241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Specifically dephosphorylates sphingosine 1-phosphate(S1P), dihydro-S1P, and phyto-S1P Does not act on ceramide 1-phoshate, lysophosphatidic acid or phosphatidic acid Regulatesthe intracellular levels of the bioactive sphingolipid metaboliteS1P that regulates diverse biological processes acting both as anextracellular receptor ligand or as an intracellular secondmessenger (PubMed:12815058, PubMed:11756451) Involved inefficient ceramide synthesis from exogenous sphingoid basesConverts S1P to sphingosine, which is readily metabolized toceramide via ceramide synthase In concert with sphingosine kinase2 (SphK2), recycles sphingosine into ceramide though aphosphorylation/dephosphorylation cycle Regulates intracellularceramide levels, which in turn regulate apoptosis (By similarity)Via S1P levels, modulates resting tone, intracellular Ca(2+) andmyogenic vasoconstriction in resistance arteries(PubMed:18583713) Also involved in unfolded protein response(UPR) and ER stress-induced autophagy via regulation ofintracellular S1P levels (PubMed:20798685)
Sphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) and sphingosine-1-phosphate (S1P), have emerged as a new class of potent bioactive molecules. Ceramide can be generated de novo or by hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase). Ceramide is subsequently metabolized by ceramidase to generate sphingosine (Sph) which in turn produces S1P through phosphorylation by sphingosine kinases 1 and 2 (SphK1, 2). Both ceramide and S1P regulate cellular responses to stress, with generally opposing effects. S1P functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled receptors, whereas ceramide activates intrinsic and extrinsic apoptotic pathways through receptor-independent mechanisms.