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ABCA3  -  ATP-binding cassette, sub-family A (ABC1),...

Homo sapiens

 
 
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Disease relevance of ABCA3

 

High impact information on ABCA3

  • Using mutational analysis of ABC3, we define an important role for such MDR-based efflux during the host penetration step of Magnaporthe grisea pathogenesis [6].
  • Mutants lacking ABC3 were completely nonpathogenic but were surprisingly capable of penetrating thin cellophane membranes to some extent [6].
  • An Abc3-green fluorescent protein fusion localized to the plasma membrane in early appressoria (and in penetration hyphae) but became predominantly vacuolar during appressorial maturity [6].
  • We propose that ABC3 function helps Magnaporthe to cope with cytotoxicity and oxidative stress within the appressoria during early stages of infection-related morphogenesis and likely imparts defense against certain antagonistic and xenobiotic conditions encountered during pathogenic development [6].
  • These cells also expressed high levels of ABCG2 and ABCA3 transporter genes and had a greater capacity to expel cytotoxic drugs, such as mitoxantrone, resulting in better survival [7].
 

Chemical compound and disease context of ABCA3

  • RECENT FINDINGS: Mutations in the genes encoding surfactant protein C, SFTPC, and a member of the adenosine triphosphate-binding cassette family of proteins, ABCA3, have been shown to result in pediatric interstitial lung diseases inherited in autosomal-dominant and autosomal-recessive patterns, respectively [8].
 

Biological context of ABCA3

  • These results suggest that ABCA3 shows ATPase activity, which is induced by lipids, and may be involved in the biogenesis of lamellar body-like structures [9].
  • Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intracellular multilamellar vesicles [9].
  • This genomic colocalization and the observation that the ABCA17P and ABCA3 genes share significant homologies in several exons (up to 98%) suggest that both genes have evolved by gene duplication [10].
  • CONCLUSION: Our results demonstrate that ABCA17P and ABCA3 form a complex of overlapping genes in the human genome from which both non-coding and protein-coding ABC A-transporter RNAs are expressed [10].
  • The human ortholog of the rodent testis-specific ABC transporter Abca17 is a ubiquitously expressed pseudogene (ABCA17P) and shares a common 5' end with ABCA3 [10].
 

Anatomical context of ABCA3

  • By analogy with ABCA3, a lamellar body membrane protein in lung alveolar type II cells, ABCA12 could function in cellular lipid trafficking in keratinocytes [11].
  • Molecular and biochemical studies show that ABCA3 is targeted to vesicle membranes and is found in the limiting membrane of lamellar bodies [12].
  • The ABCA3 gene transcript was found in cell lines of human lung origin, in ATII cells of human, rat, and mouse, as well as different tissues of rat, but the highest expression of ABCA3 was observed in ATII cells [12].
  • The detection of ABCA3 in leukemic progenitor cells merits further investigation with regard to intracellular drug transport in AML blast cells [13].
  • Although human carboxypeptidase-M is known as a marker of type I cells, the expression of this rat protein was detected in columnar epithelial cells expressing type II cell markers, SP-C and a lamellar body protein ABCA3, in developing lung [14].
 

Associations of ABCA3 with chemical compounds

  • Moreover, the transporter ABCA4 (ABCR) plays a pivotal role in retinaldehyde processing, and ABCA3 has recently implicated in lung surfactant processing [15].
  • ABCA3 is efficiently photoaffinity labeled by 8-azido-[alpha(32)P]ATP, but not by 8-azido-[gamma(32)P]ATP, when the membrane fraction is incubated in the presence of orthovanadate [9].
  • Photoaffinity labeling of ABCA3 shows unique metal ion-dependence and is largely reduced by membrane pretreatment with 5% methyl-beta-cyclodextrin, which depletes cholesterol [9].
  • ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures [16].
  • Phosphatidylcholine comprised 41 +/- 19% of the total phospholipid in the BAL fluid of the ABCA3 group compared with 78 +/- 3% and 68 +/- 18%, p = 0.008 and 0.05, of the CON and SP-B groups, respectively [3].
 

Regulatory relationships of ABCA3

 

Other interactions of ABCA3

  • Because ABCA3 is a member of a subfamily of ABC transporters that are predominantly known to be involved in the regulation of lipid transport and membrane trafficking, we speculate that this protein may play a key role in lipid organization during the formation of lamellar bodies [12].
  • Genomic analysis revealed that ABCA17P borders on another ABC A-subfamily transporter - the lung surfactant deficiency gene ABCA3 [10].
  • The gene for this novel protein, human ABC3, maps near the polycystic kidney disease type 1 (PKD1) gene on chromosome 16p13 [17].
  • 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 [18].
  • Results provided the best support for the ABC-C in the assessment of ADHD in mentally retarded children [19].
 

Analytical, diagnostic and therapeutic context of ABCA3

  • The median expression of ABCA3 was three times higher in 21 patients who had failed to achieve remission after the first course of chemotherapy than in a well-matched group of 21 patients who had achieved remission at this stage (P = 0.023) [20].

References

  1. ABC transporter ABCA3 is expressed in acute myeloid leukemia blast cells and participates in vesicular transport. Wulf, G.G., Modlich, S., Inagaki, N., Reinhardt, D., Schroers, R., Griesinger, F., Trümper, L. Haematologica (2004) [Pubmed]
  2. Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. Akiyama, M., Sugiyama-Nakagiri, Y., Sakai, K., McMillan, J.R., Goto, M., Arita, K., Tsuji-Abe, Y., Tabata, N., Matsuoka, K., Sasaki, R., Sawamura, D., Shimizu, H. J. Clin. Invest. (2005) [Pubmed]
  3. Surfactant composition and function in patients with ABCA3 mutations. Garmany, T.H., Moxley, M.A., White, F.V., Dean, M., Hull, W.M., Whitsett, J.A., Nogee, L.M., Hamvas, A. Pediatr. Res. (2006) [Pubmed]
  4. Expression of ABCA3 in Developing Lung and Other Tissues. Stahlman, M.T., Besnard, V., Wert, S.E., Weaver, T.E., Dingle, S., Xu, Y., von Zychlin, K., Olson, S.J., Whitsett, J.A. J. Histochem. Cytochem. (2007) [Pubmed]
  5. ABCA3 mutations associated with pediatric interstitial lung disease. Bullard, J.E., Wert, S.E., Whitsett, J.A., Dean, M., Nogee, L.M. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  6. A Multidrug Resistance Transporter in Magnaporthe Is Required for Host Penetration and for Survival during Oxidative Stress. Sun, C.B., Suresh, A., Deng, Y.Z., Naqvi, N.I. Plant Cell (2006) [Pubmed]
  7. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Hirschmann-Jax, C., Foster, A.E., Wulf, G.G., Nuchtern, J.G., Jax, T.W., Gobel, U., Goodell, M.A., Brenner, M.K. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Genetics of pediatric interstitial lung disease. Nogee, L.M. Curr. Opin. Pediatr. (2006) [Pubmed]
  9. Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intracellular multilamellar vesicles. Nagata, K., Yamamoto, A., Ban, N., Tanaka, A.R., Matsuo, M., Kioka, N., Inagaki, N., Ueda, K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. The human ortholog of the rodent testis-specific ABC transporter Abca17 is a ubiquitously expressed pseudogene (ABCA17P) and shares a common 5' end with ABCA3. Piehler, A.P., Wenzel, J.J., Olstad, O.K., Haug, K.B., Kierulf, P., Kaminski, W.E. BMC Mol. Biol. (2006) [Pubmed]
  11. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Lefévre, C., Audebert, S., Jobard, F., Bouadjar, B., Lakhdar, H., Boughdene-Stambouli, O., Blanchet-Bardon, C., Heilig, R., Foglio, M., Weissenbach, J., Lathrop, M., Prud'homme, J.F., Fischer, J. Hum. Mol. Genet. (2003) [Pubmed]
  12. Identification of LBM180, a lamellar body limiting membrane protein of alveolar type II cells, as the ABC transporter protein ABCA3. Mulugeta, S., Gray, J.M., Notarfrancesco, K.L., Gonzales, L.W., Koval, M., Feinstein, S.I., Ballard, P.L., Fisher, A.B., Shuman, H. J. Biol. Chem. (2002) [Pubmed]
  13. An in vivo propagated human acute myeloid leukemia expressing ABCA3. Norwood, K., Wang, R.Y., Hirschmann-Jax, C., Andreeff, M., Brenner, M.K., Goodell, M.A., Wulf, G.G. Leuk. Res. (2004) [Pubmed]
  14. Monoclonal antibody 7F9 recognizes rat protein homologous to human carboxypeptidase-M in developing and adult rat lung. Fujiwara, N., Ikeda, M., Hirabayashi, S., Mori, H., Shirasawa, M., Kansaku, A., Sunamori, M., Hata, Y. Respirology (2007) [Pubmed]
  15. ABCA2: a candidate regulator of neural transmembrane lipid transport. Schmitz, G., Kaminski, W.E. Cell. Mol. Life Sci. (2002) [Pubmed]
  16. ABC proteins: key molecules for lipid homeostasis. Takahashi, K., Kimura, Y., Nagata, K., Yamamoto, A., Matsuo, M., Ueda, K. Medical molecular morphology. (2005) [Pubmed]
  17. The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3. Connors, T.D., Van Raay, T.J., Petry, L.R., Klinger, K.W., Landes, G.M., Burn, T.C. Genomics (1997) [Pubmed]
  18. Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Efferth, T., Gillet, J.P., Sauerbrey, A., Zintl, F., Bertholet, V., de Longueville, F., Remacle, J., Steinbach, D. Mol. Cancer Ther. (2006) [Pubmed]
  19. Psychometric properties of ADHD rating scales among children with mental retardation. Miller, M.L., Fee, V.E., Jones, C.J. Research in developmental disabilities. (2004) [Pubmed]
  20. ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. Steinbach, D., Gillet, J.P., Sauerbrey, A., Gruhn, B., Dawczynski, K., Bertholet, V., de Longueville, F., Zintl, F., Remacle, J., Efferth, T. Clin. Cancer Res. (2006) [Pubmed]
 
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