The reference OMIM entry for this protein is 601498

Peroxisome biogenesis factor 6; pex6
Peroxin 6
Peroxisomal assembly factor 2; paf2
Peroxisomal-type atpase 1; pxaaa1

CLONING

Peroxisomal targeting signals (PTSs) are discrete amino acid sequences capable of directing proteins to the peroxisome. Most peroxisomal matrix proteins contain PTS1, a C-terminal tripeptide of the sequence ser-lys-leu (SKL) or a conservative variant. In contrast, the N-terminal PTS2 consists of approximately 10 amino acids (arg/lys-leu-X5-gln/his-leu) and has been observed in only 3 peroxisomal proteins. The only documented human PTS2-containing proteins are peroxisomal thiolase (604054) and phytanic acid oxidase (266500). Yahraus et al. (1996) stated that the only known human PTS2-containing protein is thiolase. The most extensively studied of the factors involved in peroxisomal protein import is the PTS1 receptor, encoded by the peroxin-5 gene (PEX5; 600414) and defective in Zellweger syndrome. Human PEX5 was originally identified by homology probing the human EST database with the S. cerevisiae PAS8 protein sequence. The continued application of this approach by Yahraus et al. (1996) led to the cloning and characterization of a novel human gene (called PXAAA1 by them) based on its similarity to PpPAS5, a gene required for peroxisome assembly in the yeast Pichia pastoris. The 980-amino acid protein product belongs to the AAA family of ATPases and appears to be a predominantly cytoplasmic protein. Yahraus et al. (1996) found that substitution of an arginine for the conserved lysine residue in the ATPase domain of the PXAAA1 protein abolished its biologic activity, suggesting that it is an ATPase. Furthermore, they showed that the protein is required for stability of the predominantly cytoplasmic PTS1 receptor. Yahraus et al. (1996) concluded that the PXAAA1 protein plays a direct role in peroxisomal protein import and is required for PTS1 receptor activity. Distel et al. (1996) listed the peroxisomal assembly factor isolated in the rat by Tsukamoto et al. (1995) as identical to PXAAA1 (or PEX6). Tsukamoto et al. (1995) isolated rat peroxisome assembly factor-2 (PAF2) cDNA by functional complementation of the peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP92, using a transient transfection assay. This cDNA encodes a 978-amino acid protein with 2 putative ATP-binding sites. The investigators stated that PAF2 is a member of a putative ATPase family which includes 2 yeast gene products essential for peroxisome assembly. The stable transformant of ZP92 with the cDNA was morphologically and biochemically restored for peroxisome biogenesis. Fibroblasts derived from patients deficient in peroxisome biogenesis (complementation group C) were also complemented with rat PAF2 cDNA, indicating that PAF2 is a strong candidate for the site of the mutation in one peroxisomal complementation group. The proteins of the ATPase family (AAA proteins) participate in a broad range of cellular processes, as indicated by the designation AAA which comes from 'ATPases associated with diverse cellular activities.' Fukuda et al. (1996) found that the 2,940-bp open reading frame of the human PAF2 cDNA encodes a 980-amino acid protein that shows 87.1% identity with rat PAF2.

GENE STRUCTURE

Zhang et al. (1999) determined that the PEX6 gene consists of 17 exons and 16 introns, spanning about 14 kb. The largest exon, exon 1, has at least 952 nucleotides.

MAPPING

To determine the chromosomal localization of PXAAA1, Yahraus et al. (1996) probed a panel of mouse/human hybrid cell lines with the full-length PXA ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 601498 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).