PPP5_HUMAN
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 03-AUG-2022, entry version 229.
DE RecName: Full=Serine/threonine-protein phosphatase 5;
DE Short=PP5;
DE EC=3.1.3.16 {ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:30699359};
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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., 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-499.
RX PubMed=7925273; DOI=10.1002/j.1460-2075.1994.tb06748.x;
RA Chen M.X., McPartlin A.E., Brown L., Chen Y.H., Barker H.M., Cohen P.T.W.;
RT "A novel human protein serine/threonine phosphatase, which possesses four
RT 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., Gusella J.F.,
RA Mohrenweiser H.W., Buckler A.J., Louis D.N.;
RT "Cloning of a highly conserved human protein serine-threonine phosphatase
RT gene from the glioma candidate region on chromosome 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 project:
RT 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., 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, ACTIVITY 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 binding
RT 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, two
RT tetratricopeptide repeat-containing subunits of the anaphase-promoting
RT 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., Abraham R.T.,
RA 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., Meek K.,
RA 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, ACTIVITY
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 is
RT 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, AND
RP 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., 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 CRY2,
RP 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, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT 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., Walther T.C.,
RA 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, ACTIVITY 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., 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 [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., Jun J.Y.,
RA 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, AND INTERACTION WITH SMAD2 AND SMAD3.
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 [25]
RP FUNCTION AS PHOSPHATASE, INTERACTION WITH S100A1; S100A2; S100A6 AND S100B,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-32; ARG-74; LYS-97 AND ARG-101.
RX PubMed=22399290; DOI=10.1074/jbc.m111.329771;
RA Yamaguchi F., Umeda Y., Shimamoto S., Tsuchiya M., Tokumitsu H., Tokuda M.,
RA Kobayashi R.;
RT "S100 proteins modulate protein phosphatase 5 function: a link between CA2+
RT 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 ASK1
RT activation by suppressing PP5.";
RL Mol. Cell 48:692-704(2012).
RN [27]
RP INTERACTION WITH HSP90AA1 AND FLCN.
RX PubMed=27353360; DOI=10.1038/ncomms12037;
RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D.,
RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W.,
RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W.,
RA Bratslavsky G., Mollapour M.;
RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance
RT drug binding.";
RL Nat. Commun. 7:12037-12037(2016).
RN [28]
RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; CDC37; PTGES3; TSC1;
RP TSC2; AKT; CDK4; RAF1 AND NR3C1.
RX PubMed=29127155; DOI=10.15252/embj.201796700;
RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L.,
RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H.,
RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.;
RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding
RT of kinase and non-kinase clients.";
RL EMBO J. 36:3650-3665(2017).
RN [29]
RP FUNCTION.
RX PubMed=30699359; DOI=10.1016/j.celrep.2019.01.018;
RA Sager R.A., Woodford M.R., Backe S.J., Makedon A.M., Baker-Williams A.J.,
RA DiGregorio B.T., Loiselle D.R., Haystead T.A., Zachara N.E., Prodromou C.,
RA Bourboulia D., Schmidt L.S., Linehan W.M., Bratslavsky G., Mollapour M.;
RT "Post-translational regulation of FNIP1 creates a rheostat for the
RT molecular chaperone Hsp90.";
RL Cell Rep. 26:1344-1356(2019).
RN [30]
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 5:
RT implications for TPR-mediated protein-protein interactions.";
RL EMBO J. 17:1192-1199(1998).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 169-499 IN COMPLEX WITH SUBSTRATE
RP 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 [32]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 23-499 IN COMPLEX WITH MANGANESE
RP IONS, INTERACTION WITH HSP90AA1, LIPID-BINDING, MAGNESIUM OR
RP MANGANESE-BINDING SITES, AND ACTIVITY 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., Cohen P.T.,
RA Barford D.;
RT "Molecular basis for TPR domain-mediated regulation of protein phosphatase
RT 5.";
RL EMBO J. 24:1-10(2005).
RN [33]
RP STRUCTURE BY NMR OF 19-147 IN COMPLEX WITH HSP90AA1 PEPTIDE, INTERACTION
RP 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 protein
RT phosphatase 5 with Hsp90.";
RL Structure 14:415-426(2006).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 176-490 IN COMPLEX WITH
RP INHIBITORS AND MANGANESE, MANGANESE-BINDING SITES, AND ACTIVITY 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 dephosphorylates a
CC myriad of proteins involved in different signaling pathways including
CC the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors
CC NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT
CC (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005,
CC PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053,
CC PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290,
CC PubMed:22781750, PubMed:23102700, PubMed:9000529, PubMed:30699359).
CC Implicated in wide ranging cellular processes, including apoptosis,
CC differentiation, DNA damage response, cell survival, regulation of ion
CC channels or circadian rhythms, in response to steroid and thyroid
CC hormones, calcium, fatty acids, TGF-beta as well as oxidative and
CC genotoxic stresses (PubMed:14734805, PubMed:14764652, PubMed:14871926,
CC PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549,
CC PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835,
CC PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:9000529,
CC PubMed:30699359). Participates in the control of DNA damage response
CC mechanisms such as checkpoint activation and DNA damage repair through,
CC for instance, the regulation ATM/ATR-signaling and dephosphorylation of
CC PRKDC and TP53BP1 (PubMed:14871926, PubMed:16260606, PubMed:21144835).
CC Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress
CC (PubMed:23102700). Plays a positive role in adipogenesis, mainly
CC through the dephosphorylation and activation of PPARG transactivation
CC function (By similarity). Also dephosphorylates and inhibits the anti-
CC adipogenic effect of NR3C1 (By similarity). Regulates the circadian
CC rhythms, through the dephosphorylation and activation of CSNK1E
CC (PubMed:16790549). May modulate TGF-beta signaling pathway by the
CC regulation of SMAD3 phosphorylation and protein expression levels
CC (PubMed:22781750). Dephosphorylates and may play a role in the
CC regulation of TAU/MAPT (PubMed:15546861). Through their
CC dephosphorylation, may play a role in the regulation of ions channels
CC such as KCNH2 (By similarity). Dephosphorylate FNIP1, disrupting
CC interaction with HSP90AA1/Hsp90 (PubMed:30699359).
CC {ECO:0000250|UniProtKB:P53042, ECO:0000250|UniProtKB:Q60676,
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:30699359, ECO:0000269|PubMed:9000529}.
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:14734805, ECO:0000269|PubMed:14764652,
CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700,
CC ECO:0000269|PubMed:30699359};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630;
CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652,
CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700,
CC ECO:0000269|PubMed:30699359};
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:14734805, ECO:0000269|PubMed:14764652,
CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652,
CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=Binds 2 Mg(2+) or Mn(2+) cations per subunit.;
CC -!- ACTIVITY REGULATION: Autoinhibited. In the autoinhibited state, the TPR
CC domain interacts with the catalytic region and prevents substrate
CC access to the catalytic pocket. Allosterically activated by various
CC polyunsaturated fatty acids, free long-chain fatty-acids and long-chain
CC fatty acyl-CoA esters, arachidonic acid being the most effective
CC activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release
CC the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and
CC GNA13 is synergistic with the one produced by fatty acids binding.
CC Inhibited by okadaic acid. {ECO:0000269|PubMed:15383005,
CC ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
CC ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:22399290,
CC 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: Probably forms a complex composed of chaperones HSP90 and
CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and
CC client protein TSC2 (PubMed:29127155). Probably forms a complex
CC composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C,
CC TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex
CC does not contain co-chaperones STIP1/HOP and PTGES3/p23
CC (PubMed:29127155). Part of a complex with HSP90/HSP90AA1 and steroid
CC receptors (By similarity). Interacts (via TPR repeats) with HSP90AA1
CC (via TPR repeat-binding motif) or HSPA1A/HSPA1B; the interaction is
CC direct and activates the phosphatase activity (PubMed:15383005,
CC PubMed:15577939, PubMed:16531226). Dissociates from HSPA1A/HSPA1B and
CC HSP90AA1 in response to arachidonic acid (PubMed:15383005). Interacts
CC with CPNE1 (via VWFA domain) (By similarity). Interacts with CDC16,
CC CDC27 (PubMed:9405394). Interacts with KLHDC10 (via the 6 Kelch
CC repeats); inhibits the phosphatase activity on MAP3K5
CC (PubMed:23102700). Interacts with ATM and ATR; both interactions are
CC induced by DNA damage and enhance ATM and ATR kinase activity
CC (PubMed:14871926). Interacts with RAD17; reduced by DNA damage
CC (PubMed:14871926). Interacts with nuclear receptors such as NR3C1/GCR
CC and PPARG (activated by agonist); regulates their transactivation
CC activities (By similarity). Interacts (via TPR repeats) with S100
CC proteins S100A1, S100A2, S100A6, S100B and S100P; the interactions are
CC calcium-dependent, strongly activate PPP5C phosphatase activity and
CC compete with HSP90AA1 and MAP3K5 interactions (PubMed:22399290).
CC Interacts with SMAD2 and SMAD3 but not with SMAD1; decreases SMAD3
CC phosphorylation and protein levels (PubMed:22781750). Interacts (via
CC TPR repeats) with CRY1 and CRY2; the interaction with CRY2 down-
CC regulates the phosphatase activity on CSNK1E (PubMed:16790549).
CC Interacts (via TPR repeats) with the active form of RAC1, GNA12 or
CC GNA13; these interactions activate the phosphatase activity and
CC translocate PPP5C to the cell membrane (PubMed:19948726). Interacts
CC with FLCN (PubMed:27353360). {ECO:0000250|UniProtKB:Q60676,
CC ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005,
CC ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:16531226,
CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:19948726,
CC ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:22781750,
CC ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:27353360,
CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:9405394}.
CC -!- INTERACTION:
CC P53041; Q9UL18: AGO1; NbExp=2; IntAct=EBI-716663, EBI-527363;
CC P53041; Q9H9G7: AGO3; NbExp=2; IntAct=EBI-716663, EBI-2267883;
CC P53041; Q16543: CDC37; NbExp=5; IntAct=EBI-716663, EBI-295634;
CC P53041; P50750: CDK9; NbExp=3; IntAct=EBI-716663, EBI-1383449;
CC P53041; Q49AN0: CRY2; NbExp=3; IntAct=EBI-716663, EBI-2212355;
CC P53041; P03372: ESR1; NbExp=4; IntAct=EBI-716663, EBI-78473;
CC P53041; Q92731: ESR2; NbExp=4; IntAct=EBI-716663, EBI-78505;
CC P53041; P07900: HSP90AA1; NbExp=12; IntAct=EBI-716663, EBI-296047;
CC P53041; P08238: HSP90AB1; NbExp=8; IntAct=EBI-716663, EBI-352572;
CC P53041; Q5SY16: NOL9; NbExp=2; IntAct=EBI-716663, EBI-1055462;
CC P53041; P30153: PPP2R1A; NbExp=3; IntAct=EBI-716663, EBI-302388;
CC P53041; P53041: PPP5C; NbExp=2; IntAct=EBI-716663, EBI-716663;
CC P53041; P31948: STIP1; NbExp=4; IntAct=EBI-716663, EBI-1054052;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15383005}. Cytoplasm
CC {ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:19948726}. Cell
CC membrane {ECO:0000269|PubMed:19948726}. Note=Predominantly nuclear
CC (PubMed:15383005). But also present in the cytoplasm (PubMed:15383005).
CC Translocates from the cytoplasm to the plasma membrane in a RAC1-
CC dependent manner (PubMed:19948726). {ECO:0000269|PubMed:15383005,
CC ECO:0000269|PubMed:19948726}.
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. {ECO:0000269|PubMed:15383005,
CC ECO:0000269|PubMed:23102700}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC subfamily. {ECO:0000305}.
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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 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 PDB; 4ZVZ; X-ray; 2.00 A; A/B/C/D=169-499.
DR PDB; 4ZX2; X-ray; 1.23 A; A=169-499.
DR PDB; 5HPE; X-ray; 2.27 A; A=175-499.
DR PDB; 5UI1; X-ray; 1.96 A; A/B/C/D=169-499.
DR PDB; 5WG8; X-ray; 1.65 A; A=169-499.
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 PDBsum; 4ZVZ; -.
DR PDBsum; 4ZX2; -.
DR PDBsum; 5HPE; -.
DR PDBsum; 5UI1; -.
DR PDBsum; 5WG8; -.
DR AlphaFoldDB; P53041; -.
DR BMRB; P53041; -.
DR SMR; P53041; -.
DR BioGRID; 111528; 143.
DR DIP; DIP-29043N; -.
DR IntAct; P53041; 83.
DR MINT; P53041; -.
DR STRING; 9606.ENSP00000012443; -.
DR BindingDB; P53041; -.
DR ChEMBL; CHEMBL3425389; -.
DR DrugBank; DB00171; ATP.
DR DEPOD; PPP5C; -.
DR GlyGen; P53041; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P53041; -.
DR MetOSite; P53041; -.
DR PhosphoSitePlus; P53041; -.
DR SwissPalm; P53041; -.
DR BioMuta; PPP5C; -.
DR DMDM; 1709744; -.
DR EPD; P53041; -.
DR jPOST; P53041; -.
DR MassIVE; P53041; -.
DR MaxQB; P53041; -.
DR PaxDb; P53041; -.
DR PeptideAtlas; P53041; -.
DR PRIDE; P53041; -.
DR ProteomicsDB; 56568; -.
DR Antibodypedia; 31446; 704 antibodies from 32 providers.
DR DNASU; 5536; -.
DR Ensembl; ENST00000012443.9; ENSP00000012443.4; ENSG00000011485.15.
DR GeneID; 5536; -.
DR KEGG; hsa:5536; -.
DR MANE-Select; ENST00000012443.9; ENSP00000012443.4; NM_006247.4; NP_006238.1.
DR UCSC; uc002pem.4; human.
DR CTD; 5536; -.
DR DisGeNET; 5536; -.
DR GeneCards; PPP5C; -.
DR HGNC; HGNC:9322; PPP5C.
DR HPA; ENSG00000011485; Low tissue specificity.
DR MIM; 600658; gene.
DR neXtProt; NX_P53041; -.
DR OpenTargets; ENSG00000011485; -.
DR PharmGKB; PA33686; -.
DR VEuPathDB; HostDB:ENSG00000011485; -.
DR eggNOG; KOG0376; Eukaryota.
DR GeneTree; ENSGT00940000158785; -.
DR InParanoid; P53041; -.
DR OMA; NHFFMSR; -.
DR OrthoDB; 671536at2759; -.
DR PhylomeDB; P53041; -.
DR TreeFam; TF105562; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; P53041; -.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-8939211; ESR-mediated signaling.
DR SABIO-RK; P53041; -.
DR SignaLink; P53041; -.
DR SIGNOR; P53041; -.
DR BioGRID-ORCS; 5536; 22 hits in 1087 CRISPR screens.
DR ChiTaRS; PPP5C; human.
DR EvolutionaryTrace; P53041; -.
DR GeneWiki; PPP5C; -.
DR GenomeRNAi; 5536; -.
DR Pharos; P53041; Tbio.
DR PRO; PR:P53041; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P53041; protein.
DR Bgee; ENSG00000011485; Expressed in cortical plate and 125 other tissues.
DR ExpressionAtlas; P53041; baseline and differential.
DR Genevisible; P53041; HS.
DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0043531; F:ADP binding; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:CAFA.
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:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IDA:ARUK-UCL.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome.
DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; TAS:ARUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:1904550; P:response to arachidonic acid; ISS:ARUK-UCL.
DR GO; GO:0010288; P:response to lead ion; ISS:ARUK-UCL.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; TAS:ProtInc.
DR CDD; cd07417; MPP_PP5_C; 1.
DR DisProt; DP00365; -.
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; IPR041753; PP5_C.
DR InterPro; IPR013235; PPP_dom.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR InterPro; IPR011236; Ser/Thr_PPase_5.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR45668:SF5; PTHR45668:SF5; 1.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF08321; PPP5; 1.
DR Pfam; PF00515; TPR_1; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
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 Cell membrane; Cytoplasm; DNA damage; DNA repair; Hydrolase; Lipid-binding;
KW Magnesium; Manganese; Membrane; Metal-binding; Neurodegeneration; Nucleus;
KW Protein phosphatase; Reference proteome; Repeat; TPR repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..499
FT /note="Serine/threonine-protein phosphatase 5"
FT /id="PRO_0000058894"
FT REPEAT 28..61
FT /note="TPR 1"
FT REPEAT 62..95
FT /note="TPR 2"
FT REPEAT 96..129
FT /note="TPR 3"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..499
FT /note="Catalytic"
FT REGION 495..499
FT /note="Required for autoinhibition"
FT /evidence="ECO:0000250|UniProtKB:P53042"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 304
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:15155720"
FT BINDING 242
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 244
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 244
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15155720"
FT BINDING 271
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 271
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15155720"
FT BINDING 303..304
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15155720"
FT BINDING 303
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 352
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 400
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15155720"
FT BINDING 427
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15155720,
FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647,
FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO,
FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61,
FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63,
FT ECO:0007744|PDB:3H64"
FT BINDING 427
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15155720"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MUTAGEN 32
FT /note="K->A: Loss of interaction with HSP90AA1. No effect
FT on interaction with S100A1, S100A2 and S100A6."
FT /evidence="ECO:0000269|PubMed:22399290"
FT MUTAGEN 74
FT /note="R->A: Loss of interaction with HSP90AA1. No effect
FT on interaction with S100A1, S100A2 and S100A6."
FT /evidence="ECO:0000269|PubMed:22399290"
FT MUTAGEN 83
FT /note="G->N: No effect on interaction with HSP90AA1."
FT /evidence="ECO:0000269|PubMed:16531226"
FT MUTAGEN 93
FT /note="K->E: Decreases interaction with RAC1 and
FT translocation to the membrane in presence of active RAC1."
FT /evidence="ECO:0000269|PubMed:19948726"
FT MUTAGEN 97
FT /note="K->A: Loss of interaction with HSP90AA1. No effect
FT on interaction with S100A1, S100A2 and S100A6. Loss of
FT interaction with RAF1."
FT /evidence="ECO:0000269|PubMed:16892053,
FT ECO:0000269|PubMed:22399290"
FT MUTAGEN 101
FT /note="R->A: Loss of interaction with HSP90AA1. No effect
FT on interaction with S100A1, S100A2 and S100A6."
FT /evidence="ECO:0000269|PubMed:22399290"
FT MUTAGEN 304
FT /note="H->Q: Catalytically inactive; no effect on
FT interaction with CRY2 but increases the stability of the
FT interaction with CSNK1E. No effect on RAF1
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:16790549,
FT ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:19948726"
FT CONFLICT 403
FT /note="S -> T (in Ref. 4; AAB60384)"
FT /evidence="ECO:0000305"
FT HELIX 22..40
FT /evidence="ECO:0007829|PDB:1A17"
FT HELIX 44..57
FT /evidence="ECO:0007829|PDB:1A17"
FT HELIX 62..74
FT /evidence="ECO:0007829|PDB:1A17"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:1A17"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2BUG"
FT HELIX 96..108
FT /evidence="ECO:0007829|PDB:1A17"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:1A17"
FT HELIX 130..164
FT /evidence="ECO:0007829|PDB:1A17"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:5UI1"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 206..221
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 247..257
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 279..292
FT /evidence="ECO:0007829|PDB:4ZX2"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:3H66"
FT HELIX 307..313
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 315..322
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:4ZX2"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:1S95"
FT HELIX 363..367
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:3H62"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 380..386
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 391..397
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 408..417
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 442..446
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 459..465
FT /evidence="ECO:0007829|PDB:4ZX2"
FT STRAND 468..476
FT /evidence="ECO:0007829|PDB:4ZX2"
FT TURN 486..489
FT /evidence="ECO:0007829|PDB:4ZX2"
FT HELIX 492..495
FT /evidence="ECO:0007829|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
