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Gene Review

APBA1  -  amyloid beta (A4) precursor protein...

Homo sapiens

Synonyms: Adapter protein X11alpha, Amyloid beta A4 precursor protein-binding family A member 1, D9S411E, LIN10, MINT1, ...
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Disease relevance of APBA1


Psychiatry related information on APBA1


High impact information on APBA1

  • Mutations in genes encoding components of the highly conserved MALS/CASK/Mint-1 complex cause presynaptic defects [7].
  • The X11 proteins, Abeta production and Alzheimer's disease [8].
  • The same CD2 antibodies that were mitogenic in the presence of PMA (9.6, X11, VIT13), but not the nonreactive ones, were also able to induce T cell proliferation via the so-called alternative pathway of T cell activation, i.e., when added pairwise in certain combinations to T cells in the absence of PMA [9].
  • Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at MINT 1, 2, 12, and 31 loci was assessed by bisulfite PCR [10].
  • These proteins include several synaptic multidomain proteins containing one or several PDZ domains (PSD95 and the proteins of the tripartite complex Veli3-CASK-Mint1), proteins of the actin/spectrin cytoskeleton and signalling proteins [11].

Chemical compound and disease context of APBA1


Biological context of APBA1

  • Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein [13].
  • This latter effect was associated with a reduced Mint binding affinity in one mutant, implying a potential mechanism for the observed alteration in release kinetics [14].
  • Dense methylation of the 5' CpG island of DAP kinase and MINT1 was well correlated with loss of gene expression [15].
  • Hippocampal slice electrophysiology uncovered a decline in spontaneous neurotransmitter release, lowered synaptic strength, and enhanced paired-pulse facilitation in Mint-deficient mice, suggesting a decreased presynaptic release probability [16].
  • Here we describe additional barriers to clonal expansion (Mint) intermediate between M1 and M2, revealed by abrogation of tumor-suppressor gene (TSG) pathways by individual human papillomavirus type 16 (HPV16) proteins [17].

Anatomical context of APBA1

  • Mint 1 and 2 are proteins that bind to munc18-1, an essential component of the synaptic vesicle fusion machinery, and are detectably expressed only in neurons [Okamoto and Südhof, J. Biol. Chem. 272, 31459-31464 (1997)] [18].
  • Mint 3 is ubiquitously expressed in all tissues, with lowest levels in brain and testis whereas mint 1 and 2 appear to be brain-specific [18].
  • This proteolytic activity was not affected by soybean trypsin inhibitor but was strongly inhibited by the tBP esters of GMCHA, APAA, and APBA, their effects roughly paralleling their inhibitions of the growth of HeLa cells [19].
  • Follow-up appointments suggest an allergic contact focal erythema caused by prolonged contact with the irritant, in this case due to use of Listerine Cool Mint PocketPaks Oral Care Strips [3].

Associations of APBA1 with chemical compounds

  • The phosphotyrosine binding domain of the neuronal protein X11alpha/mint-1 binds to the C-terminus of amyloid precursor protein (APP) and inhibits catabolism to beta-amyloid (Abeta), but the mechanism of this effect is unclear [20].
  • Similar chemistry starting from methyl D,L-2-amino-4-(diethoxyphosphinyl)butanoic acid and methyl N delta-(benzyloxycarbonyl)-L-ornithinate yielded D,L-2-[(5-deaza-5,6,7,8-tetrahydropteroyl)amino]-4-phosphonobut ano ic acid (5-dH4Pte-APBA) and N alpha-(5-deaza-5,6,7,8-tetrahydropteroyl)-L-ornithine (5-dH4PteOrn), respectively [21].
  • In contrast, Orn and APBA analogues obeyed competitive inhibition kinetics and were more potent, with Ki values as low as 30 nM [21].
  • Maalox MS Cool Mint and ES Gaviscon were the least palatable [22].
  • The mature protein consists of 71 amino acid residues arranged in six 12- or 13-mer repeats with a consensus sequence consisting of Cys-Thr-X3-Ser-X5-X6-Cys-X8-X9-Ala-X11-Thr-X1 3, where X3 and X11 tend to be charged residues, X5 tends to be Thr or Ser, X6 to be Asn or Asp, X9 to be Asn or Lys and X13 to be Ala in the 13-mers [23].

Physical interactions of APBA1

  • X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains [6].
  • We have found that the X11 PI domain binds a YENPTY motif in the intracellular domain of (beta)APP that is strikingly similar to the NPXY motifs that bind the Shc and IRS-1 PI/PTB domains [24].

Regulatory relationships of APBA1

  • We conclude that Munc18a acts through direct and indirect interactions with X11 proteins and powerfully regulates APP metabolism and Abeta secretion [25].

Other interactions of APBA1

  • XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms [26].
  • The small size of the APP cytodomain and the overlapping of its regions involved in the binding of Fe65 and X11 suggest the existence of competitive mechanisms regulating the binding of the various ligands to this cytosolic domain [27].
  • Methylation of MINT1 and MINT31 also correlated with poor prognoses (P = 0.058 and 0.041), whereas methylation of p14ARF correlated with a good prognosis (P = 0.021) [15].
  • Unlike other members of the X11 protein family, X11L2 mRNA was expressed in various tissues [28].
  • Coimmunoprecipitation experiments showed that 5-HT(2C) receptors interact with PSD95 and the Veli3-CASK-Mint1 complex in vivo [11].

Analytical, diagnostic and therapeutic context of APBA1

  • Using site-directed mutagenesis, we have identified a crucial residue within the PI domain involved in X11 and FE65 binding to (beta)APP [24].
  • CIMP status was investigated by examining the methylation status of MINT1, MINT2, MINT12, MINT25 and MINT31. p53 mutation status was examined by PCR-single strand conformation polymorphism and promoter methylation status was examined by methylation-specific PCR [29].
  • A double-blinded, 3-period, 6-sequence crossover study was conducted evaluating the antiplaque effect of the novel 0.07% high bioavailable, alcohol-free CPC rinse versus a positive control (Listerine Cool Mint containing essential oils) and a negative control (placebo CPC rinse) [30].
  • The hearing aids used were the NHS BE19 and the Lavis X11 [31].


  1. Frequent CpG island methylation in serrated adenomas of the colorectum. Park, S.J., Rashid, A., Lee, J.H., Kim, S.G., Hamilton, S.R., Wu, T.T. Am. J. Pathol. (2003) [Pubmed]
  2. Increasing genetic diversity of Salmonella enterica serovar typhi isolates from papua new guinea over the period from 1992 to 1999. Thong, K.L., Goh, Y.L., Yasin, R.M., Lau, M.G., Passey, M., Winston, G., Yoannes, M., Pang, T., Reeder, J.C. J. Clin. Microbiol. (2002) [Pubmed]
  3. Palatal erythema in patients using Listerine Cool Mint PocketPaks Oral Care Strips: case reports. Pham, C.L., Wood, A.J., Lambert, M.B., Carpenter, W. Journal of dentistry for children (Chicago, Ill.) (2005) [Pubmed]
  4. An in vitro antimicrobial comparison of miswak extract with commercially available non-alcohol mouthrinses. Almas, K., Skaug, N., Ahmad, I. International journal of dental hygiene. (2005) [Pubmed]
  5. Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible. Metwaly, H., Cheng, J., Maruyama, S., Ohshiro, K., Suzuki, I., Hoshina, Y., Saku, T. Pathol. Int. (2005) [Pubmed]
  6. X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains. Lau, K.F., McLoughlin, D.M., Standen, C., Miller, C.C. Mol. Cell. Neurosci. (2000) [Pubmed]
  7. Synaptic transmission regulated by a presynaptic MALS/Liprin-alpha protein complex. Olsen, O., Moore, K.A., Nicoll, R.A., Bredt, D.S. Curr. Opin. Cell Biol. (2006) [Pubmed]
  8. The X11 proteins, Abeta production and Alzheimer's disease. Miller, C.C., McLoughlin, D.M., Lau, K.F., Tennant, M.E., Rogelj, B. Trends Neurosci. (2006) [Pubmed]
  9. T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels. Holter, W., Fischer, G.F., Majdic, O., Stockinger, H., Knapp, W. J. Exp. Med. (1986) [Pubmed]
  10. CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability. Hawkins, N., Norrie, M., Cheong, K., Mokany, E., Ku, S.L., Meagher, A., O'Connor, T., Ward, R. Gastroenterology (2002) [Pubmed]
  11. Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic approach. Bécamel, C., Alonso, G., Galéotti, N., Demey, E., Jouin, P., Ullmer, C., Dumuis, A., Bockaert, J., Marin, P. EMBO J. (2002) [Pubmed]
  12. Bactericidal effects of mouth rinses on oral bacteria. Kasuga, Y., Ikenoya, H., Okuda, K. Bull. Tokyo Dent. Coll. (1997) [Pubmed]
  13. Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein. Taru, H., Suzuki, T. J. Biol. Chem. (2004) [Pubmed]
  14. Munc18-1 regulates early and late stages of exocytosis via syntaxin-independent protein interactions. Ciufo, L.F., Barclay, J.W., Burgoyne, R.D., Morgan, A. Mol. Biol. Cell (2005) [Pubmed]
  15. Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma. Ogi, K., Toyota, M., Ohe-Toyota, M., Tanaka, N., Noguchi, M., Sonoda, T., Kohama, G., Tokino, T. Clin. Cancer Res. (2002) [Pubmed]
  16. Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family. Ho, A., Morishita, W., Atasoy, D., Liu, X., Tabuchi, K., Hammer, R.E., Malenka, R.C., S??dhof, T.C. J. Neurosci. (2006) [Pubmed]
  17. Control of replicative life span in human cells: barriers to clonal expansion intermediate between M1 senescence and M2 crisis. Bond, J.A., Haughton, M.F., Rowson, J.M., Smith, P.J., Gire, V., Wynford-Thomas, D., Wyllie, F.S. Mol. Cell. Biol. (1999) [Pubmed]
  18. Mint 3: a ubiquitous mint isoform that does not bind to munc18-1 or -2. Okamoto, M., Südhof, T.C. Eur. J. Cell Biol. (1998) [Pubmed]
  19. Inhibition of growth of HeLa cells by new synthetic protease inhibitors. Mori, S., Kozaki, Y., Kato, M., Tendo, A., Kikawa, Y., Sekine, H., Muramatu, M. J. Biochem. (1984) [Pubmed]
  20. X11alpha impairs gamma- but not beta-cleavage of amyloid precursor protein. King, G.D., Cherian, K., Turner, R.S. J. Neurochem. (2004) [Pubmed]
  21. Side chain modified 5-deazafolate and 5-deazatetrahydrofolate analogues as mammalian folylpolyglutamate synthetase and glycinamide ribonucleotide formyltransferase inhibitors: synthesis and in vitro biological evaluation. Rosowsky, A., Forsch, R.A., Reich, V.E., Freisheim, J.H., Moran, R.G. J. Med. Chem. (1992) [Pubmed]
  22. Comparative palatability of 22 liquid antacids. Temple, M.E., Nahata, M.C. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  23. Enhancement of insect antifreeze protein activity by solutes of low molecular mass. Li, N., Andorfer, C.A., Duman, J.G. J. Exp. Biol. (1998) [Pubmed]
  24. The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Borg, J.P., Ooi, J., Levy, E., Margolis, B. Mol. Cell. Biol. (1996) [Pubmed]
  25. Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism. Ho, C.S., Marinescu, V., Steinhilb, M.L., Gaut, J.R., Turner, R.S., Stuenkel, E.L. J. Biol. Chem. (2002) [Pubmed]
  26. XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms. Sumioka, A., Imoto, S., Martins, R.N., Kirino, Y., Suzuki, T. Biochem. J. (2003) [Pubmed]
  27. Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein. Russo, T., Faraonio, R., Minopoli, G., De Candia, P., De Renzis, S., Zambrano, N. FEBS Lett. (1998) [Pubmed]
  28. X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein. Tanahashi, H., Tabira, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  29. Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma. Oshimo, Y., Oue, N., Mitani, Y., Nakayama, H., Kitadai, Y., Yoshida, K., Chayama, K., Yasui, W. Int. J. Cancer (2004) [Pubmed]
  30. Antibacterial and antiplaque effects of a novel, alcohol-free oral rinse with cetylpyridinium chloride. Witt, J., Ramji, N., Gibb, R., Dunavent, J., Flood, J., Barnes, J. The journal of contemporary dental practice [electronic resource]. (2005) [Pubmed]
  31. Insertion gain measurements using two low-powered analogue hearing aids. Norman, M., James, P. British journal of audiology. (2000) [Pubmed]
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