1xr0: Difference between revisions

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-[[Image:1xr0.png|left|200px]]
 {{STRUCTURE_1xr0|  PDB=1xr0  |  SCENE=  }}
+===Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors===
+{{ABSTRACT_PUBMED_11090629}}
-===Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors===
+==Disease==
+[[http://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:[http://omim.org/entry/101600 101600]]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.<ref>PMID:20139426</ref><ref>PMID:7874169</ref>  Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:[http://omim.org/entry/147950 147950]]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).<ref>PMID:20139426</ref><ref>PMID:12627230</ref><ref>PMID:15001591</ref><ref>PMID:15605412</ref><ref>PMID:15845591</ref><ref>PMID:16882753</ref><ref>PMID:16764984</ref><ref>PMID:16757108</ref><ref>PMID:16606836</ref><ref>PMID:17154279</ref>  Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:[http://omim.org/entry/166250 166250]]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.<ref>PMID:20139426</ref><ref>PMID:15625620</ref><ref>PMID:16470795</ref>  Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:[http://omim.org/entry/190440 190440]]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.<ref>PMID:20139426</ref><ref>PMID:11173846</ref>  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.<ref>PMID:20139426</ref>  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity.  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
-{{ABSTRACT_PUBMED_11090629}}
+==Function==
+[[http://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.<ref>PMID:20139426</ref><ref>PMID:1379697</ref><ref>PMID:1379698</ref><ref>PMID:8622701</ref><ref>PMID:8663044</ref><ref>PMID:11353842</ref><ref>PMID:12181353</ref><ref>PMID:15117958</ref><ref>PMID:16597617</ref><ref>PMID:17623664</ref><ref>PMID:17311277</ref><ref>PMID:18480409</ref><ref>PMID:19261810</ref><ref>PMID:19224897</ref><ref>PMID:21765395</ref><ref>PMID:10830168</ref><ref>PMID:19665973</ref><ref>PMID:20133753</ref> [[http://www.uniprot.org/uniprot/FRS2_HUMAN FRS2_HUMAN]] Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.<ref>PMID:12974390</ref><ref>PMID:21765395</ref>
 ==About this Structure==
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 ==Reference==
-<ref group="xtra">PMID:011090629</ref><references group="xtra"/>
+<ref group="xtra">PMID:011090629</ref><references group="xtra"/><references/>
 [[Category: Homo sapiens]]
 [[Category: Dhalluin, C.]]