High impact information on ABCD3

• Our results suggest that PMP70 plays an important role in peroxisome biogenesis and that mutations in PMP70 may be responsible for a subset of ZS patients [1].
• The peroxisomal membrane protein, with a relative molecular mass of 70,000 (M(r) 70K) (PMP70), is an important component of peroxisomal membranes and an ATP-binding cassette protein [1].
• To investigate its possible involvement in Zellweger syndrome (ZS), an inborn error of peroxisome assembly, we cloned and sequenced cDNAs for human PMP70 and mapped the gene to chromosome 1 [1].
• ALDP and PMP70 share sequence homology and both are implicated in genetic diseases [2].
• The gene, designated P70R, maps to chromosome 14q24, encodes a 73 kDa transporter most similar to PMP70, and is expressed in all human tissues examined [3].

Biological context of ABCD3

• Moreover, we were able to restore the peroxisomal beta-oxidation defect in the liver of ALDP-deficient mice by stimulation of ALDRP and PMP70 gene expression through a dietary treatment with the peroxisome proliferator fenofibrate [4].
• We report the cloning and characterization of the human PMP70 structural gene (gene symbol: PXMP1) localized on human chromosome 1p21-p22 [5].
• In more than 3 kb of Pxmp-1 5' flanking sequence we did not identify a consensus peroxisomal proliferator responsive element [5].
• PXMP1 is approximately 65 kb in length, contains 23 exons, and is quite different in structure from the gene (ALD) that encodes the related protein, ALDP [5].
• Here, we describe the first measurements of the rate of ATP binding and hydrolysis by purified nucleotide binding fold (NBF) fusion proteins of PMP70 and ALDP [6].

Anatomical context of ABCD3

• Western blot analysis showed the absence of ALDP in the brain, spinal cord, lung, and kidney and normal expression of PMP70 in the liver, lung, and kidney [7].
• Expression of either ALDP or PMP70 restores VLCFA beta-oxidation in X-ALD fibroblasts, indicating overlapping functions [8].
• Unexpectedly, overproduction of the peroxisomal ABC transporter PMP70 was found to be able to restore peroxisome biogenesis in mammalian pex2 mutant cell lines [9].
• Here we describe that efficient peroxisomal targeting of human PMP70 depends on three targeting elements in the amino-terminal protein region, namely amino acids 61 to 80 located in the cytosol as well as the first and second transmembrane domains [10].
• Further, we expressed these deletion constructs of PMP70 in fusion with the green fluorescent protein in CHO cells [11].

Associations of ABCD3 with chemical compounds

• When a C-terminal 16-mer synthetic peptide of the 70-kDa peroxisomal membrane protein was simply incubated with 9-CHO PC, it was found to be reactive in a sandwich enzyme-linked immunosorbent assay using FOH1a/DLH3 and an anti-peptide antiserum [12].
• PMP70 is suggested to be involved in metabolic transport of long-chain acyl-CoA across peroxisomal membranes [13].

Physical interactions of ABCD3

• PEX19 does not specifically bind to the targeting elements of human PMP70 [10].

Other interactions of ABCD3

• Localization to peroxisomes of membrane proteins such as Pex14p, Pex13p, and PMP70 was interfered with in CHO-K1 cells by a higher level expression of the pex16 patient-derived dysfunctional but topogenically active Pex16pR176ter comprising resides 1-176 or of the C-terminal cytoplasmic part starting from residues at 244 to the C terminus [14].
• Furthermore, peroxin 19 (PEX19) interactions are not required for targeting human PMP70 to peroxisomes [10].
• We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD peroxisomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively [15].
• The 70 kDa peroxisomal membrane protein: an ATP-binding cassette transporter protein involved in peroxisome biogenesis [16].
• When recombinant Pex5p and green fluorescent protein (GFP) carrying a peroxisome-targeting signal were co-injected into the mutant cells, the GFP fluorescence gathered over time to particulate structures where PMP70 was co-localized [17].

Analytical, diagnostic and therapeutic context of ABCD3

• The PXMP1 gene was assigned to human chromosome 1p21-p22 by in situ hybridization and its murine homologue (Pxmp-1) to chromosome 3 by interspecific backcross analysis [18].
• To identify the regions that interact with Pex19p, various truncated PMP70 were translated in the presence of Pex19p and subjected to co-immunoprecipitation [11].
• Moreover, immunoelectron microscopy using an antibody against the 70-kDa peroxisomal membrane protein (PMP70) showed large peroxisomes with various horseshoe-shaped membrane structures [19].

References