Full text data of PPP5C
PPP5C
(PPP5)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Serine/threonine-protein phosphatase 5; PP5; 3.1.3.16 (Protein phosphatase T; PP-T; PPT)
Serine/threonine-protein phosphatase 5; PP5; 3.1.3.16 (Protein phosphatase T; PP-T; PPT)
hRBCD
IPI00019812
IPI00019812 Serine/threonine protein phosphatase 5 ubiquitous, A phosphoprotein + H2O = a protein + phosphate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic but mostly nuclear n/a expected molecular weight found in band found in band around 188 kDa
IPI00019812 Serine/threonine protein phosphatase 5 ubiquitous, A phosphoprotein + H2O = a protein + phosphate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic but mostly nuclear n/a expected molecular weight found in band found in band around 188 kDa
UniProt
P53041
ID PPP5_HUMAN Reviewed; 499 AA.
AC P53041; Q16722; Q53XV2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 159.
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 MASS 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, MASS SPECTROMETRY, AND MUTAGENESIS OF
RP 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, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 DIVALENT METAL CATIONS, ACTIVE SITE, AND DIVALENT METAL
RP CATIONS-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 DIVALENT METAL CATIONS, INTERACTION WITH HSP90AA1, LIPID-BINDING,
RP DIVALENT METAL CATIONS-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 -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 2 divalent metal cation per subutnit.
CC -!- ENZYME REGULATION: Autoinhibited. The TPR domain, unique in that
CC protein family, engage to form an extensive interface with the
CC catalytic region preventig access of the substrate to the
CC catalytic pocket. Allosterically activated by various
CC polyunsaturated fatty acids, free long-chain fatty-acids and long-
CC chain fatty acyl-CoA esters, arachidonic acid being the most
CC effective activator. HSP90A and probably RAC1, GNA12 and GNA13 can
CC also release the autoinhibition by the TPR repeat. Activation by
CC RAC1, GNA12 and GNA13 is synergistic with the one produced by
CC fatty acids binding. Inhibited by okadaic acid.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.847 uM for CSNK1E (at 30 degrees Celsius);
CC KM=13.2 uM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius);
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.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-716663, EBI-716663;
CC Q16543:CDC37; NbExp=2; 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.
CC -!- PTM: Activated by at least two different proteolytic cleavages
CC producing a 56 kDa and a 50 kDa form.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC subfamily.
CC -!- SIMILARITY: Contains 3 TPR repeats.
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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 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 DIP; DIP-29043N; -.
DR IntAct; P53041; 23.
DR MINT; MINT-1411788; -.
DR STRING; 9606.ENSP00000012443; -.
DR PhosphoSite; P53041; -.
DR DMDM; 1709744; -.
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 MIM; 600658; gene.
DR neXtProt; NX_P53041; -.
DR PharmGKB; PA33686; -.
DR eggNOG; COG0639; -.
DR HOGENOM; HOG000172698; -.
DR HOVERGEN; HBG000216; -.
DR InParanoid; P53041; -.
DR KO; K04460; -.
DR OMA; FKLLYPN; -.
DR OrthoDB; EOG7V49Z3; -.
DR PhylomeDB; P53041; -.
DR SignaLink; P53041; -.
DR EvolutionaryTrace; P53041; -.
DR GeneWiki; PPP5C; -.
DR GenomeRNAi; 5536; -.
DR NextBio; 21446; -.
DR PRO; PR:P53041; -.
DR ArrayExpress; P53041; -.
DR Bgee; P53041; -.
DR CleanEx; HS_PPP5C; -.
DR Genevestigator; P53041; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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; TAS:ProtInc.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; TAS:ProtInc.
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:mitosis; TAS:ProtInc.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; 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:0006351; P:transcription, DNA-dependent; TAS:ProtInc.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR004843; PEstase_dom.
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.
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 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; Iron;
KW Lipid-binding; Manganese; Membrane; Metal-binding; Neurodegeneration;
KW Nucleus; Protein phosphatase; Reference proteome; Repeat; TPR repeat.
FT INIT_MET 1 1 Removed.
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 (By
FT similarity).
FT ACT_SITE 304 304 Proton donor/acceptor.
FT METAL 242 242 Divalent metal cation 1.
FT METAL 244 244 Divalent metal cation 1.
FT METAL 271 271 Divalent metal cation 1.
FT METAL 271 271 Divalent metal cation 2.
FT METAL 303 303 Divalent metal cation 2.
FT METAL 352 352 Divalent metal cation 2.
FT METAL 427 427 Divalent metal cation 2.
FT BINDING 244 244 Substrate.
FT BINDING 275 275 Substrate.
FT BINDING 400 400 Substrate.
FT BINDING 427 427 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MUTAGEN 32 32 K->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
FT MUTAGEN 74 74 R->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
FT MUTAGEN 83 83 G->N: No effect on interaction with
FT HSP90AA1.
FT MUTAGEN 93 93 K->E: Decreases interaction with RAC1 and
FT translocation to the membrane in presence
FT of active RAC1.
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.
FT MUTAGEN 101 101 R->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
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 CONFLICT 403 403 S -> T (in Ref. 4; AAB60384).
FT HELIX 22 40
FT HELIX 44 57
FT HELIX 62 74
FT HELIX 78 91
FT STRAND 92 94
FT HELIX 96 108
FT HELIX 112 125
FT HELIX 130 164
FT HELIX 182 184
FT HELIX 188 199
FT HELIX 206 221
FT STRAND 225 229
FT STRAND 236 240
FT HELIX 247 257
FT STRAND 266 270
FT STRAND 273 276
FT HELIX 279 292
FT TURN 294 296
FT STRAND 297 300
FT STRAND 303 306
FT HELIX 307 313
FT HELIX 315 322
FT HELIX 325 335
FT STRAND 340 344
FT TURN 345 347
FT STRAND 348 350
FT STRAND 357 359
FT HELIX 363 368
FT STRAND 372 374
FT STRAND 377 379
FT HELIX 380 386
FT STRAND 391 397
FT STRAND 401 406
FT HELIX 408 418
FT STRAND 421 425
FT STRAND 433 437
FT HELIX 438 440
FT STRAND 442 446
FT HELIX 451 453
FT STRAND 459 465
FT STRAND 468 476
FT TURN 486 489
FT HELIX 492 495
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
//
ID PPP5_HUMAN Reviewed; 499 AA.
AC P53041; Q16722; Q53XV2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 159.
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 MASS 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, MASS SPECTROMETRY, AND MUTAGENESIS OF
RP 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, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 DIVALENT METAL CATIONS, ACTIVE SITE, AND DIVALENT METAL
RP CATIONS-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 DIVALENT METAL CATIONS, INTERACTION WITH HSP90AA1, LIPID-BINDING,
RP DIVALENT METAL CATIONS-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 -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 2 divalent metal cation per subutnit.
CC -!- ENZYME REGULATION: Autoinhibited. The TPR domain, unique in that
CC protein family, engage to form an extensive interface with the
CC catalytic region preventig access of the substrate to the
CC catalytic pocket. Allosterically activated by various
CC polyunsaturated fatty acids, free long-chain fatty-acids and long-
CC chain fatty acyl-CoA esters, arachidonic acid being the most
CC effective activator. HSP90A and probably RAC1, GNA12 and GNA13 can
CC also release the autoinhibition by the TPR repeat. Activation by
CC RAC1, GNA12 and GNA13 is synergistic with the one produced by
CC fatty acids binding. Inhibited by okadaic acid.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.847 uM for CSNK1E (at 30 degrees Celsius);
CC KM=13.2 uM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius);
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.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-716663, EBI-716663;
CC Q16543:CDC37; NbExp=2; 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.
CC -!- PTM: Activated by at least two different proteolytic cleavages
CC producing a 56 kDa and a 50 kDa form.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC subfamily.
CC -!- SIMILARITY: Contains 3 TPR repeats.
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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 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 DIP; DIP-29043N; -.
DR IntAct; P53041; 23.
DR MINT; MINT-1411788; -.
DR STRING; 9606.ENSP00000012443; -.
DR PhosphoSite; P53041; -.
DR DMDM; 1709744; -.
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 MIM; 600658; gene.
DR neXtProt; NX_P53041; -.
DR PharmGKB; PA33686; -.
DR eggNOG; COG0639; -.
DR HOGENOM; HOG000172698; -.
DR HOVERGEN; HBG000216; -.
DR InParanoid; P53041; -.
DR KO; K04460; -.
DR OMA; FKLLYPN; -.
DR OrthoDB; EOG7V49Z3; -.
DR PhylomeDB; P53041; -.
DR SignaLink; P53041; -.
DR EvolutionaryTrace; P53041; -.
DR GeneWiki; PPP5C; -.
DR GenomeRNAi; 5536; -.
DR NextBio; 21446; -.
DR PRO; PR:P53041; -.
DR ArrayExpress; P53041; -.
DR Bgee; P53041; -.
DR CleanEx; HS_PPP5C; -.
DR Genevestigator; P53041; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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; TAS:ProtInc.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; TAS:ProtInc.
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:mitosis; TAS:ProtInc.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; 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:0006351; P:transcription, DNA-dependent; TAS:ProtInc.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR004843; PEstase_dom.
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.
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 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; Iron;
KW Lipid-binding; Manganese; Membrane; Metal-binding; Neurodegeneration;
KW Nucleus; Protein phosphatase; Reference proteome; Repeat; TPR repeat.
FT INIT_MET 1 1 Removed.
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 (By
FT similarity).
FT ACT_SITE 304 304 Proton donor/acceptor.
FT METAL 242 242 Divalent metal cation 1.
FT METAL 244 244 Divalent metal cation 1.
FT METAL 271 271 Divalent metal cation 1.
FT METAL 271 271 Divalent metal cation 2.
FT METAL 303 303 Divalent metal cation 2.
FT METAL 352 352 Divalent metal cation 2.
FT METAL 427 427 Divalent metal cation 2.
FT BINDING 244 244 Substrate.
FT BINDING 275 275 Substrate.
FT BINDING 400 400 Substrate.
FT BINDING 427 427 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MUTAGEN 32 32 K->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
FT MUTAGEN 74 74 R->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
FT MUTAGEN 83 83 G->N: No effect on interaction with
FT HSP90AA1.
FT MUTAGEN 93 93 K->E: Decreases interaction with RAC1 and
FT translocation to the membrane in presence
FT of active RAC1.
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.
FT MUTAGEN 101 101 R->A: Loss of interaction with HSP90AA1.
FT No effect on interaction with S100A1,
FT S100A2 and S100A6.
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 CONFLICT 403 403 S -> T (in Ref. 4; AAB60384).
FT HELIX 22 40
FT HELIX 44 57
FT HELIX 62 74
FT HELIX 78 91
FT STRAND 92 94
FT HELIX 96 108
FT HELIX 112 125
FT HELIX 130 164
FT HELIX 182 184
FT HELIX 188 199
FT HELIX 206 221
FT STRAND 225 229
FT STRAND 236 240
FT HELIX 247 257
FT STRAND 266 270
FT STRAND 273 276
FT HELIX 279 292
FT TURN 294 296
FT STRAND 297 300
FT STRAND 303 306
FT HELIX 307 313
FT HELIX 315 322
FT HELIX 325 335
FT STRAND 340 344
FT TURN 345 347
FT STRAND 348 350
FT STRAND 357 359
FT HELIX 363 368
FT STRAND 372 374
FT STRAND 377 379
FT HELIX 380 386
FT STRAND 391 397
FT STRAND 401 406
FT HELIX 408 418
FT STRAND 421 425
FT STRAND 433 437
FT HELIX 438 440
FT STRAND 442 446
FT HELIX 451 453
FT STRAND 459 465
FT STRAND 468 476
FT TURN 486 489
FT HELIX 492 495
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
//
MIM
600658
*RECORD*
*FIELD* NO
600658
*FIELD* TI
*600658 PROTEIN PHOSPHATASE 5, CATALYTIC SUBUNIT; PPP5C
;;PP5
*FIELD* TX
CLONING
read moreA variety of biologic processes, such as cell signaling, transcription,
and mitosis, are regulated by reversible protein phosphorylation at
serine and threonine residues. The serine/threonine kinases are
responsible for phosphorylation and the phosphatases are required for
dephosphorylation. A number of protein serine/threonine phosphatases are
known and molecular characterization shows that they fall into distinct
groups. One family includes the PP1 (see PPP1A, 176875), PP2A, and PP2B
(see PPP2B, 114105) genes and their relatives. Chen et al. (1994)
described a protein serine/threonine phosphatase, which they designated
PP5, that shares similarity to the yeast gene PPT1. The PP5 cDNA was
isolated by screening a human teratocarcinoma cDNA library at low
stringency with a PP2B probe. By Northern blotting they observed a
2.3-kb mRNA in all tissues they examined. The predicted PP5 protein
shares about 35 to 40% identity with other members of the superfamily
and the N-terminal domain contains tetratricopeptide-like repeats found
in several nuclear regulatory proteins. Recombinant PP5 was able to
dephosphorylate serine residues and was shown to be sensitive to the
tumor promoter okadaic acid. Antibodies showed that the protein is
predominantly found in the nucleus.
Yong et al. (1995) reported the isolation of a cDNA from a human fetal
brain library by exon amplification from a cosmid contig mapping to a
glioma candidate region on chromosome 19q13.3. A nearly full-length cDNA
was then obtained that was identical to PPP5C except for 3 additional
nucleotides. Xu et al. (1996) cloned the entire coding sequence of the
PP5 gene from a human fetal brain cDNA library using a probe generated
by a PCR-based cloning approach. The PP5 mRNA was detected in all human
tissues examined.
GENE FUNCTION
Gentile et al. (2006) identified Pp5 as an effector of Rac (see 602048)
GTPase signaling in a rat pituitary cell line. Okadaic acid, a microbial
toxin, blocked channel stimulation by thyroid hormone and by Rac, and
signaling was restored by expression of a toxin-insensitive Pp5 mutant.
Pp5 contains an N-terminal regulatory domain with 3 tetratricopeptide
(TRP) repeats that inhibit its activity. Expression of the TRP domain of
Pp5 blocked channel stimulation by thyroid hormone, and mutation of the
TRP at 2 predicted contact points with Rac-GTP prevented its inhibitory
activity.
MAPPING
By fluorescence in situ hybridization, Xu et al. (1996) mapped the PP5
gene to chromosome 19q13.3.
*FIELD* RF
1. Chen, M. X.; McPartlin, A. E.; Brown, L.; Chen, Y. H.; Barker,
H. M.; Cohen, P. T. W.: A novel human protein serine/threonine phosphatase,
which possesses four tetratricopeptide repeat motifs and localizes
to the nucleus. EMBO J. 13: 4278-4290, 1994.
2. Gentile, S.; Darden, T.; Erxleben, C.; Romeo, C.; Russo, A.; Martin,
N.; Rossie, S.; Armstrong, D. L.: Rac GTPase signaling through the
PP5 protein phosphatase. Proc. Nat. Acad. Sci. 103: 5202-5206, 2006.
3. Xu, X.; Lagercrantz, J.; Zickert, P.; Bajalica-Lagercrantz, S.;
Zetterberg, A.: Chromosomal localization and 5-prime sequence of
the human protein serine/threonine phosphatase 5-prime gene. Biochem.
Biophys. Res. Commun. 218: 514-517, 1996.
4. Yong, W. H.; Ueki, K.; Chou, D.; Reeves, S. A.; von Deimling, A.;
Gusella, J. F.; Mohrenweiser, H. W.; Buckler, A. J.; Louis, D. N.
: Cloning of a highly conserved human protein serine-threonine phosphatase
gene from the glioma candidate region on chromosome 19q13.3. Genomics 29:
533-536, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 06/09/2006
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Victor A. McKusick: 8/18/1995
*FIELD* ED
mgross: 06/09/2006
terry: 4/17/1996
mark: 3/21/1996
terry: 3/8/1996
mark: 8/18/1995
*RECORD*
*FIELD* NO
600658
*FIELD* TI
*600658 PROTEIN PHOSPHATASE 5, CATALYTIC SUBUNIT; PPP5C
;;PP5
*FIELD* TX
CLONING
read moreA variety of biologic processes, such as cell signaling, transcription,
and mitosis, are regulated by reversible protein phosphorylation at
serine and threonine residues. The serine/threonine kinases are
responsible for phosphorylation and the phosphatases are required for
dephosphorylation. A number of protein serine/threonine phosphatases are
known and molecular characterization shows that they fall into distinct
groups. One family includes the PP1 (see PPP1A, 176875), PP2A, and PP2B
(see PPP2B, 114105) genes and their relatives. Chen et al. (1994)
described a protein serine/threonine phosphatase, which they designated
PP5, that shares similarity to the yeast gene PPT1. The PP5 cDNA was
isolated by screening a human teratocarcinoma cDNA library at low
stringency with a PP2B probe. By Northern blotting they observed a
2.3-kb mRNA in all tissues they examined. The predicted PP5 protein
shares about 35 to 40% identity with other members of the superfamily
and the N-terminal domain contains tetratricopeptide-like repeats found
in several nuclear regulatory proteins. Recombinant PP5 was able to
dephosphorylate serine residues and was shown to be sensitive to the
tumor promoter okadaic acid. Antibodies showed that the protein is
predominantly found in the nucleus.
Yong et al. (1995) reported the isolation of a cDNA from a human fetal
brain library by exon amplification from a cosmid contig mapping to a
glioma candidate region on chromosome 19q13.3. A nearly full-length cDNA
was then obtained that was identical to PPP5C except for 3 additional
nucleotides. Xu et al. (1996) cloned the entire coding sequence of the
PP5 gene from a human fetal brain cDNA library using a probe generated
by a PCR-based cloning approach. The PP5 mRNA was detected in all human
tissues examined.
GENE FUNCTION
Gentile et al. (2006) identified Pp5 as an effector of Rac (see 602048)
GTPase signaling in a rat pituitary cell line. Okadaic acid, a microbial
toxin, blocked channel stimulation by thyroid hormone and by Rac, and
signaling was restored by expression of a toxin-insensitive Pp5 mutant.
Pp5 contains an N-terminal regulatory domain with 3 tetratricopeptide
(TRP) repeats that inhibit its activity. Expression of the TRP domain of
Pp5 blocked channel stimulation by thyroid hormone, and mutation of the
TRP at 2 predicted contact points with Rac-GTP prevented its inhibitory
activity.
MAPPING
By fluorescence in situ hybridization, Xu et al. (1996) mapped the PP5
gene to chromosome 19q13.3.
*FIELD* RF
1. Chen, M. X.; McPartlin, A. E.; Brown, L.; Chen, Y. H.; Barker,
H. M.; Cohen, P. T. W.: A novel human protein serine/threonine phosphatase,
which possesses four tetratricopeptide repeat motifs and localizes
to the nucleus. EMBO J. 13: 4278-4290, 1994.
2. Gentile, S.; Darden, T.; Erxleben, C.; Romeo, C.; Russo, A.; Martin,
N.; Rossie, S.; Armstrong, D. L.: Rac GTPase signaling through the
PP5 protein phosphatase. Proc. Nat. Acad. Sci. 103: 5202-5206, 2006.
3. Xu, X.; Lagercrantz, J.; Zickert, P.; Bajalica-Lagercrantz, S.;
Zetterberg, A.: Chromosomal localization and 5-prime sequence of
the human protein serine/threonine phosphatase 5-prime gene. Biochem.
Biophys. Res. Commun. 218: 514-517, 1996.
4. Yong, W. H.; Ueki, K.; Chou, D.; Reeves, S. A.; von Deimling, A.;
Gusella, J. F.; Mohrenweiser, H. W.; Buckler, A. J.; Louis, D. N.
: Cloning of a highly conserved human protein serine-threonine phosphatase
gene from the glioma candidate region on chromosome 19q13.3. Genomics 29:
533-536, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 06/09/2006
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Victor A. McKusick: 8/18/1995
*FIELD* ED
mgross: 06/09/2006
terry: 4/17/1996
mark: 3/21/1996
terry: 3/8/1996
mark: 8/18/1995