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Gene Review

RBSN  -  rabenosyn, RAB effector

Homo sapiens

Synonyms: 110 kDa protein, FYVE finger-containing Rab5 effector protein rabenosyn-5, RAB effector RBSN, Rabenosyn-5, ZFYVE20, ...
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Disease relevance of ZFYVE20


Psychiatry related information on ZFYVE20

  • This protease also cleaves a natural substrate of 110-kDa beta-amyloid precursor protein, thereby generating the 16-kDa preamyloid peptide that accumulates abnormally in familial Alzheimer's disease lymphoblastoid cells [6].

High impact information on ZFYVE20

  • These effects depend on the ability of Rabenosyn-5 to interact with Rab4 [7].
  • Here, we report that Rabenosyn-5, a previously identified Rab5 effector, also binds to Rab4 [7].
  • The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes [8].
  • Furthermore, although both EEA1 and Rabenosyn-5 are required for early endosomal fusion, only overexpression of Rabenosyn-5 inhibits cathepsin D processing, suggesting that the two proteins play distinct roles in endosomal trafficking [9].
  • Analysis by blue native gel electrophoresis revealed that the translocon of the inner envelope membranes consisted of at least six proteins with molecular weights of 36, 45, 52, 60, 100 and 110 kDa, respectively [10].

Chemical compound and disease context of ZFYVE20


Biological context of ZFYVE20

  • Simultaneous RNAi depletion of both proteins resulted in a similar phenotype to that observed with Rabenosyn-5-RNAi alone, suggesting that Rabenosyn-5 acts before EHD1 in the regulation of endocytic recycling [16].
  • To address the functional roles of EHD1 and Rabenosyn-5, we first demonstrated that RNA interference (RNAi) dramatically reduced the level of expression of each protein, either individually or in combination [16].
  • A sepB mutant of EPEC secreted only the 110-kDa polypeptide and was defective in the formation of attaching and effacing lesions and protein-tyrosine phosphorylation in tissue culture cells [17].
  • Hydrodynamic studies showed that the isolated domain is a 110-kDa trimer with a Stokes radius of 41 A. The mammalian ATCase domain and the prokaryotic enzymes have virtually identical active-site residues and are likely to have the same tertiary fold [18].
  • In addition to the 110 kDa wortmannin binding protein an equally intense band was seen migrating at 85 kDa [19].

Anatomical context of ZFYVE20


Associations of ZFYVE20 with chemical compounds

  • These isoforms migrate with apparent molecular sizes of 110 kDa and 117 kDa in SDS/polyacrylamide gels [24].
  • Additional mass is contributed by posttranslational processing, including N-glycosylation, which, based on experiments with the inhibitor tunicamycin, was found to account in large measure for alpha E migration on SDS/PAGE at approximately 110 kDa rather than at its calculated mass of 92,843 Da [25].
  • This 110-kDa cytosolic phospholipase A2 is distinct from the relatively small (14-kDa) dithiothreitol-sensitive phospholipases A2 that are secreted from many cell types [26].
  • Upon subcellular fractionation of cultured melanocytes, the 110-kDa protein was found to be present in melanosomes but absent from the vesicular fraction; phase separation performed with the nonionic detergent Triton X-114 confirmed the predicted hydrophobic nature of the protein [27].
  • Cilostamide, Ro 15-2041, milrinone, papaverine, isobutylmethylxanthine, and theophylline inhibited the 110-kDa platelet enzyme with IC50 values of 0.04, 0.13, 0.46, 1.4, 2.6, and 110 microM, respectively [28].

Physical interactions of ZFYVE20

  • Here we identify the 110-kDa caveolin-binding protein striatin as the molecular anchor that localizes ERalpha to the membrane and organizes the ERalpha-eNOS membrane signaling complex [29].
  • Previous studies with 125I-labeled IL 4 identified on resting lymphocytes a trimolecular complex consisting of a 65/70-kDa doublet and a 110-kDa protein with approximately 300 high-affinity binding sites (Kd 100 pM) and approximately 9000 low-affinity binding sites (Kd 30 nM) [30].
  • Here we report that in addition to the free form of TGF beta 2, a stable complex between a approximately 110 kDa binding protein and TGF beta 2 was isolated from glioblastoma cell supernatant [31].
  • The dissociation constant (Kd) for 125I-vWF binding to the recombinant 110-kDa protein was 1.2 +/- 0.2 nM as compared with 1.0 +/- 0.3 nM for vWF binding to purified platelet GP Ib-IX [32].
  • In this fraction a polypeptide with a molecular mass of approximately 110 kDa could be identified as a specific DNA-binding component of hTFIIIC [33].

Enzymatic interactions of ZFYVE20

  • Moreover, recombinant BLM was cleaved to 47- and 110-kDa fragments by caspase 3, but not caspase 6, in vitro [34].
  • We have reported that the proportion of 120-130 to 110 kDa carboxyl-cleaved APP present in the platelets of AD patients is significantly lower than that of platelets of age-matched controls [35].

Regulatory relationships of ZFYVE20

  • Characterization of the CD26 Ag expressed by the transfected Jurkat cells revealed that the Ag could be immunoprecipitated as a 110-kDa molecule similar to that found on peripheral blood T cells and that the Ag had dipeptidyl peptidase IV activity [36].
  • We have identified proteins of 110, 80, 65, and 43 kDa in human embryonic fibroblasts that bind specifically to the SH3 domain of phospholipase C gamma, a primary substrate of receptor tyrosine kinases, and characterized the 110-kDa band as the microtubule-activated GTPase dynamin [37].
  • Although the active 110 kDa polypeptide cannot be inhibited by anti-u-PA, it yet comprises a 37 kDa piece with some u-PA related antigenic determinants [38].
  • Binding of affinity-purified GP IIb-IIIa complex to fibronectin is inhibited by the 110-kDa FN fragment [39].
  • H. pylori infection increased the 110-kDa caseinolytic activity and induced new gelatinolytic (~35 kDa) and caseinolytic (22 kDa) activities [40].

Other interactions of ZFYVE20


Analytical, diagnostic and therapeutic context of ZFYVE20


  1. Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTP-binding proteins Rho involved in assembly of actin stress fibers. Oswald, E., Sugai, M., Labigne, A., Wu, H.C., Fiorentini, C., Boquet, P., O'Brien, A.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Protein kinase A-dependent derepression of the human prodynorphin gene via differential binding to an intragenic silencer element. Carrión, A.M., Mellström, B., Naranjo, J.R. Mol. Cell. Biol. (1998) [Pubmed]
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  6. Ca(2+)-dependent 68-kilodalton protease in familial Alzheimer's disease cells cleaves the N-terminus of beta-amyloid. Matsumoto, A., Fujiwara, Y. Biochemistry (1994) [Pubmed]
  7. Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes. de Renzis, S., Sönnichsen, B., Zerial, M. Nat. Cell Biol. (2002) [Pubmed]
  8. The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. Makarova, O.V., Makarov, E.M., Lührmann, R. EMBO J. (2001) [Pubmed]
  9. Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. Nielsen, E., Christoforidis, S., Uttenweiler-Joseph, S., Miaczynska, M., Dewitte, F., Wilm, M., Hoflack, B., Zerial, M. J. Cell Biol. (2000) [Pubmed]
  10. The chloroplastic protein import machinery contains a Rieske-type iron-sulfur cluster and a mononuclear iron-binding protein. Caliebe, A., Grimm, R., Kaiser, G., Lübeck, J., Soll, J., Heins, L. EMBO J. (1997) [Pubmed]
  11. Polyoma virus middle T antigen-pp60c-src complex associates with purified phosphatidylinositol 3-kinase in vitro. Auger, K.R., Carpenter, C.L., Shoelson, S.E., Piwnica-Worms, H., Cantley, L.C. J. Biol. Chem. (1992) [Pubmed]
  12. Regions required for CD4 binding in the external glycoprotein gp120 of simian immunodeficiency virus. Doyle, C.B., Bhattacharyya, U., Kent, K.A., Stott, J.E., Jones, I.M. J. Virol. (1995) [Pubmed]
  13. Infection of macrophage-like THP-1 cells with Mycobacterium avium results in a decrease in their ability to phosphorylate nucleolin. Garcia, R.C., Banfi, E., Pittis, M.G. Infect. Immun. (2000) [Pubmed]
  14. Molecular cloning of a GPI-anchored aminopeptidase N from Bombyx mori midgut: a putative receptor for Bacillus thuringiensis CryIA toxin. Hua, G., Tsukamoto, K., Rasilo, M.L., Ikezawa, H. Gene (1998) [Pubmed]
  15. Involvement of host cell tyrosine phosphorylation in the invasion of HEp-2 cells by Bartonella bacilliformis. Williams-Bouyer, N.M., Hill, E.M. FEMS Microbiol. Lett. (1999) [Pubmed]
  16. Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Naslavsky, N., Boehm, M., Backlund, P.S., Caplan, S. Mol. Biol. Cell (2004) [Pubmed]
  17. Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. Jarvis, K.G., Girón, J.A., Jerse, A.E., McDaniel, T.K., Donnenberg, M.S., Kaper, J.B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  18. Mammalian aspartate transcarbamylase (ATCase): sequence of the ATCase domain and interdomain linker in the CAD multifunctional polypeptide and properties of the isolated domain. Simmer, J.P., Kelly, R.E., Scully, J.L., Grayson, D.R., Rinker, A.G., Bergh, S.T., Evans, D.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  19. Wortmannin binds specifically to 1-phosphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. Thelen, M., Wymann, M.P., Langen, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  20. Reconstitution of ATP-dependent aminophospholipid translocation in proteoliposomes. Auland, M.E., Roufogalis, B.D., Devaux, P.F., Zachowski, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  21. A and B forms of the androgen receptor are present in human genital skin fibroblasts. Wilson, C.M., McPhaul, M.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  22. Laminin receptors for neurite formation. Kleinman, H.K., Ogle, R.C., Cannon, F.B., Little, C.D., Sweeney, T.M., Luckenbill-Edds, L. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  23. A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis. Zhang, C., Xu, Y., Gu, J., Schlossman, S.F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  24. Phosphorylation of ubiquitin-activating enzyme in cultured cells. Cook, J.C., Chock, P.B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  25. Fib420: a normal human variant of fibrinogen with two extended alpha chains. Fu, Y., Grieninger, G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. Clark, J.D., Milona, N., Knopf, J.L. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  27. Identification of a melanosomal membrane protein encoded by the pink-eyed dilution (type II oculocutaneous albinism) gene. Rosemblat, S., Durham-Pierre, D., Gardner, J.M., Nakatsu, Y., Brilliant, M.H., Orlow, S.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  28. Immunological identification of the major platelet low-Km cAMP phosphodiesterase: probable target for anti-thrombotic agents. Macphee, C.H., Harrison, S.A., Beavo, J.A. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  29. Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor alpha. Lu, Q., Pallas, D.C., Surks, H.K., Baur, W.E., Mendelsohn, M.E., Karas, R.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  30. Inhibition of interleukin 4 receptor expression on human lymphoid cells by cyclosporin. Foxwell, B.M., Woerly, G., Ryffel, B. Eur. J. Immunol. (1990) [Pubmed]
  31. Transforming growth factor-beta bound to soluble derivatives of the beta amyloid precursor protein of Alzheimer's disease. Bodmer, S., Podlisny, M.B., Selkoe, D.J., Heid, I., Fontana, A. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  32. Expression and characterization of functionally active fragments of the platelet glycoprotein (GP) Ib-IX complex in mammalian cells. Incorporation of GP Ib alpha into the cell surface membrane. Meyer, S., Kresbach, G., Häring, P., Schumpp-Vonach, B., Clemetson, K.J., Hadváry, P., Steiner, B. J. Biol. Chem. (1993) [Pubmed]
  33. Purification of human transcription factor IIIC and its binding to the gene for ribosomal 5S RNA. Schneider, H.R., Waldschmidt, R., Jahn, D., Seifart, K.H. Nucleic Acids Res. (1989) [Pubmed]
  34. Selective cleavage of BLM, the bloom syndrome protein, during apoptotic cell death. Bischof, O., Galande, S., Farzaneh, F., Kohwi-Shigematsu, T., Campisi, J. J. Biol. Chem. (2001) [Pubmed]
  35. Platelet APP isoform ratios in asymptomatic young adults expressing an AD-related presenilin-1 mutation. Baskin, F., Rosenberg, R.N., Iyer, L., Schellenberg, G.D., Hynan, L., Nee, L.E. J. Neurol. Sci. (2001) [Pubmed]
  36. Cloning and functional expression of the T cell activation antigen CD26. Tanaka, T., Camerini, D., Seed, B., Torimoto, Y., Dang, N.H., Kameoka, J., Dahlberg, H.N., Schlossman, S.F., Morimoto, C. J. Immunol. (1992) [Pubmed]
  37. Dynamin binds to SH3 domains of phospholipase C gamma and GRB-2. Seedorf, K., Kostka, G., Lammers, R., Bashkin, P., Daly, R., Burgess, W.H., van der Bliek, A.M., Schlessinger, J., Ullrich, A. J. Biol. Chem. (1994) [Pubmed]
  38. The contact-system dependent plasminogen activator from human plasma: identification and characterization. Binnema, D.J., Dooijewaard, G., van Iersel, J.J., Turion, P.N., Kluft, C. Thromb. Haemost. (1990) [Pubmed]
  39. Determination of the putative binding site for fibronectin on platelet glycoprotein IIb-IIIa complex through a hydropathic complementarity approach. Pasqualini, R., Chamone, D.F., Brentani, R.R. J. Biol. Chem. (1989) [Pubmed]
  40. Epithelial and bacterial metalloproteinases and their inhibitors in H. pylori infection of human gastric cells. Göõz, M., Göõz, P., Smolka, A.J. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  41. A gene pair from the human major histocompatibility complex encodes large proline-rich proteins with multiple repeated motifs and a single ubiquitin-like domain. Banerji, J., Sands, J., Strominger, J.L., Spies, T. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  42. Autosomal dominant polycystic kidney disease: clues to pathogenesis. Harris, P.C. Hum. Mol. Genet. (1999) [Pubmed]
  43. Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease. Piñeiro-Sánchez, M.L., Goldstein, L.A., Dodt, J., Howard, L., Yeh, Y., Tran, H., Argraves, W.S., Chen, W.T. J. Biol. Chem. (1997) [Pubmed]
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  45. Interferon alpha (IFN alpha) signaling in cells expressing the variant form of the type I IFN receptor. Colamonici, O.R., Domanski, P., Krolewski, J.J., Fu, X.Y., Reich, N.C., Pfeffer, L.M., Sweet, M.E., Platanias, L.C. J. Biol. Chem. (1994) [Pubmed]
  46. Characterization of three monoclonal antibodies that recognize the interferon alpha 2 receptor. Colamonici, O.R., D'Alessandro, F., Diaz, M.O., Gregory, S.A., Neckers, L.M., Nordan, R. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  47. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors. Daughaday, W.H., Kapadia, M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  48. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Patterson, J.B., Samuel, C.E. Mol. Cell. Biol. (1995) [Pubmed]
  49. Depletion of the 110-kilodalton isoform of poly(ADP-ribose) glycohydrolase increases sensitivity to genotoxic and endotoxic stress in mice. Cortes, U., Tong, W.M., Coyle, D.L., Meyer-Ficca, M.L., Meyer, R.G., Petrilli, V., Herceg, Z., Jacobson, E.L., Jacobson, M.K., Wang, Z.Q. Mol. Cell. Biol. (2004) [Pubmed]
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