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Gene Review

EPN1  -  epsin 1

Homo sapiens

Synonyms: EH domain-binding mitotic phosphoprotein, EPS-15-interacting protein 1, Epsin-1
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High impact information on EPN1


Biological context of EPN1


Anatomical context of EPN1

  • The epsin N-terminal homology (ENTH) domain (about 140 amino acid residues) is well conserved in eukaryotes and is considered to be important for actin cytoskeleton organization in endocytosis [10].
  • The enrichment of epsin within clathrin-coated vesicles purified from different tissue sources varies and correlates with sorting of multiubiquitinated cargo, and in cultured cells, polyubiquitin, rather than non-conjugable monoubiquitin, promotes rapid internalization [11].
  • Epsin 2, like epsin 1, is enriched in brain, is present in a brain-derived clathrin-coated vesicle fraction, is concentrated in the peri-Golgi region and at the cell periphery of transfected cells, and partially colocalizes with clathrin [12].
  • Surprisingly, WT epsin showed little colocalization with this chimera, whereas UIM-containing epsin constructs that lack the clathrin and AP2 binding region, strikingly colocalized with this chimera on endocytic vacuoles [13].
  • Consistent with a role in microtubule processes, the over-expression of epsin ENTH domain in PC12 cells stimulates neurite outgrowth [14].

Associations of EPN1 with chemical compounds

  • Epsin 1 and 2 are most similar in their NH(2)-terminal region, which represents a module (epsin NH(2) terminal homology domain, ENTH domain) found in a variety of other proteins of the data base [12].
  • We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF) [9].
  • Alanine scanning mutagenesis shows that clathrin binding depends on the sequence (257)LMDLADV located within the epsin 1 DPW domain [15].
  • HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains [16].

Physical interactions of EPN1

  • Here, we analyzed these sequences, which we term type II sequences, and show that the (257)LMDLA sequence in rat epsin 1 appears to be a weak clathrin-binding variant of the sequence (417)PWDLW originally found in human amphiphysin II [17].

Other interactions of EPN1


Analytical, diagnostic and therapeutic context of EPN1

  • In this study, we discovered that the U-box ubiquitin ligase carboxyl-terminus of Hsc70 interacting protein (CHIP) ubiquitylated Epsin [18].
  • The technique of RNA interference (RNAi) was exploited to generate a cell line constitutively silencing epsin expression in a sequence-specific manner In these Caco-2(eps-) cells, quantitative reverse transcription PCR (RT-PCR) revealed a severe depletion of the epsin messenger RNA (mRNA) level in cells, reaching a factor > 10(6) [20].


  1. Endocytosis: driving membranes around the bend. Hurley, J.H., Wendland, B. Cell (2002) [Pubmed]
  2. A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain. Owen, D.J., Vallis, Y., Noble, M.E., Hunter, J.B., Dafforn, T.R., Evans, P.R., McMahon, H.T. Cell (1999) [Pubmed]
  3. Curvature of clathrin-coated pits driven by epsin. Ford, M.G., Mills, I.G., Peter, B.J., Vallis, Y., Praefcke, G.J., Evans, P.R., McMahon, H.T. Nature (2002) [Pubmed]
  4. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Chen, H., Fre, S., Slepnev, V.I., Capua, M.R., Takei, K., Butler, M.H., Di Fiore, P.P., De Camilli, P. Nature (1998) [Pubmed]
  5. Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis. Morinaka, K., Koyama, S., Nakashima, S., Hinoi, T., Okawa, K., Iwamatsu, A., Kikuchi, A. Oncogene (1999) [Pubmed]
  6. Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis. Sugiyama, S., Kishida, S., Chayama, K., Koyama, S., Kikuchi, A. J. Biochem. (2005) [Pubmed]
  7. The structure and function of the beta 2-adaptin appendage domain. Owen, D.J., Vallis, Y., Pearse, B.M., McMahon, H.T., Evans, P.R. EMBO J. (2000) [Pubmed]
  8. Regulation of complex formation of POB1/epsin/adaptor protein complex 2 by mitotic phosphorylation. Kariya, K., Koyama, S., Nakashima, S., Oshiro, T., Morinaka, K., Kikuchi, A. J. Biol. Chem. (2000) [Pubmed]
  9. Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). Hyman, J., Chen, H., Di Fiore, P.P., De Camilli, P., Brunger, A.T. J. Cell Biol. (2000) [Pubmed]
  10. Solution structure of the epsin N-terminal homology (ENTH) domain of human epsin. Koshiba, S., Kigawa, T., Kikuchi, A., Yokoyama, S. J. Struct. Funct. Genomics (2002) [Pubmed]
  11. Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein. Hawryluk, M.J., Keyel, P.A., Mishra, S.K., Watkins, S.C., Heuser, J.E., Traub, L.M. Traffic (2006) [Pubmed]
  12. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. Rosenthal, J.A., Chen, H., Slepnev, V.I., Pellegrini, L., Salcini, A.E., Di Fiore, P.P., De Camilli, P. J. Biol. Chem. (1999) [Pubmed]
  13. The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin. Chen, H., De Camilli, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. A role for epsin N-terminal homology/AP180 N-terminal homology (ENTH/ANTH) domains in tubulin binding. Hussain, N.K., Yamabhai, M., Bhakar, A.L., Metzler, M., Ferguson, S.S., Hayden, M.R., McPherson, P.S., Kay, B.K. J. Biol. Chem. (2003) [Pubmed]
  15. Epsin binds to clathrin by associating directly with the clathrin-terminal domain. Evidence for cooperative binding through two discrete sites. Drake, M.T., Downs, M.A., Traub, L.M. J. Biol. Chem. (2000) [Pubmed]
  16. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains. Hyun, T.S., Rao, D.S., Saint-Dic, D., Michael, L.E., Kumar, P.D., Bradley, S.V., Mizukami, I.F., Oravecz-Wilson, K.I., Ross, T.S. J. Biol. Chem. (2004) [Pubmed]
  17. Interaction of two structurally distinct sequence types with the clathrin terminal domain beta-propeller. Drake, M.T., Traub, L.M. J. Biol. Chem. (2001) [Pubmed]
  18. The U-box ligase carboxyl-terminus of Hsc 70-interacting protein ubiquitylates Epsin. Timsit, Y.E., Miller, S.L., Mohney, R.P., O'Bryan, J.P. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. Nakashima, S., Morinaka, K., Koyama, S., Ikeda, M., Kishida, M., Okawa, K., Iwamatsu, A., Kishida, S., Kikuchi, A. EMBO J. (1999) [Pubmed]
  20. Selective blocking of clathrin-mediated endocytosis by RNA interference: epsin as target protein. Vanden Broeck, D., De Wolf, M.J. BioTechniques (2006) [Pubmed]
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