PLPP3

PLPP3 is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid.

Full Name

Phospholipid Phosphatase 3

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:9705349, PubMed:9607309, PubMed:27694435).
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:9607309, PubMed:23591818, PubMed:27694435).
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).

Biological Process

Bergmann glial cell differentiationIEA:Ensembl
Blood vessel developmentIEA:Ensembl
Canonical Wnt signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cell-cell adhesion mediated by integrinManual Assertion Based On ExperimentIDA:UniProtKB
Ceramide metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Gastrulation with mouth forming secondIEA:Ensembl
Homotypic cell-cell adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Phospholipid dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Phospholipid metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell-cell adhesionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationIEA:Ensembl
Protein stabilizationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of sphingolipid mediated signaling pathwayIEA:Ensembl
Regulation of Wnt signaling pathwayIEA:Ensembl
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulumManual Assertion Based On ExperimentIMP:UniProtKB
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Sphingolipid biosynthetic processTAS:Reactome
Sphingosine metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Wound healingManual Assertion Based On ExperimentIMP:BHF-UCL

Cellular Location

Cell membrane
Basolateral cell membrane
Endoplasmic reticulum membrane
Endoplasmic reticulum-Golgi intermediate compartment membrane
Golgi apparatus membrane
Golgi apparatus, trans-Golgi network membrane
Membrane raft
Cycles between the endoplasmic reticulum and the Golgi.

Topology

Cytoplasmic: 1-33
Helical: 34-54
Extracellular: 55-85
Helical: 86-106
Cytoplasmic: 107-122
Helical: 123-143
Extracellular: 144-193
Helical: 194-214
Cytoplasmic: 215-225
Helical: 226-243
Extracellular: 244-257
Helical: 258-278
Cytoplasmic: 279-311

PTM

N-glycosylated (PubMed:9705349).
Contains high-mannose oligosaccharides (PubMed:9705349).