PPM1A_RAT
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 03-AUG-2022, entry version 162.
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}.
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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; P20650; -.
DR PRIDE; P20650; -.
DR GeneID; 24666; -.
DR KEGG; rno:24666; -.
DR UCSC; RGD:3373; rat.
DR CTD; 5494; -.
DR RGD; 3373; Ppm1a.
DR eggNOG; KOG0697; Eukaryota.
DR HOGENOM; CLU_013173_4_0_1; -.
DR InParanoid; P20650; -.
DR OrthoDB; 957254at2759; -.
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 Genevisible; P20650; RN.
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; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
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 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:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
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; 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
