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P55739 (PPP5_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Serine/threonine-protein phosphatase 5

Short name=PP5
EC=3.1.3.16
Alternative name(s):
Protein phosphatase T
Short name=PPT
Gene names
Name:PPP5C
Synonyms:PPP5
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length42 AA.
Sequence statusFragment.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Binds 2 magnesium or manganese ions per subunit By similarity.

Enzyme regulation

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

Subunit structure

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

Subcellular location

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

Post-translational modification

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

Sequence similarities

Belongs to the PPP phosphatase family. PP-5 (PP-T) subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – 42›42Serine/threonine-protein phosphatase 5
PRO_0000058896

Regions

Region38 – 425Required for autoinhibition By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
P55739 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 5B85BC402EF4692F

FASTA424,719
        10         20         30         40 
KASYIHLRGS DLRPQFHQFT AVPHPNVKPM AYANALLQLG VM 

« Hide

References

[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.

Cross-references

3D structure databases

ProteinModelPortalP55739.
SMRP55739. Positions 1-42.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000018147.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0639.
HOGENOMHOG000172698.

Family and domain databases

ProtoNetSearch...

Entry information

Entry namePPP5_RABIT
AccessionPrimary (citable) accession number: P55739
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 14, 2014
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families