1ii4: Difference between revisions

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 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ii4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ii4 OCA], [https://pdbe.org/1ii4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ii4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ii4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ii4 ProSAT]</span></td></tr>
 </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 ==
-[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
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    <jmolCheckbox>
      <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ii/1ii4_consurf.spt"</scriptWhenChecked>
-     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>