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Gene Review

SNX1  -  sorting nexin 1

Homo sapiens

Synonyms: HsT17379, MGC8664, SNX1A, Sorting nexin-1, VPS5, ...
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Disease relevance of SNX1


High impact information on SNX1


Biological context of SNX1


Anatomical context of SNX1

  • We show that SNX2 resides primarily in early endosomes, whereas SNX1 is found partially in early endosomes and in tubulovesicular-like structures distributed throughout the cytoplasm [6].
  • Localization of the human SNX1 subgroup members in HeLa cells transfected with the full-length cDNA species revealed a similar intracellular distribution that in all cases overlapped substantially with the early endosome marker, early endosome autoantigen 1 [8].
  • These observations indicate that the mammalian retromer complex assembles by sequential association of SNX1/2 and Vps26-Vps29-Vps35 subcomplexes on endosomal membranes and that SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function [10].
  • To address the significance of PtdIns(3,4,5)P(3) binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P(3) levels were significantly elevated [11].
  • A comparison of SNX1 expressed in bacterial and in mammalian systems and analyzed by size-exclusion chromatography indicates that in cytosol SNX1 tetramers are part of a larger complex with additional proteins [12].

Associations of SNX1 with chemical compounds

  • We also found that the presence of either SNX1 or SNX2 is essential for the retrieval of the cation-independent mannose 6-phosphate receptor to the TGN [10].
  • In vitro biochemical binding assays revealed a specific interaction between a glutathione S-transferase fusion of SNX1 and PAR1 [13].
  • SNX1 contains a phox homology domain predicted to bind phosphatidylinositol-3-phosphate and a C-terminal coiled-coil region [13].
  • Regulated overexpression of the NH(2) terminus of SNX1 containing the PX domain decreased the rate of ligand-induced epidermal growth factor receptor degradation, an effect consistent with inhibition of endogenous SNX1 function in the endosome compartment [5].
  • The prototypical SNX is sorting nexin-1 (SNX1), a protein that through its PX domain binds phosphatidylinositol 3-monophosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] [14].

Physical interactions of SNX1


Regulatory relationships of SNX1


Other interactions of SNX1

  • The intracellular localization of deletion mutants and fusions with green fluorescent protein showed that the C-terminal regions of SNX1 and SNX5 are responsible for their endosomal localization [8].
  • We observe by immunofluorescence microscopy that Ent-1 and SNX1 are co-localized on vesicular and tubulovesicular structures, which are different from early endosome antigen 1-containing endosomes [15].
  • Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor [18].
  • Such data suggest that SNX1 and SNX6 exist in a stable, endosomally associated complex that is required for retromer-mediated retrieval of the cation-independent mannose-6-phosphate receptor [19].
  • Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking [20].

Analytical, diagnostic and therapeutic context of SNX1

  • Immunofluorescence and subcellular fractionation studies show that Hrs and SNX1 colocalize on early endosomes [7].
  • We identified sorting nexin 1 (SNX1) as a novel partner of Ent-1 and confirmed the specificity of interaction by co-immunoprecipitation experiments in mammalian cells [15].
  • Surface plasmon resonance analysis of the binding kinetics of selected hits from the glutathione S-transferase pull-down experiments, i.e. the tails of the virally encoded receptor US28 and the delta-opioid receptor, confirmed the expected nanomolar affinities for interaction with SNX1 [17].
  • Using video microscopy, we observed small vesicle docking and tubule budding from large green fluorescent protein-SNX1 coated endosomes, which are features consistent with their role as sorting endosomes.[12]
  • By determination of the SNX1 gene structure and an analysis of the mRNAs in a variety of tissues using RT-PCR, we demonstrated that SNX1 mRNAs are alternatively spliced [21].


  1. Sorting nexin 1 down-regulation promotes colon tumorigenesis. Nguyen, L.N., Holdren, M.S., Nguyen, A.P., Furuya, M.H., Bianchini, M., Levy, E., Mordoh, J., Liu, A., Guncay, G.D., Campbell, J.S., Parks, W.T. Clin. Cancer Res. (2006) [Pubmed]
  2. SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein. Otsuki, T., Kajigaya, S., Ozawa, K., Liu, J.M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  3. RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking. Zheng, B., Ma, Y.C., Ostrom, R.S., Lavoie, C., Gill, G.N., Insel, P.A., Huang, X.Y., Farquhar, M.G. Science (2001) [Pubmed]
  4. Enhanced degradation of EGF receptors by a sorting nexin, SNX1. Kurten, R.C., Cadena, D.L., Gill, G.N. Science (1996) [Pubmed]
  5. Endosomal localization and function of sorting nexin 1. Zhong, Q., Lazar, C.S., Tronchère, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S.D., Gill, G.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking. Gullapalli, A., Garrett, T.A., Paing, M.M., Griffin, C.T., Yang, Y., Trejo, J. Mol. Biol. Cell (2004) [Pubmed]
  7. Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor. Chin, L.S., Raynor, M.C., Wei, X., Chen, H.Q., Li, L. J. Biol. Chem. (2001) [Pubmed]
  8. A large family of endosome-localized proteins related to sorting nexin 1. Teasdale, R.D., Loci, D., Houghton, F., Karlsson, L., Gleeson, P.A. Biochem. J. (2001) [Pubmed]
  9. Identification of a family of sorting nexin molecules and characterization of their association with receptors. Haft, C.R., de la Luz Sierra, M., Barr, V.A., Haft, D.H., Taylor, S.I. Mol. Cell. Biol. (1998) [Pubmed]
  10. Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors. Rojas, R., Kametaka, S., Haft, C.R., Bonifacino, J.S. Mol. Cell. Biol. (2007) [Pubmed]
  11. The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. Cozier, G.E., Carlton, J., McGregor, A.H., Gleeson, P.A., Teasdale, R.D., Mellor, H., Cullen, P.J. J. Biol. Chem. (2002) [Pubmed]
  12. Self-assembly and binding of a sorting nexin to sorting endosomes. Kurten, R.C., Eddington, A.D., Chowdhury, P., Smith, R.D., Davidson, A.D., Shank, B.B. J. Cell. Sci. (2001) [Pubmed]
  13. Down-regulation of protease-activated receptor-1 is regulated by sorting nexin 1. Wang, Y., Zhou, Y., Szabo, K., Haft, C.R., Trejo, J. Mol. Biol. Cell (2002) [Pubmed]
  14. Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides. Carlton, J., Bujny, M., Peter, B.J., Oorschot, V.M., Rutherford, A., Mellor, H., Klumperman, J., McMahon, H.T., Cullen, P.J. Curr. Biol. (2004) [Pubmed]
  15. Enterophilin-1, a new partner of sorting nexin 1, decreases cell surface epidermal growth factor receptor. Pons, V., Hullin-Matsuda, F., Nauze, M., Barbaras, R., Pérès, C., Collet, X., Perret, B., Chap, H., Gassama-Diagne, A. J. Biol. Chem. (2003) [Pubmed]
  16. An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Gullapalli, A., Wolfe, B.L., Griffin, C.T., Magnuson, T., Trejo, J. Mol. Biol. Cell (2006) [Pubmed]
  17. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP). Heydorn, A., Søndergaard, B.P., Ersbøll, B., Holst, B., Nielsen, F.C., Haft, C.R., Whistler, J., Schwartz, T.W. J. Biol. Chem. (2004) [Pubmed]
  18. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. Parks, W.T., Frank, D.B., Huff, C., Renfrew Haft, C., Martin, J., Meng, X., de Caestecker, M.P., McNally, J.G., Reddi, A., Taylor, S.I., Roberts, A.B., Wang, T., Lechleider, R.J. J. Biol. Chem. (2001) [Pubmed]
  19. A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer. Wassmer, T., Attar, N., Bujny, M.V., Oakley, J., Traer, C.J., Cullen, P.J. J. Cell. Sci. (2007) [Pubmed]
  20. Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking. Barr, V.A., Phillips, S.A., Taylor, S.I., Haft, C.R. Traffic (2000) [Pubmed]
  21. Structural and functional characterization of the human gene for sorting nexin 1 (SNX1). Shank, B.B., Wiley, H.S., Kurten, R.C. DNA Cell Biol. (2001) [Pubmed]
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