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Database: UniProt
Entry: P53041
LinkDB: P53041
Original site: P53041 
ID   PPP5_HUMAN              Reviewed;         499 AA.
AC   P53041; Q16722; Q53XV2;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   29-OCT-2014, entry version 168.
DE   RecName: Full=Serine/threonine-protein phosphatase 5;
DE            Short=PP5;
DE            EC=3.1.3.16;
DE   AltName: Full=Protein phosphatase T;
DE            Short=PP-T;
DE            Short=PPT;
GN   Name=PPP5C; Synonyms=PPP5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 7-499.
RX   PubMed=7925273;
RA   Chen M.X., McPartlin A.E., Brown L., Chen Y.H., Barker H.M.,
RA   Cohen P.T.W.;
RT   "A novel human protein serine/threonine phosphatase, which possesses
RT   four tetratricopeptide repeat motifs and localizes to the nucleus.";
RL   EMBO J. 13:4278-4290(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 9-499.
RC   TISSUE=Fetal brain;
RX   PubMed=8666404; DOI=10.1006/geno.1995.9972;
RA   Yong W.H., Ueki K., Chou D., Reeves S.A., von Deimling A.,
RA   Gusella J.F., Mohrenweiser H.W., Buckler A.J., Louis D.N.;
RT   "Cloning of a highly conserved human protein serine-threonine
RT   phosphatase gene from the glioma candidate region on chromosome
RT   19q13.3.";
RL   Genomics 29:533-536(1995).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cervix;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-37.
RC   TISSUE=Fetal brain;
RX   PubMed=8561788; DOI=10.1006/bbrc.1996.0092;
RA   Xu X., Lagercrantz J., Zickert P., Bajalica-Lagercrantz S.,
RA   Zetterberg A.;
RT   "Chromosomal localization and 5' sequence of the human protein
RT   serine/threonine phosphatase 5' gene.";
RL   Biochem. Biophys. Res. Commun. 218:514-517(1996).
RN   [8]
RP   FUNCTION, ENZYME REGULATION, AND LIPID-BINDING.
RX   PubMed=9000529; DOI=10.1016/S0014-5793(96)01427-5;
RA   Chen M.X., Cohen P.T.;
RT   "Activation of protein phosphatase 5 by limited proteolysis or the
RT   binding of polyunsaturated fatty acids to the TPR domain.";
RL   FEBS Lett. 400:136-140(1997).
RN   [9]
RP   INTERACTION WITH CDC16 AND CDC27.
RX   PubMed=9405394; DOI=10.1074/jbc.272.51.32011;
RA   Ollendorff V., Donoghue D.J.;
RT   "The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27,
RT   two tetratricopeptide repeat-containing subunits of the anaphase-
RT   promoting complex.";
RL   J. Biol. Chem. 272:32011-32018(1997).
RN   [10]
RP   FUNCTION IN DNA DAMAGE RESPONSE, AND INTERACTION WITH ATM AND RAD17.
RX   PubMed=14871926; DOI=10.1101/gad.1176004;
RA   Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M.,
RA   Abraham R.T., Wang X.F.;
RT   "Requirement of protein phosphatase 5 in DNA-damage-induced ATM
RT   activation.";
RL   Genes Dev. 18:249-254(2004).
RN   [11]
RP   FUNCTION IN DEPHOSPHORYLATION OF ESR1 AND ESR2.
RX   PubMed=14764652; DOI=10.1210/me.2003-0308;
RA   Ikeda K., Ogawa S., Tsukui T., Horie-Inoue K., Ouchi Y., Kato S.,
RA   Muramatsu M., Inoue S.;
RT   "Protein phosphatase 5 is a negative regulator of estrogen receptor-
RT   mediated transcription.";
RL   Mol. Endocrinol. 18:1131-1143(2004).
RN   [12]
RP   FUNCTION IN DEPHOSPHORYLATION OF PRKDC.
RX   PubMed=14734805; DOI=10.1073/pnas.0307765100;
RA   Wechsler T., Chen B.P., Harper R., Morotomi-Yano K., Huang B.C.,
RA   Meek K., Cleaver J.E., Chen D.J., Wabl M.;
RT   "DNA-PKcs function regulated specifically by protein phosphatase 5.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:1247-1252(2004).
RN   [13]
RP   FUNCTION, INTERACTION WITH HSP90AA1 AND HSPA1A, LIPID-BINDING, ENZYME
RP   REGULATION, SUBCELLULAR LOCATION, CLEAVAGE, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=15383005; DOI=10.1042/BJ20040690;
RA   Zeke T., Morrice N., Vazquez-Martin C., Cohen P.T.;
RT   "Human protein phosphatase 5 dissociates from heat-shock proteins and
RT   is proteolytically activated in response to arachidonic acid and the
RT   microtubule-depolymerizing drug nocodazole.";
RL   Biochem. J. 385:45-56(2005).
RN   [14]
RP   FUNCTION IN DEPHOSPHORYLATION OF MAPT, BIOPHYSICOCHEMICAL PROPERTIES,
RP   AND TISSUE SPECIFICITY.
RX   PubMed=15546861; DOI=10.1074/jbc.M410775200;
RA   Liu F., Iqbal K., Grundke-Iqbal I., Rossie S., Gong C.X.;
RT   "Dephosphorylation of tau by protein phosphatase 5: impairment in
RT   Alzheimer's disease.";
RL   J. Biol. Chem. 280:1790-1796(2005).
RN   [15]
RP   FUNCTION IN DNA DAMAGE RESPONSE.
RX   PubMed=16260606; DOI=10.1128/MCB.25.22.9910-9919.2005;
RA   Zhang J., Bao S., Furumai R., Kucera K.S., Ali A., Dean N.M.,
RA   Wang X.F.;
RT   "Protein phosphatase 5 is required for ATR-mediated checkpoint
RT   activation.";
RL   Mol. Cell. Biol. 25:9910-9919(2005).
RN   [16]
RP   FUNCTION IN MAPK SIGNALING, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP   MUTAGENESIS OF LYS-97 AND HIS-304.
RX   PubMed=16892053; DOI=10.1038/ncb1465;
RA   von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.;
RT   "Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5.";
RL   Nat. Cell Biol. 8:1011-1016(2006).
RN   [17]
RP   FUNCTION IN DEPHOSPHORYLATION OF CSNK1E, INTERACTION WITH CRY1 AND
RP   CRY2, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-304.
RX   PubMed=16790549; DOI=10.1073/pnas.0604138103;
RA   Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.;
RT   "Posttranslational regulation of the mammalian circadian clock by
RT   cryptochrome and protein phosphatase 5.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006).
RN   [18]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS], AND CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [19]
RP   FUNCTION IN DEPHOSPHORYLATION OF TP53BP1.
RX   PubMed=19176521; DOI=10.1074/jbc.M809272200;
RA   Kang Y., Lee J.H., Hoan N.N., Sohn H.M., Chang I.Y., You H.J.;
RT   "Protein phosphatase 5 regulates the function of 53BP1 after
RT   neocarzinostatin-induced DNA damage.";
RL   J. Biol. Chem. 284:9845-9853(2009).
RN   [20]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [21]
RP   FUNCTION AS PHOSPHATASE, INTERACTION WITH RAC1, ENZYME REGULATION,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-93 AND HIS-304.
RX   PubMed=19948726; DOI=10.1074/jbc.M109.088427;
RA   Chatterjee A., Wang L., Armstrong D.L., Rossie S.;
RT   "Activated Rac1 GTPase translocates protein phosphatase 5 to the cell
RT   membrane and stimulates phosphatase activity in vitro.";
RL   J. Biol. Chem. 285:3872-3882(2010).
RN   [22]
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.,
RA   Buerckstuemmer T., 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   [23]
RP   FUNCTION IN DNA DAMAGE RESPONSE.
RX   PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005;
RA   Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y.,
RA   Jun J.Y., You H.J.;
RT   "Protein phosphatase 5 is necessary for ATR-mediated DNA repair.";
RL   Biochem. Biophys. Res. Commun. 404:476-481(2011).
RN   [24]
RP   FUNCTION IN TGF-BETA SIGNALING, INTERACTION WITH SMAD2 AND SMAD3, AND
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
RT   growth factor-? pathway.";
RL   Cell. Signal. 24:1999-2006(2012).
RN   [25]
RP   FUNCTION AS PHOSPHATASE, INTERACTION WITH S100A1; S100A2; S100A6 AND
RP   S100B, ENZYME REGULATION, AND MUTAGENESIS OF LYS-32; ARG-74; LYS-97
RP   AND ARG-101.
RX   PubMed=22399290; DOI=10.1074/jbc.M111.329771;
RA   Yamaguchi F., Umeda Y., Shimamoto S., Tsuchiya M., Tokumitsu H.,
RA   Tokuda M., Kobayashi R.;
RT   "S100 proteins modulate protein phosphatase 5 function: a link between
RT   CA2+ signal transduction and protein dephosphorylation.";
RL   J. Biol. Chem. 287:13787-13798(2012).
RN   [26]
RP   FUNCTION IN DEPHOSPHORYLATION OF MAP3K5, INTERACTION WITH KLHDC10, AND
RP   CLEAVAGE.
RX   PubMed=23102700; DOI=10.1016/j.molcel.2012.09.018;
RA   Sekine Y., Hatanaka R., Watanabe T., Sono N., Iemura S., Natsume T.,
RA   Kuranaga E., Miura M., Takeda K., Ichijo H.;
RT   "The Kelch repeat protein KLHDC10 regulates oxidative stress-induced
RT   ASK1 activation by suppressing PP5.";
RL   Mol. Cell 48:692-704(2012).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 19-177.
RX   PubMed=9482716; DOI=10.1093/emboj/17.5.1192;
RA   Das A.K., Cohen P.T.W., Barford D.;
RT   "The structure of the tetratricopeptide repeats of protein phosphatase
RT   5: implications for TPR-mediated protein-protein interactions.";
RL   EMBO J. 17:1192-1199(1998).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 169-499 IN COMPLEX WITH
RP   SUBSTRATE AND MAGNESIUM OR MANGANESES, ACTIVE SITE, AND MAGNESIUM OR
RP   MANGANESE-BINDING SITES.
RX   PubMed=15155720; DOI=10.1074/jbc.M402855200;
RA   Swingle M.R., Honkanen R.E., Ciszak E.M.;
RT   "Structural basis for the catalytic activity of human serine/threonine
RT   protein phosphatase-5.";
RL   J. Biol. Chem. 279:33992-33999(2004).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 23-499 IN COMPLEX WITH
RP   MANGANESE IONS, INTERACTION WITH HSP90AA1, LIPID-BINDING, MAGNESIUM OR
RP   MANGANESE-BINDING SITES, AND ENZYME REGULATION.
RX   PubMed=15577939; DOI=10.1038/sj.emboj.7600496;
RA   Yang J., Roe S.M., Cliff M.J., Williams M.A., Ladbury J.E.,
RA   Cohen P.T., Barford D.;
RT   "Molecular basis for TPR domain-mediated regulation of protein
RT   phosphatase 5.";
RL   EMBO J. 24:1-10(2005).
RN   [30]
RP   STRUCTURE BY NMR OF 19-147 IN COMPLEX WITH HSP90AA1 PEPTIDE,
RP   INTERACTION WITH HSP90AA1, AND MUTAGENESIS OF GLY-83.
RX   PubMed=16531226; DOI=10.1016/j.str.2005.12.009;
RA   Cliff M.J., Harris R., Barford D., Ladbury J.E., Williams M.A.;
RT   "Conformational diversity in the TPR domain-mediated interaction of
RT   protein phosphatase 5 with Hsp90.";
RL   Structure 14:415-426(2006).
RN   [31]
RP   X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 176-490 IN COMPLEX WITH
RP   INHIBITORS AND MANGANESE, MANGANESE-BINDING SITES, AND ENZYME
RP   REGULATION.
RX   PubMed=19601647; DOI=10.1021/jm900610k;
RA   Bertini I., Calderone V., Fragai M., Luchinat C., Talluri E.;
RT   "Structural basis of serine/threonine phosphatase inhibition by the
RT   archetypal small molecules cantharidin and norcantharidin.";
RL   J. Med. Chem. 52:4838-4843(2009).
CC   -!- FUNCTION: Serine/threonine-protein phosphatase that
CC       dephosphorylates a myriad of proteins involved in different
CC       signaling pathways including the kinases CSNK1E, ASK1/MAP3K5,
CC       PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2,
CC       SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular
CC       processes, including apoptosis, differentiation, DNA damage
CC       response, cell survival, regulation of ion channels or circadian
CC       rhythms, in response to steroid and thyroid hormones, calcium,
CC       fatty acids, TGF-beta as well as oxidative and genotoxic stresses.
CC       Participates in the control of DNA damage response mechanisms such
CC       as checkpoint activation and DNA damage repair through, for
CC       instance, the regulation ATM/ATR-signaling and dephosphorylation
CC       of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis
CC       induced by oxidative stress. Plays a positive role in
CC       adipogenesis, mainly through the dephosphorylation and activation
CC       of PPARG transactivation function. Also dephosphorylates and
CC       inhibits the anti-adipogenic effect of NR3C1. Regulates the
CC       circadian rhythms, through the dephosphorylation and activation of
CC       CSNK1E. May modulate TGF-beta signaling pathway by the regulation
CC       of SMAD3 phosphorylation and protein expression levels.
CC       Dephosphorylates and may play a role in the regulation of
CC       TAU/MAPT. Through their dephosphorylation, may play a role in the
CC       regulation of ions channels such as KCNH2.
CC       {ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652,
CC       ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005,
CC       ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16260606,
CC       ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:16892053,
CC       ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:19948726,
CC       ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22399290,
CC       ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:23102700,
CC       ECO:0000269|PubMed:9000529}.
CC   -!- CATALYTIC ACTIVITY: [a protein]-serine/threonine phosphate + H(2)O
CC       = [a protein]-serine/threonine + phosphate.
CC   -!- COFACTOR: Binds 2 magnesium or manganese per subunit.
CC   -!- ENZYME REGULATION: Autoinhibited. In the autoinhibited state, the
CC       TPR domain interacts with the catalytic region and prevents
CC       substrate access to the catalytic pocket. Allosterically activated
CC       by various polyunsaturated fatty acids, free long-chain fatty-
CC       acids and long-chain fatty acyl-CoA esters, arachidonic acid being
CC       the most effective activator. HSP90A and probably RAC1, GNA12 and
CC       GNA13 can also release the autoinhibition by the TPR repeat.
CC       Activation by RAC1, GNA12 and GNA13 is synergistic with the one
CC       produced by fatty acids binding. Inhibited by okadaic acid.
CC       {ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:15577939,
CC       ECO:0000269|PubMed:19601647, ECO:0000269|PubMed:19948726,
CC       ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:9000529}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.847 uM for CSNK1E (at 30 degrees Celsius)
CC         {ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549};
CC         KM=13.2 uM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549};
CC   -!- SUBUNIT: Part of a complex with HSP90/HSP90AA1 and steroid
CC       receptors. Interacts with CDC16, CDC27. Interacts with KLHDC10
CC       (via the 6 Kelch repeats); inhibits the phosphatase activity on
CC       MAP3K5. Interacts (via TPR repeats) with HSP90AA1 (via TPR repeat-
CC       binding motif) or HSPA1A/HSPA1B; the interaction is direct and
CC       activates the phosphatase activity. Dissociates from HSPA1A/HSPA1B
CC       and HSP90AA1 in response to arachidonic acid. Interacts with ATM
CC       and ATR; both interactions are induced by DNA damage and enhance
CC       ATM and ATR kinase activity. Interacts with RAD17; reduced by DNA
CC       damage. Interacts with nuclear receptors such as NR3C1/GCR and
CC       PPARG (activated by agonist); regulates their transactivation
CC       activities. Interacts (via TPR repeats) with S100 proteins S100A1,
CC       S100A2, S100A6, S100B and S100P; the interactions are calcium-
CC       dependent, strongly activate PPP5C phosphatase activity and
CC       compete with HSP90AA1 and MAP3K5 interactions. Interacts with
CC       SMAD2 and SMAD3 but not with SMAD1; decreases SMAD3
CC       phosphorylation and protein levels. Interacts (via TPR repeats)
CC       with CRY1 and CRY2; the interaction with CRY2 downregulates the
CC       phosphatase activity on CSNK1E. Interacts (via TPR repeats) with
CC       the active form of RAC1, GNA12 or GNA13; these interactions
CC       activate the phosphatase activity and translocate PPP5C to the
CC       cell membrane. {ECO:0000269|PubMed:14871926,
CC       ECO:0000269|PubMed:15155720, ECO:0000269|PubMed:15383005,
CC       ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:16531226,
CC       ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:19601647,
CC       ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:22399290,
CC       ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:23102700,
CC       ECO:0000269|PubMed:9405394}.
CC   -!- INTERACTION:
CC       Self; NbExp=2; IntAct=EBI-716663, EBI-716663;
CC       Q16543:CDC37; NbExp=4; IntAct=EBI-716663, EBI-295634;
CC       P03372:ESR1; NbExp=4; IntAct=EBI-716663, EBI-78473;
CC       Q92731:ESR2; NbExp=4; IntAct=EBI-716663, EBI-78505;
CC       P07900:HSP90AA1; NbExp=8; IntAct=EBI-716663, EBI-296047;
CC       P30153:PPP2R1A; NbExp=3; IntAct=EBI-716663, EBI-302388;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Membrane.
CC       Note=Predominantly nuclear. But also present in the cytoplasm.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15546861}.
CC   -!- PTM: Activated by at least two different proteolytic cleavages
CC       producing a 56 kDa and a 50 kDa form.
CC       {ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:23102700}.
CC   -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC       subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 3 TPR repeats. {ECO:0000255|PROSITE-
CC       ProRule:PRU00339}.
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DR   EMBL; BT007275; AAP35939.1; -; mRNA.
DR   EMBL; X89416; CAA61595.1; -; mRNA.
DR   EMBL; U25174; AAB60384.1; -; mRNA.
DR   EMBL; AC007193; AAD22669.1; -; Genomic_DNA.
DR   EMBL; CH471126; EAW57416.1; -; Genomic_DNA.
DR   EMBL; BC001970; AAH01970.1; -; mRNA.
DR   EMBL; X92121; CAA63089.1; -; mRNA.
DR   CCDS; CCDS12684.1; -.
DR   PIR; S52570; S52570.
DR   RefSeq; NP_006238.1; NM_006247.3.
DR   UniGene; Hs.654604; -.
DR   PDB; 1A17; X-ray; 2.45 A; A=16-181.
DR   PDB; 1S95; X-ray; 1.60 A; A/B=169-499.
DR   PDB; 1WAO; X-ray; 2.90 A; 1/2/3/4=23-499.
DR   PDB; 2BUG; NMR; -; A=19-147.
DR   PDB; 3H60; X-ray; 2.00 A; A/B=176-490.
DR   PDB; 3H61; X-ray; 1.45 A; A/D=176-490.
DR   PDB; 3H62; X-ray; 1.40 A; B/C=176-490.
DR   PDB; 3H63; X-ray; 1.30 A; A/C=176-490.
DR   PDB; 3H64; X-ray; 1.90 A; A/D=176-490.
DR   PDB; 3H66; X-ray; 2.59 A; A/B=176-490.
DR   PDB; 3H67; X-ray; 1.65 A; A/D=176-490.
DR   PDB; 3H68; X-ray; 1.50 A; A/D=176-490.
DR   PDB; 3H69; X-ray; 2.10 A; A/D=176-490.
DR   PDBsum; 1A17; -.
DR   PDBsum; 1S95; -.
DR   PDBsum; 1WAO; -.
DR   PDBsum; 2BUG; -.
DR   PDBsum; 3H60; -.
DR   PDBsum; 3H61; -.
DR   PDBsum; 3H62; -.
DR   PDBsum; 3H63; -.
DR   PDBsum; 3H64; -.
DR   PDBsum; 3H66; -.
DR   PDBsum; 3H67; -.
DR   PDBsum; 3H68; -.
DR   PDBsum; 3H69; -.
DR   DisProt; DP00365; -.
DR   ProteinModelPortal; P53041; -.
DR   SMR; P53041; 19-499.
DR   BioGrid; 111528; 67.
DR   DIP; DIP-29043N; -.
DR   IntAct; P53041; 29.
DR   MINT; MINT-1411788; -.
DR   STRING; 9606.ENSP00000012443; -.
DR   PhosphoSite; P53041; -.
DR   DMDM; 1709744; -.
DR   MaxQB; P53041; -.
DR   PaxDb; P53041; -.
DR   PRIDE; P53041; -.
DR   DNASU; 5536; -.
DR   Ensembl; ENST00000012443; ENSP00000012443; ENSG00000011485.
DR   GeneID; 5536; -.
DR   KEGG; hsa:5536; -.
DR   UCSC; uc002pem.3; human.
DR   CTD; 5536; -.
DR   GeneCards; GC19P046850; -.
DR   HGNC; HGNC:9322; PPP5C.
DR   HPA; CAB022641; -.
DR   HPA; HPA029065; -.
DR   HPA; HPA056933; -.
DR   MIM; 600658; gene.
DR   neXtProt; NX_P53041; -.
DR   PharmGKB; PA33686; -.
DR   eggNOG; COG0639; -.
DR   GeneTree; ENSGT00530000063173; -.
DR   HOGENOM; HOG000172698; -.
DR   HOVERGEN; HBG000216; -.
DR   InParanoid; P53041; -.
DR   KO; K04460; -.
DR   OMA; FKLLYPN; -.
DR   OrthoDB; EOG7V49Z3; -.
DR   PhylomeDB; P53041; -.
DR   TreeFam; TF105562; -.
DR   SignaLink; P53041; -.
DR   EvolutionaryTrace; P53041; -.
DR   GeneWiki; PPP5C; -.
DR   GenomeRNAi; 5536; -.
DR   NextBio; 21446; -.
DR   PRO; PR:P53041; -.
DR   Bgee; P53041; -.
DR   CleanEx; HS_PPP5C; -.
DR   ExpressionAtlas; P53041; baseline and differential.
DR   Genevestigator; P53041; -.
DR   GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IDA:HPA.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004721; F:phosphoprotein phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; TAS:ProtInc.
DR   GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR   GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR   GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0007067; P:mitotic nuclear division; TAS:ProtInc.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR   GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR   GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR   GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IMP:GOC.
DR   GO; GO:0006351; P:transcription, DNA-templated; TAS:ProtInc.
DR   Gene3D; 1.25.40.10; -; 1.
DR   Gene3D; 3.60.21.10; -; 1.
DR   InterPro; IPR004843; Calcineurin-like_PHP_apaH.
DR   InterPro; IPR029052; Metallo-depent_PP-like.
DR   InterPro; IPR013235; PPP_dom.
DR   InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR   InterPro; IPR011236; Ser/Thr_PPase_5.
DR   InterPro; IPR013026; TPR-contain_dom.
DR   InterPro; IPR011990; TPR-like_helical_dom.
DR   InterPro; IPR001440; TPR_1.
DR   InterPro; IPR019734; TPR_repeat.
DR   PANTHER; PTHR11668:SF12; PTHR11668:SF12; 1.
DR   Pfam; PF00149; Metallophos; 1.
DR   Pfam; PF08321; PPP5; 1.
DR   Pfam; PF00515; TPR_1; 2.
DR   PIRSF; PIRSF033096; PPPtase_5; 1.
DR   PRINTS; PR00114; STPHPHTASE.
DR   SMART; SM00156; PP2Ac; 1.
DR   SMART; SM00028; TPR; 3.
DR   SUPFAM; SSF56300; SSF56300; 1.
DR   PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
DR   PROSITE; PS50005; TPR; 3.
DR   PROSITE; PS50293; TPR_REGION; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alzheimer disease; Amyloid; Amyloidosis;
KW   Complete proteome; Cytoplasm; DNA damage; DNA repair; Hydrolase;
KW   Lipid-binding; Magnesium; Manganese; Membrane; Metal-binding;
KW   Neurodegeneration; Nucleus; Protein phosphatase; Reference proteome;
KW   Repeat; TPR repeat.
FT   INIT_MET      1      1       Removed. {ECO:0000269|PubMed:19413330}.
FT   CHAIN         2    499       Serine/threonine-protein phosphatase 5.
FT                                /FTId=PRO_0000058894.
FT   REPEAT       28     61       TPR 1.
FT   REPEAT       62     95       TPR 2.
FT   REPEAT       96    129       TPR 3.
FT   REGION      184    499       Catalytic.
FT   REGION      303    304       Substrate binding.
FT   REGION      495    499       Required for autoinhibition.
FT                                {ECO:0000250}.
FT   ACT_SITE    304    304       Proton donor/acceptor.
FT                                {ECO:0000269|PubMed:15155720}.
FT   METAL       242    242       Magnesium or manganese 1.
FT   METAL       244    244       Magnesium or manganese 1.
FT   METAL       271    271       Magnesium or manganese 1.
FT   METAL       271    271       Magnesium or manganese 2.
FT   METAL       303    303       Magnesium or manganese 2.
FT   METAL       352    352       Magnesium or manganese 2.
FT   METAL       427    427       Magnesium or manganese 2.
FT   BINDING     244    244       Substrate. {ECO:0000269|PubMed:15155720}.
FT   BINDING     275    275       Substrate. {ECO:0000269|PubMed:15155720}.
FT   BINDING     400    400       Substrate. {ECO:0000269|PubMed:15155720}.
FT   BINDING     427    427       Substrate. {ECO:0000269|PubMed:15155720}.
FT   MOD_RES       2      2       N-acetylalanine.
FT                                {ECO:0000269|PubMed:19413330}.
FT   MUTAGEN      32     32       K->A: Loss of interaction with HSP90AA1.
FT                                No effect on interaction with S100A1,
FT                                S100A2 and S100A6.
FT                                {ECO:0000269|PubMed:22399290}.
FT   MUTAGEN      74     74       R->A: Loss of interaction with HSP90AA1.
FT                                No effect on interaction with S100A1,
FT                                S100A2 and S100A6.
FT                                {ECO:0000269|PubMed:22399290}.
FT   MUTAGEN      83     83       G->N: No effect on interaction with
FT                                HSP90AA1. {ECO:0000269|PubMed:16531226}.
FT   MUTAGEN      93     93       K->E: Decreases interaction with RAC1 and
FT                                translocation to the membrane in presence
FT                                of active RAC1.
FT                                {ECO:0000269|PubMed:19948726}.
FT   MUTAGEN      97     97       K->A: Loss of interaction with HSP90AA1.
FT                                No effect on interaction with S100A1,
FT                                S100A2 and S100A6. Loss of interaction
FT                                with RAF1. {ECO:0000269|PubMed:16892053,
FT                                ECO:0000269|PubMed:22399290}.
FT   MUTAGEN     101    101       R->A: Loss of interaction with HSP90AA1.
FT                                No effect on interaction with S100A1,
FT                                S100A2 and S100A6.
FT                                {ECO:0000269|PubMed:22399290}.
FT   MUTAGEN     304    304       H->Q: Catalytically inactive; no effect
FT                                on interaction with CRY2 but increases
FT                                the stability of the interaction with
FT                                CSNK1E. No effect on RAF1
FT                                phosphorylation.
FT                                {ECO:0000269|PubMed:16790549,
FT                                ECO:0000269|PubMed:16892053,
FT                                ECO:0000269|PubMed:19948726}.
FT   CONFLICT    403    403       S -> T (in Ref. 4; AAB60384).
FT                                {ECO:0000305}.
FT   HELIX        22     40       {ECO:0000244|PDB:1A17}.
FT   HELIX        44     57       {ECO:0000244|PDB:1A17}.
FT   HELIX        62     74       {ECO:0000244|PDB:1A17}.
FT   HELIX        78     91       {ECO:0000244|PDB:1A17}.
FT   STRAND       92     94       {ECO:0000244|PDB:2BUG}.
FT   HELIX        96    108       {ECO:0000244|PDB:1A17}.
FT   HELIX       112    125       {ECO:0000244|PDB:1A17}.
FT   HELIX       130    164       {ECO:0000244|PDB:1A17}.
FT   HELIX       182    184       {ECO:0000244|PDB:1WAO}.
FT   HELIX       188    199       {ECO:0000244|PDB:3H63}.
FT   HELIX       206    221       {ECO:0000244|PDB:3H63}.
FT   STRAND      225    229       {ECO:0000244|PDB:3H63}.
FT   STRAND      236    240       {ECO:0000244|PDB:3H63}.
FT   HELIX       247    257       {ECO:0000244|PDB:3H63}.
FT   STRAND      266    270       {ECO:0000244|PDB:3H63}.
FT   STRAND      273    276       {ECO:0000244|PDB:3H63}.
FT   HELIX       279    292       {ECO:0000244|PDB:3H63}.
FT   TURN        294    296       {ECO:0000244|PDB:3H63}.
FT   STRAND      297    300       {ECO:0000244|PDB:3H63}.
FT   STRAND      303    306       {ECO:0000244|PDB:3H66}.
FT   HELIX       307    313       {ECO:0000244|PDB:3H63}.
FT   HELIX       315    322       {ECO:0000244|PDB:3H63}.
FT   HELIX       325    335       {ECO:0000244|PDB:3H63}.
FT   STRAND      340    344       {ECO:0000244|PDB:3H63}.
FT   TURN        345    347       {ECO:0000244|PDB:3H63}.
FT   STRAND      348    350       {ECO:0000244|PDB:3H63}.
FT   STRAND      357    359       {ECO:0000244|PDB:1S95}.
FT   HELIX       363    368       {ECO:0000244|PDB:3H63}.
FT   STRAND      372    374       {ECO:0000244|PDB:3H62}.
FT   STRAND      377    379       {ECO:0000244|PDB:3H63}.
FT   HELIX       380    386       {ECO:0000244|PDB:3H63}.
FT   STRAND      391    397       {ECO:0000244|PDB:3H63}.
FT   STRAND      401    406       {ECO:0000244|PDB:3H63}.
FT   HELIX       408    418       {ECO:0000244|PDB:3H63}.
FT   STRAND      421    425       {ECO:0000244|PDB:3H63}.
FT   STRAND      433    437       {ECO:0000244|PDB:3H63}.
FT   HELIX       438    440       {ECO:0000244|PDB:3H63}.
FT   STRAND      442    446       {ECO:0000244|PDB:3H63}.
FT   HELIX       451    453       {ECO:0000244|PDB:3H63}.
FT   STRAND      459    465       {ECO:0000244|PDB:3H63}.
FT   STRAND      468    476       {ECO:0000244|PDB:3H63}.
FT   TURN        486    489       {ECO:0000244|PDB:3H63}.
FT   HELIX       492    495       {ECO:0000244|PDB:1S95}.
SQ   SEQUENCE   499 AA;  56879 MW;  DB3B2090D8658BB3 CRC64;
     MAMAEGERTE CAEPPRDEPP ADGALKRAEE LKTQANDYFK AKDYENAIKF YSQAIELNPS
     NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY RRAASNMALG KFRAALRDYE
     TVVKVKPHDK DAKMKYQECN KIVKQKAFER AIAGDEHKRS VVDSLDIESM TIEDEYSGPK
     LEDGKVTISF MKELMQWYKD QKKLHRKCAY QILVQVKEVL SKLSTLVETT LKETEKITVC
     GDTHGQFYDL LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL
     RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI MHGGLFSEDG
     VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSISKR GVSCQFGPDV TKAFLEENNL
     DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP
     HPNVKPMAYA NTLLQLGMM
//
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