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 24-JAN-2024, entry version 220. 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}. 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; 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. DR RefSeq; XP_005267838.1; XM_005267781.1. DR RefSeq; XP_011535180.1; XM_011536878.1. DR RefSeq; XP_011535181.1; XM_011536879.2. DR RefSeq; XP_011535182.1; XM_011536880.2. DR RefSeq; XP_011535183.1; XM_011536881.2. [P35813-1] DR RefSeq; XP_011535184.1; XM_011536882.2. 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. DR RefSeq; XP_016876874.1; XM_017021385.1. DR RefSeq; XP_016876875.1; XM_017021386.1. DR RefSeq; XP_016876876.1; XM_017021387.1. 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; 145. DR IntAct; P35813; 91. DR MINT; P35813; -. DR STRING; 9606.ENSP00000327255; -. DR BindingDB; P35813; -. DR ChEMBL; CHEMBL2437; -. DR DEPOD; PPM1A; -. DR GlyCosmos; P35813; 1 site, 2 glycans. 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; 9606-ENSP00000327255; -. DR PeptideAtlas; P35813; -. DR ProteomicsDB; 55156; -. [P35813-1] DR ProteomicsDB; 55157; -. [P35813-2] DR Pumba; P35813; -. DR Antibodypedia; 11485; 538 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 AGR; HGNC:9275; -. 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; 11028at2759; -. 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; 15 hits in 1190 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 211 other cell types or tissues. DR ExpressionAtlas; P35813; baseline and differential. 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 canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IMP: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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl. 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; 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; P35813; HS. 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 //