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RASA4  -  RAS p21 protein activator 4

Homo sapiens

Synonyms: CAPRI, Calcium-promoted Ras inactivator, GAPL, KIAA0538, Ras GTPase-activating protein 4, ...
 
 
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Disease relevance of RASA4

  • Concluding remarks on the Capri symposium: myths, facts and new trends in migraine [1].
  • Gallisepticum S6 showed a strong cilia-stopping effect; M. pulmonis PG22, M. mycoides subsp. capri PG3, M. meleagridis 19729, M. neurolyticum Type A and M. arthritidis PG6 showed a mild effect; and M. pneumoniae FH, M. salivarium Hup, M. hominis type 1-C and M. orale N-C human origin and Acholeplasma laidlawii PG8 showed a weak effect [2].
  • The dnaA gene fragments were amplified from M. mycoides subsp. capri, Spiroplasma apis and S. citri [3].
  • The first mycoplasma isolated, M. mycoidesis is the aetiological agent of bovine pleuropneumonia, a disease now confined to parts of Africa and Australia. M. capri causes a similar disease in goats which is geographically more widespread [4].
  • We have not been able to discover any cases in the literature describing the development of unilateral osteonecrosis in a patient with bilateral os centrale capri [5].
 

High impact information on RASA4

  • RASAL tracks agonist-stimulated Ca2+ oscillations by repetitively associating with the plasma membrane, yet CAPRI displays a long-lasting Ca2+-triggered translocation that is refractory to cytosolic Ca2+ oscillations [6].
  • CAPRI behavior is Ca2+- and C2 domain-dependent but sustained recruitment is predominantly Ca2+ independent, necessitating integration of Ca2+ by the C2 domains with agonist-evoked plasma membrane interaction sites for the pleckstrin homology domain [6].
  • A place to die for: apoptosis in cancer and infection, Capri 2002 [7].
  • Using this system, we found that a splice variant of Ca2+-promoted Ras inactivator (CAPRI), deltaCAPRI, which is expressed in primary osteoblasts, promoted the RANKL shedding [8].
  • Here, we describe the identification of CAPRI (Ca(2+)-promoted Ras inactivator), a Ca(2+)-dependent Ras GTPase-activating protein (GAP) that switches off the Ras-MAPK pathway following a stimulus that elevates intracellular Ca(2+) [9].
 

Chemical compound and disease context of RASA4

 

Biological context of RASA4

  • Herein, we show that the PH domain of MRASAL has binding activity toward PI(4,5)P(2) and PI(3,4,5)P(3), while the PH domain of KIAA0538 does not bind these phospholipids due to an amino acid substitution at position 592 (Leu-592) [11].
  • The members of this family are GAP1(m), GAP1(IP4BP), CAPRI (Ca(2+)-promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) and, as we will discuss, they are emerging as important modulators of Ras and small GTPase signalling that are subject to regulation by a diverse array of events and second messenger signals [12].
  • For rounds 3, 4, and 5 of the CAPRI evaluation, where possible, we clustered functional residues on the surfaces of the monomers as an indication of binding sites, using sequence based evolutionary conservations [13].
  • The membrane potentials of Acholeplasma laidlawii, Mycoplasma mycoides subsp. capri, Mycoplasma gallisepticum, Streptococcus faecalis and human erythrocytes have been determined by applying a novel technique [14].
 

Anatomical context of RASA4

 

Associations of RASA4 with chemical compounds

  • Distinct phosphoinositide binding specificity of the GAP1 family proteins: characterization of the pleckstrin homology domains of MRASAL and KIAA0538 [11].
  • The peptides APLHK, EHIPA and GAPL are hydropathically equivalent peptide mimics of a fibrinogen binding domain of glycoprotein IIb/IIIa [17].
  • When these procedures were applied to the targets of CAPRI, a larger number of hits and smaller ligand root-mean-square deviations (RMSDs) were obtained at the conformational search stage in all cases, and especially Target 19 [18].
  • The CAPRI Challenge is a blind test of protein-protein-docking algorithms that predict the complex structure from the crystal structures of the interacting proteins [19].
  • Muscles included the flexor carpi ulnaris, the flexor carpi radialis, the extensor carpi ulnaris, the extensor capri radialis brevis, and the extensor carpi radialis longus [20].
 

Analytical, diagnostic and therapeutic context of RASA4

References

  1. Concluding remarks on the Capri symposium: myths, facts and new trends in migraine. Sicuteri, F. Cephalalgia : an international journal of headache. (1983) [Pubmed]
  2. Comparison of ciliostasis by mycoplasmas in mouse and chicken tracheal organ cultures. Araake, M. Microbiol. Immunol. (1982) [Pubmed]
  3. Comparison of the conserved region in the dnaA gene from three mollicute species. Suzuki, K., Miyata, M., Fukumura, T. FEMS Microbiol. Lett. (1993) [Pubmed]
  4. The importance of mycoplasmas in respiratory infections. Taylor-Robinson, D. Dev. Biol. Stand. (1975) [Pubmed]
  5. Unilateral osteonecrosis in a patient with bilateral os centrale carpi. Lane, L.B., Gould, E.S., Stein, P.D., Coffey, E. The Journal of hand surgery. (1990) [Pubmed]
  6. CAPRI and RASAL impose different modes of information processing on Ras due to contrasting temporal filtering of Ca2+. Liu, Q., Walker, S.A., Gao, D., Taylor, J.A., Dai, Y.F., Arkell, R.S., Bootman, M.D., Roderick, H.L., Cullen, P.J., Lockyer, P.J. J. Cell Biol. (2005) [Pubmed]
  7. A place to die for: apoptosis in cancer and infection, Capri 2002. Oberst, A., Baehrecke, E., Mehmet, H., Ichijo, H., Gupta, S. Cell Death Differ. (2003) [Pubmed]
  8. Identification of an alternatively spliced variant of Ca2+-promoted Ras inactivator as a possible regulator of RANKL shedding. Hikita, A., Kadono, Y., Chikuda, H., Fukuda, A., Wakeyama, H., Yasuda, H., Nakamura, K., Oda, H., Miyazaki, T., Tanaka, S. J. Biol. Chem. (2005) [Pubmed]
  9. CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway. Lockyer, P.J., Kupzig, S., Cullen, P.J. Curr. Biol. (2001) [Pubmed]
  10. Modeling oligomers with Cn or Dn symmetry: application to CAPRI target 10. Berchanski, A., Segal, D., Eisenstein, M. Proteins (2005) [Pubmed]
  11. Distinct phosphoinositide binding specificity of the GAP1 family proteins: characterization of the pleckstrin homology domains of MRASAL and KIAA0538. Minagawa, T., Fukuda, M., Mikoshiba, K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. The GAP1 family of GTPase-activating proteins: spatial and temporal regulators of small GTPase signalling. Yarwood, S., Bouyoucef-Cherchalli, D., Cullen, P.J., Kupzig, S. Biochem. Soc. Trans. (2006) [Pubmed]
  13. Protein-protein docking using 3D-Dock in rounds 3, 4, and 5 of CAPRI. Carter, P., Lesk, V.I., Islam, S.A., Sternberg, M.J. Proteins (2005) [Pubmed]
  14. A novel method for the determination of electrical potentials across cellular membranes. II. Membrane potentials of Acholeplasmas, Mycoplasmas, Streptococci and erythrocytes. Schummer, U., Schiefer, H.G., Gerhardt, U. Biochim. Biophys. Acta (1980) [Pubmed]
  15. Workshop on Trophic Factors in the Peripheral Nervous System. Capri, October 1991. Sendtner, M., Kreutzberg, G.W., Jennekens, F.G. Neuromuscul. Disord. (1992) [Pubmed]
  16. Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Bivona, T.G., Pérez De Castro, I., Ahearn, I.M., Grana, T.M., Chiu, V.K., Lockyer, P.J., Cullen, P.J., Pellicer, A., Cox, A.D., Philips, M.R. Nature (2003) [Pubmed]
  17. The peptides APLHK, EHIPA and GAPL are hydropathically equivalent peptide mimics of a fibrinogen binding domain of glycoprotein IIb/IIIa. Gartner, T.K., Loudon, R., Taylor, D.B. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  18. Biologically enhanced sampling geometric docking and backbone flexibility treatment with multiconformational superposition. Ma, X.H., Li, C.H., Shen, L.Z., Gong, X.Q., Chen, W.Z., Wang, C.X. Proteins (2005) [Pubmed]
  19. ZDOCK predictions for the CAPRI challenge. Chen, R., Tong, W., Mintseris, J., Li, L., Weng, Z. Proteins (2003) [Pubmed]
  20. Architecture of selected wrist flexor and extensor muscles. Lieber, R.L., Fazeli, B.M., Botte, M.J. The Journal of hand surgery. (1990) [Pubmed]
  21. Concordant and discordant effects on cardiovascular risks exerted by oestrogen and progestogen in women using oral contraception and hormone replacement therapy. ESHRE Capri Workshop Group. Crosignani, P.G., La Vecchia, C. Hum. Reprod. Update (1999) [Pubmed]
  22. Optimal use of infertility diagnostic tests and treatments. The ESHRE Capri Workshop Group. Crosignani, P.G., Rubin, B.L. Hum. Reprod. (2000) [Pubmed]
  23. Scoring docking models with evolutionary information. Tress, M., de Juan, D., Graña, O., Gómez, M.J., Gómez-Puertas, P., González, J.M., López, G., Valencia, A. Proteins (2005) [Pubmed]
 
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