# Comparative Genomics of Peroxisome Biogenesis Proteins: Making Sense of the PEX Proteins

**Authors:** Renate L. M. Jansen, Carlos Santana-Molina, Marco van den Noort, Damien P. Devos, Ida J. van der Klei

PMC · DOI: 10.3389/fcell.2021.654163 · Frontiers in Cell and Developmental Biology · 2021-05-20

## TL;DR

This paper uses comparative genomics to study peroxisome biogenesis proteins (PEX) across eukaryotes, revealing their evolutionary relationships and functional roles.

## Contribution

The study identifies previously unknown PEX orthologs and defines the core set of PEX proteins essential for peroxisome formation.

## Key findings

- A large number of previously unknown PEX orthologs were identified across eukaryotes.
- Core PEX proteins required for peroxisome formation were defined through comparative analysis.
- Organisms without peroxisomes still retain some PEX proteins, suggesting alternative functions.

## Abstract

PEX genes encode proteins involved in peroxisome biogenesis and proliferation. Using a comparative genomics approach, we clarify the evolutionary relationships between the 37 known PEX proteins in a representative set of eukaryotes, including all common model organisms, pathogenic unicellular eukaryotes and human. A large number of previously unknown PEX orthologs were identified. We analyzed all PEX proteins, their conservation and domain architecture and defined the core set of PEX proteins that is required to make a peroxisome. The molecular processes in peroxisome biogenesis in different organisms were put into context, showing that peroxisomes are not static organelles in eukaryotic evolution. Organisms that lack peroxisomes still contain a few PEX proteins, which probably play a role in alternative processes. Finally, the relationships between PEX proteins of two large families, the Pex11 and Pex23 families, were analyzed, thereby contributing to the understanding of their complicated and sometimes incorrect nomenclature. We provide an exhaustive overview of this important eukaryotic organelle.

## Linked entities

- **Genes:** PHEX (phosphate regulating endopeptidase X-linked) [NCBI Gene 5251]
- **Proteins:** PHEX (phosphate regulating endopeptidase X-linked)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** PEX7 (Pex7p) [NCBI Gene 851720] {aka PAS7, PEB1}, PEX15 (Pex15p) [NCBI Gene 854113] {aka PAS21}, PEX1 (AAA family ATPase peroxin 1) [NCBI Gene 853636] {aka PAS1}, FAF2 (Fas associated factor family member 2) [NCBI Gene 23197] {aka ETEA, UBXD8, UBXN3B}, PEX6 (AAA family ATPase peroxin 6) [NCBI Gene 855387] {aka PAS8}, PEX5 (Pex5p) [NCBI Gene 851831] {aka PAS10}, PXMP2 (peroxisomal membrane protein 2) [NCBI Gene 5827] {aka MPV17L3, PMP22}, UBE2L1 (ubiquitin conjugating enzyme E2 L1 (pseudogene)) [NCBI Gene 283556] {aka L-UBC, UBC4, UBCH7N3, UBCL, UBE2L7, UBE2L7P}, DNM1L (dynamin 1 like) [NCBI Gene 10059] {aka DLP1, DRP1, DVLP, DYMPLE, EMPF, EMPF1}, PEX30 (peroxisome biogenesis protein) [NCBI Gene 851034], PEX29 (Pex29p) [NCBI Gene 852090], PEX31 (peroxisome biogenesis protein) [NCBI Gene 852887], UBE2D1 (ubiquitin conjugating enzyme E2 D1) [NCBI Gene 7321] {aka E2(17)KB1, SFT, UBC4/5, UBCH5, UBCH5A}, PEX5 (peroxisomal biogenesis factor 5) [NCBI Gene 5830] {aka PBD2A, PBD2B, PTS1-BP, PTS1R, PXR1, RCDP5}, PEX2 (ubiquitin-protein ligase peroxin 2) [NCBI Gene 853219] {aka CRT1, PAS5}, MPV17 (mitochondrial inner membrane protein MPV17) [NCBI Gene 4358] {aka CMT2EE, MTDPS6, SYM1}, PEX4 (E2 ubiquitin-protein ligase peroxin 4) [NCBI Gene 853034] {aka PAS2, UBC10}, PEX17 (Pex17p) [NCBI Gene 855507] {aka PAS9}, PEX11A (peroxisomal biogenesis factor 11 alpha) [NCBI Gene 8800] {aka PEX11-ALPHA, PEX11alpha, PMP28, hsPEX11p}, PEX25 (Pex25p) [NCBI Gene 855991], PEX34 (Pex34p) [NCBI Gene 850302], FIS1 (Fis1p) [NCBI Gene 854745] {aka MDV2}, PEX1 (peroxisomal biogenesis factor 1) [NCBI Gene 5189] {aka HMLR1, PBD1A, PBD1B, ZWS, ZWS1}, PEX14 (peroxisomal biogenesis factor 14) [NCBI Gene 5195] {aka NAPP2, PBD13A, Pex14p, dJ734G22.2}, PEX21 (Pex21p) [NCBI Gene 853154], PEX11E (peroxin 11E) [NCBI Gene 825279] {aka peroxin 11E}, PEX11D (peroxin 11D) [NCBI Gene 819182] {aka F4I18.28, peroxin 11D}, PEX11 (Pex11p) [NCBI Gene 854018] {aka PMP24, PMP27}, DYSF (dysferlin) [NCBI Gene 8291] {aka FER1L1, LGMD2B, LGMDR2, MMD1}, PEX11C (peroxin 11c) [NCBI Gene 839257] {aka T1N6.24, T1N6_24, peroxin 11c}, DNM1 (dynamin 1) [NCBI Gene 1759] {aka DEE31, DEE31A, DEE31B, DNM, EIEE31}, UBC1 (E2 ubiquitin-conjugating protein UBC1) [NCBI Gene 851757], PEX11G (peroxisomal biogenesis factor 11 gamma) [NCBI Gene 92960] {aka PEX11gamma}, PEX18 (Pex18p) [NCBI Gene 856565], UBC5 (E2 ubiquitin-conjugating protein UBC5) [NCBI Gene 851631], PEX22 (ubiquitin-protein transferase activating protein PEX22) [NCBI Gene 851244] {aka YAF5}, PEX8 (Pex8p) [NCBI Gene 852968] {aka PAS6}, PEX6 (peroxisomal biogenesis factor 6) [NCBI Gene 5190] {aka HMLR2, PAF-2, PAF2, PBD4A, PDB4B, PXAAA1}, SYM1 (ethanol metabolism protein) [NCBI Gene 850953], INP1 (Inp1p) [NCBI Gene 855244], PEX19 (Pex19p) [NCBI Gene 851494] {aka PAS12}, PEX28 (Pex28p) [NCBI Gene 856555], PEX19 (peroxisomal biogenesis factor 19) [NCBI Gene 5824] {aka D1S2223E, HK33, PBD12A, PMP1, PMPI, PXF}, FIS1B (Tetratricopeptide repeat (TPR)-like superfamily protein) [NCBI Gene 831114] {aka FISSION 1B}, PEX3 (Pex3p) [NCBI Gene 851929] {aka PAS3}, PEX13 (peroxin PEX13) [NCBI Gene 850888] {aka PAS20}, PEX10 (ubiquitin-protein ligase peroxin 10) [NCBI Gene 851858] {aka PAS4}, PEX26 (peroxisomal biogenesis factor 26) [NCBI Gene 55670] {aka PBD7A, PBD7B, PEX26M1T, Pex26pM1T}, PEX27 (Pex27p) [NCBI Gene 854368], PEX11B (peroxisomal biogenesis factor 11 beta) [NCBI Gene 8799] {aka PEX11-BETA, PEX11beta, PEX14B}, DRP3A (dynamin-related protein 3A) [NCBI Gene 829506] {aka ABERRANT PEROXISOME MORPHOLOGY 1, ADL2, ADL2A, APEM1, ARABIDOPSIS DYNAMIN-LIKE 2, NOXY15}, PEX7 (peroxisomal biogenesis factor 7) [NCBI Gene 5191] {aka PBD9B, PTS2R, RCDP1, RD}, PEX14 (Pex14p) [NCBI Gene 852724], PEX12 (ubiquitin-protein ligase peroxin 12) [NCBI Gene 855041] {aka PAS11}
- **Diseases:** cancer (MESH:D009369), inherited peroxisomal disorders (MESH:D018901), sleeping sickness (MESH:D014353), toxoplasmosis (MESH:D014123), cutaneous leishmaniasis (MESH:D016773), DD (MESH:C536170), PMP (MESH:D015433), Structural protein disorder (MESH:D020914), cryptococcosis (MESH:D003453), Water mold (MESH:D000069578), potato blight (MESH:C538354), amoebiasis (MESH:D000562), peroxisome biogenesis disorders (MESH:C536664), inborn errors (MESH:D008661)
- **Chemicals:** oleic acid (MESH:D019301), BFU2016-78326-P (-), Ala (MESH:D000409), Met (MESH:D008715), hydrogen peroxide (MESH:D006861), ATP (MESH:D000255), fatty acid (MESH:D005227), glucose (MESH:D005947), Gln (MESH:D005973), PMPs (MESH:C091421), methanol (MESH:D000432), lipid (MESH:D008055), bile acids (MESH:D001647), Thr (MESH:D013912)
- **Species:** Entamoeba histolytica (species) [taxon 5759], Cryptosporidium parvum (species) [taxon 5807], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Naegleria gruberi (species) [taxon 5762], Penicillium rubens (species) [taxon 1108849], Mastigamoeba balamuthi (species) [taxon 108607], Euglena gracilis (species) [taxon 3039], Phytophthora infestans (potato late blight agent, species) [taxon 4787], Euglenozoa (phylum) [taxon 33682], PX clade (clade) [taxon 569578], Babesia bovis (species) [taxon 5865], Dictyostelium discoideum (species) [taxon 44689], Monosiga brevicollis (species) [taxon 81824], Yarrowia lipolytica (species) [taxon 4952], Theileria annulata (species) [taxon 5874], Rattus norvegicus (brown rat, species) [taxon 10116], Ogataea angusta (species) [taxon 870730], Drosophila melanogaster (fruit fly, species) [taxon 7227], Galdieria sulphuraria (species) [taxon 130081], Amoebozoa (amoebozoans, clade) [taxon 554915], Schizosaccharomyces pombe (fission yeast, species) [taxon 4896], Rhodophyta (red algae, phylum) [taxon 2763], Neurospora crassa (species) [taxon 5141], Ogataea polymorpha (species) [taxon 460523], Aspergillus niger (species) [taxon 5061], C. elegans [taxon 328850], Colletotrichum higginsianum (species) [taxon 80884], Alveolata (alveolates, clade) [taxon 33630], Rhizaria (rhizarians, clade) [taxon 543769], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Thalassiosira pseudonana (species) [taxon 35128], Mus musculus (house mouse, species) [taxon 10090], Bodo saltans (species) [taxon 75058], Schizophyllum commune (species) [taxon 5334], Blastocystis hominis (species) [taxon 12968], Cyanidioschyzon merolae (species) [taxon 45157], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Heterolobosea (phylum) [taxon 5752], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Tetrahymena thermophila (species) [taxon 5911], Toxoplasma gondii (species) [taxon 5811], Candida albicans (species) [taxon 5476], Caenorhabditis elegans (species) [taxon 6239], Komagataella pastoris (species) [taxon 4922], Komagataella phaffii (species) [taxon 460519], Fusarium fujikuroi (species) [taxon 5127], Trypanosoma brucei (species) [taxon 5691], Physcomitrium patens (species) [taxon 3218], Danio rerio (leopard danio, species) [taxon 7955]
- **Cell lines:** CHO — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_0213)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8172628/full.md

## References

117 references — full list in the complete paper: https://tomesphere.com/paper/PMC8172628/full.md

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Source: https://tomesphere.com/paper/PMC8172628