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Gene Review

APLP1  -  amyloid beta (A4) precursor-like protein 1

Homo sapiens

Synonyms: APLP, APLP-1, Amyloid-like protein 1
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Disease relevance of APLP1


Psychiatry related information on APLP1

  • This screen identified the amyloid precursor like protein 1 (APLP1), a homologue of the beta-amyloid precursor protein involved in Alzheimer's disease, as alpha(2A)-adrenergic receptor-binding protein [3].

High impact information on APLP1

  • Clues to the function of APP derive from the recent finding that it is a member of a highly conserved protein family that includes the mammalian amyloid precursor-like protein (APLP1) gene which maps to the same general region of human chromosome 19 linked to late-onset FAD [4].
  • APLP2, but not APLP1, was found to interact with hFE65L [5].
  • In fact, an antibody uptake assay revealed that expression of APLP1 reduced the rate of APP endocytosis [6].
  • As revealed by domain deletion analysis, the increase in APP shedding required the NPTY amino acid motif within the cytoplasmic domain of APLP1 [6].
  • APP and its two paralogues, APLP1 and APLP2 (APLPs), are processed in a very similar manner by the same protease activities [7].

Biological context of APLP1


Anatomical context of APLP1


Associations of APLP1 with chemical compounds

  • RA-induced APLP1 protein expression was blocked by curcumin, while the APLP2 protein levels were further increased [1].
  • Furthermore, cotransfection of alpha(2A)-adrenergic receptor and APLP1 into HEK293 cells significantly increased norepinephrine mediated inhibition of adenylate cyclase activity [3].
  • We have demonstrated that hAPLP1 represents a novel glycoprotein which carries both N- and O-linked glycans [15].

Regulatory relationships of APLP1

  • Furthermore, our results suggest that APLP1 does not undergo the same type of regulated processing as APP and APLP2 [1].

Other interactions of APLP1

  • The remaining five S/MARs were found within intronic sequences of APLP1, HSPOX1, MAG, and NPHS1 genes, and can be tentatively characterized as regulatory S/MARs [16].

Analytical, diagnostic and therapeutic context of APLP1

  • Confocal laser microscopy showed that APLP1 causes a considerable shift of the alpha(2A)-adrenergic receptor localization from plasma membrane to intracellular compartments [3].
  • GST affinity chromatography revealed that APLP1 specifically interacts with all three human alpha(2)-adrenergic receptor subtypes and deletion mutant analysis confined the APLP1 domain involved in binding to alpha(2)-adrenergic receptors to the 13 amino acid residues Ser599-Ala611 [3].
  • Western blots with antibodies to Alzheimer precursor-like proteins (APLP) indicate that APP immune reactivity is not a result of cross reactivity with APLPs [17].
  • The hAPLP1 cDNA was also expressed ectopically in COS-7 cells and the protein expression was analyzed by immunoprecipitation and western blotting [15].
  • We determined the AB0 blood group system with a PCR based technique termed APLP (Amplified Product Length Polymorphism) in the Turkish population [18].


  1. Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction. Adlerz, L., Beckman, M., Holback, S., Tehranian, R., Cortés Toro, V., Iverfeldt, K. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  2. Caspase cleavage of members of the amyloid precursor family of proteins. Galvan, V., Chen, S., Lu, D., Logvinova, A., Goldsmith, P., Koo, E.H., Bredesen, D.E. J. Neurochem. (2002) [Pubmed]
  3. Interaction of the amyloid precursor like protein 1 with the alpha(2A)-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase. Weber, B., Schaper, C., Scholz, J., Bein, B., Rodde, C., H Tonner, P. Cell. Signal. (2006) [Pubmed]
  4. Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Wasco, W., Gurubhagavatula, S., Paradis, M.D., Romano, D.M., Sisodia, S.S., Hyman, B.T., Neve, R.L., Tanzi, R.E. Nat. Genet. (1993) [Pubmed]
  5. Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. Guénette, S.Y., Chen, J., Jondro, P.D., Tanzi, R.E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein. Neumann, S., Schöbel, S., Jäger, S., Trautwein, A., Haass, C., Pietrzik, C.U., Lichtenthaler, S.F. J. Biol. Chem. (2006) [Pubmed]
  7. PAT1a Modulates Intracellular Transport and Processing of Amyloid Precursor Protein (APP), APLP1, and APLP2. Kuan, Y.H., Gruebl, T., Soba, P., Eggert, S., Nesic, I., Back, S., Kirsch, J., Beyreuther, K., Kins, S. J. Biol. Chem. (2006) [Pubmed]
  8. Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. Holback, S., Adlerz, L., Iverfeldt, K. J. Neurochem. (2005) [Pubmed]
  9. Characterization of the high affinity heparin binding site of the Alzheimer's disease beta A4 amyloid precursor protein (APP) and its enhancement by zinc(II). Multhaup, G., Mechler, H., Masters, C.L. J. Mol. Recognit. (1995) [Pubmed]
  10. Gene silencing analyses against amyloid precursor protein (APP) gene family by RNA interference. Sakai, T., Hohjoh, H. Cell Biol. Int. (2006) [Pubmed]
  11. Amyloid beta protein precursor is phosphorylated by JNK-1 independent of, yet facilitated by, JNK-interacting protein (JIP)-1. Scheinfeld, M.H., Ghersi, E., Davies, P., D'Adamio, L. J. Biol. Chem. (2003) [Pubmed]
  12. Amyloid precursor-like protein 1 accumulates in neuritic plaques in Alzheimer's disease. Bayer, T.A., Paliga, K., Weggen, S., Wiestler, O.D., Beyreuther, K., Multhaup, G. Acta Neuropathol. (1997) [Pubmed]
  13. Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains. McNamara, M.J., Ruff, C.T., Wasco, W., Tanzi, R.E., Thinakaran, G., Hyman, B.T. Brain Res. (1998) [Pubmed]
  14. Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system. Lyckman, A.W., Confaloni, A.M., Thinakaran, G., Sisodia, S.S., Moya, K.L. J. Biol. Chem. (1998) [Pubmed]
  15. Human amyloid precursor-like protein 1--cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid. Paliga, K., Peraus, G., Kreger, S., Dürrwang, U., Hesse, L., Multhaup, G., Masters, C.L., Beyreuther, K., Weidemann, A. Eur. J. Biochem. (1997) [Pubmed]
  16. Identification and mapping of nuclear matrix-attachment regions in a one megabase locus of human chromosome 19q13.12: long-range correlation of S/MARs and gene positions. Chernov, I.P., Akopov, S.B., Nikolaev, L.G., Sverdlov, E.D. J. Cell. Biochem. (2002) [Pubmed]
  17. Amyloid precursor protein is enriched in axolemma and periaxolemmal-myelin and associated clathrin-coated vesicles. Sapirstein, V.S., Durrie, R., Berg, M.J., Marks, N. J. Neurosci. Res. (1994) [Pubmed]
  18. AB0 blood subgroup allele frequencies in the Turkish population. Akbas, F., Aydin, M., Cenani, A. Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur. (2003) [Pubmed]
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