PEX5/YDR244W Summary Help

Standard Name PEX5 1
Systematic Name YDR244W
Alias PAS10 2
Feature Type ORF, Verified
Description Peroxisomal membrane signal receptor for peroxisomal matrix proteins; receptor for the C-terminal tripeptide signal sequence (PTS1) of peroxisomal matrix proteins; required for peroxisomal matrix protein import; also proposed to have PTS1-receptor independent functions (2, 3, 4, 5 and see Summary Paragraph)
Name Description PEroXin 1
Chromosomal Location
ChrIV:950563 to 952401 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All PEX5 GO evidence and references
  View Computational GO annotations for PEX5
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
overexpression
Resources
149 total interaction(s) for 78 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 6
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 30
  • Biochemical Activity: 1
  • Co-crystal Structure: 1
  • Co-fractionation: 6
  • Co-purification: 2
  • PCA: 6
  • Reconstituted Complex: 5
  • Two-hybrid: 28

Genetic Interactions
  • Dosage Growth Defect: 2
  • Negative Genetic: 48
  • Positive Genetic: 3
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 612
Molecular Weight (Da) 69,324
Isoelectric Point (pI) 4.79
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:950563 to 952401 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1839 950563..952401 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002652
SUMMARY PARAGRAPH for PEX5

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 sequences (PTS1 and PTS2). Peroxisomal membrane proteins (PMPs) are imported independently of the matrix proteins by a distinct mechanism mediated by the membrane PTS signal (mPTS) (6, 7, 8, 9 and references therein).

Pex5p mediates the import of peroxisomal matrix proteins during peroxisome biogenesis by binding to the peroxisomal targeting sequence PTS1 (8, 10). PTS1 is a carboxy-terminal tripeptide motif with the canonical sequence serine-lysine-leucine, but the first and second positions can be degenerate (3, 11 and references therein). Pex5p binds PTS1-containing proteins in the cytoplasm and delivers them to the peroxisomal membrane where the Pex5p-peroxisomal matrix protein complex interacts with the peroxisomal import machinery (12).

Two subcomplexes of the peroxisomal import machinery have been defined: the docking subcomplex comprises Pex14p, Pex17p, and Pex13p, while the translocation subcomplex contains Pex2p, Pex10p, and Pex12p. The proteins of the translocation complex expose their RING finger domains to the outer face of the peroxisomal membrane, and act downstream of Pex14p, Pex17p, and Pex13p during the peroxisomal protein import process (13). Association of both subcomplexes into a larger import complex requires Pex8p, an intraperoxisomal protein. Pex8p organizes the formation of the larger import complex from the trans side of the peroxisomal membrane and thus might enable functional communication between both sides of the membrane (13).

Although Pex5p interacts with many of the subunits in the docking and translocation complex, Pex5p may first interact with Pex14p (14). The ubiquitination of Pex5p at the peroxisomal membrane may be required for its release and recycling (15, 16, 17, 18).

Pex5p has been proposed to have multiple roles in the import of peroxisomal matrix proteins. In addition to its role as the PTS1 receptor protein, Pex5p may be involved in the import of peroxisomal matrix proteins that do not contain a PTS1 signal (5, 19). Also, Pex5p has been proposed to stabilize the formation of the docking complex (20).

Growth on oleic acid induces the expression of many peroxisomal genes. Their expression is mediated by the transcription factor complex Pip2p-Oaf1p, which binds the oleate response element (ORE) found in the promoter region of a number of these genes (21). However, although the Pip2p-Oaf1p bind the PEX5 ORE, its expression was not induced in the presence of oleic acid (22)

The carboxy-terminal region of Pex5p contains highly conserved seven tetratricopeptide repeats that are required to bind PTS1 (3, 23). The amino-terminal region contains a conserved WxxxF/Y motif that is important to bind Pex13p (24). Pex5p is conserved in fungi, plants, worms, and humans (25, 26, 27, 28). The human PEX5 encodes two isoforms, PEX5S and PEX5L. PEX5L appears to be involved in PTS2 protein import, which, in S. cerevisiae, is mediated by Pex7p, Pex18p, and Pex21p (25, 29 and references therein). Mutations in human PEX5, also known as PTS1R or PXR1, have been associated with the peroxisome biogenesis disorders neonatal adrenoleukodystrophy and Zellweger syndrome (30, 28).

Last updated: 2007-06-28 Contact SGD

References cited on this page View Complete Literature Guide for PEX5
1) Distel B, et al.  (1996) A unified nomenclature for peroxisome biogenesis factors. J Cell Biol 135(1):1-3
2) Van der Leij I, et al.  (1993) PAS10 is a tetratricopeptide-repeat protein that is essential for the import of most matrix proteins into peroxisomes of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 90(24):11782-6
3) Brocard C, et al.  (1994) The tetratricopeptide repeat-domain of the PAS10 protein of Saccharomyces cerevisiae is essential for binding the peroxisomal targeting signal-SKL. Biochem Biophys Res Commun 204(3):1016-22
4) Erdmann R and Blobel G  (1996) Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition factor. J Cell Biol 135(1):111-21
5) Klein AT, et al.  (2002) Saccharomyces cerevisiae acyl-CoA oxidase follows a novel, non-PTS1, import pathway into peroxisomes that is dependent on Pex5p. J Biol Chem 277(28):25011-9
6) Hettema EH, et al.  (2000) Saccharomyces cerevisiae pex3p and pex19p are required for proper localization and stability of peroxisomal membrane proteins. EMBO J 19(2):223-33
7) Sacksteder KA and Gould SJ  (2000) The genetics of peroxisome biogenesis. Annu Rev Genet 34:623-652
8) Purdue PE and Lazarow PB  (2001) Peroxisome biogenesis. Annu Rev Cell Dev Biol 17:701-52
9) Fujiki Y, et al.  (2006) Import of peroxisomal membrane proteins: The interplay of Pex3p- and Pex19p-mediated interactions. Biochim Biophys Acta 1763(12):1639-46
10) Brown LA and Baker A  (2003) Peroxisome biogenesis and the role of protein import. J Cell Mol Med 7(4):388-400
11) Subramani S, et al.  (2000) Import of peroxisomal matrix and membrane proteins. Annu Rev Biochem 69:399-418
12) Heiland I and Erdmann R  (2005) Biogenesis of peroxisomes. Topogenesis of the peroxisomal membrane and matrix proteins. FEBS J 272(10):2362-72
13) Agne B, et al.  (2003) Pex8p: an intraperoxisomal organizer of the peroxisomal import machinery. Mol Cell 11(3):635-46
14) Niederhoff K, et al.  (2005) Yeast Pex14p possesses two functionally distinct Pex5p and one Pex7p binding sites. J Biol Chem 280(42):35571-8
15) Platta HW, et al.  (2004) Ubiquitination of the peroxisomal import receptor Pex5p. Biochem J 384(Pt 1):37-45
16) Kiel JA, et al.  (2005) Ubiquitination of the peroxisomal targeting signal type 1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import. J Biol Chem 280(3):1921-30
17) Kragt A, et al.  (2005) The Saccharomyces cerevisiae peroxisomal import receptor Pex5p is monoubiquitinated in wild type cells. J Biol Chem 280(9):7867-74
18) Platta HW, et al.  (2007) Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. J Cell Biol 177(2):197-204
19) Parkes JA, et al.  (2003) PTS1-independent targeting of isocitrate lyase to peroxisomes requires the PTS1 receptor Pex5p. Mol Membr Biol 20(1):61-9
20) Schell-Steven A, et al.  (2005) Identification of a novel, intraperoxisomal pex14-binding site in pex13: association of pex13 with the docking complex is essential for peroxisomal matrix protein import. Mol Cell Biol 25(8):3007-18
21) Karpichev IV and Small GM  (1998) Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Mol Cell Biol 18(11):6560-70
22) Rottensteiner H, et al.  (2003) Saccharomyces cerevisiae Pip2p-Oaf1p regulates PEX25 transcription through an adenine-less ORE. Eur J Biochem 270(9):2013-22
23) Klein AT, et al.  (2001) Recognition of peroxisomal targeting signal type 1 by the import receptor Pex5p. J Biol Chem 276(18):15034-41
24) Bottger G, et al.  (2000) Saccharomyces cerevisiae PTS1 receptor Pex5p interacts with the SH3 domain of the peroxisomal membrane protein Pex13p in an unconventional, non-PXXP-related manner. Mol Biol Cell 11(11):3963-76
25) Kiel JA, et al.  (2006) PEX Genes in Fungal Genomes: Common, Rare or Redundant. Traffic 7(10):1291-303
26) Kragler F, et al.  (1998) Identification and analysis of the plant peroxisomal targeting signal 1 receptor NtPEX5. Proc Natl Acad Sci U S A 95(22):13336-41
27) Gurvitz A, et al.  (2000) Predicting the function and subcellular location of Caenorhabditis elegans proteins similar to Saccharomyces cerevisiae beta-oxidation enzymes. Yeast 17(3):188-200
28) Wiemer EA, et al.  (1995) Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. J Cell Biol 130(1):51-65
29) Dodt G, et al.  (2001) Domain mapping of human PEX5 reveals functional and structural similarities to Saccharomyces cerevisiae Pex18p and Pex21p. J Biol Chem 276(45):41769-81
30) Slawecki ML, et al.  (1995) Identification of three distinct peroxisomal protein import defects in patients with peroxisome biogenesis disorders. J Cell Sci 108 ( Pt 5):1817-29