CDNA CLONING AND MESSENGER-RNA EXPRESSION OF THE HUMAN ADRENOLEUKODYSTROPHY RELATED PROTEIN (ALDRP), A PEROXISOMAL ABC TRANSPORTER

We have cloned the cDNA containing the complete coding region of the h uman adpenoleukodystrophy related (ALDR) gene. The 2220-bp open readin g frame encodes a 740-amino-acid polypeptide with a predicted molecula r weight of 83.3 kDa. The human ALDR protein displays high similarity (62.8% identical amino acid residues) to the human adrenoleukodystroph y (ALD) gene. Analysis of ALDR expression revealed the presence of ALD R mRNA in a variety of human tissues, predominantly in brain and heart . This expression pattern is different from all other known peroxisoma l ABC-transporters. Defects in the ALD gene are the primary cause of a drenoleukodystrophy, a demyelinating disorder of the central nervous s ystem. The ATD protein (ALDP) and the ALDR gene product are peroxisoma l membrane proteins belonging to the superfamily of transporters conta ining an ATP-binding cassette (ABC-transporters), All known peroxisoma l ABC-transporters represent only one-half of a functional transporter . They are expected to form dimers either as a homodimer or as a heter odimer. ALDRP is a potential dimerization partner of ALDP or other per oxisomal ABC-transporters. The ALDR gene is a candidate for a modifier gene, accounting for the strikingly varying clinical courses of ALD o bserved even within a family. (C) 1997 Academic Press.