RASA3 explained

Ras GTPase-activating protein 3 is an enzyme that in humans is encoded by the RASA3 gene.^{[1] [2] [3]}

The protein encoded by this gene is member 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. This family member is an inositol 1,3,4,5-tetrakisphosphate-binding protein, like the closely related RAS p21 protein activator 2. The two family members have distinct pleckstrin-homology domains, with this particular member having a domain consistent with its localization to the plasma membrane.

Interactions

RASA3 has been shown to interact with HCK.^[4]

Further reading

• Hata Y, Kikuchi A, Sasaki T, etal . Inhibition of the ras p21 GTPase-activating protein-stimulated GTPase activity of c-Ha-ras p21 by smg p21 having the same putative effector domain as ras p21s . J. Biol. Chem. . 265 . 13 . 7104–7 . 1990 . 10.1016/S0021-9258(19)39083-0 . 2158984 . free .
• Hjermstad SJ, Briggs SD, Smithgall TE . Phosphorylation of the ras GTPase-activating protein (GAP) by the p93c-fes protein-tyrosine kinase in vitro and formation of GAP-fes complexes via an SH2 domain-dependent mechanism . Biochemistry . 32 . 39 . 10519–25 . 1993 . 7691175 . 10.1021/bi00090a031 .
• Briggs SD, Bryant SS, Jove R, etal . The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck . J. Biol. Chem. . 270 . 24 . 14718–24 . 1995 . 7782336 . 10.1074/jbc.270.24.14718 . free.
• Lockyer PJ, Vanlingen S, Reynolds JS, etal . Tissue-specific expression and endogenous subcellular distribution of the inositol 1,3,4,5-tetrakisphosphate-binding proteins GAP1(IP4BP) and GAP1(m) . Biochem. Biophys. Res. Commun. . 255 . 2 . 421–6 . 1999 . 10049724 . 10.1006/bbrc.1999.0217 .
• El-Daher SS, Patel Y, Siddiqua A, etal . Distinct localization and function of (1,4,5)IP(3) receptor subtypes and the (1,3,4,5)IP(4) receptor GAP1(IP4BP) in highly purified human platelet membranes . Blood . 95 . 11 . 3412–22 . 2000 . 10.1182/blood.V95.11.3412 . 10828023 .
• Cozier GE, Lockyer PJ, Reynolds JS, etal . GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association . J. Biol. Chem. . 275 . 36 . 28261–8 . 2000 . 10869341 . 10.1074/jbc.M000469200 . free .
• Koehler JA, Moran MF . RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP . Biochem. Biophys. Res. Commun. . 283 . 4 . 888–95 . 2001 . 11350068 . 10.1006/bbrc.2001.4889 .
• Walker SA, Kupzig S, Lockyer PJ, etal . Analyzing the role of the putative inositol 1,3,4,5-tetrakisphosphate receptor GAP1IP4BP in intracellular Ca2+ homeostasis . J. Biol. Chem. . 277 . 50 . 48779–85 . 2003 . 12356770 . 10.1074/jbc.M204839200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Rush J, Moritz A, Lee KA, etal . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nat. Biotechnol. . 23 . 1 . 94–101 . 2005 . 15592455 . 10.1038/nbt1046 . 7200157 .
• Battram AM, Durrant TN, Agbani EO, etal . The Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-binder Rasa3 Regulates Phosphoinositide 3-kinase (PI 3-kinase)-dependent Integrin αIIbβ3 Outside-in Signaling . J. Biol. Chem. . 2016 . 27903653 . 10.1074/jbc.M116.746867 . 292 . 5 . 5290945 . 1691–1704. free .

Notes and References

1. Cullen PJ, Hsuan JJ, Truong O, Letcher AJ, Jackson TR, Dawson AP, Irvine RF . Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family . Nature . 376 . 6540 . 527–30 . Sep 1995 . 7637787 . 10.1038/376527a0 . 1995Natur.376..527C . 4283160 .
2. Lockyer PJ, Bottomley JR, Reynolds JS, McNulty TJ, Venkateswarlu K, Potter BV, Dempsey CE, Cullen PJ . Distinct subcellular localisations of the putative inositol 1,3,4,5-tetrakisphosphate receptors GAP1IP4BP and GAP1m result from the GAP1IP4BP PH domain directing plasma membrane targeting . Curr Biol . 7 . 12 . 1007–10 . Feb 1998 . 9382842 . 10.1016/S0960-9822(06)00423-4 . free .
3. Web site: Entrez Gene: RASA3 RAS p21 protein activator 3.
4. Briggs . S D . Bryant S S . Jove R . Sanderson S D . Smithgall T E . Jun 1995 . The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck . J. Biol. Chem. . 270 . 24 . 14718–24 . UNITED STATES. 0021-9258. 7782336 . 10.1074/jbc.270.24.14718 . free.