Identification of a novel first exon of the human ABCA2 transporter gene encoding a unique N-terminus

Kristina E. Ile, Warren Davis, Jonathan T. Boyd, Athena Soulika, Kenneth D. Tew

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The human ABCA2 transporter is a member of a large family of ATP-binding proteins that transport a variety of molecules across biological membranes. Using RNA ligation-mediated PCR (RLM-PCR), we have identified a novel first exon, which we designate 1B that is located 699 bp upstream of the previously characterized first exon, which we designate 1A. These first exons are alternatively spliced to the second exon of the ABCA2 transcript resulting in a protein that has a unique amino terminus. For exon 1B, the new amino terminus encoded by the first exon is 52 amino acids and for exon 1A, 22 amino acids. We observed that among adult tissues examined, the highest expression of the 1B isoform was in peripheral blood leukocytes (PBL). Laser scanning confocal microscopy revealed that the 1A isoform and the 1B isoform co-localize with lysosome-associated membrane proteins-1 and -2 (LAMP-1 and -2). Cytotoxicity assays suggested a role for ABCA2 in estramustine and estradiol resistance, and overexpression of ABCA2 is seen in an estramustine-resistant prostate carcinoma line. Since both isoforms of the ABCA2 transporter have identical subcellular localization and both are overexpressed in a resistant cell line, we propose that they are also functionally redundant. It is likely that expression of ABCA2 by two independent promoters constitutes locus of regulation controlling expression of the protein to meet requirements in different tissues.

Original languageEnglish (US)
Pages (from-to)22-32
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Issue number1
StatePublished - Apr 16 2004
Externally publishedYes


  • ABC transporter
  • ABCA2
  • Alternative exon
  • ATP binding cassette transporter 2
  • CFTR
  • Cystic fibrosis transmembrane regulator
  • Drug resistance
  • Estramustine
  • LAMP
  • Lysosome
  • PBL
  • Peripheral blood leukocytes
  • RNA ligation-mediated PCR

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics


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