APBA2 explained

Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene.^{[1] [2]}

Structure

This protein has phosphotyrosine-binding domain (PTB domain or PID) in the middle and two PDZ domains at C-terminal.

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.^[2]

Interactions

APBA2 has been shown to interact with CLSTN1,^{[3] [4]} RELA^[5] and amyloid precursor protein.^{[3] [6] [7]}

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 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• 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 .
• 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 .
• Okamoto M, Südhof TC . Mint 3: a ubiquitous mint isoform that does not bind to munc18-1 or -2 . Eur. J. Cell Biol. . 77 . 3 . 161–5 . 1999 . 9860131 . 10.1016/s0171-9335(98)80103-9 .
• Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, Sakiyama S, Kirino Y, Suzuki T . Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein . J. Biol. Chem. . 274 . 4 . 2243–54 . 1999 . 9890987 . 10.1074/jbc.274.4.2243 . free .
• McLoughlin DM, Irving NG, Brownlees J, Brion JP, Leroy K, Miller CC . Mint2/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease . Eur. J. Neurosci. . 11 . 6 . 1988–94 . 1999 . 10336668 . 10.1046/j.1460-9568.1999.00610.x . 42411043 .
• Tomita S, Fujita T, Kirino Y, Suzuki T . PDZ domain-dependent suppression of NF-kappaB/p65-induced Abeta42 production by a neuron-specific X11-like protein . J. Biol. Chem. . 275 . 17 . 13056–60 . 2000 . 10777610 . 10.1074/jbc.C000019200 . free .
• Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J . Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction . J. Biol. Chem. . 275 . 33 . 25616–24 . 2000 . 10827173 . 10.1074/jbc.M000955200 . free .
• Lee DS, Tomita S, Kirino Y, Suzuki T . Regulation of X11L-dependent amyloid precursor protein metabolism by XB51, a novel X11L-binding protein . J. Biol. Chem. . 275 . 30 . 23134–8 . 2000 . 10833507 . 10.1074/jbc.C000302200 . 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 .
• Sutcliffe JS, Han MK, Amin T, Kesterson RA, Nurmi EL . Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures . BMC Genomics . 4 . 1 . 15 . 2003 . 12720574 . 156605 . 10.1186/1471-2164-4-15 . free .
• Sumioka A, Imoto S, Martins RN, Kirino Y, Suzuki T . XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms . Biochem. J. . 374 . Pt 1 . 261–8 . 2003 . 12780348 . 1223589 . 10.1042/BJ20030489 .

Notes and References

1. McLoughlin DM, Miller CC . The intracellular cytoplasmic domain of the Alzheimer's disease amyloid precursor protein interacts with phosphotyrosine-binding domain proteins in the yeast two-hybrid system . FEBS Lett . 397 . 2–3 . 197–200 . January 1997 . 8955346 . 10.1016/S0014-5793(96)01128-3 . free .
2. Web site: Entrez Gene: APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like).
3. Araki Y, Tomita S, Yamaguchi H, Miyagi N, Sumioka A, Kirino Y, Suzuki T . Novel cadherin-related membrane proteins, Alcadeins, enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism . J. Biol. Chem. . 278 . 49 . 49448–58 . December 2003 . 12972431 . 10.1074/jbc.M306024200 . free .
4. Araki Y, Miyagi N, Kato N, Yoshida T, Wada S, Nishimura M, Komano H, Yamamoto T, De Strooper B, Yamamoto K, Suzuki T . Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation . J. Biol. Chem. . 279 . 23 . 24343–54 . June 2004 . 15037614 . 10.1074/jbc.M401925200 . free .
5. Tomita S, Fujita T, Kirino Y, Suzuki T . PDZ domain-dependent suppression of NF-kappaB/p65-induced Abeta42 production by a neuron-specific X11-like protein . J. Biol. Chem. . 275 . 17 . 13056–60 . April 2000 . 10777610 . 10.1074/jbc.C000019200 . free .
6. 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 . 10.1523/JNEUROSCI.22-17-07340.2002 . 6757996 . free .
7. Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, Sakiyama S, Kirino Y, Suzuki T . Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein . J. Biol. Chem. . 274 . 4 . 2243–54 . January 1999 . 9890987 . 10.1074/jbc.274.4.2243 . free .