PEX5
entrez
5830
canonical
uniprot
P50542
canonical
ensembl
ENSG00000139197
resolver
ensembl
ENSG00000288217
resolver
ensp
ENSP00000266563
resolver
ensp
ENSP00000391601
resolver
ensp
ENSP00000400647
resolver
ensp
ENSP00000407401
resolver
ensp
ENSP00000410159
resolver
ensp
ENSP00000500694
resolver
ensp
ENSP00000502374
resolver
ensp
ENSP00000542615
resolver
ensp
ENSP00000542617
resolver
ensp
ENSP00000542619
resolver
ensp
ENSP00000542620
resolver
ensp
ENSP00000542621
resolver
ensp
ENSP00000542622
resolver
ensp
ENSP00000542623
resolver
ensp
ENSP00000542624
resolver
ensp
ENSP00000542628
resolver
ensp
ENSP00000542630
resolver
ensp
ENSP00000542631
resolver
ensp
ENSP00000542633
resolver
ensp
ENSP00000542634
resolver
ensp
ENSP00000542636
resolver
ensp
ENSP00000542637
resolver
ensp
ENSP00000604679
resolver
ensp
ENSP00000604684
resolver
ensp
ENSP00000604686
resolver
ensp
ENSP00000604687
resolver
ensp
ENSP00000604688
resolver
ensp
ENSP00000604696
resolver
enst
ENST00000412720
resolver
enst
ENST00000672235
resolver
genesymbol
PEX5
resolver
genesymbol_syn
PXR1
resolver
hgnc
HGNC:9719
resolver
uniprot
A0A0S2Z480
resolver
uniprot
A0A0S2Z4F3
resolver
uniprot
A0A0S2Z4H1
resolver
uniprot
A8K891
resolver
uniprot
B4DR50
resolver
uniprot
B4DZ45
resolver
uniprot
B4E0T2
resolver
uniprot
B7ZAD5
resolver
uniprot
D3DUT8
resolver
uniprot
J3KQA5
resolver
uniprot
Q15115
resolver
uniprot
Q15266
resolver
uniprot
Q96FN7
resolver
uniprot_entry
A0A0S2Z480_HUMAN
resolver
uniprot_entry
A0A0S2Z4F3_HUMAN
resolver
uniprot_entry
A0A0S2Z4H1_HUMAN
resolver
uniprot_entry
B4DR50_HUMAN
resolver
uniprot_entry
B4E0T2_HUMAN
resolver
uniprot_entry
J3KQA5_HUMAN
resolver
uniprot_entry
PEX5_HUMAN
resolver
uniprot_sec
A8K891
resolver
uniprot_sec
B4DZ45
resolver
uniprot_sec
B7ZAD5
resolver
uniprot_sec
D3DUT8
resolver
uniprot_sec
Q15115
resolver
uniprot_sec
Q15266
resolver
uniprot_sec
Q96FN7
resolver
activity_regulation
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). {ECO:0000269|PubMed:24118911}.
uniprot
proteins
amino_acid_sequence
MAMRELVEAECGGANPLMKLAGHFTQDKALRQEGLRPGPWPPGAPASEAASKPLGVASEDELVAEFLQDQNAPLVSRAPQTFKMDDLLAEMQQIEQSNFRQAPQRAPGVADLALSENWAQEFLAAGDAVDVTQDYNETDWSQEFISEVTDPLSVSPARWAEEYLEQSEEKLWLGEPEGTATDRWYDEYHPEEDLQHTASDFVAKVDDPKLANSEFLKFVRQIGEGQVSLESGAGSGRAQAEQWAAEFIQQQGTSDAWVDQFTRPVNTSALDMEFERAKSAIESDVDFWDKLQAELEEMAKRDAEAHPWLSDYDDLTSATYDKGYQFEEENPLRDHPQPFEEGLRRLQEGDLPNAVLLFEAAVQQDPKHMEAWQYLGTTQAENEQELLAISALRRCLELKPDNQTALMALAVSFTNESLQRQACETLRDWLRYTPAYAHLVTPAEEGAGGAGLGPSKRILGSLLSDSLFLEVKELFLAAVRLDPTSIDPDVQCGLGVLFNLSGEYDKAVDCFTAALSVRPNDYLLWNKLGATLANGNQSEEAVAAYRRALELQPGYIRSRYNLGISCINLGAHREAVEHFLEALNMQRKSRGPRGEGGAMSENIWSTLRLALSMLGQSDAYGAADARDLSTLLTMFGLPQ
uniprot
proteins
disease_involvement
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, ECO:0000269|PubMed:9668159}. 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 intellectual disability with spasticity. {ECO:0000269|PubMed:26220973}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
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). {ECO:0000269|PubMed:11101887, ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:12456682, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:17157249, ECO:0000269|PubMed:17428317, ECO:0000269|PubMed:21976670, ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.; FUNCTION: [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). {ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:11546814, ECO:0000269|PubMed:25538232, ECO:0000269|PubMed:33389129, ECO:0000269|PubMed:9668159}.; FUNCTION: [Isoform 2]: Does not mediate translocation of peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal. {ECO:0000269|PubMed:11546814}.
uniprot
proteins
mass_dalton
70865
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="C->A: Promotes accumulation at the peroxisomal membrane because of impaired export into the cytosol. Does not affect monoubiquitination by TRIM37."; /evidence="ECO:0000269|PubMed:19208625, ECO:0000269|PubMed:28724525, ECO:0000269|PubMed:28765278"; MUTAGEN 11; /note="C->K: Does not affect ability to mediate peroxisomal import of proteins."; /evidence="ECO:0000269|PubMed:19208625, ECO:0000269|PubMed:22371489, ECO:0000269|PubMed:24118911"; MUTAGEN 11; /note="C->S,R: Promotes accumulation at the peroxisomal membrane because of impaired export into the cytosol."; /evidence="ECO:0000269|PubMed:19208625"; MUTAGEN 62..66; /note="LVAEF->AAAAA: Abolished interaction with PEX14."; /evidence="ECO:0000269|PubMed:24235149"; MUTAGEN 118; /note="W->A: Strongly reduced interaction with PEX14."; /evidence="ECO:0000269|PubMed:11438541, ECO:0000269|PubMed:24235149"; MUTAGEN 122; /note="F->A: Strongly reduced interaction with PEX14."; /evidence="ECO:0000269|PubMed:11438541"; MUTAGEN 140; /note="W->A: Decreased interaction with PEX14."; /evidence="ECO:0000269|PubMed:24235149"; MUTAGEN 141; /note="S->A: Abolished phosphorylation by ATM, leading to impaired monoubiquitination at K-209."; /evidence="ECO:0000269|PubMed:26344566"; MUTAGEN 141; /note="S->E: Mimics phosphorylation, leading to increased pexophagy in response to reactive oxygen species (ROS)."; /evidence="ECO:0000269|PubMed:26344566"; MUTAGEN 209; /note="K->A: Does not affect monoubiquitination by TRIM37."; /evidence="ECO:0000269|PubMed:28724525"; MUTAGEN 209; /note="K->R: Abolished interaction with SQSTM1, leading to decreased pexophagy in response to reactive oxygen species (ROS)."; /evidence="ECO:0000269|PubMed:26344566"; MUTAGEN 472; /note="K->A: Abolished monoubiquitination by TRIM37, leading to decreased stability."; /evidence="ECO:0000269|PubMed:28724525"; MUTAGEN 527; /note="K->A: Does not affect monoubiquitination by TRIM37."; /evidence="ECO:0000269|PubMed:28724525"; MUTAGEN 527; /note="K->R: Does not affect PEX5 recycling."; /evidence="ECO:0000269|PubMed:24662292
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:P35056, ECO:0000269|PubMed:22371489, ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27597759, ECO:0000269|PubMed:28724525, ECO:0000269|PubMed:29884772}.; PTM: Phosphorylated at Ser-141 by ATM in response to reactive oxygen species (ROS), promoting monoubiquitination at Lys-209 and induction of pexophagy. {ECO:0000269|PubMed:26344566}.
uniprot
proteins
protein_family
Peroxisomal targeting signal receptor family
uniprot
proteins
pubmed
10462504
uniprot
proteins
pubmed
10562279
uniprot
proteins
pubmed
11101887
uniprot
proteins
pubmed
11336669
uniprot
proteins
pubmed
11438541
uniprot
proteins
pubmed
11546814
uniprot
proteins
pubmed
12456682
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16314507
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17157249
uniprot
proteins
pubmed
17428317
uniprot
proteins
pubmed
19197237
uniprot
proteins
pubmed
19208625
uniprot
proteins
pubmed
21976670
uniprot
proteins
pubmed
21980954
uniprot
proteins
pubmed
22371489
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24118911
uniprot
proteins
pubmed
24235149
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24662292
uniprot
proteins
pubmed
25538232
uniprot
proteins
pubmed
26220973
uniprot
proteins
pubmed
26344566
uniprot
proteins
pubmed
27597759
uniprot
proteins
pubmed
28724525
uniprot
proteins
pubmed
28765278
uniprot
proteins
pubmed
29884772
uniprot
proteins
pubmed
33389129
uniprot
proteins
pubmed
7706321
uniprot
proteins
pubmed
7719337
uniprot
proteins
pubmed
7790377
uniprot
proteins
pubmed
9668159
uniprot
proteins
pubmed
9820813
uniprot
proteins
sequence_length
639
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:7719337}. Peroxisome matrix {ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:11546814, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:33389129, ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337}. 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). {ECO:0000250|UniProtKB:A0A1L8FDW4, ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:19208625, ECO:0000269|PubMed:24118911, ECO:0000269|PubMed:29884772}.
uniprot
proteins