Fgd1 gene mutations result in faciogenital dysplasia (FGDY, Aarskog syndrome),an X-linked developmental disorder that adversely affects the formation of multiple skeletal structures (1). FGD1 maps to human chromosome Xp11.21 and shares a high degree of sequence identity with the FGD2 (6p21.2) and the FGD3 (9q22) proteins (1-4). FGD1 encodes a guanine nucleotide exchange factor that specifically activates the Rho GTPase Cdc42 (1,5). FGD2 is present in several diverse tissues during embryogenesis, suggesting a role in embryonic development (2). FGD3 stimulates fibroblasts to form filopodia, which are actin microspikes formed upon the stimulation of Cdc42 (1). All FGD family members contain equivalent signaling domains and a conserved structural organization, which strongly suggests that these signaling domains form a canonical core structure for members of the FGD family of RhoGEF proteins (2). These proteins control essential signals required during embryonic development (6,7).
Function:
Activates CDC42, a member of the Ras-like family of Rho-and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate.
Subcellular Location:
Cytoplasm > cytoskeleton. Cytoplasm. Nucleus. Early endosome. Early endosome membrane. Cell projection > ruffle membrane. Recruitement to the endosome and ruffle membrane requires the presence of phosphoinositides.
Similarity:
Contains 1 DH (DBL-homology) domain.
Contains 1 FYVE-type zinc finger.
Contains 2 PH domains.
SWISS:
Q7Z6J4
Gene ID:
221472
Database links:
Entrez Gene: 221472 Human
Omim: 605091 Human
SwissProt: Q7Z6J4 Human
Unigene: 509664 Human
|
|
