VDAC2

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

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. In particular, VDAC2 possesses an N-terminal longer by 11 residues compared to the other two isoforms.

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 is_associated_with::outer mitochondrial membrane. In mammalian cardiomyocytes, VDAC2 promotes mitochondrial transport of calcium ions in order to power cardiac contractions.

In addition, VDACs form part of the is_associated_with::mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis. 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. VDAC2 in particular has demonstrated a protective effect in cells undergoing mitochondrial apoptosis, and may even confer protection during aging.

Furthermore, VDAcs have been linked to spermatogenesis, sperm maturation, motility, and fertilization. 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. It also localizes to the acrosomal membrane of the sperm, where it putatively mediates calcium ion transmembrane transport.

Clinical Significance
This 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,

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.

Interactions
VDAC2 has been shown to interact with:
 * is_associated_with::BAK
 * is_associated_with::Parkin
 * is_associated_with::eNOS