Gene Symbol: USP6NL
Description: USP6 N-terminal like
Alias: RNTRE, TRE2NL, USP6NL-IT1, USP6 N-terminal-like protein, related to the N-terminus of tre
Species: human
Products:     USP6NL

Top Publications

  1. Lanzetti L, Margaria V, Melander F, Virgili L, Lee M, Bartek J, et al. Regulation of the Rab5 GTPase-activating protein RN-tre by the dual specificity phosphatase Cdc14A in human cells. J Biol Chem. 2007;282:15258-70 pubmed
    ..Finally, phosphorylation of RN-tre appears to finely modulate its catalytic activity. Our findings reveal a novel connection between the cell cycle machinery and the endocytic pathway. ..
  2. Lanzetti L, Rybin V, Malabarba M, Christoforidis S, Scita G, Zerial M, et al. The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature. 2000;408:374-7 pubmed
    ..Thus, depending on its state of association with E3b1 or RN-tre, Eps8 participates in both EGFR signalling through Rac, and trafficking through Rab5. ..
  3. Witoelar A, Rongve A, Almdahl I, Ulstein I, Engvig A, White L, et al. Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Sci Rep. 2018;8:18088 pubmed publisher
    ..We also associated USP6NL/ECHDC3 and BZRAP1-AS1 to AD, confirming findings from a follow-up transethnic study...
  4. Avanzato D, Pupo E, Ducano N, Isella C, Bertalot G, Luise C, et al. High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis. Cancer Res. 2018;78:3432-3444 pubmed publisher
    b>USP6NL, also named RN-tre, is a GTPase-activating protein involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer, mainly of the basal-like/integrative cluster 10 subtype...
  5. Matoskova B, Wong W, Nomura N, Robbins K, Di Fiore P. RN-tre specifically binds to the SH3 domain of eps8 with high affinity and confers growth advantage to NIH3T3 upon carboxy-terminal truncation. Oncogene. 1996;12:2679-88 pubmed
    ..Finally, comparison of the structure and biological activities of RN-tre and of the tre oncogene product, provided insight into the mechanism of oncogenic activation of tre. ..
  6. Fuchs E, Haas A, Spooner R, Yoshimura S, Lord J, Barr F. Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. J Cell Biol. 2007;177:1133-43 pubmed
    ..This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A-C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake...
  7. Martinu L, Santiago Walker A, Qi H, Chou M. Endocytosis of epidermal growth factor receptor regulated by Grb2-mediated recruitment of the Rab5 GTPase-activating protein RN-tre. J Biol Chem. 2002;277:50996-1002 pubmed
    ..These results 1) suggest that the ability of RN-tre to inhibit internalization of the EGFR requires Grb2-mediated binding to the receptor and 2) identify Grb2 as a critical regulator of Rab5 and EGFR endocytosis. ..
  8. Lanzetti L, Palamidessi A, Areces L, Scita G, Di Fiore P. Rab5 is a signalling GTPase involved in actin remodelling by receptor tyrosine kinases. Nature. 2004;429:309-14 pubmed
    ..This may aid crosslinking of actin fibres into actin networks at the plasma membrane. Thus, we have shown that Rab5 is a signalling GTPase and have elucidated the major molecular elements of its downstream pathway. ..
  9. Jun G, Chung J, Mez J, Barber R, Beecham G, Bennett D, et al. Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement. 2017;13:727-738 pubmed publisher
    ..polymorphism (SNP)-based tests (P < 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP...

More Information


  1. Matoskova B, Wong W, Seki N, Nagase T, Nomura N, Robbins K, et al. RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain. Oncogene. 1996;12:2563-71 pubmed
    ..Moreover, we identified, within the N-terminus of RN-tre and tre, a domain (named TrH, for Tre Homology), which is conserved within several proteins from yeast to mammals and has protein-binding properties in vitro. ..
  2. Bizimungu C, De Neve N, Burny A, Bach S, Bontemps F, Portetelle D, et al. Expression in a RabGAP yeast mutant of two human homologues, one of which is an oncogene. Biochem Biophys Res Commun. 2003;310:498-504 pubmed
    ..As two highly conserved amino acids, including the catalytic arginine, are mutated in the oncTre210p TBC domain, we restored these two amino acids and expressed the modified Tre2 cDNA in the yeast mutant. ..
  3. Zenner H, Yoshimura S, Barr F, Crump C. Analysis of Rab GTPase-activating proteins indicates that Rab1a/b and Rab43 are important for herpes simplex virus 1 secondary envelopment. J Virol. 2011;85:8012-21 pubmed publisher
  4. Haas A, Yoshimura S, Stephens D, Preisinger C, Fuchs E, Barr F. Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells. J Cell Sci. 2007;120:2997-3010 pubmed