Rho GTPases control a variety of cellular processes. There are 3 subtypes of Rho GTPases in the Ras superfamily of
small G proteins: RHO (OMIM 165370), RAC (OMIM 602048), and CDC42 (OMIM 116952). GTPase-activating proteins
(GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. Through this catalytic function, Rho GAPs
negatively regulate Rho-mediated signals. GAPs may also serve as effector molecules and play a role in signaling
downstream of Rho and other Ras-like GTPases. By screening a Jurkat cDNA library using a yeast 2-hybrid system
with an activated form of RAC as bait, followed by screening a placenta cDNA library, Toure et al. (1998) isolated a
cDNA encoding RACGAP1, which they called MGCRACGAP. The predicted 527-amino acid RACGAP1 protein has a
large N-terminal region containing a protein kinase C-like cysteine-rich motif. The authors determined
that RACGAP1 shares highest homology with the Drosophila RnRacGAP and the chimerins of rat and human . Functional analysis showed that the GAP domain of RACGAP1 exhibits strong GAP activity towards CDC42,
RAC1, and RAC2 . Northern blot analysis detected an approximately 3.2-kb RACGAP1 transcript that was
most abundantly expressed in testis, with low expression in most other tissues.
General function
Intracellular signaling cascade
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Cellular localization
Cytoplasmic
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Ovarian function
Oogenesis
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Van de Putte T, et al 2001 reported that Mice with a homozygous gene trap vector insertion in mgcRacGAP
die during pre-implantation development.
In a phenotypic screen in mice using a gene trap approach in embryonic stem
cells, the authors have identified a recessive loss-of-function mutation in the
mgcRacGAP gene. Maternal protein is present in the oocyte. and mgcRacGAP gene
transcription starts at the four-cell stage and persists throughout mouse
pre-implantation development. Total mgcRacGAP deficiency results in
pre-implantation lethality. Such E3.5 embryos display a dramatic reduction in
cell number, but undergo compaction and form a blastocoel. At E3.0-3.5,
binucleated blastomeres in which the nuclei are partially interconnected are
frequently observed, suggesting that mgcRacGAP is required for normal mitosis
and cytokinesis in the pre-implantation embryo.