Phosphatase Subfamily ACP6
Phosphatase Classification: Fold HP: Superfamily HP: Family HP, branch 2: Subfamily ACP6
Evolution
The ACP6 subfamily is found across holozoa and absent from ecdysozoa. Furthermore, BLASTing human and monosiga ACP6 against NR database showed the closest genes found in ecdysozoa belong to the ACP2 subfamily, so the ACP6 subfamily was indeed lost in ecdysozoa. And interestingly, both Drosophila melanogaster and C. elegans have remarkable expansions in another subfamily in HP1 family ACP2. The ACP6 subfamily is also absent from budding yeast, but reciprocal BLAST and internal orthology database showed many other fungi have ACP6. ACP6s were also found in some but not all basal eukaryotes, by BLAST and from internal database. In sum, the ACP6 subfamily probably emerged in opisthokont or even earlier and was lost in ecdysozoa.
Domain
The ACP6 subfamily has a single structural domain, the phosphatase domain. It also has a signal peptide at N-terminal which may target it to mitochondria [1].
Function
Human ACP6 is an LPA-specific acid phosphatase that hydrolyzes LPA to monoacylglycerol (MAG) and phosphate [2]. Lysophosphatidic acid (LPA) is an important bioactive phospholipid involved in cell signaling through G-protein-coupled receptors pathways. It is also involved in balancing the lipid composition inside the cell, and modulates the function of lipid rafts as an intermediate in phospholipid metabolism. LPA synthesis occurs through a number of pathways; LPA degradation occurs through three known pathways, including the one through ACP6 [2].
ACP6 is localized in the mitochondria with ubiquitous expression throughout all tissues, and high expression levels in kidney, heart, small intestine, muscle, and liver [1]. The active form of ACP6 is monomer, while human ACPP of ACP2 subfamily is active as dimer [2].
References
- Hiroyama M and Takenawa T. Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that is involved in the regulation of mitochondrial lipid biosynthesis. J Biol Chem. 1999 Oct 8;274(41):29172-80. DOI:10.1074/jbc.274.41.29172 |
- Li J, Dong Y, Lü X, Wang L, Peng W, Zhang XC, and Rao Z. Crystal structures and biochemical studies of human lysophosphatidic acid phosphatase type 6. Protein Cell. 2013 Jul;4(7):548-61. DOI:10.1007/s13238-013-3031-z |
