PEX19

This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of Zellweger syndrome (ZWS), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

Full Name

Peroxisomal Biogenesis Factor 19

Function

Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.

Biological Process

Chaperone-mediated protein foldingManual Assertion Based On ExperimentIDA:UniProtKB
Establishment of protein localization to peroxisomeManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of lipid bindingManual Assertion Based On ExperimentIDA:UniProtKB
Peroxisome fissionManual Assertion Based On ExperimentIMP:UniProtKB
Peroxisome membrane biogenesisIDA:UniProtKB
Peroxisome organizationManual Assertion Based On ExperimentIMP:UniProtKB
Protein import into peroxisome membraneManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein targeting to peroxisomeManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm
Peroxisome membrane
Mainly cytoplasmic. Some fraction membrane-associated to the outer surface of peroxisomes.

Involvement in disease

Peroxisome biogenesis disorder complementation group 14 (PBD-CG14):
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder 12A (PBD12A):
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.