Disease relevance of ABCA7

• We found that this amino-terminal extracellular domain contains a segment homologous to the autoantigen SS-N, an epitope of Sjögren's syndrome, and further identified that ABCA7 codes for the autoantigen SS-N [1].
• ECD1 of human ABCA7 (amino acids 45-549) was expressed in Escherichia coli as a protein fused with glutathione-S-transferase and a monoclonal antibody, KM3095, was generated [2].
• This study investigated (1) the differential impact of the child's chronic illness (CI) on 80 fathers and 80 mothers and the psychosocial variables contributing to their adaptation and (2) the suitability of the causal model based on the Double ABCX Model to predict parents' adaptation to the child's illness [3].

Psychiatry related information on ABCA7

• This study examined the factors that contribute to empowerment in parents of school-aged children with and without developmental disabilities (DD) using the Double ABCX model of family adaptation contrasted with the linear ACBX model [4].
• Adjustment in mothers of children with Asperger syndrome: an application of the double ABCX model of family adjustment [5].
• Coping with stress in families with children who have mental retardation: an evaluation of the double ABCX model [6].
• Mothers of children with autism or communication disorders: successful adaptation and the double ABCX model [7].
• This study demonstrates the effectiveness of a modified Double ABCX or FAAR model in predicting successful adaptation--good marital adjustment, few maternal depressive symptoms, and an in-home rating of family functioning--in 45 families of autistic and communication-impaired children [7].

High impact information on ABCA7

• The cell surface localization of ABCA7 and LRP1 is defective in ABCA7-deficient cells [8].
• We show that ERK signaling is required for phagocytosis of apoptotic cells and that ERK phosphorylation in response to apoptotic cells or C1q is defective in ABCA7-deficient cells [8].
• Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic cells [8].
• Induction of adipocyte differentiation from 3T3 fibroblasts in culture led to a marked increase in ABCA7 expression [9].
• ABCA7 expression was detected in hippocampal and cortical neurons by in situ hybridization and in brain and white adipose tissue by Western blotting [9].

Biological context of ABCA7

• Genomic organization of the human cholesterol-responsive ABC transporter ABCA7: tandem linkage with the minor histocompatibility antigen HA-1 gene [10].
• The ABCA7 gene spans a region of approximately 32 kb and comprises 46 exons [10].
• Alternative splicing could be involved in the post-transcriptional regulation of the expression and function of human ABCA7 [11].
• This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages [12].
• The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10 [12].

Anatomical context of ABCA7

• The recently cloned transporter ABCA7 was highly expressed in keratinocytes and HaCaT cells and upregulated during differentiation [13].
• Overexpression of ABCA7 in HeLa cells resulted in increased expression of intracellular and cell surface ceramide and elevated intracellular phosphatidylserine levels [13].
• Although ABCA7 and ABCA8 expression was relatively low in all cells, the highest expression occurred in microglia and neurons, respectively [14].
• This transporter, along with other proteins that have a high degree of homology to ABCA2, including ABCA1 and ABCA7, are up-regulated in human macrophages during cholesterol import [15].
• Immunostaining revealed that the type I ABCA7, expressed in HEK293 cells, was localized to the plasma membrane and ECD1 was exposed to the extracellular space as was the case for ABCA1 [11].

Associations of ABCA7 with chemical compounds

• Chimeric transporters, generated by substituting the C termini of either ABCA4 or ABCA7 for the endogenous terminus, demonstrated that ABCA1 could stimulate cholesterol efflux without its PDZ-binding motif but not without the VFVNFA motif [16].
• Given the observation that during terminal keratinocyte differentiation intracellular and surface ceramide levels are increased, our results render ABCA7 a candidate regulator of ceramide transport in this process [13].
• Expression of both ABCA1 and ABCA7 was induced linearly proportional to ponasterone A concentration in the medium [17].
• We analyzed the promoter of the ABCA7 gene and identified the new exon encoding 96 bp (mouse) and 95 bp (human) of the 5' untranslated region and the transcription start site at 1,122 bp (mouse) and 1,260 bp (human) upstream of the initiation methionine codon [18].

Physical interactions of ABCA7

• We identified a total of 31 exonic single-nucleotide polymorphisms (SNP) in the ABCA7/HA-1 gene complex, nine of which represent non-synonymous nucleotide alterations [19].

Other interactions of ABCA7

• Similar reductions in ABCA5, ABCA7, ABCA8b and ABCA9 mRNA were also observed [20].
• In contrast, the frequencies of all ABCA7 allelic variants and additional HA-1 polymorphisms were similar in patients and controls [19].
• When phagocytosis was induced, the messages increased for SREBP2, ABCA7, and other SREBP2-regulated proteins [18].
• The apolipoprotein A-I-mediated lipid release was not influenced by suppression of the endogenous ABCA7 with small interfering RNA in mouse fibroblasts or by its increase in ABCA1-deficient mouse cells [18].
• Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner [21].

Analytical, diagnostic and therapeutic context of ABCA7

• RT-PCR experiments suggested that human ABCA7 gene produced the type II mRNA in a tissue-specific manner [11].
• Surprisingly, sequence analysis of the ABCA7 3' gene flanking region revealed that the terminal exon of ABCA7 borders immediately on the 5' end of the coding region of the recently identified human minor histocompatibility antigen HA-1 [10].
• Strikingly, immunofluorescence studies of adult mouse kidney revealed an apical brush border membrane localization of ABCA7 in the proximal tubule, suggesting that ABCA7 may come in contact with apoA-I in the glomerular filtrate [22].
• METHODS: Ninety consecutive patients undergoing primary angioplasty with coronary stenting were randomized in a sequential alternating fashion to standard abciximab treatment (ABCX) group, intracoronary adenosine distal to the occlusion (ADO) group, or neither (CTRL) group [23].

References