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Tbio Voltage-dependent anion-selective channel protein 3

Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules.

This gene encodes a voltage-dependent anion channel (VDAC), and belongs to the mitochondrial porin family. VDACs are small, integral membrane proteins that traverse the outer mitochondrial membrane and conduct ATP and other small metabolites. They are known to bind several kinases of intermediary metabolism, thought to be involved in translocation of adenine nucleotides, and are hypothesized to form part of the mitochondrial permeability transition pore, which results in the release of cytochrome c at the onset of apoptotic cell death. Alternatively transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

 Comments

Property Summary

NCBI Gene PubMed Count 35
PubMed Score 26.57
PubTator Score 23.12

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (1)

Disease Target Count P-value
ovarian cancer 8491 3.4e-05
Waldenstrons macroglobulinemia 764 1.5e-03
lung cancer 4473 2.1e-02

Expression

  Differential Expression (3)

Disease log2 FC p
Waldenstrons macroglobulinemia 1.301 1.5e-03
lung cancer 1.600 2.1e-02
ovarian cancer 2.100 3.4e-05

Synonym

Accession Q9Y277 Q9UIS0 VDAC-3
Symbols VDAC-3
HD-VDAC3

Gene

VDAC3

PANTHER Protein Class (3)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (17)

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 GO Function (3)

 GO Component (5)

 GO Process (2)

 Compartment GO Term (42)

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 MGI Phenotype (8)

 HCA RNA Cell Line (56)

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Pathway (13)

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Protein-protein Interaction (6)

SRC   ERICH5   HRAS   RAP2A   APOE   FAM8A1  

Gene RIF (15)

PMID Text
26947058 The works available on VDAC cysteines support the notion that VDAC1, VDAC2, and VDAC3 proteins are paralogs with a similar pore-function and slightly different, but important, ancillary biological functions. (Review)
26806159 VDAC3 is able to modulate its pore size and current by exploiting the mobility of the N-terminal and forming, upon external stimuli, disulfide bridges with cysteine residues located on the barrel and exposed to the inter-membrane space.
26407725 channel gating of VDAC3 might be controlled by redox sensing under physiological conditions
25341036 These data suggest that an interaction between Mcl-1 and VDAC promotes lung cancer cell migration by a mechanism that involves Ca(2+)-dependent reactive oxygen species production.
25171321 observed electrophysiological properties of hVDAC3 are surprisingly different from the other isoforms and are discussed in relation to the proposed physiological role of the protein in mammalian cells
23388454 a VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry.
23060438 VDAC 1, 2, and 3 recruit Parkin to defective mitochondria to promote mitochondrial autophagy.
22935710 VDAC3 is present at the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes.
22190034 HIV-1 gp41 is identified to have a physical interaction with voltage-dependent anion channel 3 (VDAC3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses
20877624 Observational study of gene-disease association. (HuGE Navigator)
20434446 The substitution of the VDAC3 N-terminus with the VDAC1 N-terminus caused the chimaera to become more active than VDAC1.
20138821 VDAC3 has a limited ability to support mitochondrial respiration and has no influence in the control of ROS production.
17683036 VDAC3 is a novel target for protein S-nigrosylation in spermatozoa.
17254575 HIV-1 gp41 is identified to have a physical interaction with voltage-dependent anion channel 3 (VDAC3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses
14739283 VDAC2 and VDAC3 might have an alternative structural organization and different functions in outer dense fibers than in mitochondria

AA Sequence 

MCNTPTYCDLGKAAKDVFNKGYGFGMVKIDLKTKSCSGVEFSTSGHAYTDTGKASGNLETKYKVCNYGLT      1 - 70
FTQKWNTDNTLGTEISWENKLAEGLKLTLDTIFVPNTGKKSGKLKASYKRDCFSVGSNVDIDFSGPTIYG     71 - 140
WAVLAFEGWLAGYQMSFDTAKSKLSQNNFALGYKAADFQLHTHVNDGTEFGGSIYQKVNEKIETSINLAW    141 - 210
TAGSNNTRFGIAAKYMLDCRTSLSAKVNNASLIGLGYTQTLRPGVKLTLSALIDGKNFSAGGHKVGLGFE    211 - 280
LEA                                                                       281 - 283
//

Text Mined References (41)

PMID Year Title
26947058 2016 Role of cysteines in mammalian VDAC isoforms' function.
26806159 2016 A computational study of ion current modulation in hVDAC3 induced by disulfide bonds.
26407725 2015 VDAC3 gating is activated by suppression of disulfide-bond formation between the N-terminal region and the bottom of the pore.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25621951 2015 USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria.
25341036 2014 Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation.
25171321 2014 Recombinant human voltage dependent anion selective channel isoform 3 (hVDAC3) forms pores with a very small conductance.
23388454 2013 VDAC3 and Mps1 negatively regulate ciliogenesis.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23060438 2012 Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy.
22935710 2012 VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes.
21630459 2011 Proteomic characterization of the human sperm nucleus.
21269460 2011 Initial characterization of the human central proteome.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20833797 2011 Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes.
20434446 2010 Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell.
20138821 Characterization of human VDAC isoforms: a peculiar function for VDAC3?
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17683036 2007 Human spermatozoa contain multiple targets for protein S-nitrosylation: an alternative mechanism of the modulation of sperm function by nitric oxide?
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16381901 2006 The LIFEdb database in 2006.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15592455 2005 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14739283 2004 Voltage-dependent anion-selective channels VDAC2 and VDAC3 are abundant proteins in bovine outer dense fibers, a cytoskeletal component of the sperm flagellum.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11507092 2001 Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent anion channel type 3.
11076863 2000 DNA cloning using in vitro site-specific recombination.
11042152 2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.
10833333 2000 The tissue-specific, alternatively spliced single ATG exon of the type 3 voltage-dependent anion channel gene does not create a truncated protein isoform in vivo.
10501981 1999 Revised fine mapping of the human voltage-dependent anion channel loci by radiation hybrid analysis.
9804816 1998 A novel isoform of the mitochondrial outer membrane protein VDAC3 via alternative splicing of a 3-base exon. Functional characteristics and subcellular localization.
9781040 Isolation of a novel human voltage-dependent anion channel gene.
9653160 1998 Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.
9228078 1997 The murine voltage-dependent anion channel gene family. Conserved structure and function.