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FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF) is a protein that in humans is encoded by the ''FGD1'' gene that lies on the X chromosome.〔 Orthologs of the ''FGD1'' gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and ''C. elegans''.〔 It is a member of the FYVE, RhoGEF and PH domain containing family. FGD1 is a guanine-nucleotide exchange factor (GEF) that can activate the Rho GTPase Cdc42. It localizes preferentially to the trans-Golgi network (TGN) of mammalian cells and regulates, for example, the secretory transport of bone-specific proteins from the Golgi complex. Thus Cdc42 and FGD1 regulate secretory membrane trafficking that occurs especially during bone growth and mineralization in humans.〔 FGD1 promotes nucleotide exchange on the GTPase Cdc42, a key player in the establishment of cell polarity in all eukaryotic cells. The GEF activity of FGD1, which activates Cdc42, is harbored in its DH domain and causes the formation of filopodia, enabling the cells to migrate. FGD1 also activates the c-Jun N-terminal kinase (JNK) signaling cascade, important in cell differentiation and apoptosis.〔 It also promotes the transition through G1 during the cell cycle and causes tumorgenic transformation of NIH/3T3 fibroblasts.〔〔 The FGD1 gene is located on the short arm of the X-chromosome and is essential for normal mammalian embryonic development. Mice embryos that carried experimentally introduced mutations in the FGD1 gene had skeletal abnormalities affecting bone size, cartilage growth, vertebrae formation and distal extremities.〔 These severe phenotypes are consistent with a lack of Cdc42 activity, as it controls membrane traffic as well as the organization of the actin cytoskeleton.〔 Mutations in the ''FGD1'' gene that cause the production of non-functional proteins are responsible for the severe phenotype of the X-linked disorder faciogential dysplasia (FGDY), also called Aarskog-Scott syndrome. == Structure == The mature human protein contains several characteristic motifs and domains that are involved in the protein's function. The 961 amino acid long protein has an approximate size of 106kDa. The N-terminal is a proline-rich stretch, predicted to encode two partially overlapping src homology 3 (SH3)-binding domains, stretches from amino acid 7 – 330, followed by a DH domain (DBL homology domain), which harbors the GEF enzymatic activity, and lies between the residue 373 – 561, then a first PH domain between residues 590 – 689, a FYVE zinc finger domain (named after the four proteins it was found in Fab1, YOTB, Vac1, and EEA1) between residues 730 – 790, and a second PH domain between residues 821 – 921.〔 The DH domain is required for the activation of Cdc42, through the catalytic exchange of GDP with GTP on Cdc42, while the PH domains confer membrane binding. The prolin-rich domain interacts with cortactin and actin-binding protein 1.〔〔 FYVE-finger domains are conserved through evolution and often involved in membrane trafficking (e.g. Vac1p, Vps27p, Fab1, Hrs-2). One class of these domains was shown to bind selectively to phosphatidylinositol 3-phosphate. PH domains are known to specifically bind to polyphosphoinositides and influence the enzymatic activity of the GEF they are located in.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「FGD1」の詳細全文を読む スポンサード リンク
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