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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:Q13608
Protein Name:Peroxisome assembly factor 2
Length:980
Molecular Weight:104061.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Cytoplasm1
Substrate protein polypeptide chain

Cross database links:

RefSeq: NP_000278.3   
Entrez Gene ID: 5190   
Pfam: PF00004   
OMIM: 214100  phenotype
601498  gene+phenotype
601539  phenotype
KEGG: hsa:5190   

Gene Ontology

GO:0005829 C:cytosol
GO:0005778 C:peroxisomal membrane
GO:0005524 F:ATP binding
GO:0042623 F:ATPase activity, coupled
GO:0008022 F:protein C-terminus binding
GO:0032403 F:protein complex binding
GO:0016561 P:protein import into peroxisome matrix, tran...
GO:0050821 P:protein stabilization

References (7)

[1] “The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor.”  Yahraus T.et.al.   8670792
[2] “Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans.”  Fukuda S.et.al.   8940266
[3] “Genomic structure and identification of 11 novel mutations of the PEX6 'peroxisome assembly factor-2' gene in patients with peroxisome biogenesis disorders.”  Zhang Z.et.al.   10408779
[4] “The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6.”  Matsumoto N.et.al.   11355018
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes.”  Matsumoto N.et.al.   12717447
[7] “Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.”  Yik W.Y.et.al.   19105186

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FASTA formatted sequence
1:	MALAVLRVLE PFPTETPPLA VLLPPGGPWP AAELGLVLAL RPAGESPAGP ALLVAALEGP 
61:	DAGTEEQGPG PPQLLVSRAL LRLLALGSGA WVRARAVRRP PALGWALLGT SLGPGLGPRV 
121:	GPLLVRRGET LPVPGPRVLE TRPALQGLLG PGTRLAVTEL RGRARLCPES GDSSRPPPPP 
181:	VVSSFAVSGT VRRLQGVLGG TGDSLGVSRS CLRGLGLFQG EWVWVAQARE SSNTSQPHLA 
241:	RVQVLEPRWD LSDRLGPGSG PLGEPLADGL ALVPATLAFN LGCDPLEMGE LRIQRYLEGS 
301:	IAPEDKGSCS LLPGPPFARE LHIEIVSSPH YSTNGNYDGV LYRHFQIPRV VQEGDVLCVP 
361:	TIGQVEILEG SPEKLPRWRE MFFKVKKTVG EAPDGPASAY LADTTHTSLY MVGSTLSPVP 
421:	WLPSEESTLW SSLSPPGLEA LVSELCAVLK PRLQPGGALL TGTSSVLLRG PPGCGKTTVV 
481:	AAACSHLGLH LLKVPCSSLC AESSGAVETK LQAIFSRARR CRPAVLLLTA VDLLGRDRDG 
541:	LGEDARVMAV LRHLLLNEDP LNSCPPLMVV ATTSRAQDLP ADVQTAFPHE LEVPALSEGQ 
601:	RLSILRALTA HLPLGQEVNL AQLARRCAGF VVGDLYALLT HSSRAACTRI KNSGLAGGLT 
661:	EEDEGELCAA GFPLLAEDFG QALEQLQTAH SQAVGAPKIP SVSWHDVGGL QEVKKEILET 
721:	IQLPLEHPEL LSLGLRRSGL LLHGPPGTGK TLLAKAVATE CSLTFLSVKG PELINMYVGQ 
781:	SEENVREVFA RARAAAPCII FFDELDSLAP SRGRSGDSGG VMDRVVSQLL AELDGLHSTQ 
841:	DVFVIGATNR PDLLDPALLR PGRFDKLVFV GANEDRASQL RVLSAITRKF KLEPSVSLVN 
901:	VLDCCPPQLT GADLYSLCSD AMTAALKRRV HDLEEGLEPG SSALMLTMED LLQAAARLQP 
961:	SVSEQELLRY KRIQRKFAAC