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P55739

- PPP5_RABIT

UniProt

P55739 - PPP5_RABIT

Protein

Serine/threonine-protein phosphatase 5

Gene

PPP5C

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
  1. 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 KCNH2.1 Publication

    Catalytic activityi

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

    Cofactori

    Binds 2 magnesium or manganese ions 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.1 Publication

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. phosphoprotein phosphatase activity Source: UniProtKB-KW
    3. RNA binding Source: Ensembl
    4. signal transducer activity Source: Ensembl

    GO - Biological processi

    1. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl

    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
    Synonyms:PPP5
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Unplaced

    Subcellular locationi

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

    GO - Cellular componenti

    1. Golgi apparatus Source: Ensembl
    2. membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini‹1 – 42›42Serine/threonine-protein phosphatase 5PRO_0000058896Add
    BLAST

    Post-translational modificationi

    Activated by at least two different proteolytic cleavages producing a 56 kDa and a 50 kDa form.1 Publication

    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.1 Publication

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000018147.

    Structurei

    3D structure databases

    ProteinModelPortaliP55739.
    SMRiP55739. Positions 1-42.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni38 – 425Required for autoinhibitionBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0639.
    HOGENOMiHOG000172698.

    Sequencei

    Sequence statusi: Fragment.

    P55739-1 [UniParc]FASTAAdd to Basket

    « Hide

    KASYIHLRGS DLRPQFHQFT AVPHPNVKPM AYANALLQLG VM           42
    Length:42
    Mass (Da):4,719
    Last modified:November 1, 1997 - v1
    Checksum:i5B85BC402EF4692F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-terminal residuei1 – 11

    Cross-referencesi

    3D structure databases

    ProteinModelPortali P55739.
    SMRi P55739. Positions 1-42.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9986.ENSOCUP00000018147.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    eggNOGi COG0639.
    HOGENOMi HOG000172698.

    Family and domain databases

    ProtoNeti Search...

    Publicationsi

    1. "A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus."
      Chen M.X., McPartlin A.E., Brown L., Chen Y.H., Barker H.M., Cohen P.T.W.
      EMBO J. 13:4278-4290(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE.
      Tissue: Liver.
    2. "Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain."
      Chen M.X., Cohen P.T.
      FEBS Lett. 400:136-140(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, LIPID-BINDING, CLEAVAGE.
    3. "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.

    Entry informationi

    Entry nameiPPP5_RABIT
    AccessioniPrimary (citable) accession number: P55739
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 66 of the entry and version 1 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3