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FUNCTION Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets (PubMed:17936702, PubMed:25012651). Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1 (PubMed:17936702). Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (PubMed:20516061). In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997). May dephosphorylate CSNK1D and CSNK1E (By similarity). Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702). Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Together with PPP1CA (PP1-alpha subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response (PubMed:23499489). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35831509). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35831509). Dephosphorylates MKI67 at the onset of anaphase (PubMed:25012651). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:35831509).CATALYTIC ACTIVITY O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphateCATALYTIC ACTIVITY O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphateCOFACTOR Binds 2 manganese ions per subunit.ACTIVITY REGULATION Inactivated by binding to URI1. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.SUBUNIT PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with cyanobacterial toxin microcystin; disulfide-linked. Interacts with PPP1R3B and PPP1R7. Isoform 2 interacts with SPZ1 (By similarity). Interacts with CDCA2. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with PPP1R42; the interaction is direct (By similarity). Interacts with NOM1 and PPP1R8. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with isoform 1 and isoform 4 NEK2. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts with FOXP3. Interacts with TMEM225 (via RVxF motif) (By similarity). Interacts with MKI67 (PubMed:24867636). Interacts with RRP1B; this targets PPP1CC to the nucleolus (PubMed:20926688). Interacts with PPP1R2B (PubMed:23506001). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654). Interacts with DYNLT4 (PubMed:23789093). Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity (PubMed:34260926). Interacts with the KNL1 complex subunit KNL1; the interaction is direct and mutually exclusive with KNL1 binding to microtubules (PubMed:30100357). Component of the SHOC2-MRAS-PP1c (SMP) complex consisting of SHOC2, GTP-bound M-Ras/MRAS and the catalytic subunit of protein phosphatase 1 (either PPP1CA, PPP1CB or PPP1CC) (PubMed:35768504, PubMed:35831509). SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS; these interactions are GTP-dependent and both SHOC2 and PP1c are required to form a stable complex (PubMed:35768504, PubMed:35831509). Interacts with SHOC2 in the absence of Ras GTPases (PubMed:35768504).INTERACTION Colocalizes with SPZ1 in the nucleus (By similarity). Colocalizes with URI1 at mitochondrion (PubMed:17936702). Rapidly exchanges between the nucleolar, nucleoplasmic and cytoplasmic compartments (PubMed:11739654). Highly mobile in cells and can be relocalized through interaction with targeting subunits (PubMed:17965019). In the presence of PPP1R8 relocalizes from the nucleolus to nuclear speckles (PubMed:11739654). Shows a dynamic targeting to specific sites throughout the cell cycle (PubMed:12529430). Highly concentrated in nucleoli of interphase cells and localizes at kinetochores early in mitosis (PubMed:12529430). Relocalization to chromosome-containing regions occurs at the transition from early to late anaphase (PubMed:12529430). Also accumulates at the cleavage furrow and midbody by telophase (PubMed:12529430). Colocalizes with DYNLT4 in the microtubule organizing center (MTOC) (PubMed:23789093).ALTERNATIVE PRODUCTS Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.PTM Phosphorylated by NEK2.MISCELLANEOUS Microcystin toxin is bound to Cys-273 through a thioether bond.SIMILARITY Belongs to the PPP phosphatase family. PP-1 subfamily.CAUTION Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).ONLINE INFORMATION The things we forget - Issue 32 of March 2003
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