Class I peroxisomal membrane protein import (Homo sapiens)

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3-5, 7, 8, 10...1, 6, 9-11, 16...16, 22, 382, 10, 11, 14, 18...7, 11, 26, 32, 43peroxisomal matrixcytosolperoxisomal membranePEX16:PEX19:PEX3GDAP1 PEX16 PXMP4 PEX16 FIS1 PEX2 Class I PeroxisomalMembrane ProteinsPEX12 PEX13 SLC25A17 PEX19 PEX12 FIS1 ABCD2 SLC25A17 ALDH3A2-2 ATAD1 PXMP2 PEX16ALDH3A2-2 PEX19 ACBD5 PEX3ALDH3A2-2 PEX11B PEX19 ABCD1 PEX14 Class I PeroxisomalMembrane ProteinsPEX16 PEX16 PEX11B PEX26 PEX12 PEX14 FIS1 PXMP2 ABCD1 PEX19PEX3 GDAP1 ABCD1 PEX3 PEX3PEX14 PEX13 PEX11B PXMP4 GDAP1 PXMP4 PEX2 ABCD3 ABCD2 ACBD5 PEX11B ATAD1 ATAD1 PEX19:PEX3FIS1 PEX3:PEX19:class IPMPACBD5 ABCD1 ACBD5 PEX16 PEX13 ABCD2 PXMP2 SLC25A17 ALDH3A2-2 ABCD2 PEX12 PEX13 PEX2 PEX2 PEX3 GDAP1 PEX26 PEX19:class I PMPABCD3 PXMP2 PEX26 ABCD3 PEX14 SLC25A17 PXMP4 PEX19 ABCD3 PEX26 ATAD1 1, 6, 9, 10, 16...15341, 6, 9, 10, 16...


Description

Most peroxisomal membrane proteins (PMPs) are inserted into the peroxisomal membrane by the receptor-chaperone PEX19 and the docking receptor PEX3 (Soukupova et al. 1999, Muntau et al. 2003, Fang et al. 2004, Fujiki et al. 2006, Matsuzono and Fujiki 2006, Matsuzono et al. 2006, Pinto et al. 2006, Sato et al. 2008, Sato et al. 2010, Schmidt et al. 2010, Hattula et al. 2014, reviewed in Fujiki et al. 2014, Mayerhofer 2016). PEX19 binds the PMP as it is translated in the cytosol. Recognition of the PMP by PEX 19 appears to depend on positively charged residues in the transmembrane domain of the PMP (Costello et al. 2017). The PEX19:PMP complex then interacts with PEX3 located in the peroxisomal membrane. Through a mechanism that is not yet clear, the PMP is inserted into the peroxisomal membrane and PEX19 dissociates from PEX3. A current model involves transfer of the PMP from PEX19 to a hydrophobic region of PEX3 followed by insertion of the PMP into the membrane (Chen et al. 2014, reviewed by Giannopoulou et al. 2016). The process does not appear to require hydrolysis of ATP or GTP (Pinto et al. 2006).
Unlike other PMPs, PEX3 is inserted into the peroxisomal membrane by binding PEX19 and then docking with PEX16 (Matsuzaki and Fujiki 2008). Both PEX3 and PEX16 can also be co-translationally inserted into the endoplasmic reticulum membrane (Kim et al. 2006, Yonekawa et al. 2011, Aranovich et al. 2014, Hua et al. 2015, Mayerhofer et al. 2016). This region of the ER membrane then buds to contribute to new peroxisomes. PEX3 is also observed to insert into the mitochondrial outer membrane (Sugiura et al. 2017). Regions of the ER membrane and mitochondrial outer membrane are then released to form pre-peroxisomal vesicles which fuse to form new peroxisomes (Sugiura et al. 2017). Peroxisomes therefore appear to arise from fission of existing peroxisomes and production of new peroxisomes from precursors derived from mitochondria and the ER (Sugiura et al. 2017, reviewed in Fujiki et al. 2014, Hua and Kim 2016). View original pathway at Reactome.

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Pathway is converted from Reactome ID: 9603798
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Reactome version: 75
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Reactome Author: May, Bruce

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Bibliography

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  1. Biermanns M, von Laar J, Brosius U, Gärtner J.; ''The peroxisomal membrane targeting elements of human peroxin 2 (PEX2).''; PubMed Europe PMC Scholia
  2. Schmidt F, Dietrich D, Eylenstein R, Groemping Y, Stehle T, Dodt G.; ''The role of conserved PEX3 regions in PEX19-binding and peroxisome biogenesis.''; PubMed Europe PMC Scholia
  3. Mayerhofer PU, Bañó-Polo M, Mingarro I, Johnson AE.; ''Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER in Budding Vesicles.''; PubMed Europe PMC Scholia
  4. Sugiura A, Mattie S, Prudent J, McBride HM.; ''Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes.''; PubMed Europe PMC Scholia
  5. Hua R, Kim PK.; ''Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals.''; PubMed Europe PMC Scholia
  6. Jones JM, Morrell JC, Gould SJ.; ''Multiple distinct targeting signals in integral peroxisomal membrane proteins.''; PubMed Europe PMC Scholia
  7. Chen Y, Pieuchot L, Loh RA, Yang J, Kari TM, Wong JY, Jedd G.; ''Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins.''; PubMed Europe PMC Scholia
  8. Aranovich A, Hua R, Rutenberg AD, Kim PK.; ''PEX16 contributes to peroxisome maintenance by constantly trafficking PEX3 via the ER.''; PubMed Europe PMC Scholia
  9. Jones JM, Morrell JC, Gould SJ.; ''PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.''; PubMed Europe PMC Scholia
  10. Pinto MP, Grou CP, Alencastre IS, Oliveira ME, Sá-Miranda C, Fransen M, Azevedo JE.; ''The import competence of a peroxisomal membrane protein is determined by Pex19p before the docking step.''; PubMed Europe PMC Scholia
  11. Fujiki Y, Matsuzono Y, Matsuzaki T, Fransen M, Fransen M.; ''Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions.''; PubMed Europe PMC Scholia
  12. Fujiki Y, Okumoto K, Mukai S, Honsho M, Tamura S.; ''Peroxisome biogenesis in mammalian cells.''; PubMed Europe PMC Scholia
  13. Giannopoulou EA, Emmanouilidis L, Sattler M, Dodt G, Wilmanns M.; ''Towards the molecular mechanism of the integration of peroxisomal membrane proteins.''; PubMed Europe PMC Scholia
  14. Sato Y, Shibata H, Nakatsu T, Nakano H, Kashiwayama Y, Imanaka T, Kato H.; ''Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.''; PubMed Europe PMC Scholia
  15. Rizzo WB, Lin Z, Carney G.; ''Fatty aldehyde dehydrogenase: genomic structure, expression and mutation analysis in Sjögren-Larsson syndrome.''; PubMed Europe PMC Scholia
  16. Fransen M, Wylin T, Brees C, Mannaerts GP, Van Veldhoven PP.; ''Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences.''; PubMed Europe PMC Scholia
  17. Yagita Y, Hiromasa T, Fujiki Y.; ''Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway.''; PubMed Europe PMC Scholia
  18. Sato Y, Shibata H, Nakano H, Matsuzono Y, Kashiwayama Y, Kobayashi Y, Fujiki Y, Imanaka T, Kato H.; ''Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p: identification of TRP-104 IN Pex3p as a critical residue for the interaction.''; PubMed Europe PMC Scholia
  19. Brosius U, Dehmel T, Gärtner J.; ''Two different targeting signals direct human peroxisomal membrane protein 22 to peroxisomes.''; PubMed Europe PMC Scholia
  20. Vastiau IM, Anthonio EA, Brams M, Brees C, Young SG, Van de Velde S, Wanders RJ, Mannaerts GP, Baes M, Van Veldhoven PP, Fransen M.; ''Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells.''; PubMed Europe PMC Scholia
  21. Matsuzaki T, Fujiki Y.; ''The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p- and Pex16p-dependent pathway.''; PubMed Europe PMC Scholia
  22. Fransen M, Fransen M, Vastiau I, Brees C, Brys V, Mannaerts GP, Van Veldhoven PP.; ''Analysis of human Pex19p's domain structure by pentapeptide scanning mutagenesis.''; PubMed Europe PMC Scholia
  23. Götte K, Girzalsky W, Linkert M, Baumgart E, Kammerer S, Kunau WH, Erdmann R.; ''Pex19p, a farnesylated protein essential for peroxisome biogenesis.''; PubMed Europe PMC Scholia
  24. Mayerhofer PU.; ''Targeting and insertion of peroxisomal membrane proteins: ER trafficking versus direct delivery to peroxisomes.''; PubMed Europe PMC Scholia
  25. Liu Y, Yagita Y, Fujiki Y.; ''Assembly of Peroxisomal Membrane Proteins via the Direct Pex19p-Pex3p Pathway.''; PubMed Europe PMC Scholia
  26. Matsuzono Y, Fujiki Y.; ''In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p.''; PubMed Europe PMC Scholia
  27. Hua R, Gidda SK, Aranovich A, Mullen RT, Kim PK.; ''Multiple Domains in PEX16 Mediate Its Trafficking and Recruitment of Peroxisomal Proteins to the ER.''; PubMed Europe PMC Scholia
  28. Muntau AC, Roscher AA, Kunau WH, Dodt G.; ''The interaction between human PEX3 and PEX19 characterized by fluorescence resonance energy transfer (FRET) analysis.''; PubMed Europe PMC Scholia
  29. Yonekawa S, Furuno A, Baba T, Fujiki Y, Ogasawara Y, Yamamoto A, Tagaya M, Tani K.; ''Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells.''; PubMed Europe PMC Scholia
  30. Halbach A, Lorenzen S, Landgraf C, Volkmer-Engert R, Erdmann R, Rottensteiner H.; ''Function of the PEX19-binding site of human adrenoleukodystrophy protein as targeting motif in man and yeast. PMP targeting is evolutionarily conserved.''; PubMed Europe PMC Scholia
  31. Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ.; ''PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.''; PubMed Europe PMC Scholia
  32. Fang Y, Morrell JC, Jones JM, Gould SJ.; ''PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins.''; PubMed Europe PMC Scholia
  33. Kim PK, Mullen RT, Schumann U, Lippincott-Schwartz J.; ''The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER.''; PubMed Europe PMC Scholia
  34. Delille HK, Schrader M.; ''Targeting of hFis1 to peroxisomes is mediated by Pex19p.''; PubMed Europe PMC Scholia
  35. Biermanns M, Gärtner J.; ''Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal integral membrane protein (PMP70) to peroxisomes.''; PubMed Europe PMC Scholia
  36. Huber N, Guimaraes S, Schrader M, Suter U, Niemann A.; ''Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission.''; PubMed Europe PMC Scholia
  37. Hattula K, Hirschberg D, Kalkkinen N, Butcher SJ, Ora A.; ''Association between the intrinsically disordered protein PEX19 and PEX3.''; PubMed Europe PMC Scholia
  38. Soukupova M, Sprenger C, Gorgas K, Kunau WH, Dodt G.; ''Identification and characterization of the human peroxin PEX3.''; PubMed Europe PMC Scholia
  39. Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC.; ''Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly.''; PubMed Europe PMC Scholia
  40. Matsuzono Y, Matsuzaki T, Fujiki Y.; ''Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential for function and translocation.''; PubMed Europe PMC Scholia
  41. Schmidt F, Treiber N, Zocher G, Bjelic S, Steinmetz MO, Kalbacher H, Stehle T, Dodt G.; ''Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19.''; PubMed Europe PMC Scholia
  42. Costello JL, Castro IG, Camões F, Schrader TA, McNeall D, Yang J, Giannopoulou EA, Gomes S, Pogenberg V, Bonekamp NA, Ribeiro D, Wilmanns M, Jedd G, Islinger M, Schrader M.; ''Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells.''; PubMed Europe PMC Scholia
  43. Schueller N, Holton SJ, Fodor K, Milewski M, Konarev P, Stanley WA, Wolf J, Erdmann R, Schliebs W, Song YH, Wilmanns M.; ''The peroxisomal receptor Pex19p forms a helical mPTS recognition domain.''; PubMed Europe PMC Scholia
  44. Emmanouilidis L, Schütz U, Tripsianes K, Madl T, Radke J, Rucktäschel R, Wilmanns M, Schliebs W, Erdmann R, Sattler M.; ''Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
114795view16:29, 25 January 2021ReactomeTeamReactome version 75
113239view11:30, 2 November 2020ReactomeTeamReactome version 74
112803view17:59, 9 October 2020DeSlOntology Term : 'cellular trafficking cycle pathway' added !
112753view16:15, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABCD1 ProteinP33897 (Uniprot-TrEMBL)
ABCD2 ProteinQ9UBJ2 (Uniprot-TrEMBL)
ABCD3 ProteinP28288 (Uniprot-TrEMBL)
ACBD5 ProteinQ5T8D3 (Uniprot-TrEMBL)
ALDH3A2-2 ProteinP51648-2 (Uniprot-TrEMBL)
ATAD1 ProteinQ8NBU5 (Uniprot-TrEMBL)
Class I Peroxisomal Membrane ProteinsComplexR-HSA-9603783 (Reactome)
Class I Peroxisomal Membrane ProteinsComplexR-HSA-9603802 (Reactome)
FIS1 ProteinQ9Y3D6 (Uniprot-TrEMBL)
GDAP1 ProteinQ8TB36 (Uniprot-TrEMBL)
PEX11B ProteinO96011 (Uniprot-TrEMBL)
PEX12 ProteinO00623 (Uniprot-TrEMBL)
PEX13 ProteinQ92968 (Uniprot-TrEMBL)
PEX14 ProteinO75381 (Uniprot-TrEMBL)
PEX16 ProteinQ9Y5Y5 (Uniprot-TrEMBL)
PEX16:PEX19:PEX3ComplexR-HSA-9603800 (Reactome)
PEX16ProteinQ9Y5Y5 (Uniprot-TrEMBL)
PEX19 ProteinP40855 (Uniprot-TrEMBL)
PEX19:PEX3ComplexR-HSA-9603799 (Reactome)
PEX19:class I PMPComplexR-HSA-9603787 (Reactome)
PEX19ProteinP40855 (Uniprot-TrEMBL)
PEX2 ProteinP28328 (Uniprot-TrEMBL)
PEX26 ProteinQ7Z412 (Uniprot-TrEMBL)
PEX3 ProteinP56589 (Uniprot-TrEMBL)
PEX3:PEX19:class I PMPComplexR-HSA-9603793 (Reactome)
PEX3ProteinP56589 (Uniprot-TrEMBL)
PXMP2 ProteinQ9NR77 (Uniprot-TrEMBL)
PXMP4 ProteinQ9Y6I8 (Uniprot-TrEMBL)
SLC25A17 ProteinO43808 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
Class I Peroxisomal Membrane ProteinsArrowR-HSA-9603775 (Reactome)
Class I Peroxisomal Membrane ProteinsR-HSA-9603804 (Reactome)
PEX16:PEX19:PEX3ArrowR-HSA-9603797 (Reactome)
PEX16:PEX19:PEX3R-HSA-9603791 (Reactome)
PEX16ArrowR-HSA-9603791 (Reactome)
PEX16R-HSA-9603797 (Reactome)
PEX19:PEX3ArrowR-HSA-9603801 (Reactome)
PEX19:PEX3R-HSA-9603797 (Reactome)
PEX19:class I PMPArrowR-HSA-9603804 (Reactome)
PEX19:class I PMPR-HSA-9603784 (Reactome)
PEX19ArrowR-HSA-9603775 (Reactome)
PEX19ArrowR-HSA-9603791 (Reactome)
PEX19R-HSA-9603801 (Reactome)
PEX19R-HSA-9603804 (Reactome)
PEX3:PEX19:class I PMPArrowR-HSA-9603784 (Reactome)
PEX3:PEX19:class I PMPR-HSA-9603775 (Reactome)
PEX3ArrowR-HSA-9603775 (Reactome)
PEX3ArrowR-HSA-9603791 (Reactome)
PEX3R-HSA-9603784 (Reactome)
PEX3R-HSA-9603801 (Reactome)
R-HSA-9603775 (Reactome) The PEX19:PEX3:peroxisomal membrane protein complex dissociates, yielding cytosolic PEX19, membrane-bound PEX3, and the peroxisomal membrane protein inserted in the peroxisomal membrane (Fang et al. 2004, Matsuzono and Fujiki 2006, Schueller et al. 2010, Chen et al. 2014, reviewed in Fujiki et al. 2006). The mechanism of the reaction is not fully characterized. One current model posits the transfer of the peroxisomal membrane protein from a hydrophobic region of PEX19 to a hydrophobic region of PEX3 followed by intervention in the membrane layer to release the peroxisomal membrane protein into the membrane bilayer (Chen et al. 2014). An amphipathic helical segment in the N-terminal region of PEX19 may compete with the peroxisomal membrane protein for a binding site in the C-terminal region of PEX19 and thereby participate in the release of the peroxisomal membrane protein from PEX19 (Schueller et al. 2010).
R-HSA-9603784 (Reactome) Cytosolic PEX19 bound to a peroxisomal membrane protein binds PEX3 which is located in the peroxisomal membrane and serves as a docking receptor for PEX19 (Soukupova et al. 1999, Muntau et al. 2003, Fang et al. 2004, Matsuzono and Fujiki 2006, Matsuzono et al. 2006, Pinto et al. 2006, Sato et al. 2008, Sato et al. 2010, Schmidt et al. 2010, Hattula et al. 2014, reviewed in Fujiki et al. 2006). PEX19 bound to a cargo protein has much higher affinity for PEX3 than PEX19 alone does (Pinto et al. 2006). The insertion of the peroxisomal membrane protein into the membrane does not require ATP hydrolysis or GTP hydrolysis (Pinto et al. 2006). The N-terminal region of PEX19 binds a hydrophobic groove and acidic cluster on the surface of PEX3 (Schmidt et al. 2010, Schmidt et al. 2012) at the cytosolic apex of the PEX3 spheroid (Sato et al. 2010).
R-HSA-9603791 (Reactome) The PEX16:PEX19:PEX3 complex dissociates, yielding cytosolic PEX19 and PEX3 and PEX16 inserted in the membrane (inferred from human PEX16, human PEX19, and rat PEX3).
R-HSA-9603797 (Reactome) The cytosolic PEX19:PEX3 complex binds PEX16 located in the peroxisomal membrane (inferred from human PEX19, human PEX16, and rat Pex3). Thus PEX16 serves as a docking factor. PEX3 is believed to be inserted in the peroxisomal membrane by this pathway and by direct co-translational insertion in the membrane of the endoplasmic reticulum that then buds to generate peroxisomes.
R-HSA-9603801 (Reactome) In the cytosol, PEX19 binds to newly translated PEX3 (inferred from human PEX19 binding rat Pex3). PEX19 binds the C-terminal region of PEX3 and the membrane targeting signal of PEX3 is located in the N-terminal region (Soukupova et al. 1999, Fransen et al. 2001, Fransen et al. 2005).
R-HSA-9603804 (Reactome) In the cytosol, PEX19 binds newly synthesized class I peroxisomal membrane proteins (Sacksteder et al. 2000, Fransen et al. 2001, Jones et al. 2004, reviewed in Fujiki et al. 2006). The C-terminal region and a conserved N-terminal helical segment of PEX19 bind to peroxisomal membrane proteins (Fransen et al. 2005, Schueller et al. 2010) and PEX19 acts both as a chaperone and as an import receptor (Jones et al. 2004). PEX19 is farnesylated (Götte et al. 1998, Sacksteder et al. 2000, Vastiau et al. 2006) and the farnesyl group is buried in a hydrophobic cavity which alters the conformation of PEX19 to yield two hydrophobic pockets involved in binding peroxisomal membrane proteins (Emmanouilidis et al. 2017). The number of positively charged amino acid residues in the transmembrane domain of the PMP appears to determine binding by PEX19 and, hence, targeting to the peroxisomal membrane protein (Costello et al. 2017).
Class I membrane proteins are inserted into the peroxisomal membrane after peroxisomal progenitors have budded from the endoplasmic reticulum (Jones et al. 2004). Human class I peroxisomal membrane proteins that are bound by PEX19 include PEX10 (Sacksteder et al. 2000), PEX11B (Fransen et al. 2005), PEX12 (Sacksteder et al. 2000, Fransen et al. 2001, Fransen et al. 2005), PEX13 (Sacksteder et al. 2000, Fransen et al. 2001, Fransen et al. 2005, Vastiau et al. 2006, Liu et al. 2016), PEX14 (Sacksteder et al. 2000, Fransen et al. 2005, Vastiau et al. 2006), PEX16 (Fransen et al. 2001, Fransen et al. 2005, Matsuzono and Fujiki 2006, Schueller et al. 2010, Yagita et al. 2013, Liu et al. 2016), ), PEX26 (Fransen et al. 2005, Matsuzono and Fujiki 2006), ABCD1 (ALDP, Mayerhofer et al. 2002, Halbach et al. 2005), ABCD2 (ALDRP, Mayerhofer et al. 2002), ABCD3 (PMP70, Sacksteder et al. 2000, Mayerhofer et al. 2002), PXMP2 (PMP22, Jones et al. 2001, Brosius et al. 2002), PXMP4 (PMP24, Pinto et al. 2006), SLC25A17 (PMP34, Sacksteder et al. 2000, Liu et al. 2016), ATAD1 (Liu et al. 2016), FIS1 (Delille and Schrader 2008), and GDAP1 (Huber et al. 2013).
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