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Q60676

- PPP5_MOUSE

UniProt

Q60676 - PPP5_MOUSE

Protein

Serine/threonine-protein phosphatase 5

Gene

Ppp5c

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 3 (16 Oct 2013)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses. Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress. Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function. Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1. Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT. Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2.3 Publications

    Catalytic activityi

    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

    Cofactori

    Binds 2 magnesium or manganese per subunit.By similarity

    Enzyme regulationi

    Autoinhibited. In the autoinhibited state, the TPR domain interacts with the catalytic region and prevents substrate access to the catalytic pocket. Allosterically activated by various polyunsaturated fatty acids, free long-chain fatty-acids and long-chain fatty acyl-CoA esters, arachidonic acid being the most effective activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and GNA13 is synergistic with the one produced by fatty acids binding. Inhibited by okadaic acid.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi242 – 2421Magnesium or manganese 1By similarity
    Metal bindingi244 – 2441Magnesium or manganese 1By similarity
    Binding sitei244 – 2441SubstrateBy similarity
    Metal bindingi271 – 2711Magnesium or manganese 1By similarity
    Metal bindingi271 – 2711Magnesium or manganese 2By similarity
    Binding sitei275 – 2751SubstrateBy similarity
    Metal bindingi303 – 3031Magnesium or manganese 2By similarity
    Active sitei304 – 3041Proton donor/acceptorBy similarity
    Metal bindingi352 – 3521Magnesium or manganese 2By similarity
    Binding sitei400 – 4001SubstrateBy similarity
    Metal bindingi427 – 4271Magnesium or manganese 2By similarity
    Binding sitei427 – 4271SubstrateBy similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. phosphoprotein phosphatase activity Source: MGI
    3. protein binding Source: MGI
    4. RNA binding Source: MGI

    GO - Biological processi

    1. protein dephosphorylation Source: InterPro
    2. response to morphine Source: MGI

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein phosphatase 5 (EC:3.1.3.16)
    Short name:
    PP5
    Alternative name(s):
    Protein phosphatase T
    Short name:
    PPT
    Gene namesi
    Name:Ppp5c
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:102666. Ppp5c.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication. Membrane By similarity
    Note: Predominantly nuclear. But also present in the cytoplasm.

    GO - Cellular componenti

    1. cytosol Source: MGI
    2. membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Animals are fertile with a growth rate equivalent to that of wild-type. Males weigh less, exhibit reduced fasting glycaemia and improved glucose tolerance, but retain normal insulin sensitivity.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 499498Serine/threonine-protein phosphatase 5PRO_0000058895Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity

    Post-translational modificationi

    Activated by at least two different proteolytic cleavages producing a 56 kDa and a 50 kDa form.By similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ60676.
    PRIDEiQ60676.

    PTM databases

    PhosphoSiteiQ60676.

    Expressioni

    Tissue specificityi

    Exressed in liver (at protein level) and brain, enriched in suprachiasmatic nuclei.1 Publication

    Inductioni

    Does not show circadian oscillation.1 Publication

    Gene expression databases

    CleanExiMM_PPP5C.
    GenevestigatoriQ60676.

    Interactioni

    Subunit structurei

    Part of a complex with HSP90/HSP90AA1 and steroid receptors. Interacts with CDC16, CDC27. Interacts with KLHDC10 (via the 6 Kelch repeats); inhibits the phosphatase activity on MAP3K5. Interacts (via TPR repeats) with HSP90AA1 (via TPR repeat-binding motif) or HSPA1A/HSPA1B; the interaction is direct and activates the phosphatase activity. Dissociates from HSPA1A/HSPA1B and HSP90AA1 in response to arachidonic acid. Interacts with ATM and ATR; both interactions are induced by DNA damage and enhance ATM and ATR kinase activity. Interacts with RAD17; reduced by DNA damage. Interacts with nuclear receptors such as NR3C1/GCR and PPARG (activated by agonist); regulates their transactivation activities. Interacts (via TPR repeats) with S100 proteins S100A1, S100A2, S100A6, S100B and S100P; the interactions are calcium-dependent, strongly activate PPP5C phosphatase activity and compete with HSP90AA1 and MAP3K5 interactions. Interacts with SMAD2 and SMAD3 but not with SMAD1; decreases SMAD3 phosphorylation and protein levels. Interacts (via TPR repeats) with CRY1 and CRY2; the interaction with CRY2 downregulates the phosphatase activity on CSNK1E. Interacts (via TPR repeats) with the active form of RAC1, GNA12 or GNA13; these interactions activate the phosphatase activity and translocate PPP5C to the cell membrane.2 Publications

    Protein-protein interaction databases

    BioGridi202349. 9 interactions.
    IntActiQ60676. 4 interactions.
    MINTiMINT-1353706.

    Structurei

    3D structure databases

    ProteinModelPortaliQ60676.
    SMRiQ60676. Positions 23-499.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati28 – 6134TPR 1Add
    BLAST
    Repeati62 – 9534TPR 2Add
    BLAST
    Repeati96 – 12934TPR 3Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni184 – 499316CatalyticAdd
    BLAST
    Regioni303 – 3042Substrate bindingBy similarity
    Regioni495 – 4995Required for autoinhibitionBy similarity

    Sequence similaritiesi

    Contains 3 TPR repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, TPR repeat

    Phylogenomic databases

    eggNOGiCOG0639.
    GeneTreeiENSGT00530000063173.
    HOGENOMiHOG000172698.
    HOVERGENiHBG000216.
    InParanoidiQ60676.
    KOiK04460.
    OMAiFKLLYPN.
    OrthoDBiEOG7V49Z3.
    TreeFamiTF105562.

    Family and domain databases

    Gene3Di1.25.40.10. 1 hit.
    3.60.21.10. 1 hit.
    InterProiIPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR013235. PPP_dom.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    IPR011236. Ser/Thr_PPase_5.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR001440. TPR_1.
    IPR019734. TPR_repeat.
    [Graphical view]
    PANTHERiPTHR11668:SF12. PTHR11668:SF12. 1 hit.
    PfamiPF00149. Metallophos. 1 hit.
    PF08321. PPP5. 1 hit.
    PF00515. TPR_1. 1 hit.
    [Graphical view]
    PIRSFiPIRSF033096. PPPtase_5. 1 hit.
    PRINTSiPR00114. STPHPHTASE.
    SMARTiSM00156. PP2Ac. 1 hit.
    SM00028. TPR. 3 hits.
    [Graphical view]
    SUPFAMiSSF56300. SSF56300. 1 hit.
    PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
    PS50005. TPR. 3 hits.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q60676-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAMAEGERTE CAETPRDEPP ADGTLKRAEE LKTQANDYFK AKDYENAIKF    50
    YSQAIELNPG NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY 100
    RRAASNMALG KFRAALRDYE TVVKVKPNDK DAKMKYQECS KIVKQKAFER 150
    AIAGDEHRRS VVDSLDIESM TIEDEYSGPK LEDGKVTITF MKDLMQWYKD 200
    QKKLHRKCAY QILVQVKEVL CKLSTLVETT LKETEKITVC GDTHGQFYDL 250
    LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL 300
    RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI 350
    MHGGLFSEDG VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSVSKR 400
    GVSCQFGPDV TKAFLEENQL DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN 450
    YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP HPNVKPMAYA NTLLQLGMM 499
    Length:499
    Mass (Da):56,877
    Last modified:October 16, 2013 - v3
    Checksum:i92C5509374FD6721
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti24 – 241T → A in AAB70573. 1 PublicationCurated
    Sequence conflicti24 – 241T → A in AAH03744. (PubMed:15489334)Curated
    Sequence conflicti155 – 1551D → G in AAB18613. (PubMed:7972012)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF018262 mRNA. Translation: AAB70573.1.
    AC148976 Genomic DNA. No translation available.
    CH466654 Genomic DNA. Translation: EDL42060.1.
    BC003744 mRNA. Translation: AAH03744.1.
    U12204 mRNA. Translation: AAB18613.1.
    CCDSiCCDS20859.1.
    RefSeqiNP_035285.2. NM_011155.2.
    UniGeneiMm.3294.
    Mm.475000.

    Genome annotation databases

    EnsembliENSMUST00000003183; ENSMUSP00000003183; ENSMUSG00000003099.
    GeneIDi19060.
    KEGGimmu:19060.
    UCSCiuc009fiq.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF018262 mRNA. Translation: AAB70573.1 .
    AC148976 Genomic DNA. No translation available.
    CH466654 Genomic DNA. Translation: EDL42060.1 .
    BC003744 mRNA. Translation: AAH03744.1 .
    U12204 mRNA. Translation: AAB18613.1 .
    CCDSi CCDS20859.1.
    RefSeqi NP_035285.2. NM_011155.2.
    UniGenei Mm.3294.
    Mm.475000.

    3D structure databases

    ProteinModelPortali Q60676.
    SMRi Q60676. Positions 23-499.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202349. 9 interactions.
    IntActi Q60676. 4 interactions.
    MINTi MINT-1353706.

    PTM databases

    PhosphoSitei Q60676.

    Proteomic databases

    PaxDbi Q60676.
    PRIDEi Q60676.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000003183 ; ENSMUSP00000003183 ; ENSMUSG00000003099 .
    GeneIDi 19060.
    KEGGi mmu:19060.
    UCSCi uc009fiq.2. mouse.

    Organism-specific databases

    CTDi 5536.
    MGIi MGI:102666. Ppp5c.

    Phylogenomic databases

    eggNOGi COG0639.
    GeneTreei ENSGT00530000063173.
    HOGENOMi HOG000172698.
    HOVERGENi HBG000216.
    InParanoidi Q60676.
    KOi K04460.
    OMAi FKLLYPN.
    OrthoDBi EOG7V49Z3.
    TreeFami TF105562.

    Miscellaneous databases

    ChiTaRSi PPP5C. mouse.
    NextBioi 295562.
    PROi Q60676.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_PPP5C.
    Genevestigatori Q60676.

    Family and domain databases

    Gene3Di 1.25.40.10. 1 hit.
    3.60.21.10. 1 hit.
    InterProi IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR013235. PPP_dom.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    IPR011236. Ser/Thr_PPase_5.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR001440. TPR_1.
    IPR019734. TPR_repeat.
    [Graphical view ]
    PANTHERi PTHR11668:SF12. PTHR11668:SF12. 1 hit.
    Pfami PF00149. Metallophos. 1 hit.
    PF08321. PPP5. 1 hit.
    PF00515. TPR_1. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF033096. PPPtase_5. 1 hit.
    PRINTSi PR00114. STPHPHTASE.
    SMARTi SM00156. PP2Ac. 1 hit.
    SM00028. TPR. 3 hits.
    [Graphical view ]
    SUPFAMi SSF56300. SSF56300. 1 hit.
    PROSITEi PS00125. SER_THR_PHOSPHATASE. 1 hit.
    PS50005. TPR. 3 hits.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Ollendorff V., Donoghue D.J.
      Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor."
      Chinkers M.
      Proc. Natl. Acad. Sci. U.S.A. 91:11075-11079(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-155.
    6. "Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin."
      Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K., Chinkers M., Pratt W.B.
      J. Biol. Chem. 272:16224-16230(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH HSP90AA1 AND NR3C1.
    7. "Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5."
      Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.
      Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    8. "Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest."
      Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.
      J. Biol. Chem. 282:14690-14694(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DNA DAMAGE RESPONSE, DISRUPTION PHENOTYPE.
    9. "Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-? (PPAR?)."
      Hinds T.D. Jr., Stechschulte L.A., Cash H.A., Whisler D., Banerjee A., Yong W., Khuder S.S., Kaw M.K., Shou W., Najjar S.M., Sanchez E.R.
      J. Biol. Chem. 286:42911-42922(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEPHOSPHORYLATION OF NR3C1 AND PPARG, INTERACTION WITH NR3C1 AND PPARG, SUBCELLULAR LOCATION.
    10. "Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells."
      Grankvist N., Amable L., Honkanen R.E., Sjoeholm A., Ortsaeter H.
      Diabetologia 55:2005-2015(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN GLUCOSE HOMEOSTASIS, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiPPP5_MOUSE
    AccessioniPrimary (citable) accession number: Q60676
    Secondary accession number(s): G5E819, O35299
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: October 16, 2013
    Last modified: October 1, 2014
    This is version 135 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3