BioPAX pathway converted from "Protein localization" in the Reactome database.

Protein localization

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Mitochondrial protein import Mitochondrial protein import This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp PITRM1 proteolyzes mitochondrial targeting peptides (presequences) PITRM1 proteolyzes mitochondrial targeting peptides (presequences) This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 10637917 1 mitochondrial matrix GO 0005759 Mitochondrial targeting peptides (from inner membrane proteins) [mitochondrial matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity NDUFB8(1-28) [mitochondrial matrix] Reactome //www.joaskin.com Caenorhabditis elegans NCBI Taxonomy 6239 UniProt Q9XWJ5 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10637922 UniProt:Q22370 ucr-2.2 UniProt Q22370 Chain Coordinates 16 EQUAL 1037 EQUAL GO 0008237 GO molecular function Reactome Database ID Release 77 10637923 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637923 Reactome Database ID Release 77 10637925 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637925 Reactome R-CEL-8986181 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8986181.1 After MPP cleaves off targeting peptides (also called presequences) of proteins imported into the mitochondrial matrix, PITRM1 (also called PreP) proteolyzes the cleaved targeting peptides (Pinho et al. 2010, Alikhani et al. 2011, Teixeira et al. 2012). PITRM1 also cleaves amyloid beta peptide that is imported into the matrix (Falkevall et al. 2006). Missense mutations in PITRM1 are associated with a neurological syndrome comprising mental retardation, spinocerebellar ataxia, cognitive decline, psychosis and possible epilepsy (Brunetti et al. 2016). 21750375 Pubmed 2011 Decreased proteolytic activity of the mitochondrial amyloid-β degrading enzyme, PreP peptidasome, in Alzheimer's disease brain mitochondria Alikhani, Nyosha Guo, Lan Yan, Shiqiang Du, Heng Pinho, Catarina Moreira Chen, John Xi Glaser, Elzbieta Yan, Shirley ShiDu J. Alzheimers Dis. 27:75-87 23041349 Pubmed 2012 In vitro oxidative inactivation of human presequence protease (hPreP) Teixeira, Pedro Filipe Pinho, Catarina Moreira Branca, Rui M Lehtiö, Janne Levine, Rodney L Glaser, Elzbieta Free Radic. Biol. Med. 53:2188-95 26697887 Pubmed 2016 Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration Brunetti, Dario Torsvik, Janniche Dallabona, Cristina Teixeira, Pedro Sztromwasser, Pawel Fernandez-Vizarra, Erika Cerutti, Raffaele Reyes, Aurelio Preziuso, Carmela D'Amati, Giulia Baruffini, Enrico Goffrini, Paola Viscomi, Carlo Ferrero, Ileana Boman, Helge Telstad, Wenche Johansson, Stefan Glaser, Elzbieta Knappskog, Per M Zeviani, Massimo Bindoff, Laurence A EMBO Mol Med 8:176-90 19962426 Pubmed 2010 Genetic and biochemical studies of SNPs of the mitochondrial A beta-degrading protease, hPreP Pinho, Catarina Moreira Björk, Behnosh F Alikhani, Nyosha Bäckman, Hans G Eneqvist, Therese Fratiglioni, Laura Glaser, Elzbieta Graff, Caroline Neurosci. Lett. 469:204-8 16849325 Pubmed 2006 11月的淀粉样β蛋白的降解el mitochondrial peptidasome, PreP Falkevall, Annelie Alikhani, Nyosha Bhushan, Shashi Pavlov, Pavel F Busch, Katrin Johnson, Kenneth A Eneqvist, Therese Tjernberg, Lars Ankarcrona, Maria Glaser, Elzbieta J. Biol. Chem. 281:29096-104 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10643174 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10643174 Reactome R-CEL-1268020 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1268020.1 GO 0006626 GO biological process A human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four locations (outer membrane, intermembrane space, inner membrane, and matrix) and must be sorted accordingly (reviewed in Kutik et al. 2007, Milenkovic et al. 2007, Bolender et al. 2008, Endo and Yamano 2009, Wiedemann and Pfanner 2017, Kang et al. 2018). Newly synthesized proteins are transported from the cytosol across the outer membrane by the TOMM40:TOMM70 complex. Proteins that contain presequences first interact with the TOMM20 subunit of the complex while proteins that contain internal targeting elements first interact with the TOMM70 subunit. After initial interaction the protein is conducted across the outer membrane by TOMM40 subunits. In yeast some proteins such as Aco1, Atp1, Cit1, Idh1, and Atp2 have both presequences that interact with TOM20 and mature regions that interact with TOM70 (Yamamoto et al. 2009).
After passage across the outer membrane, proteins may be targeted to the outer membrane via the SAMM50 complex, to the inner membrane via the TIMM22 or TIMM23 complexes (reviewed in van der Laan et al. 2010), to the matrix via the TIMM23 complex (reviewed in van der Laan et al. 2010), or proteins may fold and remain in the intermembrane space (reviewed in Stojanovski et al. 2008, Deponte and Hell 2009, Sideris and Tokatlidis 2010). Presequences on matrix and inner membrane proteins cause interaction with TIMM23 complexes; internal targeting sequences cause outer membrane proteins to interact with the SAMM50 complex and inner membrane proteins to interact with the TIMM22 complex. While in the intermembrane space hydrophobic proteins are chaperoned by the TIMM8:TIMM13 complex and/or the TIMM9:TIMM10:FXC1 complex. 17998403 Pubmed 2007 Cooperation of translocase complexes in mitochondrial protein import Kutik, S Guiard, B Meyer, HE Wiedemann, N Pfanner, N J Cell Biol 179:585-91 20100523 Pubmed 2010 On the mechanism of preprotein import by the mitochondrial presequence translocase van der Laan, M Hutu, DP Rehling, P Biochim Biophys Acta 1803:732-9 19767391 Pubmed 2009 Roles of Tom70 in import of presequence-containing mitochondrial proteins Yamamoto, H Fukui, Kiyoshi Takahashi, H Kitamura, S Shiota, T Terao, K Uchida, M Esaki, M Nishikawa, S Yoshihisa, T Yamano, K Endo, T J Biol Chem 284:31635-46 17996737 Pubmed 2008 The MIA system for protein import into the mitochondrial intermembrane space Stojanovski, D Müller, JM Milenkovic, D Guiard, B Pfanner, N Chacinska, A Biochim Biophys Acta 1783:610-7 28301740 Pubmed 2017 Mitochondrial Machineries for Protein Import and Assembly Wiedemann, Nils Pfanner, Nikolaus Annu. Rev. Biochem. 86:685-714 19453276 Pubmed 2009 Multiple pathways for mitochondrial protein traffic Endo, T Yamano, K Biol Chem 390:723-30 17696772 Pubmed 2007 Diverse mechanisms and machineries for import of mitochondrial proteins Milenkovic, D Müller, J Stojanovski, D Pfanner, N Chacinska, A Biol Chem 388:891-7 20214493 Pubmed 2010 Oxidative protein folding in the mitochondrial intermembrane space Sideris, DP Tokatlidis, K Antioxid Redox Signal 13:1189-204 19720617 Pubmed 2009 Disulphide bond formation in the intermembrane space of mitochondria Deponte, M Hell, K J Biochem 146:599-608 18174896 Pubmed 2008 Multiple pathways for sorting mitochondrial precursor proteins Bolender, N Sickmann, A Wagner, R Meisinger, C Pfanner, N EMBO Rep 9:42-9 28765093 Pubmed 2018 Mitochondrial protein transport in health and disease Kang, Yilin Fielden, Laura F Stojanovski, Diana Semin. Cell Dev. Biol. 76:142-153 inferred by electronic annotation IEA GO IEA Peroxisomal protein import Peroxisomal protein import This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module) PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module) This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10638889 1 cytosol GO 0005829 PEX5S,L:Cargo protein [cytosol] PEX5S,L:Cargo protein Converted from EntitySet in Reactome Reactome DB_ID: 10638885 1 Cargo proteins containing PTS1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity acox-1.6 [cytosol] acox-1.1 [cytosol] acs-22 [cytosol] ddo-1 [cytosol] acox-3 [cytosol] maoc-1 [cytosol] ACOT2(1-483) [cytosol] agxt-1 [cytosol] AMACR [cytosol] ACOT4 [cytosol] daf-22 [cytosol] daao-1 [cytosol] idh-1 [cytosol] acs-20 [cytosol] CROT [cytosol] ACOT4 [cytosol] mlcd-1 [cytosol] ACOT4 [cytosol] BAAT [cytosol] ddo-2 [cytosol] dhrs-4 [cytosol] IDE [cytosol] acox-1.2 [cytosol] ACOT2(1-483) [cytosol] PIPOX [cytosol] acox-1.5 [cytosol] acl-7 [cytosol] BAAT [cytosol] daao-1 [cytosol] ECH1(1-328) [cytosol] MPV17 [cytosol] BAAT [cytosol] ctl-3 [cytosol] ACOT2(1-483) [cytosol] HACL1 [cytosol] HAO2 [cytosol] hpo-15 [cytosol] ndx-8 [cytosol] acox-1.6 [cytosol] CRAT [cytosol] HAO1 [cytosol] ACOT8 [cytosol] ndx-7 [cytosol] acox-1.3 [cytosol] ACOT2(1-483) [cytosol] ACOT4 [cytosol] lonp-2 [cytosol] acox-1.4 [cytosol] gstk-2 [cytosol] ddo-3 [cytosol] BAAT [cytosol] ech-8 [cytosol] HMGCL(1-325) [cytosol] UniProt Q93839 UniProt O62140 UniProt Q18916 UniProt O45307 UniProt Q20992 UniProt Q19058 UniProt B3WFZ3 UniProt Q94055 UniProt Q18122 UniProt O01862 UniProt G5EDP2 UniProt Q95XG9 UniProt H9G2T4 UniProt Q19878 UniProt A0A486WVT5 UniProt Q20048 UniProt Q9GYN3 UniProt Q19564 UniProt G5EGA6 UniProt O16249 UniProt O62137 UniProt Q18006 UniProt P34355 UniProt G5EFP8 UniProt O45003 UniProt Q20959 UniProt Q7YWV6 UniProt Q8MYL7 UniProt Q17474 UniProt B1GRK5 UniProt O76383 UniProt Q9NA25 UniProt Q17499 UniProt Q9BIA9 UniProt P91148 UniProt O62138 UniProt Q9XW87 UniProt O62139 UniProt Q18973 UniProt O01739 UniProt O17761 UniProt Q95XN1 Reactome DB_ID: 10638887 1 UniProt:Q18426 prx-5 UniProt Q18426 1 EQUAL 639 EQUAL Reactome Database ID Release 77 10638889 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638889 Reactome R-CEL-9033153 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033153.1 Reactome DB_ID: 10638891 1 peroxisomal membrane GO 0005778 PEX13:PEX14:PEX2:PEX10:PEX12 [peroxisomal membrane] PEX13:PEX14:PEX2:PEX10:PEX12 Reactome DB_ID: 10637150 1 PEX13:PEX14 [peroxisomal membrane] PEX13:PEX14 Reactome DB_ID: 10637143 1 UniProt:Q19951 prx-13 UniProt Q19951 1 EQUAL 403 EQUAL Reactome DB_ID: 10637148 1 UniProt:Q93930 prx-14 UniProt Q93930 2 EQUAL 377 EQUAL Reactome Database ID Release 77 10637150 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637150 Reactome R-CEL-9033095 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033095.1 Reactome DB_ID: 10637169 1 PEX2:PEX10:PEX12 [peroxisomal membrane] PEX2:PEX10:PEX12 Reactome DB_ID: 10637165 1 UniProt:Q19189 prx-12 UniProt Q19189 1 EQUAL 359 EQUAL Reactome DB_ID: 10637167 1 Ghost homologue of PEX2 [peroxisomal membrane] Ghost homologue of PEX2 Reactome DB_ID: 10637160 1 UniProt:Q18355 UniProt Q18355 1 EQUAL 326 EQUAL Reactome Database ID Release 77 10637169 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637169 Reactome R-CEL-8953904 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8953904.1 Reactome Database ID Release 77 10638891 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638891 Reactome R-CEL-9033606 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033606.1 Reactome DB_ID: 10638893 1 PEX5S,L:Cargo:PEX13:PEX14:PEX2:PEX10:PEX12 [peroxisomal membrane] PEX5S,L:Cargo:PEX13:PEX14:PEX2:PEX10:PEX12 Reactome DB_ID: 10638889 1 Reactome DB_ID: 10638891 1 Reactome Database ID Release 77 10638893 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638893 Reactome R-CEL-9033114 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033114.1 Reactome Database ID Release 77 10638925 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638925 Reactome R-CEL-9033236 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033236.1 PEX5S或PEX5L蛋白质包含绑定到货物PTS1 interacts with the Docking and Translocation Module (PEX13:PEX14:PEX2:PEX10:PEX12) (Gould et al. 1996, Fransen et al. 1998, Will et al. 1999, Neufeld et al. 2009, Shiozawa et al. 2009, Freitas et al. 2011, Francisco et al. 2013, Neufeld et al. 2014, Dias et al. 2017). 9653144 Pubmed 1998 Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import Fransen, M Terlecky, S R Subramani, S Proc。国家的。学会科学。美国95:8087 - 92 23963456 Pubmed 2013 A cargo-centered perspective on the PEX5 receptor-mediated peroxisomal protein import pathway Francisco, Tânia Rodrigues, Tony A Freitas, Marta O Grou, Cláudia P Carvalho, Andreia F Sá-Miranda, Clara Pinto, Manuel P Azevedo, Jorge E J. Biol. Chem. 288:29151-9 10022913 Pubmed 1999 Identification and characterization of the human orthologue of yeast Pex14p Will, G K Soukupova, M Hong, X Erdmann, K S Kiel, J A Dodt, G Kunau, W H Erdmann, R Mol. Cell. Biol. 19:2265-77 19584060 Pubmed 2009 Solution structure of human Pex5.Pex14.PTS1 protein complexes obtained by small angle X-ray scattering Shiozawa, Kumiko Konarev, Petr V Neufeld, Christian Wilmanns, Matthias Svergun, Dmitri I J. Biol. Chem. 284:25334-42 21976670 Pubmed 2011 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 Freitas, Marta O Francisco, Tânia Rodrigues, Tony A Alencastre, Inês S Pinto, Manuel P Grou, Cláudia P Carvalho, Andreia F Fransen, Marc Sá-Miranda, Clara Azevedo, Jorge E J. Biol. Chem. 286:40509-19 24235149 Pubmed 2014 A novel Pex14 protein-interacting site of human Pex5 is critical for matrix protein import into peroxisomes Neuhaus, Alexander Kooshapur, Hamed Wolf, Janina Meyer, N Helge Madl, Tobias Saidowsky, Jürgen Hambruch, Eva Lazam, Anissa Jung, Martin Sattler, M Schliebs, Wolfgang Erdmann, Ralf J. Biol. Chem. 289:437-48 19197237 Pubmed 2009 Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19 Neufeld, Christian Filipp, Fabian V Simon, Bernd Neuhaus, Alexander Schüller, Nicole David, Christine Kooshapur, Hamed Madl, Tobias Erdmann, Ralf Schliebs, Wolfgang Wilmanns, Matthias Sattler, M EMBO J. 28:745-54 28765278 Pubmed 2017 The peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo Dias, Ana F Rodrigues, Tony A Pedrosa, Ana G Barros-Barbosa, Aurora Francisco, Tânia Azevedo, Jorge E J. Biol. Chem. 292:15287-15300 8858165 Pubmed 1996 Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor Gould, S J Kalish, J E Morrell, J C Bjorkman, J Urquhart, A J Crane, D I J. Cell Biol. 135:85-95 inferred by electronic annotation IEA GO IEA Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10638893 1 Reactome DB_ID: 10637171 1 PEX5S,L:PEX13:PEX14:PEX2:PEX10:PEX12 [peroxisomal membrane] PEX5S,L:PEX13:PEX14:PEX2:PEX10:PEX12 Reactome DB_ID: 10637150 1 Reactome DB_ID: 10637155 1 1 EQUAL 639 EQUAL Reactome DB_ID: 10637169 1 Reactome Database ID Release 77 10637171 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637171 Reactome R-CEL-9033091 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033091.1 Converted from EntitySet in Reactome Reactome DB_ID: 10638921 1 peroxisomal matrix GO 0005782 Cargo proteins containing PTS1 [peroxisomal matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ACOT2(1-483) [peroxisomal matrix] HAO1 [peroxisomal matrix] ddo-3 [peroxisomal matrix] dhrs-4 [peroxisomal matrix] acox-1.1 [peroxisomal matrix] daao-1 [peroxisomal matrix] mlcd-1 [peroxisomal matrix] ctl-3 [peroxisomal matrix] acox-3 [peroxisomal matrix] BAAT [peroxisomal matrix] maoc-1 [peroxisomal matrix] ACOT4 [peroxisomal matrix] HACL1 [peroxisomal matrix] CRAT [peroxisomal matrix] acox-1.4 [peroxisomal matrix] daf-22 [peroxisomal matrix] ACOT4 [peroxisomal matrix] ech-8 [peroxisomal matrix] ECH1(1-328) [peroxisomal matrix] ACOT2(1-483) [peroxisomal matrix] ACOT2(1-483) [peroxisomal matrix] daao-1 [peroxisomal matrix] lonp-2 [peroxisomal matrix] ddo-2 [peroxisomal matrix] agxt-1 [peroxisomal matrix] hpo-15 [peroxisomal matrix] ndx-8 [peroxisomal matrix] acs-20 [peroxisomal membrane] AMACR [peroxisomal matrix] ACOT4 [peroxisomal matrix] PIPOX [peroxisomal matrix] MPV17 [peroxisomal membrane] BAAT [peroxisomal matrix] ACOT8 [peroxisomal matrix] acs-22 [peroxisomal membrane] ACOT2(1-483) [peroxisomal matrix] acox-1.5 [peroxisomal matrix] CROT [peroxisomal matrix] HAO2 [peroxisomal matrix] acox-1.2 [peroxisomal matrix] acl-7 [peroxisomal membrane] ACOT4 [peroxisomal matrix] acox-1.6 [peroxisomal matrix] BAAT [peroxisomal matrix] gstk-2 [peroxisomal matrix] IDE [peroxisomal matrix] idh-1 [peroxisomal matrix] acox-1.6 [peroxisomal matrix] HMGCL(1-325) [peroxisomal matrix] ndx-7 [peroxisomal matrix] ddo-1 [peroxisomal matrix] BAAT [peroxisomal matrix] acox-1.3 [peroxisomal matrix] Reactome Database ID Release 77 10638923 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638923 Reactome R-CEL-9033235 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033235.1 后绑定模块对接和易位comprising PEX14, PEX13, PEX2, PEX10 and PEX12 , PEX5S or PEX5L bound to a cargo protein becomes localized to the membrane (Dodt et al. 1995, Wiemer et al. 1995, Alencastre et al. 2009, Francisco et al. 2013, Dias et al. 2017). In a reaction that is not yet fully characterized, the cargo protein is released into the peroxisomal matrix while PEX5S or PEX5L remains in the membrane (Dodt et al. 1995, Wiemer et al. 1995, Alencastre et al. 2009, Franscisco et al. 2013). One model for the reaction hypothesizes that PEX13:PEX14 (associated with PEX2:PEX10:PEX12) forms a barrel in the peroxisomal membrane while PEX5S or PEX5L acts as a plunger to guide the cargo through the barrel (Dias et al. 2017, Francisco et al. 2017). Notably, the reaction does not require a source of energy such as ATP (Oliveira et al. 2003). Mutations in PEX5 cause defects in import of PTS1-containing proteins or PTS2-containing proteins or both (Eberrink et al. 2009, Barøy et al. 2015). 18712838 Pubmed 2009 Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines Ebberink, Merel S Mooyer, Petra A W Koster, J Dekker, Conny J M Eyskens, François J M Dionisi-Vici, Carlo Clayton, Peter T Barth, Peter G Wanders, Ronald J A Waterham, Hans R Hum. Mutat. 30:93-8 7719337 Pubmed 1995 Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders Dodt, G Braverman, N Wong, C Moser, A Moser, H W Watkins, P Valle, D Gould, S J Nat. Genet. 9:115-25 19632994 Pubmed 2009 Mapping the cargo protein membrane translocation step into the PEX5 cycling pathway Alencastre, Inês S Rodrigues, Tony A Grou, Cláudia P Fransen, Marc Sá-Miranda, Clara Azevedo, Jorge E J. Biol. Chem. 284:27243-51 12885776 Pubmed 2003 The energetics of Pex5p-mediated peroxisomal protein import Oliveira, Marcia E Gouveia, Alexandra M Pinto, Rui A Sá-Miranda, Clara Azevedo, Jorge E J. Biol. Chem. 278:39483-8 28787099 Pubmed 2017 Protein transport into peroxisomes: Knowns and unknowns Francisco, Tânia Rodrigues, Tony A Dias, Ana F Barros-Barbosa, Aurora Bicho, Diana Azevedo, Jorge E Bioessays 39:10.1002/bies.201700047 26220973 Pubmed 2015 A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform Barøy, Tuva Koster, J Strømme, Petter Ebberink, Merel S Misceo, Doriana Ferdinandusse, Sacha Holmgren, Asbjørn Hughes, Timothy Merckoll, Else Westvik, Jostein Woldseth, Berit Walter, John Wood, Nick Tvedt, Bjørn Stadskleiv, Kristine Wanders, Ronald J A Waterham, Hans R Frengen, Eirik Hum. Mol. Genet. 24:5845-54 7790377 Pubmed 1995 Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders Wiemer, E A Nuttley, W M Bertolaet, B L Li, X Francke, U Wheelock, M J Anné, U K Johnson, K R Subramani, S J. Cell Biol. 130:51-65 inferred by electronic annotation IEA GO IEA PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3 PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3 This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10637171 1 Reactome DB_ID: 10637175 1 Ub:UBE2D1,2,3 [cytosol] Ub:UBE2D1,2,3 Reactome DB_ID: 10572673 1 UniProt:P0CG71 ubq-1 UniProt P0CG71 1 EQUAL 76 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10637173 1 Ub-C85-UBE2D1,2,3 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ubc-19(胞质) let-70 [cytosol] ubc-24 [cytosol] UniProt Q9U1U4 UniProt P35129 UniProt Q20617 Reactome Database ID Release 77 10637175 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637175 Reactome R-CEL-8953915 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8953915.1 Reactome DB_ID: 10637177 1 PEX2:PEX10:PEX12:PEX5S,L:Ub:UBE2D1,2,3:PEX13:PEX14 [peroxisomal membrane] PEX2:PEX10:PEX12:PEX5S,L:Ub:UBE2D1,2,3:PEX13:PEX14 Reactome DB_ID: 10637175 1 Reactome DB_ID: 10637171 1 Reactome Database ID Release 77 10637177 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637177 Reactome R-CEL-8953942 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8953942.1 Reactome Database ID Release 77 10637179 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637179 Reactome R-CEL-8953917 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8953917.1 A RING E3 ubiquitin ligase complex containing PEX10, PEX12, and PEX2 ubiquitinates PEX5L. The PEX2:PEX10:PEX12 complex is believed to bind an activated E2-ubiquitin conjugate (one of Ub:UBE2D1, Ub:UBE2D2, Ub:UBE2D3) and PEX5L in a complex that also contains PEX13 and PEX14 (Chang et al. 1999, Carvalho et al. 2007, Grou et al. 2008, Grou et al. 2009, Okumoto et al. 2011). The short isoform of PEX5, PEX5S, is inferred to undergo the same reaction. 21554508 Pubmed 2011 Cysteine ubiquitination of PTS1 receptor Pex5p regulates Pex5p recycling Okumoto, Kanji Misono, Sachi Miyata, Non Matsumoto, Yui Mukai, Satoru Fujiki, Yukio Traffic 12:1067-83 10562279 Pubmed 1999 PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import Chang, C C Warren, D S Sacksteder, K A Gould, S J J. Cell Biol. 147:761-74 18359941 Pubmed 2008 Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor Grou, Cláudia P Carvalho, Andreia F Pinto, Manuel P Wiese, Sebastian Piechura, Heike Meyer, Helmut E Warscheid, Bettina Sá-Miranda, Clara Azevedo, Jorge E J. Biol. Chem. 283:14190-7 19208625 Pubmed 2009 Properties of the ubiquitin-pex5p thiol ester conjugate Grou, Cláudia P Carvalho, Andreia F Pinto, Manuel P Huybrechts, Sofie J Sá-Miranda, Clara Fransen, M Azevedo, Jorge E J. Biol. Chem. 284:10504-13 17726030 Pubmed 2007 Ubiquitination of mammalian Pex5p, the peroxisomal import receptor Carvalho, Andreia F Pinto, Manuel P Grou, Cláudia P Alencastre, Inês S Fransen, Marc Sá-Miranda, Clara Azevedo, Jorge E J. Biol. Chem. 282:31267-72 inferred by electronic annotation IEA GO IEA PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11 PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11 This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10637177 1 Reactome DB_ID: 10637186 1 PEX2:PEX10:PEX12:Ub:PEX5S,L:PEX13:PEX14 [peroxisomal membrane] PEX2:PEX10:PEX12:Ub:PEX5S,L:PEX13:PEX14 Reactome DB_ID: 10637184 1 Ub:PEX5L [peroxisomal membrane] Ub:PEX5L Reactome DB_ID: 10572673 1 1 EQUAL 76 EQUAL Reactome DB_ID: 10637182 1 S-(glycyl)-L-cysteine (Cys-Gly) at 11 (in Homo sapiens) 11 EQUAL S-(glycyl)-L-cysteine (Cys-Gly) 1 EQUAL 639 EQUAL Reactome Database ID Release 77 10637184 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637184 Reactome R-CEL-9033498 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033498.1 Reactome DB_ID: 10637150 1 Reactome DB_ID: 10637169 1 Reactome Database ID Release 77 10637186 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637186 Reactome R-CEL-9033528 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033528.1 Converted from EntitySet in Reactome Reactome DB_ID: 10603252 1 UBE2D1,2,3 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ubc-24 [cytosol] let-70 [cytosol] ubc-19(胞质) PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10637177 GO 0061630 GO molecular function Reactome Database ID Release 77 10637187 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637187 Reactome Database ID Release 77 10637189 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10637189 Reactome R-CEL-8953946 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8953946.1 的环形E3泛素连接酶sub-complex PEX2:PEX10:PEX12 catalyzes the transfer of ubiquitin from an E2-ubiquitin conjugate (one of Ub:UBE2D1, Ub:UBE2D2, or Ub:UBE2D3) to the cysteine-11 residue of the substrate PEX5L, the peroxisomal matrix protein shuttling receptor (Carvalho et al. 2007; Grou et al. 2008, Okumoto et al. 2011, Sargent et al. 2016, inferred from yeast in Dodt and Gould 1996). The thiol ester bond between ubiquitin and the cysteine residue of PEX5 is unusual among ubiquitin substrates, which usually have isopeptide bonds between ubiquitin and a lysine residue. Monoubiquitination of PEX5 at cysteine-11 is an integral and mandatory step in the PEX5-mediated peroxisomal protein transport pathway; in its absence, PEX5 cannot be extracted from the peroxisomal membrane docking/translocation machinery (the peroxisomal protein translocon), and thus transport of newly synthesized peroxisomal matrix proteins to the organelle matrix stops (Grou et al. 2009). In addition to monoubiquitinating PEX5 during peroxisomal protein import, the PEX2:PEX10:PEX12 complex has also been implicated in pexophagy, a type of selective autophagy targeting peroxisomes. Pexophagy seems to be triggered mainly by ubiquitination of PEX5, which, in this case, can occur either at its cysteine-11 or lysine-209 residues, but ubiquitination of ABCD3 (also known as PMP70) and other peroxisomal membrane proteins may also be involved (Zhang et al. 2015, inferred from mouse in Nordgren et al. 2015, Sargent et al. 2016). 8991089 Pubmed 1996 Multiple PEX genes are required for proper subcellular distribution and stability of Pex5p, the PTS1 receptor: evidence that PTS1 protein import is mediated by a cycling receptor Dodt, G Gould, S J J. Cell Biol. 135:1763-74 26344566 Pubmed 2015 ATM functions at the peroxisome to induce pexophagy in response to ROS Zhang, Jiangwei Tripathi, Durga Nand Jing, Ji Alexander, Angela Kim, Jinhee Powell, Reid T Dere, Ruhee Tait-Mulder, Jacqueline Lee, Ji-Hoon Paull, Tanya T Pandita, Raj K Charaka, Vijaya K Pandita, Tej K Kastan, Michael B Walker, Cheryl Lyn Nat. Cell Biol. 17:1259-69 26086376 Pubmed 2015 Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts Nordgren, Marcus Francisco, Tânia Lismont, Celien Hennebel, Lore Brees, Chantal Wang, Bo Van Veldhoven, Paul P Azevedo, Jorge E Fransen, Marc Autophagy 11:1326-40 27597759 Pubmed 2016 PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation Sargent, Graeme van Zutphen, Tim Shatseva, Tatiana Zhang, Ling Di Giovanni, Valeria Bandsma, Robert Kim, Peter Kijun J. Cell Biol. 214:677-90 24662292 Pubmed 2014 Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1 protein import Okumoto, Kanji Noda, Hiromi Fujiki, Yukio J. Biol. Chem. 289:14089-108 inferred by electronic annotation IEA GO IEA PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11 PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11 This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10638931 1 PEX2:PEX10:PEX12:PEX5L:Ub:UBE2D1,2,3:PEX7:PEX13:PEX14 [peroxisomal membrane] PEX2:PEX10:PEX12:PEX5L:Ub:UBE2D1,2,3:PEX7:PEX13:PEX14 Reactome DB_ID: 10637175 1 Reactome DB_ID: 10638929 1 PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12 [peroxisomal membrane] PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12 Reactome DB_ID: 10638927 1 Ghost homologue of PEX7 [peroxisomal membrane] Ghost homologue of PEX7 Reactome DB_ID: 10637150 1 Reactome DB_ID: 10637155 1 1 EQUAL 639 EQUAL Reactome DB_ID: 10637169 1 Reactome Database ID Release 77 10638929 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638929 Reactome R-CEL-9033513 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033513.1 Reactome Database ID Release 77 10638931 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638931 Reactome R-CEL-9033521 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033521.1 Converted from EntitySet in Reactome Reactome DB_ID: 10603252 1 Reactome DB_ID: 10638933 1 PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 [peroxisomal membrane] PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 Reactome DB_ID: 10637184 1 Reactome DB_ID: 10638927 1 Reactome DB_ID: 10637150 1 Reactome DB_ID: 10637169 1 Reactome Database ID Release 77 10638933 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638933 Reactome R-CEL-9033497 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033497.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10638931 Reactome Database ID Release 77 10638934 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638934 Reactome Database ID Release 77 10638936 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10638936 Reactome R-CEL-9033485 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033485.1 的环形E3泛素连接酶sub-complex PEX2:PEX10:PEX12 catalyzes the transfer of ubiquitin from an E2-ubiquitin conjugate (one of Ub:UBE2D1, Ub:UBE2D2, or Ub:UBE2D3) to the cysteine-11 residue of the substrate PEX5L, the peroxisomal matrix protein shuttling receptor (Carvalho et al. 2007; Grou et al. 2008, Okumoto et al. 2011, Sargent et al. 2016, inferred from yeast in Dodt and Gould 1996). In contrast to PEX5, PEX7 transiently associated with the docking and translocation module (which comprises PEX14, PEX13, PEX2, PEX10, and PEX12) is not ubiquitinated. The thiol ester bond between ubiquitin and the cysteine residue of PEX5 is unusual among ubiquitin substrates, which usually have isopeptide bonds between ubiquitin and a lysine residue. Monoubiquitination of PEX5 at cysteine-11 is an integral and mandatory step in the PEX5-mediated peroxisomal protein transport pathway; in its absence, PEX5 and PEX7 cannot be extracted from the peroxisomal membrane docking-translocation machinery (the peroxisomal protein translocon), and thus transport of newly synthesized peroxisomal matrix proteins to the organelle matrix stops (Grou et al. 2009). In addition to monoubiquitinating PEX5 during peroxisomal protein import, the PEX2:PEX10:PEX12 sub-complex has also been implicated in pexophagy, a type of selective autophagy targeting peroxisomes. Pexophagy seems to be triggered mainly by ubiquitination of PEX5, which, in this case, can occur either at its cysteine-11 or lysine-209 residues, but ubiquitination of ABCD3 (also known as PMP70) and other peroxisomal membrane proteins may also be involved (Zhang et al. 2015, inferred from mouse in Nordgren et al. 2015, Sargent et al. 2016). 24865970 Pubmed 2014 A PEX7-centered perspective on the peroxisomal targeting signal type 2-mediated protein import pathway Rodrigues, Tony A Alencastre, Inês S Francisco, Tânia Brites, Pedro Fransen, Marc Grou, Cláudia P Azevedo, Jorge E Mol. Cell. Biol. 34:2917-28 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10643154 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10643154 Reactome R-CEL-9033241 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9033241.1 过氧化物酶体小细胞的细胞器bounded by a single membrane and contain variable compositions of proteins depending on cell type. Peroxisomes function in oxidation of fatty acids, detoxification of glyoxylate, and synthesis of plasmalogens, glycerophospholipids containing an alcohol with a vinyl-ether bond (reviewed in Lohdi and Semenkovich 2014). All of the approximately 46 proteins contained in peroxisomal matrix are imported from the cytosol by a unique mechanism that does not require the imported proteins to be unfolded as they cross the membrane (Walton et al. 1995, reviewed in Ma et al. 2011, Fujiki et al. 2014, Baker et al. 2016, Dias et al 2016, Emmanoulidis et al. 2016, Erdmann 2016, Francisco et al. 2017). The incompletely characterized process appears to involve the transport of the proteins through a variably sized pore in the membrane comprising at least PEX5 and PEX14 (inferred from the yeast homologs in Meinecke et al. 2010, the yeast pore is reviewed in Meinecke et al. 2016). Oligomeric proteins are also observed to cross the peroxisomal membrane (Otera and Fujiki 2012) but their transport appears to be less efficient than monomeric proteins (Freitas et al. 2011, inferred from mouse homologs in Freitas et al. 2015, reviewed in Dias et al. 2016).
In the cytosol, receptor proteins, PEX5 and PEX7, bind to specific sequence motifs in cargo proteins (Dodt et al. 1995, Wiemer et al. 1995, Braverman et al. 1997). The long and short isoforms of PEX5 (PEX5L and PEX5S) bind peroxisome targeting sequence 1 (PTS1, originally identified in firefly luciferase by Gould et al. 1989) found on most peroxisomal matrix proteins; PEX7 binds PTS2 (originally identified in rat 3-ketoacyl-CoA thiolase by Swinkels et al. 1991) found on 3 imported proteins thus far in humans. The long isoform of PEX5, PEX5L, then binds the PEX7:cargo protein complex (Braverman et al. 1998, Otera et al. 2000). PEX5S,L bound to a cargo protein or PEX5L bound to PEX7:cargo protein then interacts with a complex comprising PEX13, PEX14, PEX2, PEX10, and PEX12 at the peroxisomal membrane (Gould et al. 1996, Fransen et al. 1998, inferred from rat homologs in Reguenga et al. 2001).
The ensuing step in which the cargo protein is translocated across the membrane is not completely understood. During translocation, PEX5 and PEX7 become inserted into the membrane (Wiemer et al. 1995, Dodt et al. 1995, Oliveira et al. 2003) and expose a portion of their polypeptide chains to the organellar matrix (Rodrigues et al. 2015). One current model envisages PEX5 as a plunger that inserts into a transmembrane barrel formed by PEX14, PEX13, PEX2, PEX10, and PEX12 (the Docking-Translocation Module) (Francisco et al. 2017).
After delivering cargo to the matrix, PEX5 and PEX7 are recycled back to the cytosol by a process requiring mono-ubiquitination of PEX5 and ATP hydrolysis (Imanaka et al. 1987, Thoms and Erdmann 2006, Carvalho et al. 2007). PEX7 is not ubiquitinated but its recycling requires PEX5 mono-ubiquitination. A subcomplex of the Docking-Translocation Module comprising the RING-finger proteins PEX2, PEX10, and PEX12 conjugates a single ubiquitin to a cysteine residue of PEX5 (Carvalho et al. 2007, reviewed in Platta et al. 2016). The mono-ubiquitinated PEX5 and associated PEX7 are then extracted by the exportomer complex consisting of PEX1, PEX6, PEX26, and ZFAND6 (inferred from rat homologs in Miyata et al. 2012). PEX1 and PEX6 are members of the ATPases Associated with diverse cellular Activities (AAA) family, a group of proteins that use the energy of ATP hydrolysis to remodel molecular complexes. PEX1 and PEX6 form a hetero-hexameric ring, best described as a trimer of PEX1/PEX6 dimers (inferred from yeast in Platta et al. 2005, yeast homologs reviewed in Schwerter et al. 2017). Data on the yeast PEX1:PEX6 complex suggest that these ATPases use a substrate-threading mechanism to disrupt protein-protein interactions (Gardner et al. 2018). PEX7 is also then returned to the cytosol (Rodrigues et al. 2014). Once in the cytosol, ubiquitinated PEX5 is enzymatically deubiquitinated by USP9X and may also be non-enzymatically deubiquitinated by nucleophilic attack of the thioester bond between ubiquitin and the cysteine residue of PEX5 by small metabolites such as glutathione (Grou et al. 2012).
Defects in peroxisomal import cause human diseases: Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease and rhizomelic chondrodysplasia punctata types 1 and 5 (Barøy et al. 2015, reviewed in Nagotu et al. 2012, Braverman et al. 2013, Wanders 2014, Fujiki 2016, Waterham et al. 2016). 23798008 Pubmed 2013 Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives Braverman, Nancy E D'Agostino, Maria Daniela Maclean, Gillian E Dev Disabil Res Rev 17:187-96 16007078 Pubmed 2005 Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol Platta, Harald W Grunau, Silke Rosenkranz, Katja Girzalsky, Wolfgang Erdmann, Ralf Nat. Cell Biol. 7:817-22 24508507 Pubmed 2014 Peroxisomes: a nexus for lipid metabolism and cellular signaling Lodhi, Irfan J Semenkovich, Clay F Cell Metab. 19:380-92 3693402 Pubmed 1987 Translocation of acyl-CoA oxidase into peroxisomes requires ATP hydrolysis but not a membrane potential Imanaka, T Small, G M Lazarow, P B J. Cell Biol. 105:2915-22 25177298 Pubmed 2014 Peroxisome biogenesis in mammalian cells Fujiki, Yukio Okumoto, Kanji Mukai, Satoru Honsho, Masanori Tamura, Shigehiko Front Physiol 5:307 7579687 Pubmed 1995 Import of stably folded proteins into peroxisomes Walton, P A Hill, P E Subramani, S Mol. Biol. Cell 6:675-83 26408939 Pubmed 2016 The first minutes in the life of a peroxisomal matrix protein Dias, Ana F Francisco, Tânia Rodrigues, Tony A Grou, Cláudia P Azevedo, Jorge E Biochim. Biophys. Acta 1863:814-20 27941306 Pubmed 2016 Peroxisome biogenesis and human peroxisome-deficiency disorders Fujiki, Yukio Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 92:463-477 20154681 Pubmed 2010 The peroxisomal importomer constitutes a large and highly dynamic pore Meinecke, Michael Cizmowski, Christian Schliebs, Wolfgang Krüger, Vivien Beck, Sabrina Wagner, Richard Erdmann, Ralf Nat. Cell Biol. 12:273-7 21980954 Pubmed 2012 AWP1/ZFAND6 functions in Pex5 export by interacting with cys-monoubiquitinated Pex5 and Pex6 AAA ATPase Miyata, Non Okumoto, Kanji Mukai, Satoru Noguchi, Masafumi Fujiki, Yukio Traffic 13:168-83 29321502 Pubmed 2018 The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading Gardner, Brooke M Castanzo, Dominic T Chowdhury, Saikat Stjepanovic, Goran Stefely, Matthew S Hurley, James H Lander, Gabriel C Martin, Andreas Nat Commun 9:135 26851075 Pubmed 2016 Assembly, maintenance and dynamics of peroxisomes Erdmann, Ralf Biochim. Biophys. Acta 1863:787-9 26367801 Pubmed 2016 Regulation of peroxisomal matrix protein import by ubiquitination Platta, Harald W Brinkmeier, Rebecca Reidick, Christina Galiani, Silvia Clausen, Mathias P Eggeling, Christian Biochim. Biophys. Acta 1863:838-49 22371489 Pubmed 2012 Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate Grou, Cláudia P Francisco, Tânia Rodrigues, Tony A Freitas, Marta O Pinto, Manuel P Carvalho, Andreia F Domingues, Pedro Wood, Stephen A Rodríguez-Borges, José E Sá-Miranda, Clara Fransen, Marc Azevedo, Jorge E J. Biol. Chem. 287:12815-27 26450166 Pubmed 2016 Structural biology of the import pathways of peroxisomal matrix proteins Emmanouilidis, Leonidas Gopalswamy, Mohanraj Passon, Daniel M Wilmanns, Matthias Sattler, M Biochim. Biophys. Acta 1863:804-13 22747494 Pubmed 2012 Pex5p imports folded tetrameric catalase by interaction with Pex13p Otera, Hidenori Fujiki, Yukio Traffic 13:1364-77 10767286 Pubmed 2000 The mammalian peroxin Pex5pL, the longer isoform of the mobile peroxisome targeting signal (PTS) type 1 transporter, translocates the Pex7p.PTS2 protein complex into peroxisomes via its initial docking site, Pex14p Otera, H Harano, T Honsho, M Ghaedi, K Mukai, S Tanaka, A Kawai, A Shimizu, N Fujiki, Y J. Biol. Chem. 275:21703-14 27284042 Pubmed 2016 Peroxisome protein import: a complex journey Baker, Alison Lanyon-Hogg, Thomas Warriner, Stuart L Biochem. Soc. Trans. 44:783-9 9090381 Pubmed 1997 Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata Braverman, N Steel, G Obie, C Moser, A Moser, H Gould, S J Valle, D Nat. Genet. 15:369-76 26138649 Pubmed 2015 Revisiting the intraperoxisomal pathway of mammalian PEX7 Rodrigues, Tony A Grou, Cláudia P Azevedo, Jorge E Sci Rep 5:11806 25854684 Pubmed 2015 The peroxisomal protein import machinery displays a preference for monomeric substrates Freitas, Marta O Francisco, Tânia Rodrigues, Tony A Lismont, Celien Domingues, Pedro Pinto, Manuel P Grou, Cláudia P Fransen, Marc Azevedo, Jorge E Open Biol 5:140236 26611709 Pubmed 2016 Human disorders of peroxisome metabolism and biogenesis Waterham, Hans R Ferdinandusse, Sacha Wanders, Ronald J A Biochim. Biophys. Acta 1863:922-33 9668159 Pubmed 1998 An isoform of pex5p, the human PTS1 receptor, is required for the import of PTS2 proteins into peroxisomes Braverman, N Dodt, G Gould, S J Valle, D Hum. Mol. Genet. 7:1195-205 2654139 Pubmed 1989 A conserved tripeptide sorts proteins to peroxisomes Gould, S J Keller, G A Hosken, N Wilkinson, J Subramani, S J. Cell Biol. 108:1657-64 26497277 Pubmed 2016 Peroxisomal protein import pores Meinecke, Michael Bartsch, Philipp Wagner, Richard Biochim. Biophys. Acta 1863:821-7 11397814 Pubmed 2001 Characterization of the mammalian peroxisomal import machinery: Pex2p, Pex5p, Pex12p, and Pex14p are subunits of the same protein assembly Reguenga C Oliveira, M E Gouveia, A M Sá-Miranda, C Azevedo, Jorge E J. Biol. Chem. 276:29935-42 27977397 Pubmed 2017 ATP-driven processes of peroxisomal matrix protein import Schwerter, Daniel P Grimm, Immanuel Platta, Harald W Erdmann, Ralf Biol. Chem. 398:607-624 22617146 Pubmed 2012 Molecular basis of peroxisomal biogenesis disorders caused by defects in peroxisomal matrix protein import Nagotu, Shirisha Kalel, Vishal C Erdmann, Ralf Platta, Harald W Biochim. Biophys. Acta 1822:1326-36 17028012 Pubmed 2006 Peroxisomal matrix protein receptor ubiquitination and recycling Thoms, Sven Erdmann, Ralf Biochim. Biophys. Acta 1763:1620-8 21464226 Pubmed 2011 Peroxisome assembly: matrix and membrane protein biogenesis Ma, Changle Agrawal, Gaurav Subramani, Suresh J. Cell Biol. 193:7-16 1680677 Pubmed 1991 A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase Swinkels, B W Gould, S J Bodnar, A G Rachubinski, R A Subramani, S EMBO J. 10:3255-62 inferred by electronic annotation IEA GO IEA Class I peroxisomal membrane protein import Class I peroxisomal membrane protein import This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp PEX19绑定类过氧化物酶病膜蛋白 PEX19绑定类过氧化物酶病膜蛋白 This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 10639044 1 Class I Peroxisomal Membrane Proteins [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity mspn-1 [cytosol] prx-14 [cytosol] maa-1 [cytosol] fis-2 [cytosol] prx-12 [cytosol] prx-13 [cytosol] pmp-4 [cytosol] pmp-2 [cytosol] pxmp-4 [cytosol] alh-5 [cytosol] alh-4 [cytosol] UniProt P54815 UniProt Q9XTZ5 UniProt Q6AHP8 UniProt O45730 UniProt Q18598 UniProt P91262 UniProt O44555 UniProt A0A486WWU7 Reactome DB_ID: 10591877 1 UniProt:P34453 prx-19 UniProt P34453 S-farnesyl-L-cysteine at 296 (in Homo sapiens) 296 EQUAL S-farnesyl-L-cysteine [MOD:00111] 1 EQUAL 296 EQUAL Reactome DB_ID: 10639046 1 PEX19:class I PMP [cytosol] PEX19:class I PMP Converted from EntitySet in Reactome Reactome DB_ID: 10639044 1 Reactome DB_ID: 10591877 1 S-farnesyl-L-cysteine at 296 (in Homo sapiens) 296 EQUAL 1 EQUAL 296 EQUAL Reactome Database ID Release 77 10639046 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639046 Reactome R-CEL-9603787 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603787.1 Reactome Database ID Release 77 10639062 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639062 Reactome R-CEL-9603804 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603804.1 细胞溶质,PEX19结合新合成的一堂课s 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). 18782765 Pubmed 2008 Targeting of hFis1 to peroxisomes is mediated by Pex19p Delille, Hannah K Schrader, Michael J. Biol. Chem. 283:31107-15 28325759 Pubmed 2017 Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells Costello, Joseph L Castro, Inês G Camões, Fátima Schrader, Tina A McNeall, Doug Yang, Jing Giannopoulou, Evdokia-Anastasia 戈麦斯,如果lvia Pogenberg, Vivian Bonekamp, Nina A Ribeiro, Daniela Wilmanns, Matthias Jedd, Gregory Islinger, Markus Schrader, Michael J. Cell. Sci. 130:1675-1687 20531392 Pubmed 2010 The peroxisomal receptor Pex19p forms a helical mPTS recognition domain Schueller, Nicole Holton, Simon J Fodor, Krisztian Milewski, Morlin Konarev, Petr Stanley, Will A Wolf, Janina Erdmann, Ralf Schliebs, Wolfgang Song, Young-Hwa Wilmanns, Matthias EMBO J. 29:2491-500 11402059 Pubmed 2001 Multiple distinct targeting signals in integral peroxisomal membrane proteins Jones, J M Morrell, J C Gould, S J J. Cell Biol. 153:1141-50 23460677 Pubmed 2013 Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway Yagita, Yuichi Hiromasa, Takahide Fujiki, Yukio J. Cell Biol. 200:651-66 16791427 Pubmed 2006 Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells Vastiau, I M K Anthonio, E A Brams, M Brees, C Young, S G Van de Velde, S Wanders, R J A Mannaerts, G P Baes, M Van Veldhoven, P P Fransen, M Cell. Mol. Life Sci. 63:1686-99 17069900 Pubmed 2006 Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions Fujiki, Yukio Matsuzono, Yuji Matsuzaki, Takashi Fransen, Marc Biochim. Biophys. Acta 1763:1639-46 16280322 Pubmed 2006 In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p Matsuzono, Yuji Fujiki, Yukio J. Biol. Chem. 281:36-42 10704444 Pubmed 2000 PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis Sacksteder, KA Jones, JM South, ST Li, X Liu, Y Gould, Stephen J J Cell Biol 148:931-44 11883941 Pubmed 2002 Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly Mayerhofer, Peter U Kattenfeld, T Roscher, Adelbert A Muntau, Ania C Biochem. Biophys. Res. Commun. 291:1180-6 14709540 Pubmed 2004 PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins Jones, Jacob M Morrell, James C Gould, Stephen J J. Cell Biol. 164:57-67 26777132 Pubmed 2016 Assembly of Peroxisomal Membrane Proteins via the Direct Pex19p-Pex3p Pathway Liu, Yuqiong Yagita, Yuichi Fujiki, Yukio Traffic 17:433-55 11590176 Pubmed 2002 两个不同的目标信号直接人类peroxisomal membrane protein 22 to peroxisomes Brosius, Ute Dehmel, Thomas Gärtner, Jutta J. Biol. Chem. 277:774-84 9418908 Pubmed 1998 Pex19p, a farnesylated protein essential for peroxisome biogenesis Götte, K Girzalsky, W Linkert, M Baumgart, E Kammerer, S Kunau, W H Erdmann, R Mol. Cell. Biol. 18:616-28 28281558 Pubmed 2017 Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19 Emmanouilidis, Leonidas Schütz, Ulrike Tripsianes, Konstantinos Madl, Tobias Radke, Juliane Rucktäschel, Robert Wilmanns, Matthias Schliebs, Wolfgang Erdmann, Ralf Sattler, Michael Nat Commun 8:14635 15781447 Pubmed 2005 Function of the PEX19-binding site of human adrenoleukodystrophy protein as targeting motif in man and yeast. PMP targeting is evolutionarily conserved Halbach, André Lorenzen, Stephan Landgraf, Christiane Volkmer-Engert, Rudolf Erdmann, Ralf Rottensteiner, Hanspeter J. Biol. Chem. 280:21176-82 15713480 Pubmed 2005 Analysis of human Pex19p's domain structure by pentapeptide scanning mutagenesis Fransen, Marc Vastiau, Ilse Brees, Chantal Brys, Vanessa Mannaerts, Guy P Van Veldhoven, Paul P J. Mol. Biol. 346:1275-86 11453642 Pubmed 2001 Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal integral membrane protein (PMP70) to peroxisomes Biermanns, M Gärtner, J Biochem. Biophys. Res. Commun. 285:649-55 11390669 Pubmed 2001 Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences Fransen, M Wylin, T Brees, C Mannaerts, G P Van Veldhoven, P P Mol. Cell. Biol. 21:4413-24 12751901 Pubmed 2003 The peroxisomal membrane targeting elements of human peroxin 2 (PEX2) Biermanns, Martina von Laar, Jutta Brosius, Ute Gärtner, Jutta Eur. J. Cell Biol. 82:155-62 23628762 Pubmed 2013 Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission Huber, Nina Guimaraes, Sofia Schrader, Michael Suter, Ueli Niemann, Axel EMBO Rep. 14:545-52 16980692 Pubmed 2006 The import competence of a peroxisomal membrane protein is determined by Pex19p before the docking step Pinto, Manuel P Grou, Cláudia P Alencastre, Inês S Oliveira, Marcia E Sá-Miranda, Clara Fransen, Marc Azevedo, Jorge E J. Biol. Chem. 281:34492-502 inferred by electronic annotation IEA GO IEA PEX19:class I PMP binds PEX3 PEX19:class I PMP binds PEX3 This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10591855 1 UniProt:Q18028 prx-3 UniProt Q18028 1 EQUAL 373 EQUAL Reactome DB_ID: 10639046 1 Reactome DB_ID: 10639048 1 PEX3:PEX19:class I PMP [peroxisomal membrane] PEX3:PEX19:class I PMP Reactome DB_ID: 10591855 1 1 EQUAL 373 EQUAL Reactome DB_ID: 10639046 1 Reactome Database ID Release 77 10639048 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639048 Reactome R-CEL-9603793 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603793.1 Reactome Database ID Release 77 10639060 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639060 Reactome R-CEL-9603784 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603784.1 胞质PEX19绑定到一个酶膜公关otein 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). 20554521 Pubmed 2010 Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19 Schmidt, Friederike Treiber, Nora Zocher, Georg Bjelic, Sasa Steinmetz, Michel O Kalbacher, Hubert Stehle, Thilo Dodt, Gabriele J. Biol. Chem. 285:25410-7 12924628 Pubmed 2003 The interaction between human PEX3 and PEX19 characterized by fluorescence resonance energy transfer (FRET) analysis Muntau, Ania C Roscher, Adelbert A Kunau, Wolf-H Dodt, Gabriele Eur. J. Cell Biol. 82:333-42 16895967 Pubmed 2006 Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential for function and translocation Matsuzono, Yuji Matsuzaki, Takashi Fujiki, Yukio J. Cell. Sci. 119:3539-50 18174172 Pubmed 2008 Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p: identification of TRP-104 IN Pex3p as a critical residue for the interaction Sato, Yasuhiko Shibata, Hiroyuki Nakano, Hiroaki Matsuzono, Yuji Kashiwayama, Yoshinori Kobayashi, Yuji Fujiki, Yukio Imanaka, Tsuneo Kato, Hiroaki J. Biol. Chem. 283:6136-44 21102411 Pubmed 2010 Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p Sato, Yasuhiko Shibata, Hiroyuki Nakatsu, Toru Nakano, Hiroaki Kashiwayama, Yoshinori Imanaka, Tsuneo Kato, Hiroaki EMBO J. 29:4083-93 25062251 Pubmed 2014 Association between the intrinsically disordered protein PEX19 and PEX3 Hattula, Katarina Hirschberg, Daniel Kalkkinen, Nisse Butcher, Sarah J Ora, Ari PLoS ONE 9:e103101 10430017 Pubmed 1999 Identification and characterization of the human peroxin PEX3 Soukupova, M Sprenger, C Gorgas, K Kunau, W H Dodt, G Eur. J. Cell Biol. 78:357-74 22624858 Pubmed 2012 The role of conserved PEX3 regions in PEX19-binding and peroxisome biogenesis Schmidt, Friederike Dietrich, Denise Eylenstein, Roy Groemping, Yvonne Stehle, Thilo Dodt, Gabriele Traffic 13:1244-60 15007061 Pubmed 2004 PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins Fang, Y Morrell, James C Jones, JM Gould, Stephen J J Cell Biol 164:863-75 inferred by electronic annotation IEA GO IEA PEX3:PEX19:class I PMP dissociates PEX3:PEX19:class I PMP dissociates This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10639048 1 Converted from EntitySet in Reactome Reactome DB_ID: 10639056 1 Class I Peroxisomal Membrane Proteins [peroxisomal membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity pmp-2 [peroxisomal membrane] prx-12 [peroxisomal membrane] prx-13 [peroxisomal membrane] pxmp-4 [peroxisomal membrane] prx-14 [peroxisomal membrane] alh-4 [peroxisomal membrane] pmp-4 [peroxisomal membrane] mspn-1 [peroxisomal membrane] fis-2 [peroxisomal membrane] maa-1 [peroxisomal membrane] alh-5 [peroxisomal membrane] Reactome DB_ID: 10591855 1 1 EQUAL 373 EQUAL Reactome DB_ID: 10591877 1 S-farnesyl-L-cysteine at 296 (in Homo sapiens) 296 EQUAL 1 EQUAL 296 EQUAL Reactome Database ID Release 77 10639058 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639058 Reactome R-CEL-9603775 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603775.1 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). 25517356 Pubmed 2014 Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins Chen, Yinxiao Pieuchot, Laurent Loh, Rachel Ann Yang, Jing Kari, Teuku Mahfuzh Aufar Wong, Jie Yun Jedd, Gregory Nat Commun 5:5790 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10643238 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10643238 Reactome R-CEL-9603798 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9603798.1 GO 0045046 GO biological process 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). 21768384 Pubmed 2011 Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells Yonekawa, Shusuke Furuno, Akiko Baba, Takashi Fujiki, Yukio Ogasawara, Yuta Yamamoto, A Tagaya, Mitsuo Tani, Katsuko Proc。国家的。学会科学。U.S.A. 108:12746-51 16717127 Pubmed 2006 The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER Kim, Peter K Mullen, Robert T Schumann, Uwe Lippincott-Schwartz, Jennifer J. Cell Biol. 173:521-32 26392202 Pubmed 2016 Targeting and insertion of peroxisomal membrane proteins: ER trafficking versus direct delivery to peroxisomes Mayerhofer, Peter U Biochim. Biophys. Acta 1863:870-80 19114594 Pubmed 2008 The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p- and Pex16p-dependent pathway Matsuzaki, Takashi Fujiki, Yukio J. Cell Biol. 183:1275-86 28146471 Pubmed 2017 Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes Sugiura, Ayumu Mattie, Sevan Prudent, Julien McBride, Heidi M Nature 542:251-254 26572236 Pubmed 2016 Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER in Budding Vesicles Mayerhofer, Peter U Bañó-Polo, Manuel Mingarro, Ismael Johnson, Arthur E Traffic 17:117-30 26434995 Pubmed 2016 Towards the molecular mechanism of the integration of peroxisomal membrane proteins Giannopoulou, Evdokia-Anastasia Emmanouilidis, Leonidas Sattler, Michael Dodt, Gabriele Wilmanns, Matthias Biochim. Biophys. Acta 1863:863-9 26408931 Pubmed 2016 Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals Hua, Rong Kim, Peter K Biochim. Biophys. Acta 1863:881-91 25002403 Pubmed 2014 PEX16 contributes to peroxisome maintenance by constantly trafficking PEX3 via the ER Aranovich, Alexander Hua, Rong Rutenberg, Andrew D Kim, Peter K J. Cell. Sci. 127:3675-86 25903784 Pubmed 2015 Multiple Domains in PEX16 Mediate Its Trafficking and Recruitment of Peroxisomal Proteins to the ER Hua, Rong Gidda, Satinder K Aranovich, Alexander Mullen, Robert T Kim, Peter K Traffic 16:832-52 inferred by electronic annotation IEA GO IEA Insertion of tail-anchored proteins into the endoplasmic reticulum membrane Insertion of tail-anchored proteins into the endoplasmic reticulum membrane This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp SGTA binds Tail-anchored protein SGTA binds Tail-anchored protein This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 10639510 1 Mislocalized membrane protein [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity snb-1 [cytosol] vamp-7 [cytosol] snb-7 [cytosol] snb-2 [cytosol] apl-1 [cytosol] snb-6 [cytosol] snb-5 [cytosol] UniProt Q10651 Reactome DB_ID: 10639305 1 Reactome DB_ID: 10639512 1 Mislocalized membrane protein:SGTA dimer [cytosol] Mislocalized membrane protein:SGTA dimer Converted from EntitySet in Reactome Reactome DB_ID: 10639510 1 Reactome DB_ID: 10639305 1 Reactome Database ID Release 77 10639512 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639512 Reactome R-CEL-9617602 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9617602.1 Reactome Database ID Release 77 10639514 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10639514 Reactome R-CEL-9617595 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9617595.1 Membrane proteins are not delivered to membranes with complete efficiency and a portion can end up mislocalized to the cytosol. SGTA binds the hydrophobic regions of such mislocalized proteins that are exposed to the cytosol (Leznicki and High 2012, Xu et al. 2012, Wunderly et al. 2014, Shao et al. 2017). Client proteins of SGTA include both tail-anchored proteins destined for insertion into the endoplasmic reticulum membrane (Leznicki et al. 2013) and inappropriately localized proteins such as cytosolic PRNP (PrP) (Leznicki and High 2012), which is normally located in the plasma membrane. Mislocalized proteins bound by SGTA can be routed to the proteasome via ubiquitination by the BAG6 complex (BAG6:GET4:UBL4A) (Shao et al. 2017). 23246001 Pubmed 2012 SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation Xu, Yue Cai, Mengli Yang, Yingying Huang, Lan Ye, Yihong Cell Rep 2:1633-44 23533635 Pubmed 2013 The association of BAG6 with SGTA and tail-anchored proteins Leznicki, Pawel Roebuck, Quentin P Wunderley, Lydia Clancy, Anne Krysztofinska, Ewelina M Isaacson, Rivka L Warwicker, Jim Schwappach, Blanche High, Stephen PLoS ONE 8:e59590 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10643252 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10643252 Reactome R-CEL-9609523 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9609523.1 GO 0045048 GO biological process Tail-anchored (TA)蛋白质疏水交易nsmembrane domain (TMD) located near the C-terminus ("tail") of the protein. Depending on the nature of the TMD, TA proteins can be inserted into the endoplasmic reticulum (ER) membrane by at least 4 mechanisms: cotranslational insertion by the signal recognition particle (SRP), post-translational insertion by ASNA1 (TRC40), post-translational insertion by the SRP, and post-translational insertion by a SRP-independent mechanism (SND) (Casson et al. 2017, reviewed in Borgese and Fasana 2011, Casson et al. 2016, Aviram et al. 2016, Chio et al. 2017). Much of the information about the mammalian system of insertion by ASNA1 (TRC40) has been inferred from the Saccharomyces cerevisiae homologue Get3.
Prior to post-translational insertion by ASNA1, SGTA binds the transmembrane domain of the substrate TA protein immediately after translation (Leznicki et al. 2011, Leznicki and High 2012, Xu et al. 2012, Wunderly et al. 2014, Shao et al. 2017), the SGTA:TA protein complex then binds the BAG6 complex (BAG6:GET4:UBL4A) via UBL4A (Winnefeld et al. 2006, Chartron et al. 2012, Xu et al. 2012, Leznicki et al. 2013, Mock et al. 2015, Kuwabara et al. 2015, Shao et al. 2017), and the TA protein is transferred to ASNA1 (Mariappan et al. 2010, Leznicki et al. 2011, Shao et al. 2017), also bound by the BAG6 complex via UBL4A. The ASNA1:TA protein complex then docks at the WRB:CAMLG (WRB:CAML) complex located in the ER membrane and the TA protein is inserted into the ER membrane by an uncharacterized mechanism that involves ATP and the transmembrane domain insertase activity of the WRB:CAML complex (Vilardi et al. 2011, Vilardi et al. 2014, Vogl et al. 2016, and inferred from yeast in Wang et al. 2014).
Misfolded TA proteins, overexpressed TA proteins, and membrane proteins mislocalized in the cytosol bind SGTA but are not efficiently transferred to ASNA1 and, instead, are retained by BAG6 which recruits RNF126 to ubiquitinate them, targeting them for degradation by the proteasome (Wang et al. 2011, Leznicki and High 2012, Xu et al. 2012, Rodrigo-Brenni et al. 2014, Wunderly et al. 2014, Shao et al. 2017, reviewed in Lee and Ye 2013, Casson et al. 2016, Krysztofinska et al. 2016, Guna and Hegde 2018). 25713138 Pubmed 2015 Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (ubiquitin-like protein 4a) complex reveals a novel binding interface that functions in tail-anchored protein biogenesis Kuwabara, Naoyuki Minami, Ryosuke Yokota, Naoto Matsumoto, Hirofumi Senda, Toshiya Kawahara, Hiroyuki Kato, Ryuichi J. Biol. Chem. 290:9387-98 24981174 Pubmed 2014 Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6 Rodrigo-Brenni, Monica C Gutierrez, Erik Hegde, Ramanujan S Mol. Cell 55:227-37 23417671 Pubmed 2013 Bag6/Bat3/Scythe: a novel chaperone activity with diverse regulatory functions in protein biogenesis and degradation Lee, Jin-Gu Ye, Yihong Bioessays 35:377-85 27284044 Pubmed 2016 On the road to nowhere: cross-talk between post-translational protein targeting and cytosolic quality control Casson, Joseph McKenna, Michael High, Stephen Biochem. Soc. Trans. 44:796-801 16777091 Pubmed 2006 Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest Winnefeld, Marc Grewenig, Annabel Schnölzer, Martina 春天,赫伯特 Knoch, Tobias A Gan, Eugene C Rommelaere, Jean Cziepluch, Celina Exp. Cell Res. 312:2500-14 21636303 Pubmed 2011 A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation Wang, Qiuyan Liu, Yanfen Soetandyo, Nia Baek, Kheewoong Hegde, Ramanujan Ye, Yihong Mol. Cell 42:758-70 28992441 Pubmed 2017 Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion Chio, Un Seng Cho, Hyunju Shan, Shu-ou Annu. Rev. Cell Dev. Biol. 33:417-438 24392163 Pubmed 2014 WRB and CAML are necessary and sufficient to mediate tail-anchored protein targeting to the ER membrane Vilardi, Fabio Stephan, Milena Clancy, Anne Janshoff, Andreas Schwappach, Blanche PLoS ONE 9:e85033 27905431 Pubmed 2016 The SND proteins constitute an alternative targeting route to the endoplasmic reticulum Aviram, Naama Ast, Tslil Costa, Elizabeth A Arakel, Eric C Chuartzman, Silvia G Jan, Calvin H Haßdenteufel, Sarah Dudek, Johanna Jung, Martin Schorr, Stefan Zimmermann, Richard Schwappach, Blanche Weissman, Jonathan S Schuldiner, Maya Nature 540:134-138 29689233 Pubmed 2018 Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control Guna, Alina Hegde, Ramanujan S Curr. Biol. 28:R498-R511 21444755 Pubmed 2011 WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane Vilardi, Fabio Lorenz, Holger Dobberstein, Bernhard J. Cell. Sci. 124:1301-7 23142665 Pubmed 2012 Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain reveal an interaction that forms a conserved dynamic interface Chartron, Justin W VanderVelde, David G Clemons, William M Cell Rep 2:1620-32 27193484 Pubmed 2016 Structural and functional insights into the E3 ligase, RNF126 Krysztofinska, Ewelina M Martínez-Lumbreras, Santiago Thapaliya, Arjun 埃文斯,尼古拉J High, Stephen Isaacson, Rivka L Sci Rep 6:26433 29021347 Pubmed 2017 Multiple pathways facilitate the biogenesis of mammalian tail-anchored proteins Casson, Joseph McKenna, Michael Haßdenteufel, Sarah Aviram, Naama Zimmerman, Richard High, Stephen J. Cell. Sci. 130:3851-3861 20676083 Pubmed 2010 A ribosome-associating factor chaperones tail-anchored membrane proteins Mariappan, Malaiyalam Li, Xingzhe Stefanovic, Sandra Sharma, Ajay Mateja, Agnieszka Keenan, Robert J Hegde, Ramanujan S Nature 466:1120-4 25043001 Pubmed 2014 The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase Wang, Fei Chan, Charlene Weir, Nicholas R Denic, Vladimir Nature 512:441-4 25535373 Pubmed 2015 Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain Mock, Jee-Young Chartron, Justin William Zaslaver, Ma'ayan Xu, Yue Ye, Yihong Clemons, William Melvon Proc。国家的。学会科学。U.S.A. 112:106-11 27458190 Pubmed 2016 Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing Vogl, Christian Panou, Iliana Yamanbaeva, Gulnara Wichmann, Carolin Mangosing, Sara J Vilardi, Fabio Indzhykulian, Artur A Pangršič, Tina Santarelli, Rosamaria Rodriguez-Ballesteros, Montserrat Weber, Thomas Jung, Sangyong Cardenas, Elena Wu, Xudong Wojcik, Sonja M Kwan, Kelvin Y del Castillo, Ignacio Schwappach, Blanche Strenzke, Nicola Corey, David P Lin, Shuh-Yow Moser, Tobias EMBO J. 35:2536-2552 20646998 Pubmed 2011 Targeting pathways of C-tail-anchored proteins Borgese, Nica Fasana, Elisa Biochim. Biophys. Acta 1808:937-46 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10643156 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10643156 Reactome R-CEL-9609507 1 Reactome稳定我dentifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-9609507.1 GO 0008104 GO biological process Protein localization encompasses the processes that establish and maintain proteins at specific locations. Mechanisms that target proteins to particular locations in the cell typically involve a motif in the targeted protein that interacts with proteins located at the destination (reviewed in Bauer et al. 2015).
Mitochondrial proteins encoded in the nucleus may be targeted to the outer membrane, intermembrane space, inner membrane, or the matrix (reviewed in Kutik et al. 2007, Milenkovic et al. 2007, Bolender et al. 2008, Ender and Yamano 2009, Wiedemann and Pfanner 2017, Kang et al. 2018). A presequence or an internal targeting sequence causes a protein in the cytosol to interact with the TOMM40:TOMM70 complex in the outer mitochondrial membrane. After passage across the outer membrane, sequence motifs cause proteins to be targeted to the outer membrane via the SAMM50 complex, to the inner membrane via the TIMM22 or TIMM23 complexes, to the matrix via the TIMM23 complex, or proteins may fold and remain in the intermembrane space.
All of the proteins contained in the peroxisomal matrix are imported from the cytosol by a unique mechanism that does not require the imported proteins to be unfolded as they cross the membrane (reviewed in Ma et al. 2011, Fujiki et al. 2014, Francisco et al. 2017). In the cytosol, receptor proteins, PEX5 and PEX7, bind to specific sequence motifs in cargo proteins and then interact with a protein complex containing PEX13, PEX14, PEX2, PEX10, and PEX12 in the peroxisome membrane. The cargo proteins then pass through a proteinaceous channel in the membrane and PEX5 is recycled by a mechanism involving ubiquitination and deubiquitination.
Most peroxisomal membrane proteins (PMPs) are inserted into the peroxisomal membrane by the receptor-chaperone PEX19 and the docking receptor PEX3 (reviewed in Ma et al. 2011, Fujiki et al. 2014). PEX19 binds the PMP as it is translated in the cytosol. 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. 26172624 Pubmed 2015 Mechanisms Regulating Protein Localization Bauer, Nicholas C Doetsch, Paul W Corbett, Anita H Traffic 16:1039-61 inferred by electronic annotation IEA GO IEA