1.A.101 The Peroxisomal Pore-forming Pex11 (Pex11) Family More than thirty Pex proteins are known to participate in the biogenesis of peroxisomes, oxidative organelles involved in lipid and ROS metabolism. Pex11 homologues are constituents of the Pexoxisomal Protein Importer (PPI) Family (TC# 3.A.20). They play roles, direct or indirect, in division and proliferation of peroxisomes (Schrader et al. 1998). Mindthoff et al. 2015 showed that yeast Pex11 is a pore-forming protein, possibly sharing significant sequence similarity with TRPM cation-selective channels. The Pex11 channel is moderately cation-selective (PK⁺/PCl^-=1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r~0.6nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da, and the channel's selectivity filter was localized. Overproduction of Pex11 resulted in acceleration of fatty acids beta-oxidation in intact cells but not in the corresponding lysates. Beta-oxidation in cells was affected by expression of the Pex11 protein carrying point mutations in the selectivity filter. These data suggested that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the beta-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of beta-oxidation in yeast strains expressing Pex11 with mutations mimicking constitutively phosphorylated (S165D, S167D) or unphosphorylated (S165A, S167A) protein. The results suggest that phosphorylation of Pex11 is a mechanism that can control the peroxisomal beta-oxidation rate. Pex11 is thus a non-selective channel responsible for transfer of metabolites across peroxisomal membrane.(Mindthoff et al. 2015). The PEX11B gene may be defective in peroxisome biogenesis disorder 14B (Tian et al. 2020; Taylor et al. 2017).
This family belongs to the Peroxisomal Peroxin/Unnexin (Pex/Unx) Superfamily.
References:
Jaiteh, M., A. Taly, and J. Hénin. (2016). Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors. PLoS One 11: e0151934.
Mindthoff S., Grunau S., Steinfort LL., Girzalsky W., Hiltunen JK., Erdmann R. and Antonenkov VD. (2015). Peroxisomal Pex11 is a pore-forming protein homologous to TRPM channels. Biochim Biophys Acta. 1863(2):271-283.
Schrader, M., B.E. Reuber, J.C. Morrell, G. Jimenez-Sanchez, C. Obie, T.A. Stroh, D. Valle, T.A. Schroer, and S.J. Gould. (1998). Expression of PEX11beta mediates peroxisome proliferation in the absence of extracellular stimuli. J. Biol. Chem. 273: 29607-29614.
Taylor, R.L., M.T. Handley, S. Waller, C. Campbell, J. Urquhart, A.M. Meynert, J.M. Ellingford, D. Donnelly, G. Wilcox, I.C. Lloyd, H. Mundy, D.R. FitzPatrick, C. Deshpande, J. Clayton-Smith, and G.C. Black. (2017). Novel PEX11B Mutations Extend the Peroxisome Biogenesis Disorder 14B Phenotypic Spectrum and Underscore Congenital Cataract as an Early Feature. Invest Ophthalmol Vis Sci 58: 594-603.
Tian, Y., L. Zhang, Y. Li, J. Gao, H. Yu, Y. Guo, and L. Jia. (2020). Variant analysis of PEX11B gene from a family with peroxisome biogenesis disorder 14B by whole exome sequencing. Mol Genet Genomic Med 8:.
Examples:
TC#	Name	Organismal Type	Example
1.A.101.1.1	*Pex11 of 236 aas and possibly 3 TMSs (Mindthoff et al.* 2015).**		Pex11 of Saccharomyces cerevisiae

1.A.101.1.2	Pex11 of 247 aas.		Pex11 of Homo sapiens

1.A.101.1.3	Pex11 of 248 aas		Pex11 of Arabidopsis thaliana

1.A.101.1.4	Pex11 of 222 aas		Pex11 of Leishmainia major

1.A.101.1.5	Pex11 of 234 aas		*Pex 11 of Drosophila melanogaster* (Fruit fly)**

1.A.101.1.6	Pex11C-like protein of 199 aas		Pex11C-like protein of Mombyx mori

1.A.101.1.7	Uncharacterized glycosomal protein of 220 aas		UP of Leishmania major

Examples:
TC#	Name	Organismal Type	Example
1.A.101.2.1	Putative Pex11 of 355 aas		Pex11 homologue of Aspergillus niger

1.A.101.2.2	Putative Pex11 homologue of 315 aas		Pex11 homologue of Cryptococcus neoformans (Filobasidiella neoformans)

1.A.101.2.3	Uncharacterized protein of 327 aas		UP of Bipolaris oryzae

1.A.101.2.4	Pex11 homologue of 290 aas		Pex11 homologue of Sphaerulina musiva (Poplar stem canker fungus) (Septoria musiva)

1.A.101.2.5	Uncharacterized protein of 188 aas		UP of Aphanomyces astaci

Examples:
TC#	Name	Organismal Type	Example
1.A.101.3.1	Uncharacterized protein of 317 aas		UP of Wallemia mellicola (Wallemia sebi

1.A.101.3.2	Uncharacterized protein of 410 aas		*UP of Serpula lacrymans* (Dry rot fungus)**

1.A.101.3.3	Uncharacterized protein of 334 aas		UP of Rhodosporidium toruloides (Yeast) (Rhodotorula gracilis)

1.A.101.3.4	Uncharacterized protein of 228 aas		UP of Mucor circinelloides (Mucormycosis agent) (Calyptromyces circinelloides)

Examples:
TC#	Name	Organismal Type	Example
1.A.101.4.1	Uncharacterized glycosomal protein of 225 aas		UP of Leishmania braziliensis

1.A.101.4.2	Uncharacterized protein of 253 aas		UP of Leishmania braziliensis

1.A.101.4.3	Uncharacterized protein of 247 aas		UP of Trypanosoma cruzi

Examples:
TC#	Name	Organismal Type	Example
1.A.101.5.1	Uncharacterized protein of 252 aas		UP of Emiliania huxleyi

1.A.101.5.2	Uncharacterized protein of 252 aas		UP of Saprolegnia diclina

1.A.101.5.3	Uncharacterized protein of 421 aas		UP of Emiliania huxleyi

Examples:
TC#	Name	Organismal Type	Example
1.A.101.6.1	Pex11 of 240 aas		Pex11 of Tetrahymena thermophila

1.A.101.6.2	Uncharacterized protein of 289 aas		UP of Paramecium tetraurelia

1.A.101.6.3	Pex11 domain containing protein of 235 aas		Pex11 of Oxytricha trifallax

1.A.101.6.4	Peroxin Pex11 of 243 aas		*Pex11 of Physcomitrella patens* (Moss)**

Examples:
TC#	Name	Organismal Type	Example
1.A.101.7.1	Uncharacterized protein of 244 aas		UP of Kazachstania africana (Yeast) (Kluyveromyces africanus)

1.A.101.7.2	Pex25 of 294 aas		Pex25 of Saccharomyces cerevisiae

1.A.101.7.3	Pex27 of 376 aas and 2 predicted TMSs.		Pex27 of Saccharomyces cerevisiae

Examples:
TC#	Name	Organismal Type	Example
1.A.101.8.1	Uncharacterized protein of 206 aas		*UP of Thalassiosira oceanica* (Marine diatom)**

1.A.101.8.2	Uncharacterized protein of 360 aas		UP of Phaeodactylum tricornutum

1.A.101.8.3	Uncharacterized protein of 252 aas		UP of Pythium ultimum