241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
--------------------------------
336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
--------------------------------
299 KEGG pathways;
876 Reactome pathways;
--------------------------------
last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Broad-specificity phosphohydrolase that dephosphorylatesexogenous bioactive glycerolipids and sphingolipids Catalyzes theconversion of phosphatidic acid (PA) to diacylglycerol (DG)Pivotal regulator of lysophosphatidic acid (LPA) signaling in thecardiovascular system Major enzyme responsible ofdephosphorylating LPA in platelets, which terminates signalingactions of LPA May control circulating, and possibly alsoregulate localized, LPA levels resulting from platelet activationIt has little activity towards ceramide-1-phosphate (C-1-P) andsphingosine-1-phosphate (S-1-P) The relative catalytic efficiencyis LPA > PA > S-1-P > C-1-P It's down-regulation may contributeto the development of colon adenocarcinoma
Catalytic Activity (UniProt annotation)
A 1,2-diacylglycerol 3-phosphate + H(2)O = a1,2-diacyl-sn-glycerol + phosphate
Phospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). The PLD-produced PA activates signaling proteins and acts as a node within the membrane to which signaling proteins translocate. Several signaling proteins, including Raf-1 and mTOR, directly bind PA to mediate translocation or activation, respectively.
Phagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes take part in this process in higher organisms. After opsonization with antibodies (IgG), foreign extracellular materials are recognized by Fc gamma receptors. Cross-linking of Fc gamma receptors initiates a variety of signals mediated by tyrosine phosphorylation of multiple proteins, which lead through the actin cytoskeleton rearrangements and membrane remodeling to the formation of phagosomes. Nascent phagosomes undergo a process of maturation that involves fusion with lysosomes. The acquisition of lysosomal proteases and release of reactive oxygen species are crucial for digestion of engulfed materials in phagosomes.
Fat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, dietary TAG is hydrolyzed to fatty acids (FA) and monoacylglycerols (MAG) by pancreatic lipase. These products are then emulsified with the help of phospholipids (PL) and bile acids (BA) present in bile to form micelles. Free FAs and MAGs are taken up by the enterocyte where they are rapidly resynthesized in endoplasmic reticulum (ER) to form TAG. PLs from the diet as well as bile - mainly LPA - too are absorbed by the enterocyte and are acylated to form phosphatidic acid (PA), which is also converted into TAG. Absorbed cholesterol (CL) is acylated to cholesterol esters (CE). Within the ER, TAG joins CE and apolipoprotein B (ApoB) to form chylomicrons that enter circulation through the lymph.
Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS and PI3K-AKT pathways, and transcription factors associated with oncogenesis such as hypoxia-inducible factor 1 (HIF1) mediate overexpression and activation of choline cycle enzymes, which causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These products of choline phospholipid metabolism, such as phosphocholine (PCho), diacylglycerol (DAG) and phosphatidic acid, may function as second messengers that are essential for the mitogenic activity of growth factors, particularly in the activation of the ras-raf-1-MAPK cascade and protein kinase C pathway.