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Gene Review

APPL1  -  adaptor protein, phosphotyrosine...

Homo sapiens

Synonyms: APPL, Adapter protein containing PH domain, PTB domain and leucine zipper motif 1, DCC-interacting protein 13-alpha, DIP13A, DIP13alpha, ...
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Disease relevance of APPL1

  • Brain injury induces APPL upregulation in Drosophila neurons, correlating with increased post-traumatic mortality in appl(d) mutant flies [1].

High impact information on APPL1


Biological context of APPL1


Anatomical context of APPL1


Associations of APPL1 with chemical compounds


Physical interactions of APPL1

  • Removal of the DCC-interacting domain on DIP13 alpha abolishes its ability to enhance DCC-induced apoptosis [8].
  • APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry [10].

Regulatory relationships of APPL1


Other interactions of APPL1

  • The identification of APPL may facilitate further analysis of the physiological and oncogenic activities of AKT2 [5].
  • Using this technique, we identified a novel interactor, designated APPL, which contains a pleckstrin homology (PH) domain, a phosphotyrosine binding (PTB) domain and a leucine zipper, classes of motifs defined in signaling molecules as functional interaction domains with specific targets [5].
  • The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive [7].
  • Mediation of the DCC apoptotic signal by DIP13 alpha [8].
  • Moreover, APPL1 and APPL2 associate with one another via the N-terminus of APPL1, presumably via the Bin-Amphiphysin-Rvs (BAR) domain [11].

Analytical, diagnostic and therapeutic context of APPL1

  • Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions [10].


  1. Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. Leyssen, M., Ayaz, D., Hébert, S.S., Reeve, S., De Strooper, B., Hassan, B.A. EMBO J. (2005) [Pubmed]
  2. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Miaczynska, M., Christoforidis, S., Giner, A., Shevchenko, A., Uttenweiler-Joseph, S., Habermann, B., Wilm, M., Parton, R.G., Zerial, M. Cell (2004) [Pubmed]
  3. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Mao, X., Kikani, C.K., Riojas, R.A., Langlais, P., Wang, L., Ramos, F.J., Fang, Q., Christ-Roberts, C.Y., Hong, J.Y., Kim, R.Y., Liu, F., Dong, L.Q. Nat. Cell Biol. (2006) [Pubmed]
  4. GIPC Is Recruited by APPL to Peripheral TrkA Endosomes and Regulates TrkA Trafficking and Signaling. Varsano, T., Dong, M.Q., Niesman, I., Gacula, H., Lou, X., Ma, T., Testa, J.R., Yates, J.R., Farquhar, M.G. Mol. Cell. Biol. (2006) [Pubmed]
  5. Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2. Mitsuuchi, Y., Johnson, S.W., Sonoda, G., Tanno, S., Golemis, E.A., Testa, J.R. Oncogene (1999) [Pubmed]
  6. APPL suppresses androgen receptor transactivation via potentiating Akt activity. Yang, L., Lin, H.K., Altuwaijri, S., Xie, S., Wang, L., Chang, C. J. Biol. Chem. (2003) [Pubmed]
  7. Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling. Nechamen, C.A., Thomas, R.M., Cohen, B.D., Acevedo, G., Poulikakos, P.I., Testa, J.R., Dias, J.A. Biol. Reprod. (2004) [Pubmed]
  8. Mediation of the DCC apoptotic signal by DIP13 alpha. Liu, J., Yao, F., Wu, R., Morgan, M., Thorburn, A., Finley, R.L., Chen, Y.Q. J. Biol. Chem. (2002) [Pubmed]
  9. The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. Saito, T., Jones, C.C., Huang, S., Czech, M.P., Pilch, P.F. J. Biol. Chem. (2007) [Pubmed]
  10. APPL1 Associates with TrkA and GIPC1 and Is Required for Nerve Growth Factor-Mediated Signal Transduction. Lin, D.C., Quevedo, C., Brewer, N.E., Bell, A., Testa, J.R., Grimes, M.L., Miller, F.D., Kaplan, D.R. Mol. Cell. Biol. (2006) [Pubmed]
  11. APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. Nechamen, C.A., Thomas, R.M., Dias, J.A. Mol. Cell. Endocrinol. (2007) [Pubmed]
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