ID PPM1A_RAT Reviewed; 382 AA. AC P20650; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 08-NOV-2023, entry version 167. DE RecName: Full=Protein phosphatase 1A; DE EC=3.1.3.16; DE AltName: Full=Protein phosphatase 2C isoform alpha; DE Short=PP2C-alpha; DE AltName: Full=Protein phosphatase IA; GN Name=Ppm1a; Synonyms=Pp2c1, Pppm1a; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Kidney; RX PubMed=2538815; DOI=10.1073/pnas.86.6.1796; RA Tamura S., Lynch K.R., Larner J., Fox J., Yasui A., Kikuchi K., Suzuki Y., RA Tsuiki S.; RT "Molecular cloning of rat type 2C (IA) protein phosphatase mRNA."; RL Proc. Natl. Acad. Sci. U.S.A. 86:1796-1800(1989). RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Enzyme with a broad specificity. Negatively regulates TGF- CC beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in CC their dissociation from SMAD4, nuclear export of the SMADs and CC termination of the TGF-beta-mediated signaling (By similarity). CC Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the CC termination of TNF-alpha-mediated NF-kappa-B activation through CC dephosphorylating and inactivating IKBKB/IKKB (By similarity). CC {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Note=Binds 2 magnesium or manganese ions per subunit.; CC -!- SUBUNIT: Monomer (By similarity). Interacts with SMAD2; the interaction CC dephosphorylates SMAD2 in its C-terminal SXS motif resulting in CC disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and CC termination of the TGF-beta-mediated signaling. Interacts with SMAD2; CC the interaction dephosphorylates SMAD2 in its C-terminal SXS motif CC resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear CC export and termination of the TGF-beta-mediated signaling (By CC similarity). Interacts with the phosphorylated form of IKBKB/IKKB (By CC similarity). {ECO:0000250}. CC -!- INTERACTION: CC P20650; Q00975: CACNA1B; Xeno; NbExp=3; IntAct=EBI-7491743, EBI-1055161; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P35813}. CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:P35813}. Membrane CC {ECO:0000250|UniProtKB:P35813}; Lipid-anchor CC {ECO:0000250|UniProtKB:P35813}. Note=Weakly associates at the membrane CC and N-myristoylation mediates the membrane localization. CC {ECO:0000250|UniProtKB:P49443}. CC -!- PTM: N-myristoylation is essential for the recognition of its CC substrates for dephosphorylation. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04503; AAA41917.1; -; mRNA. DR PIR; A32399; A32399. DR RefSeq; NP_058734.1; NM_017038.1. DR RefSeq; XP_017449523.1; XM_017594034.1. DR AlphaFoldDB; P20650; -. DR SMR; P20650; -. DR BioGRID; 246798; 1. DR IntAct; P20650; 4. DR MINT; P20650; -. DR STRING; 10116.ENSRNOP00000008238; -. DR iPTMnet; P20650; -. DR PhosphoSitePlus; P20650; -. DR jPOST; P20650; -. DR PaxDb; 10116-ENSRNOP00000008238; -. DR GeneID; 24666; -. DR KEGG; rno:24666; -. DR UCSC; RGD:3373; rat. DR AGR; RGD:3373; -. DR CTD; 5494; -. DR RGD; 3373; Ppm1a. DR eggNOG; KOG0697; Eukaryota. DR HOGENOM; CLU_013173_4_0_1; -. DR InParanoid; P20650; -. DR OrthoDB; 11028at2759; -. DR PhylomeDB; P20650; -. DR TreeFam; TF313590; -. DR Reactome; R-RNO-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-RNO-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR PRO; PR:P20650; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; ISO:RGD. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:RGD. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:RGD. DR GO; GO:0070412; F:R-SMAD binding; ISS:UniProtKB. DR GO; GO:0044325; F:transmembrane transporter binding; IDA:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD. DR GO; GO:0016311; P:dephosphorylation; ISO:RGD. DR GO; GO:0006499; P:N-terminal protein myristoylation; ISS:UniProtKB. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:RGD. DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB. DR GO; GO:0006611; P:protein export from nucleus; ISO:RGD. DR CDD; cd00143; PP2Cc; 1. DR Gene3D; 1.10.10.430; Phosphatase 2C, C-terminal domain suprefamily; 1. DR Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1. DR InterPro; IPR015655; PP2C. DR InterPro; IPR000222; PP2C_BS. DR InterPro; IPR012911; PP2C_C. DR InterPro; IPR036580; PP2C_C_sf. DR InterPro; IPR036457; PPM-type-like_dom_sf. DR InterPro; IPR001932; PPM-type_phosphatase-like_dom. DR PANTHER; PTHR47992; PROTEIN PHOSPHATASE; 1. DR PANTHER; PTHR47992:SF121; PROTEIN PHOSPHATASE 1A; 1. DR Pfam; PF00481; PP2C; 1. DR Pfam; PF07830; PP2C_C; 1. DR SMART; SM00332; PP2Cc; 1. DR SUPFAM; SSF81606; PP2C-like; 1. DR SUPFAM; SSF81601; Protein serine/threonine phosphatase 2C, C-terminal domain; 1. DR PROSITE; PS01032; PPM_1; 1. DR PROSITE; PS51746; PPM_2; 1. DR Genevisible; P20650; RN. PE 1: Evidence at protein level; KW Cytoplasm; Direct protein sequencing; Hydrolase; Lipoprotein; Magnesium; KW Manganese; Membrane; Metal-binding; Myristate; Nucleus; Phosphoprotein; KW Protein phosphatase; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P35813" FT CHAIN 2..382 FT /note="Protein phosphatase 1A" FT /id="PRO_0000057744" FT DOMAIN 23..291 FT /note="PPM-type phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082" FT BINDING 60 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 60 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 61 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 239 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 282 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35813" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P49443" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250|UniProtKB:P35813" SQ SEQUENCE 382 AA; 42417 MW; C1C386E935374F89 CRC64; MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ETWSFFAVYD GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSAE AVKKEAELDK YLENRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA VYNRLNPYKN DDTDSASTDD MW //