Disease relevance of APBA2

• Sporadic serrated adenomas had significantly more frequent methylation of MINT1 (48%, 10 of 22) and MINT2 (71%, 15 of 21) than tubular adenomas (9%, 3 of 34, P = 0.001; and 18%, 6 of 34, P = 0.0001), respectively [1].
• Hypermethylation was largely confined to the carcinomas with only three loci (E-cad, DAP kinase, and MINT2) harboring methylation in some normal pancreata (36, 21, and 14%, respectively) [2].
• We evaluated methylation status at p16, MINT2, and MINT31 loci, which are frequently methylated in colorectal carcinomas, in 108 colorectal adenomas from a prospective study of 50 patients without cancer [3].

Psychiatry related information on APBA2

• Because expression of the human X11L gene is specific to brain, the present observations should contribute to shedding light on the molecular mechanism of APP processing in Alzheimer's disease [4].

High impact information on APBA2

• Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR [5].
• RNAi silencing of APBA2 also lowered Abeta levels, but apparently not via attenuation of gamma-secretase cleavage of APP [6].
• Together, our data suggest that LIN-10 uses distinct modular domains for its functions in neurons and epithelial cells and that during evolution its vertebrate ortholog Mint2 has retained the ability to direct AMPAR localization in neurons [7].
• X11L stabilizes APP metabolism and suppresses the secretion of the amyloid beta-protein (Abeta) that are the pathogenic agents of Alzheimer's disease (AD) [8].
• The mammalian homologue, mLin-7, forms a ternary complex with the mammalian homologues of LIN-2 and LIN-10 and localizes at cell-cell junctions in epithelial cells, but the mechanism of this localization of mLin-7 is unknown [9].

Biological context of APBA2

• Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures [10].
• The duplicated copies, containing the first coding exon of APBA2, can be distinguished by single nucleotide sequence differences and are transcriptionally inactive [10].
• The gene encoding an amyloid precursor protein-binding protein (APBA2) was previously mapped to the distal portion of the interval commonly deleted in Prader-Willi and Angelman syndromes and duplicated in cases of autism [10].
• Overexpression of hX11L and the PDZ domain of dX11L resulted in identical eye phenotypes [11].
• Our findings suggest that the X11L family may be involved with the regulation of apoptosis during neural cell development and that aberrant X11L function could be contribute in this way to the neuronal degeneration observed in Alzheimer's disease [11].

Anatomical context of APBA2

• Finally, we demonstrate that Mint2 is associated with the neuritic plaques found in Alzheimer's disease but not with neurofibrillary tangles [12].
• Mint2 also colocalizes with APP in transfected CHO cells [12].
• Biochemical and genetic analyses revealed that mint1 and LIN-10, a homolog in C. elegans, comprise macromolecular complexes in the presynaptic and postsynaptic terminals, thereby bringing synaptic vesicles to the exocytotic transmitter release site and localizing receptors and ion channels in the specific membrane domains [13].

Associations of APBA2 with chemical compounds

• LIN-7 is known to play an essential role in the basolateral localization of the LET-23 tyrosine kinase receptor, by linking the receptor to LIN-2 and LIN-10 proteins [14].

Regulatory relationships of APBA2

• X11L is a neuron-specific adaptor protein that is known to down-regulate APP (beta-amyloid precursor protein) metabolism by associating with the cytoplasmic domain of APP, but the detailed mechanisms are still unknown [15].

Other interactions of APBA2

• Adjacent to APBA2 maps a gene termed KIAA0574 [10].

References