Pathway Human Homo sapiens

Peroxisomal protein import

R-HSA-9033241 in Reactome release 97: under Protein localization, with 63 genes placed in it by the mapping files and 1 child pathway in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9033241 (mouse), R-RNO-9033241 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9033241.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2018-03-18
Last updated: 2018-06-13
Events inside: 20, counted from the record

Peroxisomes are small cellular organelles that are 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).

Literature Reactome attaches

Peroxisomes: a nexus for lipid metabolism and cellular signalingCell Metab., 2014, vol. 19, p. 380-92PubMed 24508507
The first minutes in the life of a peroxisomal matrix proteinBiochim. Biophys. Acta, 2016, vol. 1863, p. 814-20PubMed 26408939
Protein transport into peroxisomes: Knowns and unknownsBioessays, 2017, vol. 39, p. 10.1002/bies.201700047PubMed 28787099
Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectivesDev Disabil Res Rev, 2013, vol. 17, p. 187-96PubMed 23798008
Peroxisomal protein import poresBiochim. Biophys. Acta, 2016, vol. 1863, p. 821-7PubMed 26497277
Regulation of peroxisomal matrix protein import by ubiquitinationBiochim. Biophys. Acta, 2016, vol. 1863, p. 838-49PubMed 26367801
ATP-driven processes of peroxisomal matrix protein importBiol. Chem., 2017, vol. 398, p. 607-624PubMed 27977397

Reactome's record lists 12 orthologous events, R-RNO-9033241 (Rattus norvegicus), R-MMU-9033241 (Mus musculus) among the species this site serves, and 10 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-02 ET · Reactome pathway browser"Peroxisomal protein import". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9033241 with StableID: R-HSA-9033241.5 (accessed 2026-10-02 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 63 genes in this human pathway; showing 1 to 63, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneACAA1	AuthorityHGNC:82	Mapping file id30 NCBI file	EvidenceIEA, TAS
GeneACOT2	AuthorityHGNC:18431	Mapping file id10965 NCBI file	EvidenceIEA, TAS
GeneACOT4	AuthorityHGNC:19748	Mapping file id122970 NCBI file	EvidenceIEA, TAS
GeneACOT8	AuthorityHGNC:15919	Mapping file id10005 NCBI file	EvidenceIEA, TAS
GeneACOX1	AuthorityHGNC:119	Mapping file id51 NCBI file	EvidenceIEA, TAS
GeneACOX2	AuthorityHGNC:120	Mapping file id8309 NCBI file	EvidenceIEA, TAS
GeneACOX3	AuthorityHGNC:121	Mapping file id8310 NCBI file	EvidenceIEA, TAS
GeneAGPS	AuthorityHGNC:327	Mapping file id8540 NCBI file	EvidenceIEA, TAS
GeneAGXT	AuthorityHGNC:341	Mapping file id189 NCBI file	EvidenceIEA, TAS
GeneAMACR	AuthorityHGNC:451	Mapping file id23600 NCBI file	EvidenceIEA, TAS
GeneBAAT	AuthorityHGNC:932	Mapping file id570 NCBI file	EvidenceIEA, TAS
GeneCAT	AuthorityHGNC:1516	Mapping file id847 NCBI file	EvidenceIEA, TAS
GeneCRAT	AuthorityHGNC:2342	Mapping file id1384 NCBI file	EvidenceIEA, TAS
GeneCROT	AuthorityHGNC:2366	Mapping file id54677 NCBI file	EvidenceIEA, TAS
GeneDAO	AuthorityHGNC:2671	Mapping file id1610 NCBI file	EvidenceIEA, TAS
GeneDDO	AuthorityHGNC:2727	Mapping file id8528 NCBI file	EvidenceIEA, TAS
GeneDECR2	AuthorityHGNC:2754	Mapping file id26063 NCBI file	EvidenceIEA, TAS
GeneDHRS4	AuthorityHGNC:16985	Mapping file id10901 NCBI file	EvidenceIEA, TAS
GeneECH1	AuthorityHGNC:3149	Mapping file id1891 NCBI file	EvidenceIEA, TAS
GeneECI2	AuthorityHGNC:14601	Mapping file id10455 NCBI file	EvidenceIEA, TAS
GeneEHHADH	AuthorityHGNC:3247	Mapping file id1962 NCBI file	EvidenceIEA, TAS
GeneEPHX2	AuthorityHGNC:3402	Mapping file id2053 NCBI file	EvidenceIEA, TAS
GeneGNPAT	AuthorityHGNC:4416	Mapping file id8443 NCBI file	EvidenceIEA, TAS
GeneGSTK1	AuthorityHGNC:16906	Mapping file id373156 NCBI file	EvidenceIEA, TAS
GeneHACL1	AuthorityHGNC:17856	Mapping file id26061 NCBI file	EvidenceIEA, TAS
GeneHAO1	AuthorityHGNC:4809	Mapping file id54363 NCBI file	EvidenceIEA, TAS
GeneHAO2	AuthorityHGNC:4810	Mapping file id51179 NCBI file	EvidenceIEA, TAS
GeneHMGCL	AuthorityHGNC:5005	Mapping file id3155 NCBI file	EvidenceIEA, TAS
GeneHSD17B4	AuthorityHGNC:5213	Mapping file id3295 NCBI file	EvidenceIEA, TAS
GeneIDE	AuthorityHGNC:5381	Mapping file id3416 NCBI file	EvidenceIEA, TAS
GeneIDH1	AuthorityHGNC:5382	Mapping file id3417 NCBI file	EvidenceIEA, TAS
GeneLONP2	AuthorityHGNC:20598	Mapping file id83752 NCBI file	EvidenceIEA, TAS
GeneMLYCD	AuthorityHGNC:7150	Mapping file id23417 NCBI file	EvidenceIEA, TAS
GeneMPV17	AuthorityHGNC:7224	Mapping file id4358 NCBI file	EvidenceIEA, TAS
GeneNOS2	AuthorityHGNC:7873	Mapping file id4843 NCBI file	EvidenceIEA, TAS
GeneNUDT19	AuthorityHGNC:32036	Mapping file id390916 NCBI file	EvidenceIEA, TAS
GeneNUDT7	AuthorityHGNC:8054	Mapping file id283927 NCBI file	EvidenceIEA, TAS
GenePAOX	AuthorityHGNC:20837	Mapping file id196743 NCBI file	EvidenceIEA, TAS
GenePECR	AuthorityHGNC:18281	Mapping file id55825 NCBI file	EvidenceIEA, TAS
GenePEX1	AuthorityHGNC:8850	Mapping file id5189 NCBI file	EvidenceIEA, TAS
GenePEX10	AuthorityHGNC:8851	Mapping file id5192 NCBI file	EvidenceIEA, TAS
GenePEX12	AuthorityHGNC:8854	Mapping file id5193 NCBI file	EvidenceIEA, TAS
GenePEX13	AuthorityHGNC:8855	Mapping file id5194 NCBI file	EvidenceIEA, TAS
GenePEX14	AuthorityHGNC:8856	Mapping file id5195 NCBI file	EvidenceIEA, TAS
GenePEX2	AuthorityHGNC:9717	Mapping file id5828 NCBI file	EvidenceIEA, TAS
GenePEX26	AuthorityHGNC:22965	Mapping file id55670 NCBI file	EvidenceIEA, TAS
GenePEX5	AuthorityHGNC:9719	Mapping file id5830 NCBI file	EvidenceIEA, TAS
GenePEX6	AuthorityHGNC:8859	Mapping file id5190 NCBI file	EvidenceIEA, TAS
GenePEX7	AuthorityHGNC:8860	Mapping file id5191 NCBI file	EvidenceIEA, TAS
GenePHYH	AuthorityHGNC:8940	Mapping file id5264 NCBI file	EvidenceIEA, TAS
GenePIPOX	AuthorityHGNC:17804	Mapping file id51268 NCBI file	EvidenceIEA, TAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneSCP2	AuthorityHGNC:10606	Mapping file id6342 NCBI file	EvidenceIEA, TAS
GeneSLC27A2	AuthorityHGNC:10996	Mapping file id11001 NCBI file	EvidenceIEA, TAS
GeneTYSND1	AuthorityHGNC:28531	Mapping file id219743 NCBI file	EvidenceIEA, TAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA, TAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceIEA, TAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceIEA, TAS
GeneUBE2D1	AuthorityHGNC:12474	Mapping file id7321 NCBI file	EvidenceTAS
GeneUBE2D2	AuthorityHGNC:12475	Mapping file id7322 NCBI file	EvidenceTAS
GeneUBE2D3	AuthorityHGNC:12476	Mapping file id7323 NCBI file	EvidenceTAS
GeneUSP9X	AuthorityHGNC:12632	Mapping file id8239 NCBI file	EvidenceIEA, TAS
GeneZFAND6	AuthorityHGNC:30164	Mapping file id54469 NCBI file	EvidenceIEA, TAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Protein localizationR-HSA-9609507164 genes

Children

TYSND1 cleaves peroxisomal proteinsR-HSA-90335007 genes

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.