Disease relevance of ABCA2

• Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation [1].
• ABCA2, the second member the A subfamily to be identified, was highly expressed in ovarian carcinoma cells resistant to the anti-cancer agent, estramustine, and more recently, in human vestibular schwannomas [2].
• Expression of ABCA2 protein in human vestibular schwannoma and peripheral nerve [3].
• The expression patterns of ABCA2 in combination with other markers showed phenotypic heterogeneity in schwannomas [3].
• In conclusion, ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance [4].

Psychiatry related information on ABCA2

• ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease [5].

High impact information on ABCA2

• Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far [6].
• Using specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete, punctate intracellular vesicles [6].
• Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2) [6].
• The sequestration of the steroid into the lysosomal/endosomal compartment indicates a potential substrate specificity for ABCA2 [6].
• Analysis of mRNA expression levels indicated that ABCA2 is highest in human brain and has a broad expression pattern in a panel of tumor cell lines [6].

Chemical compound and disease context of ABCA2

• The notion that the ATP-binding cassette transporter-A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression [7].

Biological context of ABCA2

• Here we report the cloning, molecular characterization and tissue distribution of ABC2/ABCA2, which belongs to the ABC1 subfamily [8].
• The ABCA2 gene comprises 48 exons which are localized within a genomic region of only 21 kb [9].
• Our results suggest a potential role for ABCA2 in macrophage lipid metabolism and neural development [9].
• Analysis of the putative ABCA2 promoter sequence revealed potential binding sites for transcription factors that are involved in the differentiation of myeloid and neural cells [9].
• Complete coding sequence, promoter region, and genomic structure of the human ABCA2 gene and evidence for sterol-dependent regulation in macrophages [9].

Anatomical context of ABCA2

• These data reveal that cellular reduction of mitoxantrone in a mitoxantrone-resistant cell line is associated with overexpression of ABCA2 [1].
• Examination of brain by in situ hybridization determined that ABC2 is expressed at high levels in the white matter, indicating that it is expressed in the oligodendrocytes [8].
• Immunoblot analysis showed that proteins of 260 and 250 kDa were detected in COS-1 cells transfected with ABC2 having a haemagglutinin tag, while no band was detected in mock-transfected cells [8].
• ABCA2 is expressed in a variety of tissues, with greatest abundance in the central nervous system and macrophages [2].
• Here, we demonstrate by immunoblot and immunohistochemistry that ABCA2 is expressed in benign vestibular schwannomas, which contain neither axons nor compact myelin [3].

Associations of ABCA2 with chemical compounds

• ABCA2 is known to be involved in resistance to estramustine [1].
• After incubation with N-glycosidase F, the mobilities of the two proteins increased and a single band was detected, suggesting that ABC2 is a glycoprotein [8].
• Photoaffinity labelling with 8-azido-[alpha-(32)P]ATP confirmed that ATP binds to the ABC2 protein in the presence of Mg(2+) [8].
• Gene expression analysis in human macrophages showed that ABCA2 mRNA is induced during cholesterol import indicating that ABCA2 is a cholesterol-responsive gene [9].
• Upon cotreatment of RNAi for ABCA2 with methotrexate and vinblastine, a partial decrease of ABCA2 expression as well as a simultaneous increase of ABCA3 expression was observed [4].

Other interactions of ABCA2

• ABC2, therefore, is a glycosylated ABC transporter protein, and may play an especially important role in the brain [8].
• Here we report the complete cDNA and the genomic organization of ABCA2, another member of the human ABC A transporter subfamily [9].
• These newly identified transporters include additional members of the MRP family, ABC2, and a new half-transporter, MXR/BCRP/ABCP1 [10].
• Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells [4].
• Reciprocal regulation of expression of the human adenosine 5'-triphosphate binding cassette, sub-family A, transporter 2 (ABCA2) promoter by the early growth response-1 (EGR-1) and Sp-family transcription factors [11].

References