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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:O43933
Protein Name:Peroxisome biogenesis factor 1
Length:1283
Molecular Weight:142867.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Cytoplasm1
Substrate protein polypeptide chain

Cross database links:

RefSeq: NP_000457.1   
Entrez Gene ID: 5189   
Pfam: PF00004    PF09262    PF09263   
OMIM: 202370  phenotype
266510  phenotype
601539  phenotype
602136  gene+phenotype
KEGG: hsa:5189   

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:0060152 P:microtubule-based peroxisome localization
GO:0016558 P:protein import into peroxisome matrix

References (13)

[1] “Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.”  Portsteffen H.et.al.   9398848
[2] “Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.”  Reuber B.E.et.al.   9398847
[3] “Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.”  Tamura S.et.al.   9539740
[4] “Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction.”  Tamura S.et.al.   11439091
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “Human chromosome 7: DNA sequence and biology.”  Scherer S.W.et.al.   12690205
[7] “The DNA sequence of human chromosome 7.”  Hillier L.W.et.al.   12853948
[8] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[9] “The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes.”  Matsumoto N.et.al.   12717447
[10] “Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry.”  Denis N.J.et.al.   17370265
[11] “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.”  Matsuoka S.et.al.   17525332
[12] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330
[13] “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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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MWGSDRLAGA GGGGAAVTVA FTNARDCFLH LPRRLVAQLH LLQNQAIEVV WSHQPAFLSW 
61:	VEGRHFSDQG ENVAEINRQV GQKLGLSNGG QVFLKPCSHV VSCQQVEVEP LSADDWEILE 
121:	LHAVSLEQHL LDQIRIVFPK AIFPVWVDQQ TYIFIQIVAL IPAASYGRLE TDTKLLIQPK 
181:	TRRAKENTFS KADAEYKKLH SYGRDQKGMM KELQTKQLQS NTVGITESNE NESEIPVDSS 
241:	SVASLWTMIG SIFSFQSEKK QETSWGLTEI NAFKNMQSKV VPLDNIFRVC KSQPPSIYNA 
301:	SATSVFHKHC AIHVFPWDQE YFDVEPSFTV TYGKLVKLLS PKQQQSKTKQ NVLSPEKEKQ 
361:	MSEPLDQKKI RSDHNEEDEK ACVLQVVWNG LEELNNAIKY TKNVEVLHLG KVWIPDDLRK 
421:	RLNIEMHAVV RITPVEVTPK IPRSLKLQPR ENLPKDISEE DIKTVFYSWL QQSTTTMLPL 
481:	VISEEEFIKL ETKDGLKEFS LSIVHSWEKE KDKNIFLLSP NLLQKTTIQV LLDPMVKEEN 
541:	SEEIDFILPF LKLSSLGGVN SLGVSSLEHI THSLLGRPLS RQLMSLVAGL RNGALLLTGG 
601:	KGSGKSTLAK AICKEAFDKL DAHVERVDCK ALRGKRLENI QKTLEVAFSE AVWMQPSVVL 
661:	LDDLDLIAGL PAVPEHEHSP DAVQSQRLAH ALNDMIKEFI SMGSLVALIA TSQSQQSLHP 
721:	LLVSAQGVHI FQCVQHIQPP NQEQRCEILC NVIKNKLDCD INKFTDLDLQ HVAKETGGFV 
781:	ARDFTVLVDR AIHSRLSRQS ISTREKLVLT TLDFQKALRG FLPASLRSVN LHKPRDLGWD 
841:	KIGGLHEVRQ ILMDTIQLPA KYPELFANLP IRQRTGILLY GPPGTGKTLL AGVIARESRM 
901:	NFISVKGPEL LSKYIGASEQ AVRDIFIRAQ AAKPCILFFD EFESIAPRRG HDNTGVTDRV 
961:	VNQLLTQLDG VEGLQGVYVL AATSRPDLID PALLRPGRLD KCVYCPPPDQ VSRLEILNVL 
1021:	SDSLPLADDV DLQHVASVTD SFTGADLKAL LYNAQLEALH GMLLSSGLQD GSSSSDSDLS 
1081:	LSSMVFLNHS SGSDDSAGDG ECGLDQSLVS LEMSEILPDE SKFNMYRLYF GSSYESELGN 
1141:	GTSSDLSSQC LSAPSSMTQD LPGVPGKDQL FSQPPVLRTA SQEGCQELTQ EQRDQLRADI 
1201:	SIIKGRYRSQ SGEDESMNQP GPIKTRLAIS QSHLMTALGH TRPSISEDDW KNFAELYESF 
1261:	QNPKRRKNQS GTMFRPGQKV TLA