Voltage-dependent anion-selective channel protein 1 (VDAC1)
The protein contains 283 amino acids for an estimated molecular weight of 30773 Da.
Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It 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 (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Anion transport
Apoptotic process
Behavioral fear response
Epithelial cell differentiation
Learning
Macroautophagy
Mitochondrial calcium ion transmembrane transport
Negative regulation of apoptotic process
Negative regulation of calcium import into the mitochondrion
Negative regulation of reactive oxygen species metabolic process
Neuron-neuron synaptic transmission
Positive regulation of mitophagy
Pyruvate metabolic process
Regulation of autophagy of mitochondrion
Viral process
The reference OMIM entry for this protein is 604492
Voltage-dependent anion channel 1; vdac1
Porin
Omp2, yeast, human complement of
DESCRIPTION
The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane is a small, abundant outer membrane pore-forming protein found in the outer membranes of all eukaryotic mitochondria. The VDAC protein is thought to form the major pathway for movement of adenine nucleotides through the outer membrane and to be the mitochondrial binding site for hexokinase (see 142600) and glycerol kinase (GK; 300474) (summary by Blachly-Dyson et al., 1993). At low transmembrane voltage, VDAC is open for anions such as phosphate, chloride, and adenine nucleotides. At higher transmembrane voltage, VDAC functions as a selective channel for cations and uncharged molecules. These features make VDAC likely to play a role in mitochondrial energy metabolism (summary by Huizing et al., 1996).CLONING
Blachly-Dyson et al. (1993) identified and characterized 2 human cDNAs encoding VDAC homologs, which they called HVDAC1 and HVDAC2 (VDAC2; 193245). Each human cDNA was expressed in essentially all human cell lines and tissues examined. Huizing et al. (1998) studied by Northern and Western blot analyses the human tissue distribution of mitochondrial transmembrane metabolite carriers. They found that VDAC1 mRNA has a ubiquitous distribution, with most pronounced expression in heart, liver, and skeletal muscle, whereas the VDAC2 (193245) isoform appears to be expressed only in the heart.GENE STRUCTURE
Messina et al. (2000) determined that the VDAC1 gene contains 9 exons and spans about 33 kb. The first exon is noncoding. The promoter region lacks a canonical TATA box, but it is GC rich and has a sterol repressor element and binding sites for SRY (480000) and NRF2 (NFE2L2; 600492).MAPPING
Blachly-Dyson et al. (1994) had mapped the VDAC1 to chromosome Xq13-q21; however, screening the human chromosome X cosmid library by Messina et al. (1999) resulted in the isolation only of processed pseudogenes, finely mapped to Xq22 and Xp11.2. By fluorescence in situ hybridization of a pool of 3 probes designed to VDAC1, Messina et al. (1999) mapped the VDAC1 gene to chromosome 5q31. The homologous mouse gene resides on proximal chromosome 11, in a region showing homology of synteny with human 5q31.GENE FUNCTION
Blachly-Dyson et al. (1993) found that mitochondria expressing VDAC1 were capable of specifically binding hexokinase, whereas mitochondria expressing VDAC2 only bound hexokinase at background levels. They expressed the 2 human VDAC isoforms in yeast lacking the endogenous VDAC gene. The human proteins isolated from yeast mitochondria formed channels with the characteristics expected of VDAC when incorporated into planar lipid bilayers. Furthermore, expression of the human proteins in the deficient strains complemented phenotypic defects associated with elimination of the endogenous yeast VDAC gene. The mutant of S. cerevisiae was known as omp2. The existence of multiple genes encoding VDAC isoforms in mammals was not unexpected. Antibodies generated to VDAC1 purified from mitochondria appeared to crossreact immunocytochemically with the plasma membrane. Biochemical and physiologic studies had also suggested that VDAC-like proteins may be present in the plasma membrane. Lewis et al. (1994) used post-embedding immunolabeling to investigate the presence of VDAC in the semitendinosus muscle of the cane toad Bufo marinus and found labeling not only of the outer mitochondrial membrane but also of the ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 13, 2019: Protein entry updated
Automatic update: OMIM entry 604492 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).