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The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor.
- Source :
-
The EMBO journal [EMBO J] 1996 Jun 17; Vol. 15 (12), pp. 2914-23. - Publication Year :
- 1996
-
Abstract
- In humans, defects in peroxisome assembly result in the peroxisome biogenesis disorders (PBDs), a group of genetically heterogeneous, lethal recessive diseases. We have identified the human gene PXAAA1 based upon its similarity to PpPAS5, a gene required for peroxisome assembly in the yeast Pichia pastoris. Expression of PXAAA1 restored peroxisomal protein import in fibroblasts from 16 unrelated members of complementation group 4 (CG4) of the PBD. Consistent with this observation, CG4 patients carry mutations in PXAAA1. The product of this gene, Pxaaa1p, belongs to the AAA family of ATPases and appears to be a predominantly cytoplasmic protein. Substitution of an arginine for the conserved lysine residue in the ATPase domain of Pxaaa1p abolished its biological activity, suggesting that Pxaaa1p is an ATPase. Furthermore, Pxaaa1p is required for stability of the predominantly cytoplasmic PTS1 receptor, Pxr1p. We conclude that Pxaaa1p plays a direct role in peroxisomal protein import and is required for PTS1 receptor activity.
- Subjects :
- Adenosine Triphosphatases metabolism
Amino Acid Sequence
Base Sequence
Biological Transport
Cells, Cultured
Chromosome Mapping
Chromosomes, Human, Pair 6
DNA, Complementary
Genetic Complementation Test
Humans
Molecular Sequence Data
Mutation
Peroxisome-Targeting Signal 1 Receptor
Proteins metabolism
Adenosine Triphosphatases genetics
Cytoplasm enzymology
Peroxisomal Disorders genetics
Receptors, Cytoplasmic and Nuclear genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 8670792