PPM1A_HUMAN
ID PPM1A_HUMAN Reviewed; 382 AA.
AC P35813; B5BU11; J3KNM0; O75551;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Protein phosphatase 1A;
DE EC=3.1.3.16 {ECO:0000255|PROSITE-ProRule:PRU01082, ECO:0000269|PubMed:30267671};
DE AltName: Full=Protein phosphatase 2C isoform alpha;
DE Short=PP2C-alpha;
DE AltName: Full=Protein phosphatase IA;
GN Name=PPM1A; Synonyms=PPPM1A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
RX PubMed=1311954; DOI=10.1016/0167-4781(92)90471-b;
RA Mann D.J., Campbell D.G., McGowan C.H., Cohen P.T.W.;
RT "Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and
RT comparative analysis of amino acid sequences.";
RL Biochim. Biophys. Acta 1130:100-104(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
RX PubMed=9707433; DOI=10.1093/emboj/17.16.4744;
RA Takekawa M., Maeda T., Saito H.;
RT "Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and
RT JNK MAPK pathways.";
RL EMBO J. 17:4744-4752(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
RC TISSUE=Colon, and Lung;
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 [8]
RP INTERACTION WITH SMAD2 AND SMAD3, FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ASP-239.
RX PubMed=16751101; DOI=10.1016/j.cell.2006.03.044;
RA Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M.,
RA Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A.,
RA Feng X.H.;
RT "PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.";
RL Cell 125:915-928(2006).
RN [9]
RP FUNCTION, AND INTERACTION WITH IKBKB.
RX PubMed=18930133; DOI=10.1016/j.cellsig.2008.09.012;
RA Sun W., Yu Y., Dotti G., Shen T., Tan X., Savoldo B., Pass A.K., Chu M.,
RA Zhang D., Lu X., Fu S., Lin X., Yang J.;
RT "PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced
RT IKKbeta-NF-kappaB activation.";
RL Cell. Signal. 21:95-102(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [16]
RP CATALYTIC ACTIVITY, COFACTOR, AND METAL-BINDING SITES.
RX PubMed=30267671; DOI=10.1016/j.bbabio.2018.09.369;
RA Gonzalez-Mariscal I., Martin-Montalvo A., Vazquez-Fonseca L.,
RA Pomares-Viciana T., Sanchez-Cuesta A., Fernandez-Ayala D.J., Navas P.,
RA Santos-Ocana C.;
RT "The mitochondrial phosphatase PPTC7 orchestrates mitochondrial metabolism
RT regulating coenzyme Q10 biosynthesis.";
RL Biochim. Biophys. Acta 1859:1235-1248(2018).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), AND COFACTOR.
RX PubMed=9003755; DOI=10.1002/j.1460-2075.1996.tb01071.x;
RA Das A.K., Helps N.R., Cohen P.T.W., Barford D.;
RT "Crystal structure of the protein serine/threonine phosphatase 2C at 2.0-A
RT resolution.";
RL EMBO J. 15:6798-6809(1996).
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. Dephosphorylates PRKAA1
CC and PRKAA2. Plays an important role in the termination of TNF-alpha-
CC mediated NF-kappa-B activation through dephosphorylating and
CC inactivating IKBKB/IKKB. {ECO:0000269|PubMed:16751101,
CC ECO:0000269|PubMed:18930133}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU01082};
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 Evidence={ECO:0000269|PubMed:30267671};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:30267671};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:30267671};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU01082};
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. Interacts
CC with the phosphorylated form of IKBKB/IKKB.
CC {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:18930133}.
CC -!- INTERACTION:
CC P35813; P49407: ARRB1; NbExp=4; IntAct=EBI-989143, EBI-743313;
CC P35813; P32121: ARRB2; NbExp=3; IntAct=EBI-989143, EBI-714559;
CC P35813; O15169: AXIN1; NbExp=2; IntAct=EBI-989143, EBI-710484;
CC P35813; P00533: EGFR; NbExp=2; IntAct=EBI-989143, EBI-297353;
CC P35813; P08069: IGF1R; NbExp=2; IntAct=EBI-989143, EBI-475981;
CC P35813; P28482: MAPK1; NbExp=19; IntAct=EBI-989143, EBI-959949;
CC P35813; Q16539: MAPK14; NbExp=2; IntAct=EBI-989143, EBI-73946;
CC P35813; Q9H6Z4: RANBP3; NbExp=4; IntAct=EBI-989143, EBI-992681;
CC P35813; Q15796: SMAD2; NbExp=2; IntAct=EBI-989143, EBI-1040141;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16751101}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:22781750}. Membrane
CC {ECO:0000269|PubMed:20213681, ECO:0000269|PubMed:25255805}; Lipid-
CC anchor {ECO:0000269|PubMed:20213681, ECO:0000269|PubMed:25255805}.
CC Note=Weakly associates at the membrane and N-myristoylation mediates
CC the membrane localization. {ECO:0000250|UniProtKB:P49443}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Alpha-1;
CC IsoId=P35813-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=P35813-2; Sequence=VSP_005085, VSP_005086;
CC Name=3;
CC IsoId=P35813-3; Sequence=VSP_045687;
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; S87759; AAB21784.1; -; mRNA.
DR EMBL; AF070670; AAC28354.1; -; mRNA.
DR EMBL; AK097843; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB451247; BAG70061.1; -; mRNA.
DR EMBL; AL132778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW80774.1; -; Genomic_DNA.
DR EMBL; BC026691; AAH26691.1; -; mRNA.
DR EMBL; BC063243; AAH63243.1; -; mRNA.
DR CCDS; CCDS45120.1; -. [P35813-3]
DR CCDS; CCDS9744.1; -. [P35813-1]
DR CCDS; CCDS9745.1; -. [P35813-2]
DR PIR; S22423; S22423.
DR RefSeq; NP_066283.1; NM_021003.4. [P35813-1]
DR RefSeq; NP_808820.1; NM_177951.2. [P35813-2]
DR RefSeq; NP_808821.2; NM_177952.2. [P35813-3]
DR RefSeq; XP_005267836.1; XM_005267779.1. [P35813-1]
DR RefSeq; XP_005267838.1; XM_005267781.1. [P35813-1]
DR RefSeq; XP_011535180.1; XM_011536878.1. [P35813-1]
DR RefSeq; XP_011535181.1; XM_011536879.2. [P35813-1]
DR RefSeq; XP_011535182.1; XM_011536880.2. [P35813-1]
DR RefSeq; XP_011535183.1; XM_011536881.2. [P35813-1]
DR RefSeq; XP_011535184.1; XM_011536882.2. [P35813-1]
DR RefSeq; XP_011535185.1; XM_011536883.1. [P35813-1]
DR RefSeq; XP_011535186.1; XM_011536884.1.
DR RefSeq; XP_016876873.1; XM_017021384.1. [P35813-1]
DR RefSeq; XP_016876874.1; XM_017021385.1. [P35813-1]
DR RefSeq; XP_016876875.1; XM_017021386.1. [P35813-1]
DR RefSeq; XP_016876876.1; XM_017021387.1. [P35813-1]
DR PDB; 1A6Q; X-ray; 2.00 A; A=1-382.
DR PDB; 3FXJ; X-ray; 2.50 A; A=1-382.
DR PDB; 3FXK; X-ray; 2.10 A; A=1-382.
DR PDB; 3FXL; X-ray; 2.30 A; A=1-382.
DR PDB; 3FXM; X-ray; 2.50 A; A=1-382.
DR PDB; 3FXO; X-ray; 2.50 A; A=1-382.
DR PDB; 4RA2; X-ray; 1.94 A; A=2-368.
DR PDB; 4RAF; X-ray; 2.00 A; A=2-368.
DR PDB; 4RAG; X-ray; 1.85 A; A=2-368.
DR PDB; 6B67; X-ray; 2.20 A; A/B/C=2-297.
DR PDBsum; 1A6Q; -.
DR PDBsum; 3FXJ; -.
DR PDBsum; 3FXK; -.
DR PDBsum; 3FXL; -.
DR PDBsum; 3FXM; -.
DR PDBsum; 3FXO; -.
DR PDBsum; 4RA2; -.
DR PDBsum; 4RAF; -.
DR PDBsum; 4RAG; -.
DR PDBsum; 6B67; -.
DR AlphaFoldDB; P35813; -.
DR SMR; P35813; -.
DR BioGRID; 111489; 125.
DR IntAct; P35813; 89.
DR MINT; P35813; -.
DR STRING; 9606.ENSP00000327255; -.
DR BindingDB; P35813; -.
DR ChEMBL; CHEMBL2437; -.
DR DEPOD; PPM1A; -.
DR GlyGen; P35813; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; P35813; -.
DR MetOSite; P35813; -.
DR PhosphoSitePlus; P35813; -.
DR BioMuta; PPM1A; -.
DR DMDM; 548442; -.
DR EPD; P35813; -.
DR jPOST; P35813; -.
DR MassIVE; P35813; -.
DR MaxQB; P35813; -.
DR PaxDb; P35813; -.
DR PeptideAtlas; P35813; -.
DR PRIDE; P35813; -.
DR ProteomicsDB; 55156; -. [P35813-1]
DR ProteomicsDB; 55157; -. [P35813-2]
DR Antibodypedia; 11485; 475 antibodies from 38 providers.
DR DNASU; 5494; -.
DR Ensembl; ENST00000325642.7; ENSP00000327255.3; ENSG00000100614.18. [P35813-3]
DR Ensembl; ENST00000325658.3; ENSP00000314850.3; ENSG00000100614.18. [P35813-2]
DR Ensembl; ENST00000395076.9; ENSP00000378514.4; ENSG00000100614.18. [P35813-1]
DR GeneID; 5494; -.
DR KEGG; hsa:5494; -.
DR MANE-Select; ENST00000395076.9; ENSP00000378514.4; NM_021003.5; NP_066283.1.
DR UCSC; uc001xew.5; human. [P35813-1]
DR CTD; 5494; -.
DR DisGeNET; 5494; -.
DR GeneCards; PPM1A; -.
DR HGNC; HGNC:9275; PPM1A.
DR HPA; ENSG00000100614; Tissue enhanced (bone).
DR MIM; 606108; gene.
DR neXtProt; NX_P35813; -.
DR OpenTargets; ENSG00000100614; -.
DR PharmGKB; PA33603; -.
DR VEuPathDB; HostDB:ENSG00000100614; -.
DR eggNOG; KOG0697; Eukaryota.
DR GeneTree; ENSGT00940000154832; -.
DR HOGENOM; CLU_013173_4_0_1; -.
DR InParanoid; P35813; -.
DR OrthoDB; 957254at2759; -.
DR PhylomeDB; P35813; -.
DR TreeFam; TF313590; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; P35813; -.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR SABIO-RK; P35813; -.
DR SignaLink; P35813; -.
DR SIGNOR; P35813; -.
DR BioGRID-ORCS; 5494; 14 hits in 1090 CRISPR screens.
DR ChiTaRS; PPM1A; human.
DR EvolutionaryTrace; P35813; -.
DR GeneWiki; PPM1A; -.
DR GenomeRNAi; 5494; -.
DR Pharos; P35813; Tchem.
DR PRO; PR:P35813; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P35813; protein.
DR Bgee; ENSG00000100614; Expressed in sperm and 209 other tissues.
DR ExpressionAtlas; P35813; baseline and differential.
DR Genevisible; P35813; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:UniProtKB.
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:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0070412; F:R-SMAD binding; IPI:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; IDA:BHF-UCL.
DR GO; GO:0006499; P:N-terminal protein myristoylation; ISS:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0010991; P:negative regulation of SMAD protein complex assembly; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:Reactome.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:Reactome.
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 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Lipoprotein;
KW Magnesium; Manganese; Membrane; Metal-binding; Myristate; Nucleus;
KW Phosphoprotein; Protein phosphatase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..382
FT /note="Protein phosphatase 1A"
FT /id="PRO_0000057741"
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:0000269|PubMed:9003755,
FT ECO:0007744|PDB:1A6Q"
FT BINDING 60
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9003755,
FT ECO:0007744|PDB:1A6Q"
FT BINDING 61
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9003755,
FT ECO:0007744|PDB:1A6Q"
FT BINDING 239
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9003755,
FT ECO:0007744|PDB:1A6Q"
FT BINDING 282
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9003755,
FT ECO:0007744|PDB:1A6Q"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49443"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:20213681,
FT ECO:0000269|PubMed:25255805"
FT VAR_SEQ 1
FT /note="M -> MFCSGRKWVAEATICTKLMKREKRRMGKRRAKKAKREEKKKGGERRR
FT NEKRGNQMKRMCERKKYETDLEDQDIM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045687"
FT VAR_SEQ 318..324
FT /note="EIIKKQG -> GGSFNKK (in isoform Alpha-2)"
FT /evidence="ECO:0000303|PubMed:9707433"
FT /id="VSP_005085"
FT VAR_SEQ 325..382
FT /note="Missing (in isoform Alpha-2)"
FT /evidence="ECO:0000303|PubMed:9707433"
FT /id="VSP_005086"
FT MUTAGEN 239
FT /note="D->N: No effect on binding SMAD2."
FT /evidence="ECO:0000269|PubMed:16751101"
FT CONFLICT 342
FT /note="I -> T (in Ref. 3; AK097843)"
FT /evidence="ECO:0000305"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:4RAG"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4RA2"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 66..80
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 94..119
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 136..146
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 169..177
FT /evidence="ECO:0007829|PDB:4RAG"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:4RAG"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 239..242
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 247..258
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 264..277
FT /evidence="ECO:0007829|PDB:4RAG"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 299..320
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 330..339
FT /evidence="ECO:0007829|PDB:4RAG"
FT TURN 347..350
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:4RAG"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:4RAG"
FT CONFLICT P35813-3:54
FT /note="Q -> R (in Ref. 3; AK097843)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 42448 MW; D48EF508B4A76687 CRC64;
MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ESWSFFAVYD
GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH
GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG
SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG
IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE
AVKKEAELDK YLECRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA
VYNRLNPYKN DDTDSTSTDD MW
