P50542 · PEX5_HUMAN

  • Protein
    Peroxisomal targeting signal 1 receptor
  • Gene
    PEX5
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) (PubMed:11101887, PubMed:11336669, PubMed:12456682, PubMed:16314507, PubMed:17157249, PubMed:17428317, PubMed:21976670, PubMed:26344566, PubMed:7706321, PubMed:7719337, PubMed:7790377).
Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 docking complex along with cargo proteins (PubMed:12456682, PubMed:17157249, PubMed:21976670, PubMed:26344566).
PEX5 receptor is then retrotranslocated into the cytosol, leading to release of bound cargo in the peroxisome matrix, and reset for a subsequent peroxisome import cycle (PubMed:11336669, PubMed:24662292).

Isoform 1

In addition to promoting peroxisomal translocation of proteins containing a PTS1 peroxisomal targeting signal, mediates peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal via its interaction with PEX7 (PubMed:11336669, PubMed:11546814, PubMed:25538232, PubMed:33389129, PubMed:9668159).
Interaction with PEX7 only takes place when PEX7 is associated with cargo proteins containing a PTS2 peroxisomal targeting signal (PubMed:25538232).
PEX7 along with PTS2-containing cargo proteins are then translocated through the PEX13-PEX14 docking complex together with PEX5 (PubMed:25538232).

Isoform 2

Does not mediate translocation of peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.

Activity regulation

Cys-11 acts as a sensor of redox state (PubMed:24118911).
In response to oxidative stress, monoubiquitination at Cys-11 is prevented (PubMed:24118911).

Features

Showing features for site.

TypeIDPosition(s)Description
Site11Sensor of redox state

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular ComponentGolgi apparatus
Cellular Componentmembrane
Cellular Componentmitochondrion
Cellular Componentperoxisomal matrix
Cellular Componentperoxisomal membrane
Cellular Componentperoxisome
Cellular Componentprotein-containing complex
Molecular Functionenzyme binding
Molecular Functionperoxisome matrix targeting signal-1 binding
Molecular Functionperoxisome membrane targeting sequence binding
Molecular Functionperoxisome targeting sequence binding
Molecular Functionprotein carrier chaperone
Molecular Functionsmall GTPase binding
Biological Processcell development
Biological Processcellular response to reactive oxygen species
Biological Processcerebral cortex cell migration
Biological Processcerebral cortex neuron differentiation
Biological Processendoplasmic reticulum organization
Biological Processfatty acid beta-oxidation
Biological Processmitochondrial membrane organization
Biological Processnegative regulation of protein-containing complex assembly
Biological Processneuromuscular process
Biological Processneuron migration
Biological Processpexophagy
Biological Processpositive regulation of multicellular organism growth
Biological Processprotein import into peroxisome matrix
Biological Processprotein import into peroxisome matrix, docking
Biological Processprotein import into peroxisome matrix, receptor recycling
Biological Processprotein import into peroxisome matrix, substrate release
Biological Processprotein import into peroxisome matrix, translocation
Biological Processprotein import into peroxisome membrane
Biological Processprotein targeting to peroxisome
Biological Processprotein tetramerization
Biological Processvery long-chain fatty acid metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Peroxisomal targeting signal 1 receptor
  • Short names
    PTS1 receptor
    ; PTS1R
  • Alternative names
    • PTS1-BP
    • Peroxin-5
    • Peroxisomal C-terminal targeting signal import receptor
    • Peroxisome receptor 1

Gene names

    • Name
      PEX5
    • Synonyms
      PXR1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P50542
  • Secondary accessions
    • A8K891
    • B4DZ45
    • B7ZAD5
    • D3DUT8
    • Q15115

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, cytosol
Peroxisome matrix
Note: Cycles between the cytosol and the peroxisome matrix (PubMed:11336669, PubMed:16314507).
Following binding to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, recruited to the docking complex, composed of PEX13 and PEX14, leading to translocation into the peroxisome matrix along with cargo proteins (By similarity).
Export and recycling to the cytosol is initiated by binding to the PEX2-PEX10-PEX12 ligase complex via its unstructured N-terminus that inserts into the ligase pore and emerges in the cytosol (By similarity).
Cys-11 of PEX5 is then monoubiquitinated, promoting its extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex (PubMed:16314507, PubMed:19208625, PubMed:24118911, PubMed:29884772).
Extraction is accompanied by unfolding of the TPR repeats and release of bound cargo in the peroxisome matrix (By similarity).
The TPR repeats refold in the cytosol and ubiquitination is removed by deubiquitinating enzymes, resetting PEX5 for a subsequent import cycle (By similarity).

Keywords

Disease & Variants

Involvement in disease

Peroxisome biogenesis disorder 2A (PBD2A)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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.
  • See also
    MIM:214110

Peroxisome biogenesis disorder 2B (PBD2B)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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.
  • See also
    MIM:202370
Natural variants in PBD2B
Variant IDPosition(s)ChangeDescription
VAR_087153427-639missingin PBD2B; impaired ability to mediate peroxisomal import of proteins containing both a C-terminal PTS1- and PTS2-type targeting signals
VAR_007543526N>Kin PBD2B; neonatal adrenoleukodystrophy; strongly affects peroxisomal protein import containing a C-terminal PTS1-type targeting signal without affecting import of proteins with a PTS2 targeting signal; dbSNP:rs61752138
VAR_031328600S>Win PBD2B; infantile Refsum disease; mildly affects peroxisomal protein import

Rhizomelic chondrodysplasia punctata 5 (RCDP5)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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 intellectual disability with spasticity.
  • See also
    MIM:616716

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis11Promotes accumulation at the peroxisomal membrane because of impaired export into the cytosol. Does not affect monoubiquitination by TRIM37.
Mutagenesis11Does not affect ability to mediate peroxisomal import of proteins.
Mutagenesis11Promotes accumulation at the peroxisomal membrane because of impaired export into the cytosol.
Mutagenesis62-66Abolished interaction with PEX14.
Mutagenesis118Strongly reduced interaction with PEX14.
Mutagenesis122Strongly reduced interaction with PEX14.
Mutagenesis140Decreased interaction with PEX14.
Mutagenesis141Abolished phosphorylation by ATM, leading to impaired monoubiquitination at K-209.
Mutagenesis141Mimics phosphorylation, leading to increased pexophagy in response to reactive oxygen species (ROS).
Mutagenesis209Does not affect monoubiquitination by TRIM37.
Mutagenesis209Abolished interaction with SQSTM1, leading to decreased pexophagy in response to reactive oxygen species (ROS).
Natural variantVAR_087152218found in a family with congenital cataract; likely pathogenic; impaired interaction with PEX7; impaired ability to mediate peroxisomal import of proteins containing a C-terminal PTS2-type targeting signal without affecting import of proteins with a PTS1 targeting signal
Natural variantVAR_087153427-639in PBD2B; impaired ability to mediate peroxisomal import of proteins containing both a C-terminal PTS1- and PTS2-type targeting signals
Mutagenesis472Abolished monoubiquitination by TRIM37, leading to decreased stability.
Natural variantVAR_007543526in PBD2B; neonatal adrenoleukodystrophy; strongly affects peroxisomal protein import containing a C-terminal PTS1-type targeting signal without affecting import of proteins with a PTS2 targeting signal; dbSNP:rs61752138
Mutagenesis527Does not affect monoubiquitination by TRIM37.
Mutagenesis527Does not affect PEX5 recycling.
Natural variantVAR_031328600in PBD2B; infantile Refsum disease; mildly affects peroxisomal protein import

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 854 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, cross-link, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00001063051-639UniProtPeroxisomal targeting signal 1 receptor
Cross-link11UniProtGlycyl cysteine thioester (Cys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue (large scale data)58PRIDEPhosphoserine
Modified residue115UniProtPhosphoserine
Modified residue141UniProtPhosphoserine; by ATM
Modified residue153UniProtPhosphoserine
Modified residue155UniProtPhosphoserine
Modified residue (large scale data)155PRIDEPhosphoserine
Modified residue167UniProtPhosphoserine
Modified residue (large scale data)167PRIDEPhosphoserine
Cross-link209UniProtGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue (large scale data)268PRIDEPhosphoserine
Modified residue279UniProtPhosphoserine
Modified residue (large scale data)279PRIDEPhosphoserine
Cross-link472UniProtGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link527UniProtGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Post-translational modification

Monoubiquitinated at Cys-11 by PEX2 during PEX5 passage through the retrotranslocation channel (By similarity).
Cys-11 monoubiquitination acts as a recognition signal for the PEX1-PEX6 complex and is required for PEX5 extraction and export from peroxisomes (PubMed:29884772).
Monoubiquitination at Cys-11 is removed by USP9X in the cytosol, resetting PEX5 for a subsequent import cycle (PubMed:22371489).
When PEX5 recycling is compromised, polyubiquitinated by PEX10 during its passage through the retrotranslocation channel, leading to its degradation (By similarity).
Monoubiquitination at Lys-472 by TRIM37 promotes its stability by preventing its polyubiquitination and degradation by the proteasome (PubMed:28724525).
Ubiquitination at Lys-527 is not mediated by the PEX2-PEX10-PEX12 ligase complex and is not related to PEX5 recycling (PubMed:24662292).
Monoubiquitinated at Lys-209 by PEX2 following phosphorylation by ATM in response to starvation or reactive oxygen species (ROS), leading to PEX5 recognition by p62/SQSTM1 and induction of pexophagy (PubMed:26344566, PubMed:27597759).
Phosphorylated at Ser-141 by ATM in response to reactive oxygen species (ROS), promoting monoubiquitination at Lys-209 and induction of pexophagy.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts (via WxxxF/Y and LVxEF motifs) with PEX14; promoting translocation through the PEX13-PEX14 docking complex (PubMed:11438541, PubMed:19197237, PubMed:24235149, PubMed:24662292, PubMed:28765278).
Interacts with PEX12 (PubMed:10562279).
Interacts (Cys-linked ubiquitinated) with ZFAND6 (PubMed:21980954).
Interacts (when ubiquitinated at Lys-209) with p62/SQSTM1 (PubMed:26344566).
Interacts with DDO; the interaction is direct and required for localization of DDO to the peroxisome (PubMed:9820813).

Isoform 1

Interacts with PEX7, promoting peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, motif, repeat.

TypeIDPosition(s)Description
Region11-33Amphipathic helix 1 (AH1)
Region33-53Disordered
Motif62-66LVxEF motif
Region81-99Amphipathic helix 2 (AH2)
Motif118-122WxxxF/Y motif 1
Motif140-144WxxxF/Y motif 2
Motif159-163WxxxF/Y motif 3
Motif184-188WxxxF/Y motif 4
Region190-206Amphipathic helix 3 (AH3)
Motif243-247WxxxF/Y motif 5
Motif257-261WxxxF/Y motif 6
Region284-300Amphipathic helix 4 (AH4)
Motif308-312WxxxF/Y motif 7
Repeat335-368TPR 1
Repeat369-402TPR 2
Repeat403-436TPR 3
Repeat452-485TPR 4
Repeat488-521TPR 5
Repeat522-555TPR 6
Repeat556-589TPR 7

Domain

The TPR repeats mediate interaction with proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type).
The WxxxF/Y motifs mediate interaction with PEX14, promoting association with the PEX13-PEX14 docking complex.
The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for PEX5 retrotranslocation and recycling (By similarity).
AH2 mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex (By similarity).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete

This entry describes 4 isoforms produced by Alternative splicing.

P50542-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    PEX5L
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    639
  • Mass (Da)
    70,865
  • Last updated
    2006-12-12 v3
  • Checksum
    9D6951F58AED31AC
MAMRELVEAECGGANPLMKLAGHFTQDKALRQEGLRPGPWPPGAPASEAASKPLGVASEDELVAEFLQDQNAPLVSRAPQTFKMDDLLAEMQQIEQSNFRQAPQRAPGVADLALSENWAQEFLAAGDAVDVTQDYNETDWSQEFISEVTDPLSVSPARWAEEYLEQSEEKLWLGEPEGTATDRWYDEYHPEEDLQHTASDFVAKVDDPKLANSEFLKFVRQIGEGQVSLESGAGSGRAQAEQWAAEFIQQQGTSDAWVDQFTRPVNTSALDMEFERAKSAIESDVDFWDKLQAELEEMAKRDAEAHPWLSDYDDLTSATYDKGYQFEEENPLRDHPQPFEEGLRRLQEGDLPNAVLLFEAAVQQDPKHMEAWQYLGTTQAENEQELLAISALRRCLELKPDNQTALMALAVSFTNESLQRQACETLRDWLRYTPAYAHLVTPAEEGAGGAGLGPSKRILGSLLSDSLFLEVKELFLAAVRLDPTSIDPDVQCGLGVLFNLSGEYDKAVDCFTAALSVRPNDYLLWNKLGATLANGNQSEEAVAAYRRALELQPGYIRSRYNLGISCINLGAHREAVEHFLEALNMQRKSRGPRGEGGAMSENIWSTLRLALSMLGQSDAYGAADARDLSTLLTMFGLPQ

P50542-2

  • Name
    2
  • Synonyms
    PEX5S
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P50542-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P50542-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 45-45: P → PASEAVSVLEVESPGA

Computationally mapped potential isoform sequences

There are 12 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
J3KPV0J3KPV0_HUMANPEX5410
H0YGT8H0YGT8_HUMANPEX531
B4E0T2B4E0T2_HUMANPEX5660
F5GZ41F5GZ41_HUMANPEX5115
F5GXX3F5GXX3_HUMANPEX5104
F5GYB4F5GYB4_HUMANPEX5128
F5H5C0F5H5C0_HUMANPEX5272
F5H637F5H637_HUMANPEX5168
F5H3X7F5H3X7_HUMANPEX5248
F5H432F5H432_HUMANPEX5102
F5H0L9F5H0L9_HUMANPEX5118
F5H205F5H205_HUMANPEX5114

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_04363945in isoform 4
Alternative sequenceVSP_021880215-251in isoform 2
Alternative sequenceVSP_024106283-290in isoform 3
Sequence conflict425in Ref. 1; AAC50103

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U19721
EMBL· GenBank· DDBJ
AAC50103.1
EMBL· GenBank· DDBJ
mRNA
Z48054
EMBL· GenBank· DDBJ
CAA88131.1
EMBL· GenBank· DDBJ
mRNA
X84899
EMBL· GenBank· DDBJ
CAA59324.1
EMBL· GenBank· DDBJ
mRNA
AK292256
EMBL· GenBank· DDBJ
BAF84945.1
EMBL· GenBank· DDBJ
mRNA
AK302742
EMBL· GenBank· DDBJ
BAG63957.1
EMBL· GenBank· DDBJ
mRNA
AK316250
EMBL· GenBank· DDBJ
BAH14621.1
EMBL· GenBank· DDBJ
mRNA
AC018653
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471116
EMBL· GenBank· DDBJ
EAW88671.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471116
EMBL· GenBank· DDBJ
EAW88674.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471116
EMBL· GenBank· DDBJ
EAW88672.1
EMBL· GenBank· DDBJ
Genomic DNA
BC010621
EMBL· GenBank· DDBJ
AAH10621.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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