Primary structure of human PMP69, a putative peroxisomal ABC-transporter

We have cloned the cDNA of a novel human ABC-half-transporter highly similar to peroxisomal ABC-half-transporters such as the adrenoleukodystrophy protein (ALDP) and the peroxisomal protein 70 (PMP70). This 2927-bp cDNA codes for a 606 aminoacid (68.6 kDa) protein that was designated PMP69 (putative peroxisomal membrane protein). PMP69 is ubiquitously expressed. Transcript variants resulting from alternative polyadenylation and splicing events including one that confers an alternative C-terminus have been found. The PMP69 gene is localized on chromosome 14q24.3. ABC-half-transporters require a partner ABC-half-transporter to constitute a functional complex, either as a homodimer or a heterodimer. Defects in the gene coding for ALDP are the cause of adrenoleukodystrophy, a demyelinating disorder of the nervous system with strikingly varying clinical courses. PMP70 was implicated in the pathogenesis of a subgroup of Zellweger syndrome, a heterogenous group of peroxisome assembly disorders. PMP69 might be a heterodimer partner for one of these proteins, thus playing a role in modifying the clinical course of ALD or, alternatively, in peroxisome biogenesis.