PPM1A_MOUSE
ID PPM1A_MOUSE Reviewed; 382 AA.
AC P49443;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
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=Pppm1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8056349; DOI=10.1016/0378-1119(94)90026-4;
RA Kato S., Kobayashi T., Terasawa T., Ohnishi M., Sasahara Y., Kanamaru R.,
RA Tamura S.;
RT "The cDNA sequence encoding mouse Mg2+ -dependent protein phosphatase
RT alpha.";
RL Gene 145:311-312(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375 AND SER-377, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003;
RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.;
RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth
RT factor-beta pathway.";
RL Cell. Signal. 24:1999-2006(2012).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MYRISTOYLATION AT GLY-2.
RX PubMed=23088624; DOI=10.1042/bj20121201;
RA Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T.,
RA Tamura S., Kobayashi T.;
RT "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to
RT dephosphorylate their physiological substrates in cells.";
RL Biochem. J. 449:741-749(2013).
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. {ECO:0000250,
CC ECO:0000269|PubMed:23088624}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P35813}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:22781750,
CC ECO:0000269|PubMed:23088624}. Membrane {ECO:0000269|PubMed:23088624};
CC Lipid-anchor {ECO:0000269|PubMed:23088624}. Note=Weakly associates at
CC the membrane and N-myristoylation mediates the membrane localization.
CC {ECO:0000269|PubMed:23088624}.
CC -!- PTM: N-myristoylation is essential for the recognition of its
CC substrates for dephosphorylation. {ECO:0000269|PubMed:23088624}.
CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}.
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DR EMBL; D28117; BAA05662.1; -; mRNA.
DR EMBL; BC008595; AAH08595.1; -; mRNA.
DR CCDS; CCDS25970.1; -.
DR PIR; I53823; I53823.
DR RefSeq; NP_032936.1; NM_008910.3.
DR RefSeq; XP_006515666.1; XM_006515603.3.
DR AlphaFoldDB; P49443; -.
DR SMR; P49443; -.
DR BioGRID; 202332; 12.
DR STRING; 10090.ENSMUSP00000021514; -.
DR ChEMBL; CHEMBL3309056; -.
DR iPTMnet; P49443; -.
DR PhosphoSitePlus; P49443; -.
DR SwissPalm; P49443; -.
DR EPD; P49443; -.
DR MaxQB; P49443; -.
DR PaxDb; P49443; -.
DR PeptideAtlas; P49443; -.
DR PRIDE; P49443; -.
DR ProteomicsDB; 291835; -.
DR Antibodypedia; 11485; 475 antibodies from 38 providers.
DR DNASU; 19042; -.
DR Ensembl; ENSMUST00000021514; ENSMUSP00000021514; ENSMUSG00000021096.
DR GeneID; 19042; -.
DR KEGG; mmu:19042; -.
DR UCSC; uc007nvu.2; mouse.
DR CTD; 5494; -.
DR MGI; MGI:99878; Ppm1a.
DR VEuPathDB; HostDB:ENSMUSG00000021096; -.
DR eggNOG; KOG0697; Eukaryota.
DR GeneTree; ENSGT00940000154832; -.
DR HOGENOM; CLU_013173_4_0_1; -.
DR InParanoid; P49443; -.
DR OMA; CTACVGL; -.
DR OrthoDB; 957254at2759; -.
DR PhylomeDB; P49443; -.
DR TreeFam; TF313590; -.
DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR BioGRID-ORCS; 19042; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ppm1a; mouse.
DR PRO; PR:P49443; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P49443; protein.
DR Bgee; ENSMUSG00000021096; Expressed in cleaving embryo and 274 other tissues.
DR ExpressionAtlas; P49443; baseline and differential.
DR Genevisible; P49443; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; ISO:MGI.
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:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0070412; F:R-SMAD binding; ISS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:MGI.
DR GO; GO:0016311; P:dephosphorylation; ISO:MGI.
DR GO; GO:0006499; P:N-terminal protein myristoylation; IDA:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0010991; P:negative regulation of SMAD protein complex assembly; ISO:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0006611; P:protein export from nucleus; IMP:MGI.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 1.10.10.430; -; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR InterPro; IPR000222; PP2C_BS.
DR InterPro; IPR012911; PP2C_C.
DR InterPro; IPR036580; PP2C_C_sf.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR Pfam; PF00481; PP2C; 1.
DR Pfam; PF07830; PP2C_C; 1.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81601; SSF81601; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS01032; PPM_1; 1.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein 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:0000269|PubMed:23088624"
FT CHAIN 2..382
FT /note="Protein phosphatase 1A"
FT /id="PRO_0000057742"
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:0007744|PubMed:21183079"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:23088624"
SQ SEQUENCE 382 AA; 42433 MW; DC206610E1583870 CRC64;
MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ETWSFFAVYD
GHAGSQVAKY CCEHLLDHIT NNQDFRGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH
GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG
SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG
IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPSAPKVSAE
AVKKEAELDK YLESRVEEII KKQVEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA
VYNRLNPYKN DDTDSASTDD MW
