1ev2 - Revision history

OCA at 10:06, 20 March 2024

OCA — Wed, 20 Mar 2024 10:06:44 GMT

←Older revision		Revision as of 10:06, 20 March 2024
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	<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<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]] 2.2Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[1cvs\|1cvs]], [[1evt\|1evt]]~~</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [https://pdbe.org/1ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev2 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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [https://pdbe.org/1ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev2 ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:[https://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> [:]<ref>PMID:7581378</ref> <ref>PMID:7987400</ref> <ref>PMID:7874170</ref> <ref>PMID:7655462</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:8946174</ref> <ref>PMID:8956050</ref> <ref>PMID:9002682</ref> <ref>PMID:9152842</ref> <ref>PMID:9677057</ref> <ref>PMID:9521581</ref> <ref>PMID:10574673</ref> <ref>PMID:11173845</ref> <ref>PMID:11380921</ref> <ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[https://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref> <ref>PMID:7874170</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:9677057</ref> <ref>PMID:9385368</ref> Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:[https://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.<ref>PMID:15190072</ref> <ref>PMID:19387476</ref> <ref>PMID:9002682</ref> <ref>PMID:9677057</ref> <ref>PMID:11781872</ref> <ref>PMID:7668257</ref> <ref>PMID:11390973</ref> <ref>PMID:7719344</ref> <ref>PMID:9452027</ref> Defects in FGFR2 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. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).<ref>PMID:16844695</ref> <ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:8644708</ref> <ref>PMID:9002682</ref> <ref>PMID:11173845</ref> <ref>PMID:11781872</ref> <ref>PMID:7719333</ref> <ref>PMID:7719345</ref> <ref>PMID:9150725</ref> <ref>PMID:9693549</ref> <ref>PMID:9719378</ref> <ref>PMID:10394936</ref> <ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:[https://omim.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref> <ref>PMID:8696350</ref> <ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[https://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[https://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref> <ref>PMID:18056630</ref> <ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[https://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref> <ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[https://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref> <ref>PMID:22387015</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref> <ref>PMID:8663044</ref> [[https://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<ref>PMID:8961926</ref> <ref>PMID:8663044</ref> <ref>PMID:12529371</ref> <ref>PMID:15190072</ref> <ref>PMID:15629145</ref> <ref>PMID:16597617</ref> <ref>PMID:16844695</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18374639</ref> <ref>PMID:19410646</ref> <ref>PMID:19103595</ref> <ref>PMID:21596750</ref> <ref>PMID:19387476</ref> <ref>PMID:16384934</ref>	+	[https://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref> <ref>PMID:8663044</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</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=1ev2 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=1ev2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	To elucidate the structural determinants governing specificity in fibroblast growth factor (FGF) signaling, we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively. Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes. Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing. These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing.
-
-	Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.,Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M Cell. 2000 May 12;101(4):413-24. PMID:10830168<ref>PMID:10830168</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1ev2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hubbard~~, S R~~]]	+	[[Category: Hubbard SR]]
-	[[Category: Mohammadi, M]]	+	[[Category: Mohammadi M]]
-	[[Category: Plotnikov~~, A N~~]]	+	[[Category: Plotnikov AN]]
-	[[Category: Schlessinger, J]]	+	[[Category: Schlessinger J]]
-	~~[[Category: B-trefoil fold]]~~	+
-	~~[[Category: Growth factor-growth factor receptor complex~~]]	+

OCA at 15:06, 3 November 2021

OCA — Wed, 03 Nov 2021 15:06:51 GMT

←Older revision		Revision as of 15:06, 3 November 2021
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	<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cvs\|1cvs]], [[1evt\|1evt]]</div></td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cvs\|1cvs]], [[1evt\|1evt]]</div></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Hubbard, S R]]		[[Category: Hubbard, S R]]

OCA at 07:15, 17 March 2021

OCA — Wed, 17 Mar 2021 07:15:49 GMT

←Older revision		Revision as of 07:15, 17 March 2021
Line 3:		Line 3:
	<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cvs\|1cvs]], [[1evt\|1evt]]</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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [~~http~~://pdbe.org/1ev2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ev2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev2 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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [https://pdbe.org/1ev2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ev2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:[~~http~~://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> [:]<ref>PMID:7581378</ref> <ref>PMID:7987400</ref> <ref>PMID:7874170</ref> <ref>PMID:7655462</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:8946174</ref> <ref>PMID:8956050</ref> <ref>PMID:9002682</ref> <ref>PMID:9152842</ref> <ref>PMID:9677057</ref> <ref>PMID:9521581</ref> <ref>PMID:10574673</ref> <ref>PMID:11173845</ref> <ref>PMID:11380921</ref> <ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[~~http~~://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref> <ref>PMID:7874170</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:9677057</ref> <ref>PMID:9385368</ref> Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:[~~http~~://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.<ref>PMID:15190072</ref> <ref>PMID:19387476</ref> <ref>PMID:9002682</ref> <ref>PMID:9677057</ref> <ref>PMID:11781872</ref> <ref>PMID:7668257</ref> <ref>PMID:11390973</ref> <ref>PMID:7719344</ref> <ref>PMID:9452027</ref> Defects in FGFR2 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. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).<ref>PMID:16844695</ref> <ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:8644708</ref> <ref>PMID:9002682</ref> <ref>PMID:11173845</ref> <ref>PMID:11781872</ref> <ref>PMID:7719333</ref> <ref>PMID:7719345</ref> <ref>PMID:9150725</ref> <ref>PMID:9693549</ref> <ref>PMID:9719378</ref> <ref>PMID:10394936</ref> <ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:[~~http~~://omim.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref> <ref>PMID:8696350</ref> <ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[~~http~~://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[~~http~~://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref> <ref>PMID:18056630</ref> <ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[~~http~~://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref> <ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[~~http~~://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref> <ref>PMID:22387015</ref>	+	[[https://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:[https://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> [:]<ref>PMID:7581378</ref> <ref>PMID:7987400</ref> <ref>PMID:7874170</ref> <ref>PMID:7655462</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:8946174</ref> <ref>PMID:8956050</ref> <ref>PMID:9002682</ref> <ref>PMID:9152842</ref> <ref>PMID:9677057</ref> <ref>PMID:9521581</ref> <ref>PMID:10574673</ref> <ref>PMID:11173845</ref> <ref>PMID:11380921</ref> <ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[https://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref> <ref>PMID:7874170</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:9677057</ref> <ref>PMID:9385368</ref> Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:[https://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.<ref>PMID:15190072</ref> <ref>PMID:19387476</ref> <ref>PMID:9002682</ref> <ref>PMID:9677057</ref> <ref>PMID:11781872</ref> <ref>PMID:7668257</ref> <ref>PMID:11390973</ref> <ref>PMID:7719344</ref> <ref>PMID:9452027</ref> Defects in FGFR2 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. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).<ref>PMID:16844695</ref> <ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:8644708</ref> <ref>PMID:9002682</ref> <ref>PMID:11173845</ref> <ref>PMID:11781872</ref> <ref>PMID:7719333</ref> <ref>PMID:7719345</ref> <ref>PMID:9150725</ref> <ref>PMID:9693549</ref> <ref>PMID:9719378</ref> <ref>PMID:10394936</ref> <ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:[https://omim.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref> <ref>PMID:8696350</ref> <ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[https://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[https://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref> <ref>PMID:18056630</ref> <ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[https://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref> <ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[https://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref> <ref>PMID:22387015</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref> <ref>PMID:8663044</ref> [[~~http~~://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<ref>PMID:8961926</ref> <ref>PMID:8663044</ref> <ref>PMID:12529371</ref> <ref>PMID:15190072</ref> <ref>PMID:15629145</ref> <ref>PMID:16597617</ref> <ref>PMID:16844695</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18374639</ref> <ref>PMID:19410646</ref> <ref>PMID:19103595</ref> <ref>PMID:21596750</ref> <ref>PMID:19387476</ref> <ref>PMID:16384934</ref>	+	[[https://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref> <ref>PMID:8663044</ref> [[https://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<ref>PMID:8961926</ref> <ref>PMID:8663044</ref> <ref>PMID:12529371</ref> <ref>PMID:15190072</ref> <ref>PMID:15629145</ref> <ref>PMID:16597617</ref> <ref>PMID:16844695</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18374639</ref> <ref>PMID:19410646</ref> <ref>PMID:19103595</ref> <ref>PMID:21596750</ref> <ref>PMID:19387476</ref> <ref>PMID:16384934</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[Fibroblast growth factor\|Fibroblast growth factor]]	+	*[[Fibroblast growth factor 3D structures\|Fibroblast growth factor 3D structures]]
-	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]	+	*[[Fibroblast growth factor receptor 3D receptor\|Fibroblast growth factor receptor 3D receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:34, 12 June 2019

OCA — Wed, 12 Jun 2019 06:34:06 GMT

←Older revision		Revision as of 06:34, 12 June 2019
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)==		==CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)==
-	<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='1ev2' size='340' side='right'caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ev/1ev2_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ev/1ev2_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>
Line 39:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Hubbard, S R]]		[[Category: Hubbard, S R]]
	[[Category: Mohammadi, M]]		[[Category: Mohammadi, M]]

OCA at 03:48, 6 September 2017

OCA — Wed, 06 Sep 2017 03:48:07 GMT

←Older revision		Revision as of 03:48, 6 September 2017
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)==		==CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)==
	<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ev2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [http://pdbe.org/1ev2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [http://www.ebi.ac.uk/pdbsum/1ev2 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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [http://pdbe.org/1ev2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [http://www.ebi.ac.uk/pdbsum/1ev2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ev2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	<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=1ev2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Hubbard, S R]]		[[Category: Hubbard, S R]]
	[[Category: Mohammadi, M]]		[[Category: Mohammadi, M]]

OCA at 15:46, 11 September 2015

OCA — Fri, 11 Sep 2015 15:46:14 GMT

←Older revision		Revision as of 15:46, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [http://www.ebi.ac.uk/pdbsum/1ev2 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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [http://pdbe.org/1ev2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [http://www.ebi.ac.uk/pdbsum/1ev2 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	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 1ev2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Hubbard, S R]]		[[Category: Hubbard, S R]]
	[[Category: Mohammadi, M]]		[[Category: Mohammadi, M]]

OCA at 00:08, 23 December 2014

OCA — Tue, 23 Dec 2014 00:08:38 GMT

←Older revision		Revision as of 00:08, 23 December 2014
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-	~~{{STRUCTURE_1ev2\| PDB=1ev2 \| SCENE= }}~~	+	==CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)==
-	===CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)===	+	<StructureSection load='1ev2' size='340' side='right' caption='[[1ev2]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_10830168}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1ev2]] 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=1EV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EV2 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cvs\|1cvs]], [[1evt\|1evt]]</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=1ev2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ev2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ev2 RCSB], [http://www.ebi.ac.uk/pdbsum/1ev2 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:[http://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> [:]<ref>PMID:7581378</ref> <ref>PMID:7987400</ref> <ref>PMID:7874170</ref> <ref>PMID:7655462</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:8946174</ref> <ref>PMID:8956050</ref> <ref>PMID:9002682</ref> <ref>PMID:9152842</ref> <ref>PMID:9677057</ref> <ref>PMID:9521581</ref> <ref>PMID:10574673</ref> <ref>PMID:11173845</ref> <ref>PMID:11380921</ref> <ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[http://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref> <ref>PMID:7874170</ref> <ref>PMID:8528214</ref> <ref>PMID:8644708</ref> <ref>PMID:9677057</ref> <ref>PMID:9385368</ref> Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:[http://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.<ref>PMID:15190072</ref> <ref>PMID:19387476</ref> <ref>PMID:9002682</ref> <ref>PMID:9677057</ref> <ref>PMID:11781872</ref> <ref>PMID:7668257</ref> <ref>PMID:11390973</ref> <ref>PMID:7719344</ref> <ref>PMID:9452027</ref> Defects in FGFR2 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. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).<ref>PMID:16844695</ref> <ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:8644708</ref> <ref>PMID:9002682</ref> <ref>PMID:11173845</ref> <ref>PMID:11781872</ref> <ref>PMID:7719333</ref> <ref>PMID:7719345</ref> <ref>PMID:9150725</ref> <ref>PMID:9693549</ref> <ref>PMID:9719378</ref> <ref>PMID:10394936</ref> <ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:[http://omim.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref> <ref>PMID:8696350</ref> <ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[http://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref> <ref>PMID:17803937</ref> <ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[http://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref> <ref>PMID:18056630</ref> <ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[http://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref> <ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[http://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref> <ref>PMID:22387015</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref> <ref>PMID:8663044</ref> [[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<ref>PMID:8961926</ref> <ref>PMID:8663044</ref> <ref>PMID:12529371</ref> <ref>PMID:15190072</ref> <ref>PMID:15629145</ref> <ref>PMID:16597617</ref> <ref>PMID:16844695</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18374639</ref> <ref>PMID:19410646</ref> <ref>PMID:19103595</ref> <ref>PMID:21596750</ref> <ref>PMID:19387476</ref> <ref>PMID:16384934</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/ev/1ev2_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 ==
		+	To elucidate the structural determinants governing specificity in fibroblast growth factor (FGF) signaling, we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively. Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes. Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing. These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing.

-	~~==Disease==~~	+	Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.,Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M Cell. 2000 May 12;101(4):413-24. PMID:10830168<ref>PMID:10830168</ref>
-	~~[[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause~~ of Crouzon syndrome (CS) [MIM:[http://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref><ref>PMID:17803937</ref>[:]<ref>PMID:7581378</ref><ref>PMID:7987400</ref><ref>PMID:7874170</ref><ref>PMID:7655462</ref><ref>PMID:8528214</ref><ref>PMID:8644708</ref><ref>PMID:8946174</ref><ref>PMID:8956050</ref><ref>PMID:9002682</ref><ref>PMID:9152842</ref><ref>PMID:9677057</ref><ref>PMID:9521581</ref><ref>PMID:10574673</ref><ref>PMID:11173845</ref><ref>PMID:11380921</ref><ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[http://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref><ref>PMID:7874170</ref><ref>PMID:8528214</ref><ref>PMID:8644708</ref><ref>PMID:9677057</ref><ref>PMID:9385368</ref> Defects in FGFR2 are a cause of ~~Apert syndrome (APRS) [MIM:[http://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio~~-~~cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia~~. ~~The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second~~, ~~third~~, ~~and fourth digits. Intellectual deficit is frequent and often severe~~, usually being associated with cerebral malformations.<ref>PMID:15190072</ref><ref>PMID:19387476</ref><ref>PMID:9002682</ref><ref>PMID:9677057</ref><ref>PMID:11781872</ref><ref>PMID:7668257</ref><ref>PMID:11390973</ref><ref>PMID:7719344</ref><ref>PMID:9452027</ref> Defects in FGFR2 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~~. ~~Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1)~~; ~~cloverleaf skull, elbow ankylosis, early death, sporadic~~ (~~type 2~~)~~; craniosynostosis, early demise, sporadic (type 3).<ref>PMID~~:16844695</ref><ref>PMID:19387476</ref><ref>PMID:17803937</ref><ref>PMID:8644708</ref><ref>PMID:9002682</ref><ref>PMID:11173845</ref><ref>PMID:11781872</ref><ref>PMID:7719333</ref><ref>PMID:7719345</ref><ref>PMID:9150725</ref><ref>PMID:9693549</ref><ref>PMID:9719378</ref><ref>PMID:10394936</ref><ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-~~Stevenson cutis gyrata syndrome (BSCGS) [MIM:[http://omim~~.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref><ref>PMID:8696350</ref><ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[http://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref><ref>PMID:17803937</ref><ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[http://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref><ref>PMID:18056630</ref><ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[http://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref><ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[http://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref><ref>PMID:~~22387015~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival~~, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref><ref>PMID:8663044</ref> [[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of ~~cell proliferation, differentiation, migration and apoptosis, and in~~ the ~~regulation of embryonic development~~. ~~Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development~~. ~~Plays an essential role in the regulation~~ of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<~~ref~~>PMID:8961926</ref><ref>PMID:8663044</ref><ref>PMID:12529371</ref><ref>PMID:15190072</ref><ref>PMID:15629145</ref><ref>PMID:16597617</ref><ref>PMID:16844695</ref><ref>PMID:17623664</ref><ref>PMID:17311277</ref><ref>PMID:18374639</ref><ref>PMID:19410646</ref><ref>PMID:19103595</ref><ref>PMID:21596750</ref><ref>PMID:19387476</ref><ref>PMID:16384934</~~ref~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~1ev2~~]] ~~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=1EV2 OCA~~].	+	*[[Fibroblast growth factor\|Fibroblast growth factor]]
-		+	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]
-	==~~Reference~~==	+	== References ==
-	~~<ref group="xtra">PMID:010830168</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Hubbard, S R.]]	+	[[Category: Hubbard, S R]]
-	[[Category: Mohammadi, M.]]	+	[[Category: Mohammadi, M]]
-	[[Category: Plotnikov, A N.]]	+	[[Category: Plotnikov, A N]]
-	[[Category: Schlessinger, J.]]	+	[[Category: Schlessinger, J]]
	[[Category: B-trefoil fold]]		[[Category: B-trefoil fold]]
	[[Category: Growth factor-growth factor receptor complex]]		[[Category: Growth factor-growth factor receptor complex]]

OCA at 21:40, 24 March 2013

OCA — Sun, 24 Mar 2013 21:40:05 GMT

←Older revision		Revision as of 21:40, 24 March 2013
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-	[[Image:1ev2.png\|left\|200px]]
-
	{{STRUCTURE_1ev2\| PDB=1ev2 \| SCENE= }}		{{STRUCTURE_1ev2\| PDB=1ev2 \| SCENE= }}
		+	===CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)===
		+	{{ABSTRACT_PUBMED_10830168}}

-	===~~CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR~~ 2 (FGFR2)~~===~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:[http://omim.org/entry/123500 123500]]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.<ref>PMID:19387476</ref><ref>PMID:17803937</ref>[:]<ref>PMID:7581378</ref><ref>PMID:7987400</ref><ref>PMID:7874170</ref><ref>PMID:7655462</ref><ref>PMID:8528214</ref><ref>PMID:8644708</ref><ref>PMID:8946174</ref><ref>PMID:8956050</ref><ref>PMID:9002682</ref><ref>PMID:9152842</ref><ref>PMID:9677057</ref><ref>PMID:9521581</ref><ref>PMID:10574673</ref><ref>PMID:11173845</ref><ref>PMID:11380921</ref><ref>PMID:11781872</ref> Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:[http://omim.org/entry/123150 123150]]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.<ref>PMID:19387476</ref><ref>PMID:7874170</ref><ref>PMID:8528214</ref><ref>PMID:8644708</ref><ref>PMID:9677057</ref><ref>PMID:9385368</ref> Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:[http://omim.org/entry/101200 101200]]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.<ref>PMID:15190072</ref><ref>PMID:19387476</ref><ref>PMID:9002682</ref><ref>PMID:9677057</ref><ref>PMID:11781872</ref><ref>PMID:7668257</ref><ref>PMID:11390973</ref><ref>PMID:7719344</ref><ref>PMID:9452027</ref> Defects in FGFR2 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. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).<ref>PMID:16844695</ref><ref>PMID:19387476</ref><ref>PMID:17803937</ref><ref>PMID:8644708</ref><ref>PMID:9002682</ref><ref>PMID:11173845</ref><ref>PMID:11781872</ref><ref>PMID:7719333</ref><ref>PMID:7719345</ref><ref>PMID:9150725</ref><ref>PMID:9693549</ref><ref>PMID:9719378</ref><ref>PMID:10394936</ref><ref>PMID:10945669</ref> Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:[http://omim.org/entry/123790 123790]]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.<ref>PMID:19387476</ref><ref>PMID:8696350</ref><ref>PMID:12000365</ref> Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:[http://omim.org/entry/609579 609579]]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.<ref>PMID:19387476</ref><ref>PMID:17803937</ref><ref>PMID:16061565</ref> Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:[http://omim.org/entry/149730 149730]]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.<ref>PMID:19387476</ref><ref>PMID:18056630</ref><ref>PMID:16501574</ref> Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:[http://omim.org/entry/207410 207410]]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.<ref>PMID:19387476</ref><ref>PMID:10633130</ref> Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:[http://omim.org/entry/614592 614592]]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.<ref>PMID:19387476</ref><ref>PMID:22387015</ref>

		+	==Function==
		+	[[http://www.uniprot.org/uniprot/FGF2_HUMAN FGF2_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:1721615</ref><ref>PMID:8663044</ref> [[http://www.uniprot.org/uniprot/FGFR2_HUMAN FGFR2_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.<ref>PMID:8961926</ref><ref>PMID:8663044</ref><ref>PMID:12529371</ref><ref>PMID:15190072</ref><ref>PMID:15629145</ref><ref>PMID:16597617</ref><ref>PMID:16844695</ref><ref>PMID:17623664</ref><ref>PMID:17311277</ref><ref>PMID:18374639</ref><ref>PMID:19410646</ref><ref>PMID:19103595</ref><ref>PMID:21596750</ref><ref>PMID:19387476</ref><ref>PMID:16384934</ref>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:010830168</ref><references group="xtra"/>	+	<ref group="xtra">PMID:010830168</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hubbard, S R.]]		[[Category: Hubbard, S R.]]

OCA: Protected "1ev2" [edit=sysop:move=sysop]

OCA — Wed, 14 Nov 2012 07:26:31 GMT

Protected "1ev2" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:26, 14 November 2012

OCA at 07:26, 14 November 2012

OCA — Wed, 14 Nov 2012 07:26:29 GMT

←Older revision		Revision as of 07:26, 14 November 2012
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-	{{Seed}}
	[[Image:1ev2.png\|left\|200px]]		[[Image:1ev2.png\|left\|200px]]

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	{{STRUCTURE_1ev2\| PDB=1ev2 \| SCENE= }}		{{STRUCTURE_1ev2\| PDB=1ev2 \| SCENE= }}

	===CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)===		===CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)===

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	==About this Structure==		==About this Structure==
-	~~1EV2~~ is a 8 ~~chains~~ structure ~~of sequences~~ 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=1EV2 OCA].	+	[[1ev2]] 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=1EV2 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~10830168~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:010830168</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hubbard, S R.]]		[[Category: Hubbard, S R.]]
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	[[Category: Schlessinger, J.]]		[[Category: Schlessinger, J.]]
	[[Category: B-trefoil fold]]		[[Category: B-trefoil fold]]
-		+	[[Category: Growth factor-growth factor receptor complex]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Wed Feb 18 02:38:51 2009''~~	+