VDAC2

VDAC2
Identifiers
Gene ontology
Molecular function	porin activity nucleotide binding voltage-gated anion channel activity protein binding
Cellular component	integral component of membrane membrane synaptic vesicle myelin sheath mitochondrial outer membrane mitochondrion mitochondrial inner membrane membrane raft mitochondrial nucleoid extracellular exosome pore complex nucleus acrosomal vesicle
Biological process	negative regulation of intrinsic apoptotic signaling pathway ion transport transmembrane transport negative regulation of protein polymerization regulation of anion transmembrane transport anion transport anion transmembrane transport transport binding of sperm to zona pellucida inorganic anion transport
Sources:Amigo / QuickGO

Ensembl				ENSG00000165637	ENSMUSG00000021771
UniProt	P45880 Q5JSD1	Q60930
RefSeq (mRNA)	NM_001184783 NM_001184823 NM_003375 NM_001324087 NM_001324088 NM_001324089 NM_001324090 NM_001391963	NM_011695
RefSeq (protein)	NP_001171712 NP_001171752 NP_001311016 NP_001311017 NP_001311018 NP_001311019 NP_003366	NP_035825
Location (UCSC)	Chr 10: 75.21 – 75.23 Mb	Chr 14: 21.88 – 21.9 Mb
PubMed search	[3]	[4]

Wikidata

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Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10.^[5][6] This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms.^[7][8][9] VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis.^{[10][11][12][13]} Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases.^[10][11] VDAC2 also mediates immune response to infectious bursal disease (IBD).^[11]

Structure

The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore. The sequence of the VDAC2 isoform contains an abundance of cysteines, which allow for the formation of disulfide bridges and, ultimately, affect the flexibility of the β-barrel. VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane.^[14] In particular, VDAC2 possesses an N-terminal longer by 11 residues compared to the other two isoforms.^[9]

Function

VDAC2 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms. VDACs generally are involved in cellular energy metabolism by transporting ATP and other small ions and metabolites across the

In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis.^[10][15] VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP.^[11][13][15] VDAC2 in particular has demonstrated a protective effect in cells undergoing mitochondrial apoptosis, and may even confer protection during aging.^[16][17]

Furthermore, VDAcs have been linked to spermatogenesis, sperm maturation, motility, and fertilization.^[13] Though all VDAC isoforms are ubiquitously expressed, VDAC2 is majorly found in the sperm outer dense fiber (ODF), where it is hypothesized to promote proper assembly and maintenance of sperm flagella.^[18][19] It also localizes to the acrosomal membrane of the sperm, where it putatively mediates calcium ion transmembrane transport.^[20]

Clinical significance

The VDAC2 protein belongs to a group of mitochondrial membrane channels involved in translocation of

development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.

The VDAC2 protein has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart.^[23] Although a large burst of reactive oxygen species (ROS) is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC2 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death.

The VDAC2 protein has been linked persistent pulmonary hypertension of the newborn (PPHN), which causes a large majority of neonatal morbidity and mortality, due to its role as a major regulator of endothelium-dependent nitric oxide synthase (eNOS) in the pulmonary endothelium. eNOS has been attributed with regulating NOS activity in response to physiological stimuli, which is vital to maintain NO production for proper blood circulation to the lungs. As a result, VDAC2 is significantly involved in pulmonary circulation and may become a therapeutic target for treating diseases such as pulmonary hypertension,^[11]

VDAC2 may also serve an immune function, as it has been hypothesized to detect and induce apoptosis in cells infected by the IBD virus. IBD, the equivalent HIV in birds, can compromise their immune systems and even cause fatal injury to the lymphoid organ, Studies of this process indicate that VDAC2 interacts with the viral protein V5 to mediate cell death.^[13]

Interactions

VDAC2 has been shown to

with:

• BAK^[13][16]
• Parkin^[24]
• eNOS^[11]

See also

• Voltage-dependent anion channel

References

Further reading

• Blachly-Dyson E, Zambronicz EB, Yu WH, Adams V, McCabe ER, Adelman J, Colombini M, Forte M (Jan 1993). "Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel". The Journal of Biological Chemistry. 268 (3): 1835–41.
  PMID 8420959
  .
• Valis K, Neubauerova J, Man P, Pompach P, Vohradsky J, Kovar J (Apr 2008). "VDAC2 and aldolase A identified as membrane proteins of K562 cells with increased expression under iron deprivation". Molecular and Cellular Biochemistry. 311 (1–2): 225–31.
  S2CID 20774884
  .
• Mannella CA (1998). "Conformational changes in the mitochondrial channel protein, VDAC, and their functional implications". Journal of Structural Biology. 121 (2): 207–18.
  PMID 9615439
  .
• Bogenhagen DF, Rousseau D, Burke S (Feb 2008). "The layered structure of human mitochondrial DNA nucleoids". The Journal of Biological Chemistry. 283 (6): 3665–75.
  PMID 18063578
  .
• Chandra D, Choy G, Daniel PT, Tang DG (May 2005). "Bax-dependent regulation of Bak by voltage-dependent anion channel 2". The Journal of Biological Chemistry. 280 (19): 19051–61.
  PMID 15757910
  .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48.
  S2CID 7827573
  .
• Yoo BC, Fountoulakis M, Cairns N, Lubec G (Jan 2001). "Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down syndrome". Electrophoresis. 22 (1): 172–9.
  S2CID 44748465
  .
• Ahmed M, Forsberg J, Bergsten P (2005). "Protein profiling of human pancreatic islets by two-dimensional gel electrophoresis and mass spectrometry". Journal of Proteome Research. 4 (3): 931–40.
  PMID 15952740
  .
• Ha H, Hajek P, Bedwell DM, Burrows PD (Jun 1993). "A mitochondrial porin cDNA predicts the existence of multiple human porins". The Journal of Biological Chemistry. 268 (16): 12143–9.
  PMID 7685033
  .
• Yu WH, Wolfgang W, Forte M (Jun 1995). "Subcellular localization of human voltage-dependent anion channel isoforms". The Journal of Biological Chemistry. 270 (23): 13998–4006.
  PMID 7539795
  .
• Hinsch KD, De Pinto V, Aires VA, Schneider X, Messina A, Hinsch E (Apr 2004). "Voltage-dependent anion-selective channels VDAC2 and VDAC3 are abundant proteins in bovine outer dense fibers, a cytoskeletal component of the sperm flagellum". The Journal of Biological Chemistry. 279 (15): 15281–8.
  PMID 14739283
  .
• Decker WK, Bowles KR, Schatte EC, Towbin JA, Craigen WJ (Oct 1999). "Revised fine mapping of the human voltage-dependent anion channel loci by radiation hybrid analysis". Mammalian Genome. 10 (10): 1041–2.
  S2CID 27663120
  .
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (Jan 2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83.
  S2CID 4344740
  .
• Bernhard OK, Cunningham AL, Sheil MM (Apr 2004). "Analysis of proteins copurifying with the CD4/lck complex using one-dimensional polyacrylamide gel electrophoresis and mass spectrometry: comparison with affinity-tag based protein detection and evaluation of different solubilization methods". Journal of the American Society for Mass Spectrometry. 15 (4): 558–67.
  PMID 15047060
  .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89.
  PMID 17353931
  .

External links

• VDAC2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)