85 kDa calcium-independent phospholipase A2, also known as 85/88 kDa calcium-independent phospholipase A2, Group VI phospholipase A2, Intracellular membrane-associated calcium-independent phospholipase A2 beta, or Patatin-like phospholipase domain-containing protein 9 is an enzyme that in humans is encoded by the PLA2G6gene.
Structure
The PLA2G6 gene is located on the p arm of chromosome 22 at position 13.1 and it spans 80,605 base pairs. The PLA2G6 gene produces an 18.6 kDa protein composed of 166 amino acids. The resulting protein's structure has been shown to contain a lipasemotif and 8 ankyrin repeats. Different from rodent PLA2G6, which is known to share 90% overall amino acid sequence identity with that of the humans, the human PLA2G6 protein contains a 54-residue insertion which codes for a proline-rich region. This insertion has been shown to disrupt the last putativeankyrin repeat, as well as function as a linker region that segregates the N-terminal protein-binding domain from the C-terminalcatalytic domain.
Function
The PLA2G6 gene encodes for a phospholipase A2 enzyme, which is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. This type of enzyme is responsible for breaking down phospholipids. Phospholipid metabolism is essential for many body processes, including helping to maintain the integrity of the cell membrane. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane. The encoded protein may also play a role in phospholipid remodelling, arachidonic acid release, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. It addition, it has a role in cardiolipindeacylation, and is required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actinpolymerization at the pseudopods. Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of PLA2G6 activity. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.
Catalytic activity
Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Model organisms
s have been used in the study of PLA2G6 function. A conditional knockout mouse line called Pla2g6tm1aWtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping.
s are a diverse class of hereditary degenerative spinal cord disorders characterized by a slow, gradual, progressive weakness and spasticity of the legs. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms may appear, or the weakness and stiffness may spread to other parts of the body. Rate of progression and the severity of symptoms are quite variable. Another disease associated with mutations in this gene is infantile neuroaxonal dystrophy.
