PLPP3
Domain
The integrin-binding motif mediates the binding to integrin alpha-5/beta-1 (ITGA5:ITGB1) and integrin alpha-V/beta-3 (ITGAV:ITGB3) and is required for the function in integrin-mediated cell-cell adhesion.
The dityrosine basolateral targeting motif mediates localization to the basolateral membrane in polarized cells.
Function
Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P (PubMed:27694435, PubMed:9607309, PubMed:9705349). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (PubMed:9607309). Has both an extracellular and an intracellular phosphatase activity, allowing the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:23591818, PubMed:27694435, PubMed:9607309). Through the dephosphorylation of extracellular sphingosine-1-phosphate and the regulation of its extra- and intracellular availability, plays a role in vascular homeostasis, regulating endothelial cell migration, adhesion, survival, proliferation and the production of pro-inflammatory cytokines (PubMed:27694435). By maintaining the appropriate levels of this lipid in the cerebellum, also ensure its proper development and function (By similarity). Through its intracellular lipid phosphatase activity may act in early compartments of the secretory pathway, regulating the formation of Golgi to endoplasmic reticulum retrograde transport carriers (PubMed:23591818).
Independently of this phosphatase activity may also function in the Wnt signaling pathway and the stabilization of beta-catenin/CTNNB1, thereby regulating cell proliferation, migration and differentiation in angiogenesis or yet in tumor growth (PubMed:20123964, PubMed:21569306). Also plays a role in integrin-mediated cell-cell adhesion in angiogenesis (PubMed:12660161, PubMed:16099422).
Pathway
Lipid metabolism; phospholipid metabolism.
Post-translational modifications
N-glycosylated (PubMed:9705349). Contains high-mannose oligosaccharides (PubMed:9705349).
Sequence Similarities
Belongs to the PA-phosphatase related phosphoesterase family.
Tissue Specificity
Ubiquitously expressed (PubMed:12660161, PubMed:9305923). Highly expressed in heart and placenta (PubMed:9305923).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Endoplasmic reticulum-Golgi intermediate compartment membrane
- Multi-pass membrane protein
- Golgi apparatus membrane
- Multi-pass membrane protein
- Golgi apparatus
- trans-Golgi network membrane
- Multi-pass membrane protein
- Membrane raft
- Multi-pass membrane protein
- Cycles between the endoplasmic reticulum and the Golgi.
Alternative names
LPP3, PPAP2B, PLPP3, Phospholipid phosphatase 3, Lipid phosphate phosphohydrolase 3, PAP2-beta, Phosphatidate phosphohydrolase type 2b, Phosphatidic acid phosphatase 2b, Vascular endothelial growth factor and type I collagen-inducible protein, PAP-2b, PAP2b, VCIP