PEX12/YMR026C Summary Help

Standard Name PEX12 1, 2
Systematic Name YMR026C
Alias PAS11
Feature Type ORF, Verified
Description C3HC4-type RING-finger peroxin and E3 ubiquitin ligase; required for peroxisome biogenesis and peroxisomal matrix protein import; forms translocation subcomplex with Pex2p and Pex10p; mutations in human homolog cause peroxisomal disorder (2, 3, 4, 5 and see Summary Paragraph)
Name Description PEroXin 1
Chromosomal Location
ChrXIII:325435 to 324236 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All PEX12 GO evidence and references
  View Computational GO annotations for PEX12
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 9 genes
Classical genetics
Large-scale survey
160 total interaction(s) for 96 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 16
  • Co-localization: 1
  • Co-purification: 4
  • PCA: 8
  • Protein-peptide: 1
  • Two-hybrid: 2

Genetic Interactions
  • Negative Genetic: 98
  • Positive Genetic: 20
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 399
Molecular Weight (Da) 45,992
Isoelectric Point (pI) 9.86
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXIII:325435 to 324236 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1200 325435..324236 2011-02-03 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 SGDIDS000004628

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).

Pex12p is an integral peroxisomal membrane protein required for peroxisome biogenesis and peroxisomal matrix protein import (3). Pex12p contains a degenerate RING finger domain of the C3HC4 type in its essential carboxy-terminus, and forms the translocation subcomplex of the peroxisomal import machinery with RING-finger peroxins Pex2p and Pex10p (4). Localization studies demonstrate that the N-terminus of Pex12p faces the peroxisomal lumen and the C-terminus faces the cytosol (2).

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 (10). 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 (10).

The pex12delta deletion strain fails to import peroxisomal matrix proteins through both the PTS1 and PTS2 pathways. Pex12p-deficient cells retain particular structures that contain peroxisomal membrane proteins consistent with the existence of peroxisomal membrane remnants, or "ghosts", indicating that pex12delta cells are not impaired in peroxisomal membrane biogenesis. In immunoisolation experiments, Pex12p was co-purified with the RING finger protein Pex10p, the PTS1 receptor Pex5p and the docking proteins for the PTS1 and the PTS2 receptors at the peroxisomal membrane, Pex13p and Pex14p (2).

The human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases characterized by severe mental retardation, neuronal, hepatic and renal abnormalities, and death in early infancy (11). 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 (11, 3).

Pex12p in humans exhibits the same peroxisomal membrane localization as yeast Pex12p. PEX12 expression restores peroxisomal protein import in fibroblasts from PBD patients of complementation group 3 (CG3) and frameshift mutations in PEX12 have been detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import (3). Mutations in PEX12 have also been associated with Zellweger syndrome.

Last updated: 2005-03-08 Contact SGD

References cited on this page View Complete Literature Guide for PEX12
1) Distel B, et al.  (1996) A unified nomenclature for peroxisome biogenesis factors. J Cell Biol 135(1):1-3
2) Albertini M, et al.  (2001) Pex12p of Saccharomyces cerevisiae is a component of a multi-protein complex essential for peroxisomal matrix protein import. Eur J Cell Biol 80(4):257-70
3) Chang CC, et al.  (1997) Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders. Nat Genet 15(4):385-8
4) Hazra PP, et al.  (2002) Peroxisome remnants in pex3delta cells and the requirement of Pex3p for interactions between the peroxisomal docking and translocation subcomplexes. Traffic 3(8):560-74
5) Platta HW, et al.  (2009) Pex2 and pex12 function as protein-ubiquitin ligases in peroxisomal protein import. Mol Cell Biol 29(20):5505-16
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) Agne B, et al.  (2003) Pex8p: an intraperoxisomal organizer of the peroxisomal import machinery. Mol Cell 11(3):635-46
11) 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