RAS p21 protein activator 1
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RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:
- Inactivation of Ras from its active GTP-bound form to its unactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain
- Mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains
The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues.[1]
[edit] Domains
RasGAP contains one SH3 domain and two SH2 domains, a PH domain, and a GAP domain.
[edit] References
[edit] Further reading
- Tocque B, Delumeau I, Parker F, et al. (1997). "Ras-GTPase activating protein (GAP): a putative effector for Ras.". Cell. Signal. 9 (2): 153–8. PMID 9113414.
- Boon LM, Mulliken JB, Vikkula M (2005). "RASA1: variable phenotype with capillary and arteriovenous malformations.". Curr. Opin. Genet. Dev. 15 (3): 265–9. doi:. PMID 15917201.
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