P55739 (PPP5_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 65. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein phosphatase 5
Protein phosphatase T
|Organism||Oryctolagus cuniculus (Rabbit) [Reference proteome]|
|Taxonomic identifier||9986 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus|
|Sequence length||42 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.2
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
Binds 2 magnesium or manganese ions per subunit By similarity.
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. Ref.2
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. Ref.3
Activated by at least two different proteolytic cleavages producing a 56 kDa and a 50 kDa form.
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||positive regulation of I-kappaB kinase/NF-kappaB signaling|
Inferred from electronic annotation. Source: Ensembl
Inferred from electronic annotation. Source: Ensemblmembrane
Inferred from electronic annotation. Source: UniProtKB-SubCellnucleus
Inferred from electronic annotation. Source: UniProtKB-SubCell
Inferred from electronic annotation. Source: Ensemblmetal ion binding
Inferred from electronic annotation. Source: UniProtKB-KWphosphoprotein phosphatase activity
Inferred from electronic annotation. Source: UniProtKB-KWsignal transducer activity
Inferred from electronic annotation. Source: Ensembl
|Complete GO annotation...|
Sequence annotation (Features)
|||"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.
|||"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.
|||"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.
3D structure databases
|SMR||P55739. Positions 1-42. |
Protein-protein interaction databases
Protocols and materials databases
Family and domain databases
|Accession||Primary (citable) accession number: P55739|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families