ID PPM1A_BOVIN Reviewed; 382 AA. AC O62829; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 27-MAR-2024, entry version 155. DE RecName: Full=Protein phosphatase 1A; DE EC=3.1.3.16; DE AltName: Full=Protein phosphatase 2C isoform alpha; DE Short=PP2C-alpha; GN Name=PPM1A; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Retina; RX PubMed=9486768; RX DOI=10.1002/(sici)1097-4547(19980201)51:3<328::aid-jnr6>3.0.co;2-i; RA Klumpp S., Selke D., Fischer D., Baumann A., Mueller F., Thanos S.; RT "Protein phosphatase type-2C isozymes present in vertebrate retinae: RT purification, characterization, and localization in photoreceptors."; RL J. Neurosci. Res. 51:328-338(1998). 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. 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 -!- 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; AJ005457; CAA06554.1; -; mRNA. DR RefSeq; NP_001289701.1; NM_001302772.1. DR RefSeq; NP_776854.1; NM_174429.3. DR RefSeq; XP_015328708.1; XM_015473222.1. DR AlphaFoldDB; O62829; -. DR SMR; O62829; -. DR STRING; 9913.ENSBTAP00000057716; -. DR PaxDb; 9913-ENSBTAP00000024128; -. DR Ensembl; ENSBTAT00000024128.4; ENSBTAP00000024128.3; ENSBTAG00000018127.5. DR GeneID; 281994; -. DR KEGG; bta:281994; -. DR CTD; 5494; -. DR VEuPathDB; HostDB:ENSBTAG00000018127; -. DR VGNC; VGNC:112633; PPM1A. DR eggNOG; KOG0697; Eukaryota. DR GeneTree; ENSGT00940000154832; -. DR HOGENOM; CLU_013173_4_0_1; -. DR InParanoid; O62829; -. DR OrthoDB; 11028at2759; -. DR TreeFam; TF313590; -. DR Reactome; R-BTA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-BTA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Proteomes; UP000009136; Chromosome 10. DR Bgee; ENSBTAG00000018127; Expressed in longissimus thoracis muscle and 106 other cell types or tissues. DR ExpressionAtlas; O62829; baseline and differential. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. 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; ISS:AgBase. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0070412; F:R-SMAD binding; ISS:UniProtKB. DR GO; GO:0006499; P:N-terminal protein myristoylation; ISS:UniProtKB. 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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:AgBase. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB. 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. PE 2: Evidence at transcript level; KW Cytoplasm; Hydrolase; Lipoprotein; Magnesium; Manganese; Membrane; KW Metal-binding; Myristate; Nucleus; Phosphoprotein; Protein phosphatase; KW 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_0000057740" 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; 42530 MW; A716B3FA0E7E21C2 CRC64; MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ETWSFFAVYD GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVYFF TQDHKPSNPL EKERIQNAGG SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE AVKKEEELDK YLESRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA VYNRLNPYKN DDTDSTSTDD MW //