Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Mayuko Ichimura
  • Atsuko Nakanishi
  • Yasuko Kitagishi
  • Satoru MatsudaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101776


 RUFY1: FYVE-finger containing protein; Rab4a interacting protein; Rab4aip; Rabip4; RUN and FYVE domain-containing 1; ZFYVE12

 RUFY2: Denn; KIAA1537; LZ-FYVE; Rabip4R; RABIP4R; RUN and FYVE domain-containing 2; ZFYVE13

 RUFY3: RIPX; Rap2 interacting protein X; RUN and FYVE domain-containing 3; SINGAR1; Single axon-related 1; ZFYVE30

 RUFY4: RUN and FYVE domain-containing 4; ZFYVE31

Historical Background

The RUFY proteins ( RUN and FYVE domain-containing protein family) have an amino-terminal RUN domain and a carboxyl-terminal FYVE domain, which associates with phosphatidylinositol 3-phosphate (PI3P) in early endosomes (Yang et al. 2002). As shown in Fig. 1, genome DNA analyses have revealed that a RUFY family consists of four members of RUFY proteins (Yoshida et al. 2010). The RUN domains, named from RPIP8, UNC-14, and NESCA proteins, might function as effectors of the small GTPase superfamily (MacDonald et al. 2004). For example, yeast two-hybrid assays for Rab binding...
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  1. Bofill-De Ros X, Santos M, Vila-Casadesús M, Villanueva E, Andreu N, Dierssen M, Fillat C. Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges. BMC Genomics. 2015;16:907.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Cormont M, Mari M, Galmiche A, Hofman P, Le Marchand-Brustel Y. A FYVE-finger-containing protein, Rabip4, is a Rab4 effector involved in early endosomal traffic. Proc Natl Acad Sci USA. 2001;98:1637–42.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Fukuda M, Kobayashi H, Ishibashi K, Ohbayashi N. Genome-wide investigation of the Rab binding activity of RUN domains: development of a novel tool that specifically traps GTP-Rab35. Cell Struct Funct. 2011;36:155–70.PubMedPubMedCentralCrossRefGoogle Scholar
  4. He J, Vora M, Haney RM, Filonov GS, Musselman CA, Burd CG, Kutateladze AG, Verkhusha VV, Stahelin RV, Kutateladze TG. Membrane insertion of the FYVE domain is modulated by pH. Proteins. 2009;76:852–60.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ivan V, Martinez-Sanchez E, Sima LE, Oorschot V, Klumperman J, Petrescu SM, van der Sluijs P. AP-3 and Rabip4′ coordinately regulate spatial distribution of lysosomes. PLoS One. 2012;7:e48142.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Kitagishi Y, Matsuda S. RUFY, Rab and Rap family proteins involved in a regulation of cell polarity and membrane trafficking. Int J Mol Sci. 2013;14:6487–98.PubMedPubMedCentralCrossRefGoogle Scholar
  7. MacDonald JI, Kubu CJ, Meakin SO. Nesca, a novel adapter, translocates to the nuclear envelope and regulates neurotrophin-induced neurite outgrowth. J Cell Biol. 2004;164:851–62.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Mari M, Macia E, Le Marchand-Brustel Y, Cormont M. Role of the FYVE finger and the RUN domain for the subcellular localization of Rabip4. J Biol Chem. 2001;276:42501–8.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Mari M, Monzo P, Kaddai V, Keslair F, Gonzalez T, Le Marchand-Brustel Y, Cormont M. The Rab4 effector Rabip4 plays a role in the endocytotic trafficking of Glut 4 in 3 T3-L1 adipocytes. J Cell Sci. 2006;119:1297–306.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Mori T, Wada T, Suzuki T, Kubota Y, Inagaki N. Singar1, a novel RUN domain-containing protein, suppresses formation of surplus axons for neuronal polarity. J Biol Chem. 2007;282:19884–93.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ogura K, Goshima Y. The autophagy-related kinase UNC-51 and its binding partner UNC-14 regulate the subcellular localization of the Netrin receptor UNC-5 in Caenorhabditis elegans. Development. 2006;133:3441–50.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Pankiv S, Alemu EA, Brech A, Bruun JA, Lamark T, Overvatn A, Bjørkøy G, Johansen T. FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. J Cell Biol. 2010;188:253–69.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T. Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain. Mol Biol Cell. 2010;21:4162–72.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Terawaki S, Camosseto V, Prete F, Wenger T, Papadopoulos A, Rondeau C, Combes A, Rodriguez Rodrigues C, Vu Manh TP, Fallet M, English L, Santamaria R, Soares AR, Weil T, Hammad H, Desjardins M, Gorvel JP, Santos MA, Gatti E, Pierre P. RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4. J Cell Biol. 2015;210:1133–52.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Terawaki S, Camosseto V, Pierre P, Gatti E. RUFY4: immunity piggybacking on autophagy? Autophagy. 2016;12:598–600.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Wang G, Zhang Q, Song Y, Wang X, Guo Q, Zhang J, Li J, Han Y, Miao Z, Li F. PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion. Cell Death Dis. 2015;6:e1682.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Wei Z, Sun M, Liu X, Zhang J, Jin Y. Rufy3, a protein specifically expressed in neurons, interacts with actin-bundling protein Fascin to control the growth of axons. J Neurochem. 2014;130:678–92.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Yamamoto H, Koga H, Katoh Y, Takahashi S, Nakayama K, Shin HW. Functional cross-talk between Rab14 and Rab4 through a dual effector, RUFY1/Rabip4. Mol Biol Cell. 2010;21:2746–55.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Yang J, Kim O, Wu J, Qiu Y. Interaction between tyrosine kinase Etk and a RUN domain- and FYVE domain-containing protein RUFY1. A possible role of ETK in regulation of vesicle trafficking. J Biol Chem. 2002;277:30219–26.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Yoshida H, Okumura N, Kitagishi Y, Shirafuji N, Matsuda S. Rab5(Q79L) interacts with the carboxyl terminus of RUFY3. Int J Biol Sci. 2010;6:187–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Yoshida H, Kitagishi Y, Okumura N, Murakami M, Nishimura Y, Matsuda S. How do you RUN on? FEBS Lett. 2011;585:1707–10.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, Lynch KD, Chen J, Robinson HE, Shim HS, Chmielecki J, Pao W, Engelman JA, Iafrate AJ, Le LP. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20:1479–84.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Mayuko Ichimura
    • 1
  • Atsuko Nakanishi
    • 1
  • Yasuko Kitagishi
    • 1
  • Satoru Matsuda
    • 1
    Email author
  1. 1.Department of Food Science and NutritionNara Women’s UniversityNaraJapan