Primary Structure of Human PMP69, a Putative Peroxisomal ABC-Transporter

Abstract

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 (putativeperoxisomalmembraneprotein). 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.