APBA1 explained

Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adaptor protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilises APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion.^[3]

Interactions

APBA1 has been shown to interact with KCNJ12,^{[4] [5]} CCS,^[6] CASK^{[7] [8]} and Amyloid precursor protein.^{[9] [10]}

Further reading

• van der Geer P, Pawson T . The PTB domain: a new protein module implicated in signal transduction. . Trends Biochem. Sci. . 20 . 7 . 277–80 . 1995 . 7545337 . 10.1016/S0968-0004(00)89043-X .
• Chen WJ, Goldstein JL, Brown MS . NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. . J. Biol. Chem. . 265 . 6 . 3116–23 . 1990 . 10.1016/S0021-9258(19)39742-X . 1968060 . free .
• Borg JP, Ooi J, Levy E, Margolis B . The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. . Mol. Cell. Biol. . 16 . 11 . 6229–41 . 1996 . 8887653 . 231626 . 10.1128/mcb.16.11.6229.
• Zhang Z, Lee CH, Mandiyan V, Borg JP, Margolis B, Schlessinger J, Kuriyan J . Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain. . EMBO J. . 16 . 20 . 6141–50 . 1997 . 9321393 . 1326298 . 10.1093/emboj/16.20.6141 .
• Okamoto M, Südhof TC . Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. . J. Biol. Chem. . 272 . 50 . 31459–64 . 1998 . 9395480 . 10.1074/jbc.272.50.31459 . free .
• Blanco G, Irving NG, Brown SD, Miller CC, McLoughlin DM . Mapping of the human and murine X11-like genes (APBA2 and apba2), the murine Fe65 gene (Apbb1), and the human Fe65-like gene (APBB2): genes encoding phosphotyrosine-binding domain proteins that interact with the Alzheimer's disease amyloid precursor protein. . Mamm. Genome . 9 . 6 . 473–5 . 1998 . 9585438 . 10.1007/s003359900800 . 31066473 .
• Borg JP, Yang Y, De Taddéo-Borg M, Margolis B, Turner RS . The X11alpha protein slows cellular amyloid precursor protein processing and reduces Abeta40 and Abeta42 secretion. . J. Biol. Chem. . 273 . 24 . 14761–6 . 1998 . 9614075 . 10.1074/jbc.273.24.14761 . free .
• Butz S, Okamoto M, Südhof TC . A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. . Cell . 94 . 6 . 773–82 . 1998 . 9753324 . 10.1016/S0092-8674(00)81736-5 . 12465062 . free .
• Borg JP, Straight SW, Kaech SM, de Taddéo-Borg M, Kroon DE, Karnak D, Turner RS, Kim SK, Margolis B . Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting. . J. Biol. Chem. . 273 . 48 . 31633–6 . 1998 . 9822620 . 10.1074/jbc.273.48.31633 . free .
• Borg JP, Lõpez-Figueroa MO, de Taddèo-Borg M, Kroon DE, Turner RS, Watson SJ, Margolis B . Molecular analysis of the X11-mLin-2/CASK complex in brain. . J. Neurosci. . 19 . 4 . 1307–16 . 1999 . 9952408 . 10.1523/JNEUROSCI.19-04-01307.1999. 6786035 . free .
• Maximov A, Südhof TC, Bezprozvanny I . Association of neuronal calcium channels with modular adaptor proteins. . J. Biol. Chem. . 274 . 35 . 24453–6 . 1999 . 10455105 . 10.1074/jbc.274.35.24453 . free .
• Mueller HT, Borg JP, Margolis B, Turner RS . Modulation of amyloid precursor protein metabolism by X11alpha /Mint-1. A deletion analysis of protein-protein interaction domains. . J. Biol. Chem. . 275 . 50 . 39302–6 . 2001 . 11010978 . 10.1074/jbc.M008453200 . free .
• Biederer T, Südhof TC . Mints as adaptors. Direct binding to neurexins and recruitment of munc18. . J. Biol. Chem. . 275 . 51 . 39803–6 . 2001 . 11036064 . 10.1074/jbc.C000656200 . free .
• Lau KF, McLoughlin DM, Standen C, Miller CC . X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains. . Mol. Cell. Neurosci. . 16 . 5 . 557–65 . 2001 . 11083918 . 10.1006/mcne.2000.0898 . 54389955 .
• McLoughlin DM, Standen CL, Lau KF, Ackerley S, Bartnikas TP, Gitlin JD, Miller CC . The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity. . J. Biol. Chem. . 276 . 12 . 9303–7 . 2001 . 11115513 . 10.1074/jbc.M010023200 . free .
• Bécamel C, Alonso G, Galéotti N, Demey E, Jouin P, Ullmer C, Dumuis A, Bockaert J, Marin P . Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic approach. . EMBO J. . 21 . 10 . 2332–42 . 2002 . 12006486 . 126011 . 10.1093/emboj/21.10.2332 .
• Ho CS, Marinescu V, Steinhilb ML, Gaut JR, Turner RS, Stuenkel EL . Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism. . J. Biol. Chem. . 277 . 30 . 27021–8 . 2002 . 12016213 . 10.1074/jbc.M201823200 . free .

Notes and References

1. Duclos F, Boschert U, Sirugo G, Mandel JL, Hen R, Koenig M . Gene in the region of the Friedreich ataxia locus encodes a putative transmembrane protein expressed in the nervous system . Proc Natl Acad Sci U S A . 90 . 1 . 109–13 . February 1993 . 7678331 . 45609 . 10.1073/pnas.90.1.109 . 1993PNAS...90..109D . free .
2. Duclos F, Koenig M . Comparison of primary structure of a neuron-specific protein, X11, between human and mouse . Mamm Genome . 6 . 1 . 57–8 . May 1995 . 7719031 . 10.1007/BF00350899 . 20220507 .
3. Web site: Entrez Gene: APBA1 amyloid beta (A4) precursor protein-binding, family A, member 1 (X11).
4. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM, Adams ME, Froehner SC, Yates JR, Vandenberg CA . Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins . J. Biol. Chem. . 279 . 21 . 22331–46 . May 2004 . 15024025 . 10.1074/jbc.M400285200 . free .
5. Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA . A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels . J. Biol. Chem. . 279 . 18 . 19051–63 . April 2004 . 14960569 . 10.1074/jbc.M400284200 . free .
6. McLoughlin DM, Standen CL, Lau KF, Ackerley S, Bartnikas TP, Gitlin JD, Miller CC . The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity . J. Biol. Chem. . 276 . 12 . 9303–7 . March 2001 . 11115513 . 10.1074/jbc.M010023200 . free .
7. Borg JP, Straight SW, Kaech SM, de Taddéo-Borg M, Kroon DE, Karnak D, Turner RS, Kim SK, Margolis B . Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting . J. Biol. Chem. . 273 . 48 . 31633–6 . November 1998 . 9822620 . 10.1074/jbc.273.48.31633 . free .
8. Borg JP, Lõpez-Figueroa MO, de Taddèo-Borg M, Kroon DE, Turner RS, Watson SJ, Margolis B . Molecular analysis of the X11-mLin-2/CASK complex in brain . J. Neurosci. . 19 . 4 . 1307–16 . February 1999 . 9952408 . 6786035 . 10.1523/JNEUROSCI.19-04-01307.1999.
9. Biederer T, Cao X, Südhof TC, Liu X . Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms . J. Neurosci. . 22 . 17 . 7340–51 . September 2002 . 12196555 . 6757996 . 10.1523/JNEUROSCI.22-17-07340.2002.
10. Borg JP, Ooi J, Levy E, Margolis B . The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein . Mol. Cell. Biol. . 16 . 11 . 6229–41 . November 1996 . 8887653 . 231626 . 10.1128/mcb.16.11.6229.