3oj2 - Revision history

OCA at 09:40, 6 September 2023

OCA — Wed, 06 Sep 2023 09:40:17 GMT

←Older revision		Revision as of 09:40, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3oj2' size='340' side='right'caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3oj2' size='340' side='right'caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OJ2 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;'>[[1evt\|1evt]]~~, [[~~1djs~~\|~~1djs~~]]~~, [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</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='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>FGF1, FGFA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN]), BEK, FGFR2, KGFR, KSAM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td~~><~~/tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [https://pdbe.org/3oj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [https://www.ebi.ac.uk/pdbsum/3oj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oj2 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=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [https://pdbe.org/3oj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [https://www.ebi.ac.uk/pdbsum/3oj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oj2 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/FGF1_HUMAN FGF1_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:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</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/FGF1_HUMAN FGF1_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:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 31:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Beenken A]]
-	[[Category: Beenken, A]]	+	[[Category: Mohammadi M]]
-	[[Category: Mohammadi, M]]	+
-	~~[[Category: Beta trefoil motif]]~~	+
-	~~[[Category: Cytokine-signaling protein complex]]~~	+
-	~~[[Category: Extracellular]]~~	+
-	~~[[Category: Growth factor]]~~	+
-	~~[[Category: Growth factor receptor]]~~	+
-	~~[[Category: Immunoglobulin-like domain~~]]	+

OCA at 10:45, 18 May 2022

OCA — Wed, 18 May 2022 10:45:27 GMT

←Older revision		Revision as of 10:45, 18 May 2022
Line 1:		Line 1:

	==Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation==		==Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation==
-	<StructureSection load='3oj2' size='340' side='right' caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='3oj2' size='340' side='right'caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OJ2 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">[[1evt\|1evt]], [[1djs\|1djs]], [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1evt\|1evt]], [[1djs\|1djs]], [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BEK, FGFR2, KGFR, KSAM ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BEK, FGFR2, KGFR, KSAM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://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=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [~~http~~://pdbe.org/3oj2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3oj2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3oj2 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=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [https://pdbe.org/3oj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [https://www.ebi.ac.uk/pdbsum/3oj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oj2 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/FGF1_HUMAN FGF1_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:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</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/FGF1_HUMAN FGF1_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:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==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/>
Line 32:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Beenken, A]]		[[Category: Beenken, A]]

OCA at 08:16, 4 August 2016

OCA — Thu, 04 Aug 2016 08:16:33 GMT

←Older revision		Revision as of 08:16, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation==		==Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation==
	<StructureSection load='3oj2' size='340' side='right' caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3oj2' size='340' side='right' caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OJ2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OJ2 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">[[1evt\|1evt]], [[1djs\|1djs]], [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1evt\|1evt]], [[1djs\|1djs]], [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), BEK, FGFR2, KGFR, KSAM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BEK, FGFR2, KGFR, KSAM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [http://www.ebi.ac.uk/pdbsum/3oj2 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=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [http://pdbe.org/3oj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [http://www.ebi.ac.uk/pdbsum/3oj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3oj2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 3oj2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 31:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Beenken, A]]		[[Category: Beenken, A]]

OCA at 07:20, 19 December 2014

OCA — Fri, 19 Dec 2014 07:20:15 GMT

←Older revision		Revision as of 07:20, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3oj2\| PDB=3oj2 \| SCENE= }}~~	+	==Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation==
-	===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===	+	<StructureSection load='3oj2' size='340' side='right' caption='[[3oj2]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22057274}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3oj2]] is a 4 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=3OJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OJ2 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">[[1evt\|1evt]], [[1djs\|1djs]], [[1ry7\|1ry7]], [[3ojm\|3ojm]], [[3ojv\|3ojv]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BEK, FGFR2, KGFR, KSAM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oj2 RCSB], [http://www.ebi.ac.uk/pdbsum/3oj2 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/FGF1_HUMAN FGF1_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:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</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 style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tissue-specific alternative splicing in the second half of Ig-like domain 3 (D3) of fibroblast growth factor receptors 1-3 (FGFR1 to -3) generates epithelial FGFR1b-FGFR3b and mesenchymal FGFR1c-FGFR3c splice isoforms. This splicing event establishes a selectivity filter to restrict the ligand binding specificity of FGFRb and FGFRc isoforms to mesenchymally and epithelially derived fibroblast growth factors (FGFs), respectively. FGF1 is termed the "universal FGFR ligand" because it overrides this specificity barrier. To elucidate the molecular basis for FGF1 cross-reactivity with the "b" and "c" splice isoforms of FGFRs, we determined the first crystal structure of FGF1 in complex with an FGFRb isoform, FGFR2b, at 2.1 A resolution. Comparison of the FGF1-FGFR2b structure with the three previously published FGF1-FGFRc structures reveals that plasticity in the interactions of the N-terminal region of FGF1 with FGFR D3 is the main determinant of FGF1 cross-reactivity with both isoforms of FGFRs. In support of our structural data, we demonstrate that substitution of three N-terminal residues (Gly-19, His-25, and Phe-26) of FGF2 (a ligand that does not bind FGFR2b) for the corresponding residues of FGF1 (Phe-16, Asn-22, and Tyr-23) enables the FGF2 triple mutant to bind and activate FGFR2b. These findings taken together with our previous structural data on receptor binding specificity of FGF2, FGF8, and FGF10 conclusively show that sequence divergence at the N termini of FGFs is the primary regulator of the receptor binding specificity and promiscuity of FGFs.

-	~~==Disease==~~	+	Plasticity in interactions of fibroblast growth factor 1 (FGF1) N terminus with FGF receptors underlies promiscuity of FGF1.,Beenken A, Eliseenkova AV, Ibrahimi OA, Olsen SK, Mohammadi M J Biol Chem. 2012 Jan 27;287(5):3067-78. Epub 2011 Nov 4. PMID:22057274<ref>PMID:22057274</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/FGF1_HUMAN FGF1_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:8663044</ref><ref>PMID:16597617</ref><ref>PMID:20145243</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==
-	[[~~3oj2~~]] ~~is a 4 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=3OJ2 OCA~~].	+	*[[Fibroblast growth factor\|Fibroblast growth factor]]
-		+	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]
-	==~~Reference~~==	+	== References ==
-	~~<ref group="xtra">PMID:022057274</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Beenken, A.]]	+	[[Category: Beenken, A]]
-	[[Category: Mohammadi, M.]]	+	[[Category: Mohammadi, M]]
	[[Category: Beta trefoil motif]]		[[Category: Beta trefoil motif]]
	[[Category: Cytokine-signaling protein complex]]		[[Category: Cytokine-signaling protein complex]]

OCA at 10:23, 24 March 2013

OCA — Sun, 24 Mar 2013 10:23:39 GMT

←Older revision		Revision as of 10:23, 24 March 2013
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	{{STRUCTURE_3oj2\| PDB=3oj2 \| SCENE= }}		{{STRUCTURE_3oj2\| PDB=3oj2 \| SCENE= }}
-
	===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===		===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===
		+	{{ABSTRACT_PUBMED_22057274}}

		+	==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==
-	~~The line below this paragraph~~, ~~{{ABSTRACT_PUBMED_22057274}}~~, ~~adds the Publication Abstract to the page~~	+	[[http://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_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:8663044</ref><ref>PMID:16597617</ref><ref>PMID:20145243</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>
-	(as ~~it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 22057274~~ is the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_22057274}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022057274</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022057274</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 04:58, 8 March 2012

OCA — Thu, 08 Mar 2012 04:58:46 GMT

←Older revision		Revision as of 04:58, 8 March 2012
Line 1:		Line 1:
-	[[Image:3oj2.~~jpg~~\|left\|200px]]	+	[[Image:3oj2.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===		===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22057274}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22057274 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22057274}}

	==About this Structure==		==About this Structure==
	[[3oj2]] is a 4 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=3OJ2 OCA].		[[3oj2]] is a 4 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=3OJ2 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022057274</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA: Protected "3oj2" [edit=sysop:move=sysop]

OCA — Wed, 31 Aug 2011 06:53:52 GMT

Protected "3oj2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:53, 31 August 2011

OCA at 06:53, 31 August 2011

OCA — Wed, 31 Aug 2011 06:53:48 GMT

←Older revision		Revision as of 06:53, 31 August 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3oj2.jpg\|left\|200px]]

-	The ~~entry 3oj2~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3oj2", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3oj2\| PDB=3oj2 \| SCENE= }}

-	~~Authors: Beenken, A., Mohammadi, M.~~	+	===Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation===

-	Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Sep 29 07~~:56:~~16 2010''~~	+	==About this Structure==
		+	[[3oj2]] is a 4 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=3OJ2 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Beenken, A.]]
		+	[[Category: Mohammadi, M.]]
		+	[[Category: Beta trefoil motif]]
		+	[[Category: Cytokine-signaling protein complex]]
		+	[[Category: Extracellular]]
		+	[[Category: Growth factor]]
		+	[[Category: Growth factor receptor]]
		+	[[Category: Immunoglobulin-like domain]]

OCA at 04:47, 29 September 2010

OCA — Wed, 29 Sep 2010 04:47:01 GMT

←Older revision		Revision as of 04:47, 29 September 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3oj2 is ON HOLD	+	The entry 3oj2 is ON HOLD until Paper Publication

	Authors: Beenken, A., Mohammadi, M.		Authors: Beenken, A., Mohammadi, M.

-	Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b	+	Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep ~~1 09~~:36:55 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 29 07:56:16 2010''

OCA: New page: '''Unreleased structure''' The entry 3oj2 is ON HOLD Authors: Beenken, A., Mohammadi, M. Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b ''Page seeded b...

OCA — Wed, 01 Sep 2010 05:28:47 GMT

New page: '''Unreleased structure''' The entry 3oj2 is ON HOLD Authors: Beenken, A., Mohammadi, M. Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b ''Page seeded b...

New page

'''Unreleased structure'''

The entry 3oj2 is ON HOLD

Authors: Beenken, A., Mohammadi, M.

Description: Crystal structure of FGF1 complexed with the ectodomain of FGFR2b

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 1 09:36:55 2010''