UniProt functional annotation for P50542



	UniProt functional annotation for P50542

UniProt code: P50542.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. {ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.

Subunit: Interacts with PEX7 and PEX13 (By similarity). Interacts with PEX12 and PEX14. Interacts (Cys-linked ubiquitinated) with ZFAND6. Interacts with VWA8 in a PEX7-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q920N5, ECO:0000269|PubMed:10562279, ECO:0000269|PubMed:11101887, ECO:0000269|PubMed:11438541, ECO:0000269|PubMed:17157249, ECO:0000269|PubMed:19197237, ECO:0000269|PubMed:21980954}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:7719337}. Peroxisome membrane {ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337}; Peripheral membrane protein. Note=Its distribution appears to be dynamic. It is probably a cycling receptor found mainly in the cytoplasm and as well associated to the peroxisomal membrane through a docking factor (PEX13).

Tissue specificity: Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.

Ptm: Monoubiquitination at Cys-11 is required for proper export from peroxisomes and recycling. {ECO:0000250|UniProtKB:Q920N5}.

Disease: Peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically 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. {ECO:0000269|PubMed:7719337}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370]: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. {ECO:0000269|PubMed:10462504, ECO:0000269|PubMed:7719337}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Rhizomelic chondrodysplasia punctata 5 (RCDP5) [MIM:616716]: A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe mental retardation with spasticity. {ECO:0000269|PubMed:26220973}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peroxisomal targeting signal receptor family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. {ECO:0000269\|PubMed:7706321, ECO:0000269\|PubMed:7719337, ECO:0000269\|PubMed:7790377}.


Subunit:		Interacts with PEX7 and PEX13 (By similarity). Interacts with PEX12 and PEX14. Interacts (Cys-linked ubiquitinated) with ZFAND6. Interacts with VWA8 in a PEX7-dependent manner (By similarity). {ECO:0000250\|UniProtKB:Q920N5, ECO:0000269\|PubMed:10562279, ECO:0000269\|PubMed:11101887, ECO:0000269\|PubMed:11438541, ECO:0000269\|PubMed:17157249, ECO:0000269\|PubMed:19197237, ECO:0000269\|PubMed:21980954}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:7719337}. Peroxisome membrane {ECO:0000269\|PubMed:7706321, ECO:0000269\|PubMed:7719337}; Peripheral membrane protein. Note=Its distribution appears to be dynamic. It is probably a cycling receptor found mainly in the cytoplasm and as well associated to the peroxisomal membrane through a docking factor (PEX13).
Tissue specificity:		Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. {ECO:0000269\|PubMed:7706321, ECO:0000269\|PubMed:7719337, ECO:0000269\|PubMed:7790377}.
Ptm:		Monoubiquitination at Cys-11 is required for proper export from peroxisomes and recycling. {ECO:0000250\|UniProtKB:Q920N5}.
Disease:		Peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically 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. {ECO:0000269\|PubMed:7719337}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370]: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. {ECO:0000269\|PubMed:10462504, ECO:0000269\|PubMed:7719337}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Rhizomelic chondrodysplasia punctata 5 (RCDP5) [MIM:616716]: A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe mental retardation with spasticity. {ECO:0000269\|PubMed:26220973}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peroxisomal targeting signal receptor family. {ECO:0000305}.