Gene Symbol: RASA3
Description: RAS p21 protein activator 3
Alias: GAP1IP4BP, GAPIII, ras GTPase-activating protein 3, GTPase activating protein III, GTPase-activating protein 1 family, inositol 1,3,4,5-tetrakisphosphate-binding protein, Ins(1,3,4,5)P4-binding protein, ins P4-binding protein
Species: human
Products:     RASA3

Top Publications

  1. El Daher S, Patel Y, Siddiqua A, Hassock S, Edmunds S, Maddison B, et al. 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. 2000;95:3412-22 pubmed
  2. Schulze K, Bhatt A, Azamian M, Sundgren N, Zapata G, Hernandez P, et al. Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy. Genet Med. 2019;: pubmed publisher
    ..g., CACNA1C, TRIO, ANKRD11) or genes known to influence embryonic development (e.g., BRAX1, RASA3). Further, we identified allele-specific methylation (ASM) at 11 of these loci, within which 61...
  3. Hauer N, Popp B, Taher L, Vogl C, Dhandapany P, Büttner C, et al. Evolutionary conserved networks of human height identify multiple Mendelian causes of short stature. Eur J Hum Genet. 2019;: pubmed publisher
    ..Eleven of the candidate genes mapped to 21 of these clusters, including CPZ, EDEM3, FBRS, IFT81, KCND1, PLXNA3, RASA3, SLC7A8, UBR4, USP45, and ZFHX3...
  4. Wu B, Zhang S, Guo Z, Wang G, Zhang G, Xie L, et al. RAS P21 Protein Activator 3 (RASA3) Specifically Promotes Pathogenic T Helper 17 Cell Generation by Repressing T-Helper-2-Cell-Biased Programs. Immunity. 2018;49:886-898.e5 pubmed publisher
    ..We found that Ras p21 protein activator 3 (RASA3) was highly expressed by pTh17 cells relative to non-pTh17 cells and was required specifically for pTh17 ..
  5. Dhawan D, Hahn N, Ramos Vara J, Knapp D. Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer. PLoS Genet. 2018;14:e1007571 pubmed publisher
    ..The enriched genes included MMP9, SERPINE2, CAV1, KRT14, and RASA3 in basal tumors, and PPARG, LY6E, CTSE, CDK3, and TBX2 in luminal tumors...
  6. Stefanini L, Paul D, Robledo R, Chan E, Getz T, Campbell R, et al. RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J Clin Invest. 2015;125:1419-32 pubmed publisher
    ..Here, we provide evidence that the GAP, RASA3, inhibits platelet activation and provides a link between P2Y12 and activation of the RAP1 signaling pathway...
  7. Moni M, Liò P. Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies. BMC Bioinformatics. 2014;15:333 pubmed publisher
    ..Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process...
  8. Molina Ortiz P, Orban T, Martin M, Habets A, Dequiedt F, Schurmans S. Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism. PLoS Genet. 2018;14:e1007195 pubmed publisher
    b>Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1...
  9. Choi Y, Lee S, Kim M, Jung S, Hur S, Chung Y, et al. Whole-exome sequencing identified the genetic origin of a mucinous neoplasm in a mature cystic teratoma. Pathology. 2016;48:372-6 pubmed publisher
    ..putative driver gene mutations catalogued in COSMIC database (KRAS, GNAS, ZBTB38, ENAM, HTR5A, BAI1, ADAMTS8 and RASA3)...

More Information


  1. Stefanini L, Bergmeier W. RAP1-GTPase signaling and platelet function. J Mol Med (Berl). 2016;94:13-9 pubmed publisher
    ..Our recent studies demonstrate that the antagonistic balance between the RAP1 regulators, CalDAG-GEFI and RASA3, is critical for the modulation of platelet adhesiveness, both in circulation and at sites of vascular injury...
  2. Minor P, Lane B, Mimms S, Bar P. Scientific consultation on the safety and containment of new poliovirus strains for vaccine production, clinical/regulatory testing and research. Report of a meeting held at NIBSC, Potters Bar, Hertfordshire, UK, 6/7th July 2016. Biologicals. 2017;48:92-100 pubmed publisher
    ..Work on polioviruses must be contained in accordance with GAPIII (the third version of the Global Action Plan of WHO)...
  3. Nafisi H, Banihashemi B, Daigle M, Albert P. GAP1(IP4BP)/RASA3 mediates Galphai-induced inhibition of mitogen-activated protein kinase. J Biol Chem. 2008;283:35908-17 pubmed publisher
    ..library was done using constitutively active Galphai3-Q204L, and multiple clones of the RasGAP cDNA GAP1(IP4BP)/RASA3 were identified...
  4. Schurmans S, Polizzi S, Scoumanne A, Sayyed S, Molina Ortiz P. The Ras/Rap GTPase activating protein RASA3: from gene structure to in vivo functions. Adv Biol Regul. 2015;57:153-61 pubmed publisher
    RASA3 (or GTPase Activating Protein III, R-Ras GTPase-activating protein, GAP1(IP4BP)) is a GTPase activating protein of the GAP1 subfamily which targets Ras and Rap1...
  5. Peters L, Paw B, Blanc L. The scat mouse model highlights RASA3, a GTPase activating protein, as a key regulator of vertebrate erythropoiesis and megakaryopoiesis. Small Gtpases. 2013;4:47-50 pubmed publisher
    ..in the scat (severe combined anemia and thrombocytopenia) mouse model a missense mutation (G125V) in the Rasa3 gene, encoding a Ras GTPase activating protein (GAP)...
  6. Cullen P, Hsuan J, Truong O, Letcher A, Jackson T, Dawson A, et al. Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature. 1995;376:527-30 pubmed
    ..In vitro it shows GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited by phospholipids and is specifically stimulated by Ins(1,3,4,5)P4. ..
  7. O Rourke F, Matthews E, Feinstein M. Isolation of InsP4 and InsP6 binding proteins from human platelets: InsP4 promotes Ca2+ efflux from inside-out plasma membrane vesicles containing 104 kDa GAP1IP4BP protein. Biochem J. 1996;315 ( Pt 3):1027-34 pubmed
    ..A 104 kDa InsP4 binding protein (KD for InsP4 = 12 nM), probably identical to GAP1IP4BP described by Cullen, Hsuan, Truong, Letcher, Jackson, Dawson and Irvine [(1995) Nature (London) 376, 527-530], ..
  8. Lockyer P, Bottomley J, Reynolds J, McNulty T, Venkateswarlu K, Potter B, et al. 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. 1997;7:1007-10 pubmed
    ..This difference in localisation has fundamental significance for our understanding of the second messenger functions of IP4. ..
  9. Cozier G, Lockyer P, Reynolds J, Kupzig S, Bottomley J, Millard T, et al. GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association. J Biol Chem. 2000;275:28261-8 pubmed
  10. Battram A, Durrant T, Agbani E, Heesom K, Paul D, Piatt R, et al. The Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) Binder Rasa3 Regulates Phosphoinositide 3-kinase (PI3K)-dependent Integrin αIIbβ3 Outside-in Signaling. J Biol Chem. 2017;292:1691-1704 pubmed publisher
    ..Here, we identify Ras/Rap1GAP Rasa3 (GAP1IP4BP) as a major phosphatidylinositol 3,4,5-trisphosphate-binding protein in human platelets and ..
  11. Cullen P, Loomis Husselbee J, Dawson A, Irvine R. Inositol 1,3,4,5-tetrakisphosphate and Ca2+ homoeostasis: the role of GAP1IP4BP. Biochem Soc Trans. 1997;25:991-6 pubmed
  12. Qamra A, Xing M, Padmanabhan N, Kwok J, Zhang S, Xu C, et al. Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma. Cancer Discov. 2017;7:630-651 pubmed publisher
    ..mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3)...
  13. Hata Y, Kikuchi A, Sasaki T, Schaber M, Gibbs J, Takai Y. 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. 1990;265:7104-7 pubmed
    ..c-Ha-ras p21 did not inhibit the smg p21 GAP1- or -2-stimulated GTPase activity of smg p21. These results indicate that ras p21 GAP interacts with smg p21 without the subsequent stimulation of its GTPase activity. ..
  14. Walker S, Kupzig S, Lockyer P, Bilu S, Zharhary D, Cullen P. Analyzing the role of the putative inositol 1,3,4,5-tetrakisphosphate receptor GAP1IP4BP in intracellular Ca2+ homeostasis. J Biol Chem. 2002;277:48779-85 pubmed
    ..Thus, using various approaches to manipulate the function of endogenous GAP1(IP4BP) in intact HeLa cells, we have been unable to observe any detectable effect of GAP1(IP4BP) on [Ca(2+)](i). ..
  15. Kupzig S, Bouyoucef Cherchalli D, Yarwood S, Sessions R, Cullen P. The ability of GAP1IP4BP to function as a Rap1 GTPase-activating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb. Mol Cell Biol. 2009;29:3929-40 pubmed publisher
  16. Lockyer P, Vanlingen S, Reynolds J, McNulty T, Irvine R, Parys J, et al. 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. 1999;255:421-6 pubmed
    ..As GAP1(m) is primarily localised to the cytosol of unstimulated cells it may be spatially regulated in order to interact with Ras at the plasma membrane. ..
  17. Zhang C, Li X, Adelmant G, Dobbins J, Geisen C, Oser M, et al. Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21. Proc Natl Acad Sci U S A. 2015;112:15372-7 pubmed publisher
  18. Koehler J, Moran M. RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP. Biochem Biophys Res Commun. 2001;283:888-95 pubmed
    ..Finally, serine/threonine phosphorylation appears to be involved in regulating this association. These results suggest that p120GAP and RACK1 interact in vivo in a manner dependent upon both the PH and C2/CaLB domains of GAP. ..
  19. Briggs S, Bryant S, Jove R, Sanderson S, Smithgall T. The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck. J Biol Chem. 1995;270:14718-24 pubmed
    ..These data implicate the Hck SH3 domain in GAP interaction, and suggest a general function for the SH3 domains of Src family kinases in recognition of GAP via its proline-rich N-terminal domain. ..
  20. Hjermstad S, Briggs S, Smithgall T. 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. 1993;32:10519-25 pubmed
    ..Stimulation of c-fes autophosphorylation in vivo may induce interaction with GAP, resulting in altered p21ras function. ..
  21. Cuellar J, Valpuesta J, Wittinghofer A, Sot B. Domain topology of human Rasal. Biol Chem. 2017;: pubmed publisher
    ..multi-domain protein of the GAP1 (GTPase-activating protein 1) family; its four known members, GAP1m, Rasal, GAP1IP4BP and Capri, have a Ras GTPase-activating domain (RasGAP)...