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Gene Review

RASSF5  -  Ras association (RalGDS/AF-6) domain...

Homo sapiens

Synonyms: Maxp1, NORE1, NORE1A, NORE1B, New ras effector 1, ...
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Disease relevance of RASSF5


High impact information on RASSF5

  • Here we show that a novel isoform of Rapl GTPase-activating protein, called rap1GAPII, binds specifically to the alpha-subunits of the G(i) family of heterotrimeric G-proteins [6].
  • Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes [7].
  • Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion [7].
  • RAPL regulated the localization and kinase activity of Mst1. 'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the induction of both a polarized morphology and integrin LFA-1 clustering and adhesion triggered by chemokines and T cell receptor ligation [7].
  • Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes [8].

Chemical compound and disease context of RASSF5

  • There were no changes in hematological parameters nore in the activity of malate and lactate dehydrogenases during normoxia and hypoxia, which suggest that these adaptive mechanisms may not be involved during hypoxia [9].

Biological context of RASSF5

  • In addition, our data suggest that the nuclear localization of RASSF5 is critical for its cell growth control activity [10].
  • Overexpression of constitutively active Ki-RasG12V promotes apoptosis in a variety of cell lines; Ha-RasG12V is a much less potent proapoptotic agent; however, a Ha-RasG12V effector loop mutant (E37G) that binds NORE, but not Raf or PI 3-kinase, exhibits proapoptotic efficacy approaching that of Ki-RasG12V [11].
  • However, contrary to RASSF1A, gene silencing by methylation of the CpG islands at which the two NORE1 transcripts initiate is not a common event in human primary tumors [12].
  • RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1 [12].
  • In addition, disconnection of Rap1 and RAPL by expression of a RAPL mutant also perturbed wound healing [8].

Anatomical context of RASSF5


Associations of RASSF5 with chemical compounds

  • Thus, it is suggested that, in the presence of insulin resistance, the responsiveness of B-cells will determine whether the glucose tolerance will be nore homeostasis in other conditions associated with glucose intolerance, the metabolic basis of which is undefined [16].
  • The guanine exchange factor C3G was found to be associated with CrkL at similar levels before and after RA treatment, but Rapl activation downstream of C3G was not inducible by RA [17].
  • 2-Deoxy-D-glucose showed neither net reabsorption nore secretion [18].

Physical interactions of RASSF5


Other interactions of RASSF5

  • NORE is homologous to the putative tumor suppressor RASSF1 and to the Caenorhabditis elegans polypeptide T24F1 [11].
  • However, our results demonstrate that the epigenetic alteration of NORE1A is confined to lung tumors with a wild-type K-ras: 88% (15 of 17) of the tumors with NORE1 hypermethylation did not harbor a K-ras mutation (P=0.008, Fisher's exact test) [20].
  • We review the role and mechanism of specific effectors in regulating the antiapoptotic (Raf, phosphatidylinositol 3-kinase and Tiam1) and apoptotic (Nore1 and RASSF1) actions of oncogenic Ras, and discuss the possibility that the effector actions of p120RasGAP make a significant contribution to Ras regulation of apoptotic events [21].
  • However, TCDD did not selectively alter LFA-1 or Rapl expression in T-cell subsets [22].
  • FNBP2 gene was linked to IKBKE and NORE1 genes on human chromosome 1q32 [23].


  1. Frequent epigenetic inactivation of RASSF1A and BLU genes located within the critical 3p21.3 region in gliomas. Hesson, L., Bièche, I., Krex, D., Criniere, E., Hoang-Xuan, K., Maher, E.R., Latif, F. Oncogene (2004) [Pubmed]
  2. Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Agathanggelou, A., Cooper, W.N., Latif, F. Cancer Res. (2005) [Pubmed]
  3. The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas. Chen, J., Lui, W.O., Vos, M.D., Clark, G.J., Takahashi, M., Schoumans, J., Khoo, S.K., Petillo, D., Lavery, T., Sugimura, J., Astuti, D., Zhang, C., Kagawa, S., Maher, E.R., Larsson, C., Alberts, A.S., Kanayama, H.O., Teh, B.T. Cancer Cell (2003) [Pubmed]
  4. Inhibition of cell growth of human hepatoma cell line (Hep G2) by a farnesyl protein transferase inhibitor: a preferential suppression of ras farnesylation. Nagase, T., Kawata, S., Tamura, S., Matsuda, Y., Inui, Y., Yamasaki, E., Ishiguro, H., Ito, T., Matsuzawa, Y. Int. J. Cancer (1996) [Pubmed]
  5. Identification of the 'NORE' (N-Oct-3 responsive element), a novel structural motif and composite element. Alazard, R., Blaud, M., Elbaz, S., Vossen, C., Icre, G., Joseph, G., Nieto, L., Erard, M. Nucleic Acids Res. (2005) [Pubmed]
  6. Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i). Mochizuki, N., Ohba, Y., Kiyokawa, E., Kurata, T., Murakami, T., Ozaki, T., Kitabatake, A., Nagashima, K., Matsuda, M. Nature (1999) [Pubmed]
  7. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Katagiri, K., Imamura, M., Kinashi, T. Nat. Immunol. (2006) [Pubmed]
  8. Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. Fujita, H., Fukuhara, S., Sakurai, A., Yamagishi, A., Kamioka, Y., Nakaoka, Y., Masuda, M., Mochizuki, N. J. Biol. Chem. (2005) [Pubmed]
  9. The effect of hypoxia and recuperation on carbohydrate metabolism in pacu (Piaractus mesopotamicus). Panepucci, R.A., Panepucci, L., Fernandes, M.N., Sanches, R.J., Rantin, F.T. Brazilian journal of biology = Revista brasleira de biologia. (2001) [Pubmed]
  10. Nuclear Transport of Ras-associated Tumor Suppressor Proteins: Different Transport Receptor Binding Specificities for Arginine-rich Nuclear Targeting Signals. Kumari, G., Singhal, P.K., Rao, M.R., Mahalingam, S. J. Mol. Biol. (2007) [Pubmed]
  11. Identification of a novel Ras-regulated proapoptotic pathway. Khokhlatchev, A., Rabizadeh, S., Xavier, R., Nedwidek, M., Chen, T., Zhang, X.F., Seed, B., Avruch, J. Curr. Biol. (2002) [Pubmed]
  12. RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1. Tommasi, S., Dammann, R., Jin, S.G., Zhang Xf, X.F., Avruch, J., Pfeifer, G.P. Oncogene (2002) [Pubmed]
  13. Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Aoyama, Y., Avruch, J., Zhang, X.F. Oncogene (2004) [Pubmed]
  14. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. Katagiri, K., Shimonaka, M., Kinashi, T. J. Biol. Chem. (2004) [Pubmed]
  15. Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues. Kinashi, T., Katagiri, K. Immunology (2005) [Pubmed]
  16. Insulin resistance in obesity as analyzed by the response of glucose kinetics to glucagon infusion. Vranic, M., Morita, S., Steiner, G. Diabetes (1980) [Pubmed]
  17. All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in acute promyelocytic leukemia cells. Alsayed, Y., Modi, S., Uddin, S., Mahmud, N., Druker, B.J., Fish, E.N., Hoffman, R., Platanias, L.C. Exp. Hematol. (2000) [Pubmed]
  18. Renal sugar transport in the winter flounder. I. Renal clearance studies. Pritchard, J.B., Kleinzeller, A. Am. J. Physiol. (1976) [Pubmed]
  19. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Ortiz-Vega, S., Khokhlatchev, A., Nedwidek, M., Zhang, X.F., Dammann, R., Pfeifer, G.P., Avruch, J. Oncogene (2002) [Pubmed]
  20. CpG island promoter hypermethylation of the Ras-effector gene NORE1A occurs in the context of a wild-type K-ras in lung cancer. Irimia, M., Fraga, M.F., Sanchez-Cespedes, M., Esteller, M. Oncogene (2004) [Pubmed]
  21. The dark side of Ras: regulation of apoptosis. Cox, A.D., Der, C.J. Oncogene (2003) [Pubmed]
  22. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on leukocyte function-associated antigen-1 mediated splenocyte adhesion. Park, S.J., Yoon, W.K., Son, H.Y., Cho, S.W., Jung, J.Y., Jeong, K.S., Kim, T.H., Kim, S.H., Ryu, S.Y. Anticancer Res. (2006) [Pubmed]
  23. FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains. Katoh, M., Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
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