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 27-MAR-2024, entry version 238. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7ZR5; EM; 3.90 A; P=17-499. DR PDB; 7ZR6; EM; 4.20 A; P=17-499. DR PDB; 8GAE; EM; 3.30 A; E=1-499. DR PDB; 8GFT; EM; 3.80 A; E=1-499. 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 PDBsum; 7ZR5; -. DR PDBsum; 7ZR6; -. DR PDBsum; 8GAE; -. DR PDBsum; 8GFT; -. DR AlphaFoldDB; P53041; -. DR BMRB; P53041; -. DR EMDB; EMD-14883; -. DR EMDB; EMD-14884; -. DR SMR; P53041; -. DR BioGRID; 111528; 175. DR DIP; DIP-29043N; -. DR IntAct; P53041; 87. 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; 9606-ENSP00000012443; -. DR PeptideAtlas; P53041; -. DR ProteomicsDB; 56568; -. DR Pumba; P53041; -. DR Antibodypedia; 31446; 769 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 AGR; HGNC:9322; -. 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; 1107740at2759; -. 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; 24 hits in 1178 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 127 other cell types or tissues. DR ExpressionAtlas; P53041; baseline and differential. 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:0101031; C:protein folding chaperone complex; IDA:UniProtKB. 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:0006351; P:DNA-templated transcription; TAS:ProtInc. 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 canonical NF-kappaB signal transduction; 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 CDD; cd07417; MPP_PP5_C; 1. DR Gene3D; 3.60.21.10; -; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 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; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR45668; SERINE/THREONINE-PROTEIN PHOSPHATASE 5-RELATED; 1. DR PANTHER; PTHR45668:SF5; SERINE_THREONINE-PROTEIN PHOSPHATASE 5; 1. DR Pfam; PF00149; Metallophos; 1. DR Pfam; PF08321; PPP5; 1. DR Pfam; PF00515; TPR_1; 1. DR PIRSF; PIRSF033096; PPPtase_5; 1. DR PRINTS; PR00114; STPHPHTASE. DR SMART; SM00156; PP2Ac; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF56300; Metallo-dependent phosphatases; 1. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR Genevisible; P53041; HS. 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 //