PP1A_HUMAN
ID PP1A_HUMAN Reviewed; 330 AA.
AC P62136; A6NNR3; B2R908; P08129; P20653; P22802; Q07161;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Serine/threonine-protein phosphatase PP1-alpha catalytic subunit;
DE Short=PP-1A;
DE EC=3.1.3.16 {ECO:0000269|PubMed:26083323};
GN Name=PPP1CA; Synonyms=PPP1A;
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 1).
RC TISSUE=Lung;
RX PubMed=8392016; DOI=10.1016/0378-1119(93)90282-8;
RA Song Q., Khanna K.K., Lu H., Lavin M.F.;
RT "Cloning and characterization of a human protein phosphatase 1-encoding
RT cDNA.";
RL Gene 129:291-295(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=8384581; DOI=10.1101/gad.7.4.555;
RA Durfee T., Becherer K., Chen P.L., Yeh S.H., Yang Y., Kilburn A.E.,
RA Lee W.H., Elledge S.J.;
RT "The retinoblastoma protein associates with the protein phosphatase type 1
RT catalytic subunit.";
RL Genes Dev. 7:555-569(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Tung L.;
RL Submitted (APR-1991) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovial cell;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, Pancreas, and Placenta;
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 PROTEIN SEQUENCE OF 2-15 AND 247-261, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (OCT-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-330 (ISOFORM 1).
RX PubMed=2161401; DOI=10.1016/0888-7543(90)90536-4;
RA Barker H.M., Jones T.A., da Cruz e Silva E.F., Spurr N.K., Sheer D.,
RA Cohen P.T.W.;
RT "Localization of the gene encoding a type I protein phosphatase catalytic
RT subunit to human chromosome band 11q13.";
RL Genomics 7:159-166(1990).
RN [10]
RP INTERACTION WITH PPP1R15A, AND INTERACTION WITH HHV-1 ICP34.5 (MICROBIAL
RP INFECTION).
RX PubMed=9023344; DOI=10.1073/pnas.94.3.843;
RA He B., Gross M., Roizman B.;
RT "The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein
RT phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic
RT translation initiation factor 2 and preclude the shutoff of protein
RT synthesis by double-stranded RNA-activated protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:843-848(1997).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PPP1R8.
RX PubMed=11739654; DOI=10.1242/jcs.114.23.4219;
RA Trinkle-Mulcahy L., Sleeman J.E., Lamond A.I.;
RT "Dynamic targeting of protein phosphatase 1 within the nuclei of living
RT mammalian cells.";
RL J. Cell Sci. 114:4219-4228(2001).
RN [12]
RP INTERACTION WITH PPP1R15A.
RX PubMed=11564868; DOI=10.1128/mcb.21.20.6841-6850.2001;
RA Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S.;
RT "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel
RT signaling complex containing protein phosphatase 1 and inhibitor 1.";
RL Mol. Cell. Biol. 21:6841-6850(2001).
RN [13]
RP INTERACTION WITH PPP1R7.
RX PubMed=12226088; DOI=10.1074/jbc.m206838200;
RA Ceulemans H., Vulsteke V., De Maeyer M., Tatchell K., Stalmans W.,
RA Bollen M.;
RT "Binding of the concave surface of the Sds22 superhelix to the alpha
RT 4/alpha 5/alpha 6-triangle of protein phosphatase-1.";
RL J. Biol. Chem. 277:47331-47337(2002).
RN [14]
RP REVIEW.
RX PubMed=11839776; DOI=10.1242/jcs.115.2.241;
RA Cohen P.T.W.;
RT "Protein phosphatase 1 -- targeted in many directions.";
RL J. Cell Sci. 115:241-256(2002).
RN [15]
RP INTERACTION WITH PPP1R16B AND RPSA.
RX PubMed=16263087; DOI=10.1016/j.bbrc.2005.10.089;
RA Kim K., Li L., Kozlowski K., Suh H.S., Cao W., Ballermann B.J.;
RT "The protein phosphatase-1 targeting subunit TIMAP regulates LAMR1
RT phosphorylation.";
RL Biochem. Biophys. Res. Commun. 338:1327-1334(2005).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=15705855; DOI=10.1126/science.1101902;
RA Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D.,
RA Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J.;
RT "A selective inhibitor of eIF2alpha dephosphorylation protects cells from
RT ER stress.";
RL Science 307:935-939(2005).
RN [17]
RP INTERACTION WITH FER, AND PHOSPHORYLATION AT THR-320.
RX PubMed=16732323; DOI=10.1038/sj.onc.1209695;
RA Pasder O., Shpungin S., Salem Y., Makovsky A., Vilchick S., Michaeli S.,
RA Malovani H., Nir U.;
RT "Downregulation of Fer induces PP1 activation and cell-cycle arrest in
RT malignant cells.";
RL Oncogene 25:4194-4206(2006).
RN [18]
RP IDENTIFICATION IN A COMPLEX WITH ILF2; ILF3; YLPM1; KHDRBS1; RBMX AND
RP NCOA5, AND INTERACTION WITH YLPM1.
RX PubMed=17890166; DOI=10.1016/j.bbapap.2007.07.015;
RA Ulke-Lemee A., Trinkle-Mulcahy L., Chaulk S., Bernstein N.K., Morrice N.,
RA Glover M., Lamond A.I., Moorhead G.B.G.;
RT "The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside
RT kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G.";
RL Biochim. Biophys. Acta 1774:1339-1350(2007).
RN [19]
RP FUNCTION, INTERACTION WITH NEK2, AND DEPHOSPHORYLATION.
RX PubMed=17283141; DOI=10.1158/0008-5472.can-06-3071;
RA Mi J., Guo C., Brautigan D.L., Larner J.M.;
RT "Protein phosphatase-1alpha regulates centrosome splitting through Nek2.";
RL Cancer Res. 67:1082-1089(2007).
RN [20]
RP INTERACTION WITH NEK2.
RX PubMed=17626005; DOI=10.1074/jbc.m704969200;
RA Wu W., Baxter J.E., Wattam S.L., Hayward D.G., Fardilha M., Knebel A.,
RA Ford E.M., da Cruz e Silva E.F., Fry A.M.;
RT "Alternative splicing controls nuclear translocation of the cell cycle-
RT regulated Nek2 kinase.";
RL J. Biol. Chem. 282:26431-26440(2007).
RN [21]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NOM1.
RX PubMed=17965019; DOI=10.1074/jbc.m706708200;
RA Gunawardena S.R., Ruis B.L., Meyer J.A., Kapoor M., Conklin K.F.;
RT "NOM1 targets protein phosphatase I to the nucleolus.";
RL J. Biol. Chem. 283:398-404(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP CAUTION.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-22; THR-320 AND
RP SER-325, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP CAUTION, AND RETRACTION NOTICE OF PUBMED:23186163.
RX PubMed=24336203; DOI=10.1038/nature12896;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "Retraction: GlcNAcylation of a histone methyltransferase in retinoic-acid-
RT induced granulopoiesis.";
RL Nature 505:574-574(2014).
RN [30]
RP INTERACTION WITH DAB2.
RX PubMed=19581931; DOI=10.1038/onc.2009.157;
RA Jiang Y., Luo W., Howe P.H.;
RT "Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by
RT preventing protein phosphatase 1 (PP1)-Axin interactions.";
RL Oncogene 28:2999-3007(2009).
RN [31]
RP IDENTIFICATION IN THE PTW/PP1 PHOSPHATASE COMPLEX, AND INTERACTION WITH
RP WDR82; PPP1R8 AND PPP1R10/PNUTS.
RX PubMed=20516061; DOI=10.1074/jbc.m110.109801;
RA Lee J.H., You J., Dobrota E., Skalnik D.G.;
RT "Identification and characterization of a novel human PP1 phosphatase
RT complex.";
RL J. Biol. Chem. 285:24466-24476(2010).
RN [32]
RP INTERACTION WITH TRIM28.
RX PubMed=20424263; DOI=10.1126/scisignal.2000781;
RA Li X., Lin H.H., Chen H., Xu X., Shih H.M., Ann D.K.;
RT "SUMOylation of the transcriptional co-repressor KAP1 is regulated by the
RT serine and threonine phosphatase PP1.";
RL Sci. Signal. 3:RA32-RA32(2010).
RN [33]
RP FUNCTION IN CIRCADIAN CLOCK.
RX PubMed=21712997; DOI=10.1371/journal.pone.0021325;
RA Schmutz I., Wendt S., Schnell A., Kramer A., Mansuy I.M., Albrecht U.;
RT "Protein phosphatase 1 (PP1) is a post-translational regulator of the
RT mammalian circadian clock.";
RL PLoS ONE 6:E21325-E21325(2011).
RN [34]
RP INTERACTION WITH PEAK1, PPP1CC AND SHC1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=23846654; DOI=10.1038/nature12308;
RA Zheng Y., Zhang C., Croucher D.R., Soliman M.A., St-Denis N.,
RA Pasculescu A., Taylor L., Tate S.A., Hardy W.R., Colwill K., Dai A.Y.,
RA Bagshaw R., Dennis J.W., Gingras A.C., Daly R.J., Pawson T.;
RT "Temporal regulation of EGF signalling networks by the scaffold protein
RT Shc1.";
RL Nature 499:166-171(2013).
RN [35]
RP FUNCTION, INTERACTION WITH FOXP3, AND INDUCTION.
RX PubMed=23396208; DOI=10.1038/nm.3085;
RA Nie H., Zheng Y., Li R., Guo T.B., He D., Fang L., Liu X., Xiao L.,
RA Chen X., Wan B., Chin Y.E., Zhang J.Z.;
RT "Phosphorylation of FOXP3 controls regulatory T cell function and is
RT inhibited by TNF-alpha in rheumatoid arthritis.";
RL Nat. Med. 19:322-328(2013).
RN [36]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ATG16L1.
RX PubMed=26083323; DOI=10.1080/15548627.2015.1060386;
RA Song H., Pu J., Wang L., Wu L., Xiao J., Liu Q., Chen J., Zhang M., Liu Y.,
RA Ni M., Mo J., Zheng Y., Wan D., Cai X., Cao Y., Xiao W., Ye L., Tu E.,
RA Lin Z., Wen J., Lu X., He J., Peng Y., Su J., Zhang H., Zhao Y., Lin M.,
RA Zhang Z.;
RT "ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2
RT and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes
RT during hypoxia/reoxygenation.";
RL Autophagy 11:1308-1325(2015).
RN [37]
RP FUNCTION, AND INTERACTION WITH CENPA.
RX PubMed=25556658; DOI=10.1016/j.devcel.2014.11.030;
RA Yu Z., Zhou X., Wang W., Deng W., Fang J., Hu H., Wang Z., Li S., Cui L.,
RA Shen J., Zhai L., Peng S., Wong J., Dong S., Yuan Z., Ou G., Zhang X.,
RA Xu P., Lou J., Yang N., Chen P., Xu R.M., Li G.;
RT "Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-
RT dependent deposition at centromeres.";
RL Dev. Cell 32:68-81(2015).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [39]
RP INTERACTION WITH VENEZUELAN EQUINE ENCEPHALITIS VIRUS CAPSID PROTEIN
RP (MICROBIAL INFECTION), SUBCELLULAR LOCATION (MICROBIAL INFECTION), AND
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=29769351; DOI=10.1128/jvi.02068-17;
RA Carey B.D., Ammosova T., Pinkham C., Lin X., Zhou W., Liotta L.A.,
RA Nekhai S., Kehn-Hall K.;
RT "Protein phosphatase 1alpha interacts with Venezuelan equine encephalitis
RT virus capsid protein and regulates viral replication through modulation of
RT capsid phosphorylation.";
RL J. Virol. 92:0-0(2018).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 7-300 IN COMPLEX WITH INHIBITORS,
RP COFACTOR, MANGANESE-BINDING SITES, AND SUBUNIT.
RX PubMed=18992256; DOI=10.1016/j.jmb.2008.10.053;
RA Kelker M.S., Page R., Peti W.;
RT "Crystal structures of protein phosphatase-1 bound to nodularin-R and
RT tautomycin: a novel scaffold for structure-based drug design of
RT serine/threonine phosphatase inhibitors.";
RL J. Mol. Biol. 385:11-21(2009).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 7-330 IN COMPLEX WITH RAT PPP1R9A
RP AND PPP1R9B.
RX PubMed=20305656; DOI=10.1038/nsmb.1786;
RA Ragusa M.J., Dancheck B., Critton D.A., Nairn A.C., Page R., Peti W.;
RT "Spinophilin directs protein phosphatase 1 specificity by blocking
RT substrate binding sites.";
RL Nat. Struct. Mol. Biol. 17:459-464(2010).
RN [42] {ECO:0007744|PDB:4XPN}
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 552-591, AND INTERACTION WITH
RP PPP1R15A.
RX PubMed=26095357; DOI=10.1016/j.celrep.2015.05.043;
RA Choy M.S., Yusoff P., Lee I.C., Newton J.C., Goh C.W., Page R.,
RA Shenolikar S., Peti W.;
RT "Structural and Functional Analysis of the GADD34:PP1 eIF2alpha
RT Phosphatase.";
RL Cell Rep. 11:1885-1891(2015).
CC -!- FUNCTION: Protein phosphatase that associates with over 200 regulatory
CC proteins to form highly specific holoenzymes which dephosphorylate
CC hundreds of biological targets. Protein phosphatase 1 (PP1) is
CC essential for cell division, and participates in the regulation of
CC glycogen metabolism, muscle contractility and protein synthesis.
CC Involved in regulation of ionic conductances and long-term synaptic
CC plasticity. May play an important role in dephosphorylating substrates
CC such as the postsynaptic density-associated Ca(2+)/calmodulin dependent
CC protein kinase II. Component of the PTW/PP1 phosphatase complex, which
CC plays a role in the control of chromatin structure and cell cycle
CC progression during the transition from mitosis into interphase.
CC Regulates NEK2 function in terms of kinase activity and centrosome
CC number and splitting, both in the presence and absence of radiation-
CC induced DNA damage. Regulator of neural tube and optic fissure closure,
CC and enteric neural crest cell (ENCCs) migration during development. In
CC balance with CSNK1D and CSNK1E, determines the circadian period length,
CC through the regulation of the speed and rhythmicity of PER1 and PER2
CC phosphorylation. May dephosphorylate CSNK1D and CSNK1E.
CC Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells
CC (Treg) from patients with rheumatoid arthritis, thereby inactivating
CC FOXP3 and rendering Treg cells functionally defective
CC (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658).
CC Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation
CC of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy
CC (PubMed:26083323). {ECO:0000269|PubMed:17283141,
CC ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208,
CC ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323}.
CC -!- FUNCTION: (Microbial infection) Necessary for alphaviruses replication.
CC {ECO:0000269|PubMed:29769351}.
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 Evidence={ECO:0000269|PubMed:26083323};
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:26083323};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:18992256};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:18992256};
CC -!- ACTIVITY REGULATION: The phosphatase activity of the PPP1R15A-PP1
CC complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug
CC that protects cells from endoplasmic reticulum stress.
CC {ECO:0000269|PubMed:15705855}.
CC -!- SUBUNIT: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC,
CC which is folded into its native form by inhibitor 2 and glycogen
CC synthetase kinase 3, and then complexed to one or several targeting or
CC regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to
CC myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C,
CC PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts
CC with PPP1R39 (By similarity). Interacts with BTBD10 (By similarity).
CC Interacts with KCTD20 (By similarity). Interacts with PPP1R9A and
CC PPP1R9B. Part of a complex containing PPP1R15B, PP1 and NCK1/2.
CC Interacts with PHACTR4; which acts as an activator of PP1 activity (By
CC similarity). Interacts with PPP1R15A and PPP1R15B; the interactions
CC mediate binding to EIF2S1 (PubMed:26095357). Interacts with PPP1R7.
CC Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1,
CC RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with
CC PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B.
CC Component of the PTW/PP1 phosphatase complex, composed of
CC PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts
CC with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of
CC PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates
CC TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site.
CC Interacts with isoform 1 and isoform 4 of NEK2. Interacts with FER;
CC this promotes phosphorylation at Thr-320. Interacts with DAB2; the
CC interaction is mutually exclusive with the AXIN1:PPP1CA interaction.
CC Interacts with FOXP3 (PubMed:23396208). Interacts with CENPA
CC (PubMed:25556658). Interacts with ATG16L1 (PubMed:26083323). Found in a
CC complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).
CC {ECO:0000250|UniProtKB:P62137, ECO:0000250|UniProtKB:P62139,
CC ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:11739654,
CC ECO:0000269|PubMed:12226088, ECO:0000269|PubMed:16263087,
CC ECO:0000269|PubMed:16732323, ECO:0000269|PubMed:17283141,
CC ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:17890166,
CC ECO:0000269|PubMed:17965019, ECO:0000269|PubMed:18992256,
CC ECO:0000269|PubMed:19581931, ECO:0000269|PubMed:20305656,
CC ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20516061,
CC ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23846654,
CC ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323,
CC ECO:0000269|PubMed:9023344}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HHV-1 ICP34.5.
CC {ECO:0000269|PubMed:9023344}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Venezuelan equine
CC encephalitis virus (VEEV) capsid protein; this interaction
CC dephosphorylates the capsid protein, which increases its ability to
CC bind to the viral genome. {ECO:0000269|PubMed:29769351}.
CC -!- INTERACTION:
CC P62136; Q6ZMQ8: AATK; NbExp=3; IntAct=EBI-357253, EBI-2008380;
CC P62136; P31749: AKT1; NbExp=4; IntAct=EBI-357253, EBI-296087;
CC P62136; O14727: APAF1; NbExp=2; IntAct=EBI-357253, EBI-446492;
CC P62136; P05067: APP; NbExp=3; IntAct=EBI-357253, EBI-77613;
CC P62136; O15169: AXIN1; NbExp=4; IntAct=EBI-357253, EBI-710484;
CC P62136; P38398: BRCA1; NbExp=2; IntAct=EBI-357253, EBI-349905;
CC P62136; O95400: CD2BP2; NbExp=2; IntAct=EBI-357253, EBI-768015;
CC P62136; Q99459: CDC5L; NbExp=2; IntAct=EBI-357253, EBI-374880;
CC P62136; P12830: CDH1; NbExp=2; IntAct=EBI-357253, EBI-727477;
CC P62136; Q8TEP8: CEP192; NbExp=2; IntAct=EBI-357253, EBI-2339778;
CC P62136; Q9NX63: CHCHD3; NbExp=2; IntAct=EBI-357253, EBI-743375;
CC P62136; Q6PJW8: CNST; NbExp=4; IntAct=EBI-357253, EBI-750390;
CC P62136; Q96S65: CSRNP1; NbExp=8; IntAct=EBI-357253, EBI-4311573;
CC P62136; Q9H175: CSRNP2; NbExp=10; IntAct=EBI-357253, EBI-5235958;
CC P62136; Q92796: DLG3; NbExp=2; IntAct=EBI-357253, EBI-80440;
CC P62136; P05198: EIF2S1; NbExp=2; IntAct=EBI-357253, EBI-1056162;
CC P62136; P55199: ELL; NbExp=2; IntAct=EBI-357253, EBI-1245868;
CC P62136; Q9BZS1: FOXP3; NbExp=2; IntAct=EBI-357253, EBI-983719;
CC P62136; P42858: HTT; NbExp=10; IntAct=EBI-357253, EBI-466029;
CC P62136; Q8NI77: KIF18A; NbExp=3; IntAct=EBI-357253, EBI-355426;
CC P62136; Q8NG31: KNL1; NbExp=2; IntAct=EBI-357253, EBI-1001161;
CC P62136; Q5S007: LRRK2; NbExp=6; IntAct=EBI-357253, EBI-5323863;
CC P62136; O00566: MPHOSPH10; NbExp=2; IntAct=EBI-357253, EBI-5235884;
CC P62136; Q96QC0: PPP1R10; NbExp=4; IntAct=EBI-357253, EBI-1210346;
CC P62136; Q96KQ4: PPP1R13B; NbExp=11; IntAct=EBI-357253, EBI-1105153;
CC P62136; Q8WUF5: PPP1R13L; NbExp=8; IntAct=EBI-357253, EBI-5550163;
CC P62136; O75807: PPP1R15A; NbExp=12; IntAct=EBI-357253, EBI-714746;
CC P62136; Q5SWA1: PPP1R15B; NbExp=5; IntAct=EBI-357253, EBI-2815482;
CC P62136; Q96T49: PPP1R16B; NbExp=4; IntAct=EBI-357253, EBI-10293968;
CC P62136; Q6NYC8: PPP1R18; NbExp=5; IntAct=EBI-357253, EBI-2557469;
CC P62136; P41236: PPP1R2; NbExp=11; IntAct=EBI-357253, EBI-1056517;
CC P62136; Q5T8A7: PPP1R26; NbExp=2; IntAct=EBI-357253, EBI-308500;
CC P62136; Q86WC6: PPP1R27; NbExp=5; IntAct=EBI-357253, EBI-5235602;
CC P62136; Q6NXS1: PPP1R2B; NbExp=3; IntAct=EBI-357253, EBI-10251630;
CC P62136; O14990: PPP1R2C; NbExp=3; IntAct=EBI-357253, EBI-12404293;
CC P62136; Q7Z5V6: PPP1R32; NbExp=3; IntAct=EBI-357253, EBI-4311771;
CC P62136; O75864: PPP1R37; NbExp=5; IntAct=EBI-357253, EBI-5235692;
CC P62136; Q86XI6: PPP1R3B; NbExp=4; IntAct=EBI-357253, EBI-3918864;
CC P62136; Q9UQK1: PPP1R3C; NbExp=5; IntAct=EBI-357253, EBI-2506727;
CC P62136; O95685: PPP1R3D; NbExp=3; IntAct=EBI-357253, EBI-1045661;
CC P62136; Q15435: PPP1R7; NbExp=7; IntAct=EBI-357253, EBI-1024281;
CC P62136; Q12972: PPP1R8; NbExp=7; IntAct=EBI-357253, EBI-716633;
CC P62136; Q12972-1: PPP1R8; NbExp=6; IntAct=EBI-357253, EBI-16012257;
CC P62136; Q12972-2: PPP1R8; NbExp=7; IntAct=EBI-357253, EBI-12252736;
CC P62136; Q96SB3: PPP1R9B; NbExp=6; IntAct=EBI-357253, EBI-351275;
CC P62136; P60484: PTEN; NbExp=2; IntAct=EBI-357253, EBI-696162;
CC P62136; P06400: RB1; NbExp=2; IntAct=EBI-357253, EBI-491274;
CC P62136; Q5UIP0: RIF1; NbExp=4; IntAct=EBI-357253, EBI-711331;
CC P62136; Q14684: RRP1B; NbExp=3; IntAct=EBI-357253, EBI-372051;
CC P62136; P04271: S100B; NbExp=3; IntAct=EBI-357253, EBI-458391;
CC P62136; A8K8P3: SFI1; NbExp=2; IntAct=EBI-357253, EBI-743371;
CC P62136; Q562F6: SGO2; NbExp=4; IntAct=EBI-357253, EBI-989213;
CC P62136; Q9H788: SH2D4A; NbExp=3; IntAct=EBI-357253, EBI-747035;
CC P62136; Q8TEC5: SH3RF2; NbExp=3; IntAct=EBI-357253, EBI-2130111;
CC P62136; P63208: SKP1; NbExp=3; IntAct=EBI-357253, EBI-307486;
CC P62136; Q7Z699: SPRED1; NbExp=4; IntAct=EBI-357253, EBI-5235340;
CC P62136; P43405-2: SYK; NbExp=3; IntAct=EBI-357253, EBI-25892332;
CC P62136; Q9HCH5: SYTL2; NbExp=2; IntAct=EBI-357253, EBI-2690103;
CC P62136; Q14C87: TMEM132D; NbExp=2; IntAct=EBI-357253, EBI-5235567;
CC P62136; Q5JTV8: TOR1AIP1; NbExp=2; IntAct=EBI-357253, EBI-2559665;
CC P62136; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-357253, EBI-11952721;
CC P62136; Q13625: TP53BP2; NbExp=9; IntAct=EBI-357253, EBI-77642;
CC P62136; Q4KMQ1: TPRN; NbExp=3; IntAct=EBI-357253, EBI-3942777;
CC P62136; Q4KMQ1-2: TPRN; NbExp=6; IntAct=EBI-357253, EBI-11978969;
CC P62136; Q8TEL6: TRPC4AP; NbExp=2; IntAct=EBI-357253, EBI-2559060;
CC P62136; P49815: TSC2; NbExp=2; IntAct=EBI-357253, EBI-396587;
CC P62136; P55072: VCP; NbExp=2; IntAct=EBI-357253, EBI-355164;
CC P62136; Q9Y2W2: WBP11; NbExp=4; IntAct=EBI-357253, EBI-714455;
CC P62136; Q9H4A3: WNK1; NbExp=2; IntAct=EBI-357253, EBI-457907;
CC P62136; P16989: YBX3; NbExp=3; IntAct=EBI-357253, EBI-358193;
CC P62136; P49750: YLPM1; NbExp=3; IntAct=EBI-357253, EBI-712871;
CC P62136; Q9HBF4: ZFYVE1; NbExp=2; IntAct=EBI-357253, EBI-4401611;
CC P62136; O95405: ZFYVE9; NbExp=3; IntAct=EBI-357253, EBI-296817;
CC P62136; O08785: Clock; Xeno; NbExp=2; IntAct=EBI-357253, EBI-79859;
CC P62136; P36313: ICP34.5; Xeno; NbExp=4; IntAct=EBI-357253, EBI-6149234;
CC P62136; K9N4V7: N; Xeno; NbExp=2; IntAct=EBI-357253, EBI-25592177;
CC P62136; Q76TK5: ORF23; Xeno; NbExp=2; IntAct=EBI-357253, EBI-14033469;
CC P62136; O35867: Ppp1r9a; Xeno; NbExp=3; IntAct=EBI-357253, EBI-7092421;
CC P62136; O35274: Ppp1r9b; Xeno; NbExp=8; IntAct=EBI-357253, EBI-80022;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11739654,
CC ECO:0000269|PubMed:29769351}. Nucleus {ECO:0000269|PubMed:11739654,
CC ECO:0000269|PubMed:17965019}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:17965019}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:17965019}.
CC Note=Primarily nuclear and largely excluded from the nucleolus. Highly
CC mobile in cells and can be relocalized through interaction with
CC targeting subunits. NOM1 plays a role in targeting this protein to the
CC nucleolus. In the presence of PPP1R8 relocalizes from the nucleus to
CC nuclear speckles. Shuttles toward the cytosol during infection with
CC VEEV (PubMed:29769351). {ECO:0000269|PubMed:29769351}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P62136-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P62136-2; Sequence=VSP_043377;
CC Name=3;
CC IsoId=P62136-3; Sequence=VSP_046754;
CC -!- INDUCTION: Up-regulated in synovial fluid mononuclear cells and
CC peripheral blood mononuclear cells from patients with rheumatoid
CC arthritis. {ECO:0000269|PubMed:23396208}.
CC -!- PTM: Phosphorylated. Dephosphorylated at Thr-320 in the presence of
CC ionizing radiation. {ECO:0000269|PubMed:16732323}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be part of the MLL5-L complex, at
CC least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and
CC OGT (PubMed:19377461). However, the corresponding article has been
CC retracted (PubMed:24336203). {ECO:0000269|PubMed:19377461,
CC ECO:0000269|PubMed:24336203}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The things we forget - Issue
CC 32 of March 2003;
CC URL="https://web.expasy.org/spotlight/back_issues/032";
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DR EMBL; X70848; CAA50197.1; -; mRNA.
DR EMBL; S57501; AAB26015.1; -; mRNA.
DR EMBL; M63960; AAA36508.1; -; mRNA.
DR EMBL; AK313586; BAG36355.1; -; mRNA.
DR EMBL; BT006629; AAP35275.1; -; mRNA.
DR EMBL; AP003419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001888; AAH01888.1; -; mRNA.
DR EMBL; BC004482; AAH04482.1; -; mRNA.
DR EMBL; BC008010; AAH08010.1; -; mRNA.
DR EMBL; J04759; AAA36475.1; -; mRNA.
DR CCDS; CCDS31618.1; -. [P62136-2]
DR CCDS; CCDS8160.1; -. [P62136-1]
DR CCDS; CCDS8161.1; -. [P62136-3]
DR RefSeq; NP_001008709.1; NM_001008709.1. [P62136-2]
DR RefSeq; NP_002699.1; NM_002708.3. [P62136-1]
DR RefSeq; NP_996756.1; NM_206873.1. [P62136-3]
DR PDB; 3E7A; X-ray; 1.63 A; A/B=7-300.
DR PDB; 3E7B; X-ray; 1.70 A; A/B=7-300.
DR PDB; 3EGG; X-ray; 1.85 A; A/B=7-330.
DR PDB; 3EGH; X-ray; 2.00 A; A/B=7-330.
DR PDB; 3HVQ; X-ray; 2.20 A; A/B=7-330.
DR PDB; 3N5U; X-ray; 3.20 A; A/B=1-300.
DR PDB; 3V4Y; X-ray; 2.10 A; A/C/E/G=7-307.
DR PDB; 4G9J; X-ray; 3.10 A; A/B=1-330.
DR PDB; 4MOV; X-ray; 1.45 A; A/B=7-300.
DR PDB; 4MOY; X-ray; 2.20 A; A=7-300.
DR PDB; 4MP0; X-ray; 2.10 A; A/C=7-300.
DR PDB; 4XPN; X-ray; 2.29 A; A/C=7-300.
DR PDB; 5IOH; X-ray; 2.57 A; A/C=7-300.
DR PDB; 6ALZ; X-ray; 2.21 A; A/B=7-300.
DR PDB; 6CZO; X-ray; 2.95 A; A/C=7-300.
DR PDB; 6DCX; X-ray; 3.41 A; A/B=1-330.
DR PDB; 6DNO; X-ray; 1.45 A; A=7-300.
DR PDB; 6G0I; X-ray; 2.00 A; A=1-330.
DR PDB; 6G0J; X-ray; 2.10 A; A=1-330.
DR PDB; 6GHM; X-ray; 2.15 A; A/B=7-330.
DR PDB; 6OBN; X-ray; 2.70 A; A/B=1-300.
DR PDB; 6OBP; X-ray; 2.70 A; A=1-300.
DR PDB; 6OBQ; X-ray; 1.84 A; A/B=7-300.
DR PDB; 6OBR; X-ray; 1.50 A; A/B=7-300.
DR PDB; 6OBS; X-ray; 1.80 A; A/B=7-300.
DR PDB; 6OBU; X-ray; 1.95 A; A/B=7-300.
DR PDB; 6ZEE; X-ray; 1.90 A; A/B/I/K/P/Q=7-300.
DR PDB; 6ZEF; X-ray; 1.94 A; A/B=7-300.
DR PDB; 6ZEG; X-ray; 1.09 A; A/B=7-304.
DR PDB; 6ZEH; X-ray; 1.30 A; A/B=7-304.
DR PDB; 6ZEI; X-ray; 1.39 A; A/B=7-304.
DR PDB; 6ZEJ; X-ray; 1.78 A; A/D/F/I/L/O=7-304.
DR PDB; 6ZK6; X-ray; 1.90 A; A=1-330.
DR PDBsum; 3E7A; -.
DR PDBsum; 3E7B; -.
DR PDBsum; 3EGG; -.
DR PDBsum; 3EGH; -.
DR PDBsum; 3HVQ; -.
DR PDBsum; 3N5U; -.
DR PDBsum; 3V4Y; -.
DR PDBsum; 4G9J; -.
DR PDBsum; 4MOV; -.
DR PDBsum; 4MOY; -.
DR PDBsum; 4MP0; -.
DR PDBsum; 4XPN; -.
DR PDBsum; 5IOH; -.
DR PDBsum; 6ALZ; -.
DR PDBsum; 6CZO; -.
DR PDBsum; 6DCX; -.
DR PDBsum; 6DNO; -.
DR PDBsum; 6G0I; -.
DR PDBsum; 6G0J; -.
DR PDBsum; 6GHM; -.
DR PDBsum; 6OBN; -.
DR PDBsum; 6OBP; -.
DR PDBsum; 6OBQ; -.
DR PDBsum; 6OBR; -.
DR PDBsum; 6OBS; -.
DR PDBsum; 6OBU; -.
DR PDBsum; 6ZEE; -.
DR PDBsum; 6ZEF; -.
DR PDBsum; 6ZEG; -.
DR PDBsum; 6ZEH; -.
DR PDBsum; 6ZEI; -.
DR PDBsum; 6ZEJ; -.
DR PDBsum; 6ZK6; -.
DR AlphaFoldDB; P62136; -.
DR SASBDB; P62136; -.
DR SMR; P62136; -.
DR BioGRID; 111493; 524.
DR CORUM; P62136; -.
DR DIP; DIP-221N; -.
DR DIP; DIP-38195N; -.
DR ELM; P62136; -.
DR IntAct; P62136; 433.
DR MINT; P62136; -.
DR STRING; 9606.ENSP00000326031; -.
DR BindingDB; P62136; -.
DR ChEMBL; CHEMBL2164; -.
DR DrugBank; DB02506; 2,6,8-Trimethyl-3-Amino-9-Benzyl-9-Methoxynonanoic Acid.
DR MoonDB; P62136; Predicted.
DR DEPOD; PPP1CA; -.
DR GlyGen; P62136; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P62136; -.
DR PhosphoSitePlus; P62136; -.
DR SwissPalm; P62136; -.
DR BioMuta; PPP1CA; -.
DR DMDM; 49065811; -.
DR OGP; P08129; -.
DR EPD; P62136; -.
DR jPOST; P62136; -.
DR MassIVE; P62136; -.
DR MaxQB; P62136; -.
DR PaxDb; P62136; -.
DR PeptideAtlas; P62136; -.
DR PRIDE; P62136; -.
DR ProteomicsDB; 1632; -.
DR ProteomicsDB; 57365; -. [P62136-1]
DR ProteomicsDB; 57366; -. [P62136-2]
DR TopDownProteomics; P62136-1; -. [P62136-1]
DR Antibodypedia; 3872; 625 antibodies from 40 providers.
DR DNASU; 5499; -.
DR Ensembl; ENST00000312989.11; ENSP00000326031.7; ENSG00000172531.16. [P62136-2]
DR Ensembl; ENST00000358239.8; ENSP00000350974.4; ENSG00000172531.16. [P62136-3]
DR Ensembl; ENST00000376745.9; ENSP00000365936.4; ENSG00000172531.16. [P62136-1]
DR GeneID; 5499; -.
DR KEGG; hsa:5499; -.
DR MANE-Select; ENST00000376745.9; ENSP00000365936.4; NM_002708.4; NP_002699.1.
DR UCSC; uc001oku.2; human. [P62136-1]
DR CTD; 5499; -.
DR DisGeNET; 5499; -.
DR GeneCards; PPP1CA; -.
DR HGNC; HGNC:9281; PPP1CA.
DR HPA; ENSG00000172531; Low tissue specificity.
DR MIM; 176875; gene.
DR neXtProt; NX_P62136; -.
DR OpenTargets; ENSG00000172531; -.
DR PharmGKB; PA33609; -.
DR VEuPathDB; HostDB:ENSG00000172531; -.
DR eggNOG; KOG0374; Eukaryota.
DR GeneTree; ENSGT00940000153472; -.
DR HOGENOM; CLU_004962_8_1_1; -.
DR InParanoid; P62136; -.
DR OMA; YLVMESR; -.
DR PhylomeDB; P62136; -.
DR TreeFam; TF354243; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; P62136; -.
DR Reactome; R-HSA-163560; Triglyceride catabolism.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-HSA-400253; Circadian Clock.
DR SignaLink; P62136; -.
DR SIGNOR; P62136; -.
DR BioGRID-ORCS; 5499; 431 hits in 1090 CRISPR screens.
DR ChiTaRS; PPP1CA; human.
DR EvolutionaryTrace; P62136; -.
DR GeneWiki; PPP1CA; -.
DR GenomeRNAi; 5499; -.
DR Pharos; P62136; Tchem.
DR PRO; PR:P62136; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P62136; protein.
DR Bgee; ENSG00000172531; Expressed in endometrium epithelium and 201 other tissues.
DR ExpressionAtlas; P62136; baseline and differential.
DR Genevisible; P62136; HS.
DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0042587; C:glycogen granule; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IEA:Ensembl.
DR GO; GO:0072357; C:PTW/PP1 phosphatase complex; IDA:UniProtKB.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IEA:Ensembl.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IEA:Ensembl.
DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:CACAO.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; TAS:ARUK-UCL.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; TAS:ARUK-UCL.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:CACAO.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IC:ParkinsonsUK-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; IEA:Ensembl.
DR GO; GO:0005981; P:regulation of glycogen catabolic process; IEA:Ensembl.
DR GO; GO:0036496; P:regulation of translational initiation by eIF2 alpha dephosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010288; P:response to lead ion; ISS:ARUK-UCL.
DR Gene3D; 3.60.21.10; -; 1.
DR IDEAL; IID00311; -.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR037979; PPP1CA.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR InterPro; IPR031675; STPPase_N.
DR PANTHER; PTHR11668:SF377; PTHR11668:SF377; 1.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF16891; STPPase_N; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Carbohydrate metabolism;
KW Cell cycle; Cell division; Cytoplasm; Direct protein sequencing;
KW Glycogen metabolism; Host-virus interaction; Hydrolase; Manganese;
KW Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:22814378"
FT CHAIN 2..330
FT /note="Serine/threonine-protein phosphatase PP1-alpha
FT catalytic subunit"
FT /id="PRO_0000058774"
FT REGION 306..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 66
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 248
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:22814378"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 305
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62137"
FT MOD_RES 306
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P62137"
FT MOD_RES 320
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16732323,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 18
FT /note="E -> EGSRVLTPHCAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8384581"
FT /id="VSP_043377"
FT VAR_SEQ 19..62
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046754"
FT HELIX 9..18
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 32..48
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 69..79
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 100..113
FT /evidence="ECO:0007829|PDB:6ZEG"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:6ALZ"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:6ZEG"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:4G9J"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 146..156
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:6ZEG"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 229..239
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:6ZEG"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:6ZEG"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 280..285
FT /evidence="ECO:0007829|PDB:6ZEG"
FT STRAND 290..297
FT /evidence="ECO:0007829|PDB:6ZEG"
SQ SEQUENCE 330 AA; 37512 MW; 60C37E1AD9831DAC CRC64;
MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK
ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL
LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL
QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVQGWGEND RGVSFTFGAE VVAKFLHKHD
LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAD
KNKGKYGQFS GLNPGGRPIT PPRNSAKAKK
