Voltage-dependent anion-selective channel protein 3 (VDAC3)

The protein contains 283 amino acids for an estimated molecular weight of 30659 Da.

 

Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 67

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The reference OMIM entry for this protein is 610029

Voltage-dependent anion channel 3; vdac3

DESCRIPTION

VDAC3 belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for hexokinase (see HK1; 142600) and glycerol kinase (GK; 300474) (Rahmani et al., 1998).

CLONING

By PCR of a human liver cDNA library, Rahmani et al. (1998) cloned VDAC3. The deduced 283-amino acid protein is 67% identical to VDAC1 (604492) and 73% identical to VDAC2 (193245). Northern blot analysis detected a 1.4-kb transcript in all tissues examined, with high expression in testis. SDS-PAGE of transfected COS-1 cells showed epitope-tagged VDAC3 at about 30 kD.

GENE FUNCTION

Yogoda et al. (2007) described the mechanism of action of the selective antitumor agent erastin, involving the RAS-RAF-MEK signaling pathway functioning in cell proliferation, differentiation, and survival. Erastin exhibits greater lethality in human tumor cells harboring mutations in the oncogenes HRAS (190020), KRAS (190070), or BRAF (164757). Using affinity purification and mass spectrometry, Yogoda et al. (2007) discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs), a novel target for anticancer drugs. Yogoda et al. (2007) showed that erastin treatment of cells harboring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, nonapoptotic mechanism. RNA interference-mediated knockdown of VDAC2 (193245) or VDAC3 caused resistance to erastin, implicating these 2 VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, Yogoda et al. (2007) found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabeled analog and a filter-binding assay, Yogoda et al. (2007) showed that erastin binds directly to VDAC2. Yogoda et al. (2007) concluded that ligands to VDAC proteins can induce nonapoptotic cell death selectively in some tumor cells harboring activating mutations in the RAS-RAF-MEK pathway.

MAPPING

Using FISH, Rahmani et al. (1998) mapped the VDAC3 gene to chromosome 8p11.2. They stated that the mouse Vdac3 gene maps to a proximal region of chromosome 8 that shares homology of synteny with human chromosome 8p.

ANIMAL MODEL

Sampson et al. (2001) found that Vdac3-null mice were born at the expected mendelian ratio. Mutant females were fertile, but males were not due to markedly reduced sperm motility. The majority of epididymal axonemes showed structural defects, most commonly loss of a single microtubule doublet at a conserved position within the axoneme. In testicular sperm, the defect was only rarely observed, suggesting that instability of a normally formed axoneme occurred during sperm maturation. In contrast, tracheal epithelial cilia showed no structural abnormalities, but there was a reduced number of ciliated cells. In skeletal muscle, mitochondria were abnormally shaped, and the activities of respiratory chain complex enzymes were reduced. Citrate synthase (CS; 118950) activity was unchanged, suggesting an absence of mitochondrial proliferation that commonly occurs in response to respiratory chain defects. Anflous-Pharayra et al. (2007) found that Vdac3 -/- mice were indistinguishable from wildtype. Soleus muscle from Vdac3 -/- mice showed normal hexokinase-2 (HK2; 601125) protein content and activity and ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610029 was added.