PEX6/YNL329C Summary Help

Standard Name PEX6 1
Systematic Name YNL329C
Alias PAS8 2
Feature Type ORF, Verified
Description AAA-peroxin; heterodimerizes with AAA-peroxin Pex1p and participates in the recycling of peroxisomal signal receptor Pex5p from the peroxisomal membrane to the cystosol (2, 3, 4 and see Summary Paragraph)
Name Description PEroXin 1
Chromosomal Location
ChrXIV:22633 to 19541 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All PEX6 GO evidence and references
  View Computational GO annotations for PEX6
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 8 genes
Classical genetics
reduction of function
Large-scale survey
69 total interaction(s) for 44 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 4
  • Co-fractionation: 13
  • PCA: 3
  • Reconstituted Complex: 3
  • Two-hybrid: 10

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 9
  • Phenotypic Suppression: 1
  • Positive Genetic: 3
  • Synthetic Growth Defect: 12
  • Synthetic Lethality: 5

Expression Summary
Length (a.a.) 1,030
Molecular Weight (Da) 115,570
Isoelectric Point (pI) 5.44
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXIV:22633 to 19541 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..3093 22633..19541 1996-07-31 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005273

The biogenesis of peroxisomes requires a group of protein factors referred to as peroxins which are encoded by the PEX genes. Peroxisomal proteins are synthesized on free polyribosomes and imported posttranslationally. The transport of peroxisomal matrix proteins from the cytoplasm to the peroxisome is mediated by two peroxisome-targeting signal (PTS1 and PTS2) sequences, whereas the transport of proteins destined for peroxisomal membranes is mediated by the membrane PTS signals (mPTS) and occurs independently of the matrix proteins by a distinct mechanism (reviewed in 5, 6 and 7). The import of peroxisomal matrix proteins can be divided into four main steps: 1) cargo recognition/transport; 2) docking of the cargo-loaded receptors on the peroxisomal membrane; 3) cargo release and translocation; and 4) receptor recycling (reviewed in 8, 7 and 6).

Pex6p and Pex1p are large AAA-ATPase family members (ATPases associated with a wide range of cellular activities) that contain two AAA-cassettes, each of which is characterized by Walker A (ATP binding) and Walker B (ATP hydrolysis) motifs (9, 2). Pex6p, Pex1p and several other peroxins (Pex4p, Pex15p and Pex22p) are involved in the ATP-dependent relocation of the PTS1 import receptor Pex5p from the peroxisomal membrane back to the cytosol after cargo release (reviewed in 7). Pex1p and Pex6p interact to form a stable heterodimer in the cytosol (3, 10). This interaction involves the N-terminal AAA-cassettes of both peroxins and requires ATP-binding but not hydrolysis by the C-terminal AAA-cassette of Pex1p (3, 11). The cytosolic Pex1p-Pex6p complex is then recruited to the peroxisomal membrane by direct interactions between Pex6p and Pex15p, a type II integral membrane protein that functions as a membrane anchor for the AAA-peroxin complex (12, 10). This interaction requires ATP binding by Pex6p and dissociation requires ATP hydrolysis, suggesting an ATP-dependent cycle of recruitment and release (12). The membrane-anchored form of the Pex1p-Pex6p complex mediates the dislocation of the docked, ubiquitinated Pex5p receptor from the peroxisomal membrane, resulting in either receptor recycling or degradation (4, 13).

PEX6 was originally identified using a positive selection procedure to isolate mutants with defective peroxisomal function (14). pex6 mutants are unable to utilize oleic acid as sole carbon source, mislocalize peroxisomal matrix proteins to the cytosol, and lack morphologically detectable peroxisomal structures (14).

The human peroxisome biogenesis disorders (PBDs; OMIM) are a group of genetically heterogeneous diseases with more than ten complementation groups that are characterized by severe mental retardation, neuronal, hepatic and renal abnormalities, and death in early infancy (15). Clinical features of PBD patients vary, but all exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologs of yeast PEX genes are defective in some groups of PBD patients. Pex6p is conserved from yeast to humans, and the human AAA-peroxins interact with each other similarly to the yeast proteins, suggesting conservation of function (16 and reviewed in 17). The human PEX6 gene (OMIM) is mutated in PBD patients in complementation group 4 (CG4) and the human ortholog is able to morphologically restore peroxisomes in peroxisome deficient human CG4 fibroblasts (18, 19).

Last updated: 2007-07-27 Contact SGD

References cited on this page View Complete Literature Guide for PEX6
1) Distel B, et al.  (1996) A unified nomenclature for peroxisome biogenesis factors. J Cell Biol 135(1):1-3
2) Voorn-Brouwer T, et al.  (1993) Sequence of the PAS8 gene, the product of which is essential for biogenesis of peroxisomes in Saccharomyces cerevisiae. Biochim Biophys Acta 1216(2):325-8
3) Birschmann I, et al.  (2005) Structural and functional analysis of the interaction of the AAA-peroxins Pex1p and Pex6p. FEBS J 272(1):47-58
4) Platta HW, et al.  (2005) Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol 7(8):817-22
5) Sacksteder KA and Gould SJ  (2000) The genetics of peroxisome biogenesis. Annu Rev Genet 34:623-652
6) Purdue PE and Lazarow PB  (2001) Peroxisome biogenesis. Annu Rev Cell Dev Biol 17:701-52
7) Brown LA and Baker A  (2003) Peroxisome biogenesis and the role of protein import. J Cell Mol Med 7(4):388-400
8) Gould SJ and Collins CS  (2002) Opinion: peroxisomal-protein import: is it really that complex? Nat Rev Mol Cell Biol 3(5):382-9
9) Erdmann R, et al.  (1991) PAS1, a yeast gene required for peroxisome biogenesis, encodes a member of a novel family of putative ATPases. Cell 64(3):499-510
10) Rosenkranz K, et al.  (2006) Functional association of the AAA complex and the peroxisomal importomer. FEBS J 273(16):3804-15
11) Krause T, et al.  (1994) Effect of site-directed mutagenesis of conserved lysine residues upon Pas1 protein function in peroxisome biogenesis. Yeast 10(12):1613-20
12) Birschmann I, et al.  (2003) Pex15p of Saccharomyces cerevisiae provides a molecular basis for recruitment of the AAA peroxin Pex6p to peroxisomal membranes. Mol Biol Cell 14(6):2226-36
13) Platta HW, et al.  (2007) Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. J Cell Biol 177(2):197-204
14) Van der Leij I, et al.  (1992) Isolation of peroxisome assembly mutants from Saccharomyces cerevisiae with different morphologies using a novel positive selection procedure. J Cell Biol 119(1):153-62
15) Warren DS, et al.  (1998) Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders. Am J Hum Genet 63(2):347-59
16) Tamura S, et al.  (1998) A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p. Biochem Biophys Res Commun 245(3):883-6
17) Kiel JA, et al.  (2006) PEX Genes in Fungal Genomes: Common, Rare or Redundant. Traffic 7(10):1291-303
18) Vehring S, et al.  (2007) Flip-flop of fluorescently labeled phospholipids in proteoliposomes reconstituted with Saccharomyces cerevisiae microsomal proteins. Eukaryot Cell 6(9):1625-34
19) Basyuni M, et al.  (2007) Cloning and Functional Expression of Cycloartenol Synthases from Mangrove Species Rhizophora stylosa Griff. and Kandelia candel (L.) Druce. Biosci Biotechnol Biochem 71(7):1788-92