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3.A.20.1.1
The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p. Peroxisomal biogenesis factor PEX26 is a membrane anchor for the multi-subunit PEX1-PEX6 protein complex that controls ubiquitination and dislocation of PEX5 cargo receptors for peroxisomal matrix protein import. PEX26 associates with the peroxisomal translocation pore via PEX14 (Guder et al. 2018). Luminal peroxisomal proteins are imported from the cytosol by mobile receptors, which then recycle back to the cytosol by a poorly understood process (Feng et al. 2022). Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprising three RING finger domain-containing proteins (Pex2, Pex10 and Pex12). Feng et al. 2022 reported a cryo-EM structure of the ligase complex, which together with biochemical and in vivo experiments reveals its function as a retrotranslocation channel for peroxisomal import receptors. Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel. The three ring finger domains form a cytosolic tower, with ring finger 2 (RF2) positioned above the channel pore. The N terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable extraction into the cytosol. If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded. This polyubiquitylation pathway also maintains the homeostasis of other peroxisomal import factors. Thus, a crucial step during peroxisomal protein import is clarified, and it explains why mutations in the ligase complex cause human disease (Feng et al. 2022).

Accession Number:Q92968
Protein Name:Peroxisomal membrane protein PEX13
Length:403
Molecular Weight:44130.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Peroxisome membrane1 / Single-pass membrane protein2
Substrate protein polypeptide chain

Cross database links:

RefSeq: NP_002609.1   
Entrez Gene ID: 5194   
Pfam: PF04088    PF00018   
OMIM: 202370  phenotype
601789  gene+phenotype
KEGG: hsa:5194   

Gene Ontology

GO:0005779 C:integral to peroxisomal membrane
GO:0005624 C:membrane fraction
GO:0005515 F:protein binding
GO:0021795 P:cerebral cortex cell migration
GO:0001561 P:fatty acid alpha-oxidation
GO:0007626 P:locomotory behavior
GO:0060152 P:microtubule-based peroxisome localization
GO:0001764 P:neuron migration
GO:0016560 P:protein import into peroxisome matrix, docking
GO:0001967 P:suckling behavior

References (9)

[1] “Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import.”  Fransen M.et.al.   9653144
[2] “Isolation, characterization and mutation analysis of PEX13-defective Chinese hamster ovary cell mutants.”  Toyama R.et.al.   10441330
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor.”  Gould S.J.et.al.   8858165
[6] “PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.”  Sacksteder K.A.et.al.   10704444
[7] “Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences.”  Fransen M.et.al.   11390669
[8] “PEX13 is mutated in complementation group 13 of the peroxisome-biogenesis disorders.”  Liu Y.et.al.   10441568
[9] “Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders.”  Shimozawa N.et.al.   10332040

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MASQPPPPPK PWETRRIPGA GPGPGPGPTF QSADLGPTLM TRPGQPALTR VPPPILPRPS 
61:	QQTGSSSVNT FRPAYSSFSS GYGAYGNSFY GGYSPYSYGY NGLGYNRLRV DDLPPSRFVQ 
121:	QAEESSRGAF QSIESIVHAF ASVSMMMDAT FSAVYNSFRA VLDVANHFSR LKIHFTKVFS 
181:	AFALVRTIRY LYRRLQRMLG LRRGSENEDL WAESEGTVAC LGAEDRAATS AKSWPIFLFF 
241:	AVILGGPYLI WKLLSTHSDE VTDSINWASG EDDHVVARAE YDFAAVSEEE ISFRAGDMLN 
301:	LALKEQQPKV RGWLLASLDG QTTGLIPANY VKILGKRKGR KTVESSKVSK QQQSFTNPTL 
361:	TKGATVADSL DEQEAAFESV FVETNKVPVA PDSIGKDGEK QDL