| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
1.B.8.1.1 | Voltage-dependent anion channel-1 (VDAC1; OMP2; Por1) porin. It is a component of the mitochondrial permeability transition pore (mPTP) which includes cyclophilin D, VDAC and the adenine nucleotide translocator (TC subfamily 2.A.29.1) (Austin et al. 2013). Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires the transport of their precursors, phosphatidic acid and phosphatidylserine, respectively, to the mitochondrial inner membrane. The Ups1-Mdm35 and Ups2-Mdm35 complexes transfer phosphatidic acid and phosphatidylserine, respectively, between the mitochondrial outer and inner membranes. A Ups1-independent CL accumulation pathway requires several mitochondrial proteins with unknown functions including Mdm31. Miyata et al. 2018 identified VDAC1 (Por1) as a protein that interacts with both Mdm31 and Mdm35. Depletion of the porins Por1 and Por2 destabilized Ups1 and Ups2, decreased CL levels by ~90%, and caused loss of Ups2-dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased CL levels. Using HeLa cells, the authors showed that mammalian porins also function in mitochondrial CL metabolism. Thus, yeast porins function in mitochondrial phospholipid metabolism, and porin-mediated regulation of CL metabolism appears to be evolutionarily conserved. VDACs are targeted to mitocondria via a C-terminal hydrophobic β-strand terminated by a hydrophiic residue (Klinger et al. 2019). Pentenediol-type compounds bind to VDAC1 (Unten et al. 2019). VDACs play a major role in the mitochondrial permeability transition, and inhibition of the MPT improves bone fracture repair (Shares et al. 2020). Gallic acid inhibits the celecoxib-induced mitochondrial permeability transition and reduces its toxicity (Salimi et al. 2021). Small molecules targeting VDAC (sorafenib, regorafenib and lenvatinib) have synergetic effects on hepatocarcinoma cell proliferation and survival (Ventura et al. 2023). Phosphorylation has the potential to modulate Por1, causing a marked effect on mitochondrial function. It also impacts cell morphology and growth both in respiratory and in fermenting conditions (Sousa et al. 2024). | Eukaryota |
Fungi, Ascomycota | Mitochondrial outer membrane VDAC of Saccharomyces cerevisiae |
|
1.B.8.1.2 | VDAC3 porin. The human orthologue forms small pores in membranes (Checchetto et al. 2014). VDAC3 is a sensor of the oxidative state in the mitochondrial intermembrane space, and cysteyl residue modification appears to play a role (Reina et al. 2016). Post translational modifications of VDAC3 that can impact its protective role against reactive oxygen species (ROS), which is particularly important in the ALS context (Pittalà et al. 2022). | Eukaryota |
Metazoa, Chordata | Mitochondrial outer membrane VDAC3 of Mus musculus |
|
1.B.8.1.3 | VDAC1, VDAC-1 or VDAC porin of 283 aas, which is > 99% identical to human (P21796) and mouse (60932) VDAC1. Mammals possess three VDACs (VDAC1, 2 and 3) encoded by three genes, but they are all similar in sequence (~60-70% identical) (Messina et al., 2011). The 3-d structure of the human VDAC1 is known (PDB ID 2JK4; Bayrhuber et al. 2008). Reviewed by Shoshan-Barmatz et al. 2015. VDAC1 is found both in mitochondria and the plasma membrane (Lawen et al. 2005) where it may cause cytoplasmic ATP loss.. It may be involved in cancer (Shoshan-Barmatz et al. 2017) and Alzheimer's disease (AD) (Shoshan-Barmatz et al. 2018). Along with its low toxicity profile and high antioxidant activity, the gallic acid derivative, AntiOxBEN3, strongly inhibits calcium-dependent mitochondrial permeability transition pore (mPTP) opening (Teixeira et al. 2018). VDAC dimerization plays a role in mitochondrial metabolic regulation and apoptosis in response to cytosolic acidification during cellular stress, and E73 is involved (Bergdoll et al. 2018). Inhibiting VDAC1 overproduction and plasma membrane insertion in β-cells preserves insulin secretion in diabetes (Zhang et al. 2018). βII and βIII-tubulin, bound to VDAC, regulate VDAC permeability (Puurand et al. 2019). This VDAC porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring efficient transfer of the precursors to the inner membrane translocase (Ellenrieder et al. 2019). A method has been develped to determine the number of VDAC1 channels (and other integral membrane proteins) in nanodiscs under various assembly conditions (Häusler et al. 2020). Stable low-conducting states of human VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. Conductance jumps reveal entropy as a key factor for VDAC gating (Preto et al. 2022). The lysyl residue at position 12 in the pore interior is responsible for most of VDAC's voltage sensitivity (Ngo et al. 2022). Oral administration of VDAC1-derived small peptides increases circulating testosterone levels in male rats (Martinez-Arguelles et al. 2022). Possible alternative conformational states of VDAC have been considered for the closed state (Mannella 2023). HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in hepatocellular carcinoma (Zhang et al. 2023). Silencing the mitochondrial gatekeeper, VDAC1, is a potential treatment for bladder cancer (Alhozeel et al. 2024). TRO19622 at 5 μM and 50 μM is an inhibitor of VDACs (Garriga et al. 2024). VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants (Lv et al. 2024).
| Eukaryota |
Metazoa, Chordata | Mitochondrial and plasma membrane VDAC1 of Bos taurus. The human ortholog is almost identical. |
|
1.B.8.1.4 | Eukaryota |
Viridiplantae, Streptophyta | Mitochondrial outer membrane VDAC of Triticum aestivum | |
|
1.B.8.1.5 | Non green plastid porin | Eukaryota |
Viridiplantae, Streptophyta | Plastid porin of Pisum sativum |
|
1.B.8.1.6 | Voltage-dependent anion-selective porin1 (Porin-1, VDAC or Por-1) (De Pinto et al. 1989; Aiello et al., 2004) (one of three paralogues). Mutations in VDAC leads to neurologic dysfunction and male infertility in Drosophila (Graham et al., 2010). Porin 1 is abundantly expressed in both male and female germ cell tissues; Porin 2 is abundant in testis but in small amounts in ovaries. The immuno-histological stain of ovaries shows that Porin isoform 1 is selectively targeted to follicular cells while Porin isoform 2 is present in mitochondria of the epithelial sheath cells of the ovariole (Guarino et al. 2006; Specchia et al. 2008). | Eukaryota |
Metazoa, Arthropoda | Porin 1 of Drosophila melanogaster (Q94920) |
|
1.B.8.1.7 | Voltage-independent, cation-selective porin2 (Porin-2 or Por-2) (converted to anion selective by changing Glu-66 and Glu-163 to lysines; Aiello et al., 2004). One of three paralogues (Craigen and Graham, 2008). Porin 1 is abundantly expressed in both male and female germ cell tissues; Porin 2 is abundant in testis but in small amounts in ovaries. The immuno-histological stain of ovaries shows that Porin 1 is selectively targeted to follicular cells while Porin 2 is present in mitochondria of the epithelial sheath cells of the ovariole (Specchia et al. 2008). | Eukaryota |
Metazoa, Arthropoda | Porin 2 of Drosophila melanogaster (Q9VKP2) |
|
1.B.8.1.8 |
Rice VDAC4. Channels formed in planar bilayers exhibit large conductance (4.6 ± 0.3 nS in 1 M KCl), strong voltage dependence and weak anion selectivity. The open state of the channel is permeable to ATP (Godbole et al. 2011). | Eukaryota |
Viridiplantae, Streptophyta | VDAC4 of Oryza sativa |
|
1.B.8.1.9 | Mitochondrial outer membrane porin, VDAC, of 292 aas (De Pinto et al. 1989). Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response of insects to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication.Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV) (Zhu et al. 2024). | Eukaryota |
Metazoa, Arthropoda | VDAC of Drosophila melanogaster |
|
1.B.8.1.10 | Outer membrane porin, VDAC of 346 aas. This protein may function in the thylacoid membrane of the chloroplast as a non-selective voltage-indiependent porin (see TC# 1.B.8.8.7 and Kojima et al. 2018). | Eukaryota |
Rhodophyta | VDAC of Galdieria sulphuraria |
|
1.B.8.1.11 | Porin, VDAC of 309 aas | Eukaryota |
Rhodophyta | VDAC of Galdieria sulphuraria |
|
1.B.8.1.12 | Mitochondrial outer membrane voltage-dependent anion-selective channel protein 2, VDAC-2 of 294 aas. Protein:micelle ratios and cysteine residues in the protein influence VDAC2 stability and unfolding rates (Maurya and Mahalakshmi 2014). VDAC-2 performs a different subset of regulatory functions than VDAC1. It has anti-apoptotic features and contributes to gametogenesis.It may also regulate ROS, steroidogenesis and mitochondria-associated endoplasmic reticulum membrane regulatory pathways (Maurya and Mahalakshmi 2015). Plays a role in mitochondrial import of Bak and tBid-induced apoptosis (Naghdi et al. 2015). VDAC2 plasticity and stability in the mitochondrial outer membrane are modulated by physical properties of the bilayer (Srivastava et al. 2018). VDAC1 and VDAC2 are overall, very similar, exhibiting similar dynamic behavior and conformational homogeneity (Eddy et al. 2019). Altered skeletal muscle microtubule-mitochondrial VDAC2 binding is related to bioenergetic impairments after paclitaxel but not vinblastine chemotherapies (Ramos et al. 2019). Intramolecular disulfide bridges are present in VDAC2 from Rattus norvegicus (Pittalà et al. 2024). Voltage-dependent anion channel 2 (VDAC2) plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. | Eukaryota |
Metazoa, Chordata | VDAC2 of Homo sapiens |
|
1.B.8.1.13 | Mitochondrial outer membrane porin, PorA or VDAC (Troll et al. 1992). | Eukaryota |
Evosea | Mitochondrial outer membrane porin of Dictyostelium discoideum (Q01501) |
|
1.B.8.1.14 | Voltage-dependent anion-selective channel (VDAC) protein of 282 aas | Eukaryota |
Oomycota | VDAC of Albugo laibachii |
|
1.B.8.1.15 | VDAC1 of 276 aas, one of five isoforms. A knock out mutation (Δvdac1) resulted in abnormal ovule formation during female gametogenesis, and both the mitochondrial transmembrane potential and ATP synthesis were reduced (Pan et al. 2014). Targeting and surface recognition of mitochondrial β-barrel proteins in yeast, humans and plants depends on the hydrophobicity of the last β-hairpin of the β-barrel, but the presence of a hydrophilic amino acid at the C-terminus of the penultimate β-strand is also required for mitochondrial targeting (Klinger et al. 2019). Kanwar et al. 2020 presented a comparative overview to provide an integrative picture of Klinger et al. 2019). Kanwar et al. 2020 presented a comparative overview to provide an integrative picture of the interactions of VDAC with different proteins in both animals and plants. | Eukaryota |
Viridiplantae, Streptophyta | VDAC1 of Arabidopsis thaliana |
|
1.B.8.1.16 | Voltage-dependent anion channel, VDAC, of 283 aas | Eukaryota |
Metazoa, Chordata | VDAC of Paralichthys olivaceus (Bastard halibut) (Hippoglossus olivaceus) |
|
1.B.8.1.17 | Non-selective channel of the thylakoid membrane of 275 aas and one TMSs, CpTPOR (Kojima et al. 2018). The channels are large enough for permeation of small organic compounds (e.g. carbohydrates and amino acids with Mr < 1500). The pore has an estimated radius of ∼1.3 nm and exhibits a typical single-channel conductance of 1.8 nS in 1 m KCl with infrequent closing transitions. CpTPOR exhibits no obvious selectivity for anions and no voltage-dependent gating. It presumably enables rapid transfer of various metabolites between the lumen and stroma (Kojima et al. 2018). | Eukaryota |
TPOR of Cyanophora paradoxa chloroplasts (muroplasts) | |
|
1.B.8.1.18 | VDAC2 of 281 aas, 1 N-terminal α-TMS and 19 β-TMSs. Forms channels much like those of VDAC1 (Guardiani et al. 2018). | Eukaryota |
Fungi, Ascomycota | VDAC2 of Saccharomyces cerevisiae |
|
1.B.8.1.19 | Outer membrane porin, VDAC3 (HSR2) of 274 aas. This protein may function in the thylacoid membrane of the chloroplast as a non-selective voltage-indiependent porin (see TC# 1.B.8.8.7 and Kojima et al. 2018). | Eukaryota |
Viridiplantae, Streptophyta | HSR2 of Arabidopsis thaliana (Mouse-ear cress) |
|
1.B.8.1.20 | Miltochondrial outer membrane porin, VDAC, of 283 aas. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. The absence of VDAC is associated with increased reactive oxygen species (ROS) production (Shuvo et al. 2019). | Eukaryota |
Fungi, Ascomycota | VDAC of Neurospora crassa |
|
1.B.8.2.1 | 19 β-stranded barrel translocase across the outer membrane, Tom40 (Pfam Porin 3 Superfamily). | Eukaryota |
Fungi, Ascomycota | Tom40 of Saccharomyces cerevisiae |
|
1.B.8.2.2 | Tom40 of 344 aas | Eukaryota |
Metazoa, Arthropoda | Tom40 of Drosophila melanogaster |
|
1.B.8.2.3 | Eukaryotic porin family, Tom40-2 of 310 aas | Eukaryota |
Viridiplantae, Streptophyta | Tom40 of Arabidopsis thaliana |
|
1.B.8.2.4 | Tom40 of 361 aas | Eukaryota |
Discosea | Tom40 of Acanthamoeba castellanii |
|
1.B.8.2.5 | Mitochondrial import receptor, Tom40 of 361 aas | Eukaryota |
Metazoa, Chordata | Tom40 of Homo sapiens |
|
1.B.8.2.6 | Tom40 of 314 aas | Eukaryota |
Evosea | Tom40 of Dictyostelium discoideum |
|
1.B.8.2.7 | Tom40 of 264 aas | Eukaryota |
Bacillariophyta | Tom40 of Thalassiosira occanica |
|
1.B.8.2.8 | Tom40 of 301 aas | Eukaryota |
Metazoa, Nematoda | Tom40 of Caenorhabditis elegans |
|
1.B.8.2.9 | Mitochondrial import receptor, Tom40 of 394 aas | Eukaryota |
Apicomplexa | Tom40 of Plasmodium knowlesi |
|
1.B.8.2.10 | Porin protein of 368 aas | Eukaryota |
Ciliophora | Porin protein of Tetrahymena thermophila |
|
1.B.8.2.11 | Putative porin of 284 aas | Eukaryota |
Fungi, Microsporidia | Putative porin of Encephalitozoon cuniculi |
|
1.B.8.2.12 | Entamoeba histolytica, an anaerobic intestinal parasite causing dysentery and extra-intestinal abscesses in humans, possesses highly reduced and divergent mitochondrion-related organelles (MROs) called mitosomes. This organelle lacks many features associated with canonical aerobic mitochondria and even other MROs such as hydrogenosomes. The Entamoeba mitosome has been found to have a compartmentalized sulfate activation pathway, which has a role in amebic stage conversion. It also features a unique shuttle system that delivers proteins from the cytosol to the mitosome. Only Entamoeba mitosomes possess a novel subclass of β-barrel outer membrane protein called MBOMP30.The mitosome protein import complex consisting of at least two proteins, TOM40, which provides the channel, and TOM60, which seems to be necessary for protein import (Makiuchi et al. 2013; Santos et al. 2016). | Eukaryota |
Evosea | TOM40/TOM60 of Entamoeba histolytica |
|
1.B.8.2.13 | TOM40 (377 aas)/TOM22 (105 aas)/TOM7 (66 aas) of the mitochondrial import receptor, 3 subunits (Wunderlich 2022). | Eukaryota |
Apicomplexa | TOM complex of Plasmodium falciparum |
|
1.B.8.3.1 | Putative mitochondrial porin of 309 aas (Porin3_VDAC superfamily) | Eukaryota |
Ciliophora | MPP family member of Tetrahymena thermophila (Q22Z08) |
|
1.B.8.3.2 | Mitochondrial porin of 305aas (Porin3_VDAC superfamily). Exhibits the properties of a voltage-dependent general diffusion porin with cation-selectivity and a pore diameter of 1.3 nm (Ludwig et al. 1989). | Eukaryota |
Ciliophora | MPP family member of Paramecium tetraurelia (Q3SE03) |
|
1.B.8.3.3 | Putative mitochondrial porin of 301aas (Porin3_VDAC superfamily) | Eukaryota |
Ciliophora | MPP family member of Oxytricha trifallax (J9JBL0) |
|
1.B.8.4.1 | VDAC homologue of 277 aas | Eukaryota |
Euglenozoa | VDAC of Leishmania mexicana |
|
1.B.8.5.1 | VDAC homologue | Eukaryota |
Apicomplexa | VDAC of Theileria orientalis |
|
1.B.8.5.2 | VDAC (OMPP) homologue of 289 aas and 0 TMSs. | Eukaryota |
Apicomplexa | VDAC of Plasmodium falciprarum |
|
1.B.8.6.1 | The Mdm10 protein of 493 aas, a putative eukaryotic porin. It belongs to the eukaryotic porin 3 superfamily together with VDAC and Tom40 (Flinner et al. 2013). This protein is also listed under TC# 1.B.33.3.1 and TC#9.B.58.1.1 as part of two complexes: the mitochondrial Sorting and Assembly Machinery (SAM) and the TULIP complex, respectively. | Eukaryota |
Fungi, Ascomycota | Mdm10 of Saccharomyces cerevisiae |
|
1.B.8.6.2 | Mdm10 protein of 646 aas | Eukaryota |
Fungi, Basidiomycota | Mdm10 of Ustilago maydis |
|
1.B.8.6.3 | Mdm10 protein of 317 aas | Eukaryota |
Discosea | Mdm10 of Acanthamoeba castellanii |
|
1.B.8.6.4 | Uncharacterized protein of 323 aas | Eukaryota |
Evosea | Mdm10 of Dictyostelium discoideum |
|
1.B.8.6.5 | Uncharacterized protein of 435 aas | Eukaryota |
Fungi, Ascomycota | UP of Pyrenophora tritici-repentis |
|
1.B.8.7.1 | Porin protein of 290 aas | Eukaryota |
Euglenozoa | Porin protein of Euglena gracilis |
|
1.B.8.8.1 | Pore-forming β-barrel porin of 308 aas in hydrogenosomes, Tom40-1 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-1 of Trichomonas vaginalis |
|
1.B.8.8.2 | Pore-forming β-barrel porin of 290 aas, present in hydrogenosomes, Tom40-2 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-2 of Trichomonas vaginalis |
|
1.B.8.8.3 | Pore-forming β-barrel porin of 305 aas in hydrogenosomes, Tom40-3 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-3 of Trichomonas vaginalis |
|
1.B.8.8.4 | Pore-forming β-barrel porin of 296 aas in hydrogenosomes, Tom40-4 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-4 of Trichomonas vaginalis |
|
1.B.8.8.5 | Pore-forming β-barrel porin of 397 aas in hydrogenosomes, Tom40-5 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-5 of Trichomonas vaginalis |
|
1.B.8.8.6 | Pore-forming β-barrel porin of 298 aas in hydrogenosomes, Tom40-6 (Makki et al. 2019). | Eukaryota |
Parabasalia | Tom40-6 of Trichomonas vaginalis |