR
[[Category: Unreleased Structures]]
[[Category: Bunney, T.D]]
[[Category: Thiyagarajan, N]]
[[Category: Katan, M]]