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Q60676 (PPP5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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.8 Ref.9 Ref.10

Catalytic activity

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

Cofactor

Binds 2 divalent metal cation per subutnit By similarity.

Enzyme regulation

Autoinhibited. The TPR domain, unique in that protein family, engage to form an extensive interface with the catalytic region preventig access of the substrate 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.

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.6 Ref.9

Subcellular location

Nucleus. Cytoplasm. Membrane By similarity. Note: Predominantly nuclear. But also present in the cytoplasm. Ref.9

Tissue specificity

Exressed in liver (at protein level) and brain, enriched in suprachiasmatic nuclei. Ref.7

Induction

Does not show circadian oscillation. Ref.7

Post-translational modification

May be proteocally activated by at least two different cleavages which leads to products of 56 and 50 kDa By similarity.

Disruption phenotype

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. Ref.8 Ref.10

Sequence similarities

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

Contains 3 TPR repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 499498Serine/threonine-protein phosphatase 5
PRO_0000058895

Regions

Repeat28 – 6134TPR 1
Repeat62 – 9534TPR 2
Repeat96 – 12934TPR 3
Region184 – 499316Catalytic
Region303 – 3042Substrate binding By similarity
Region495 – 4995Required for autoinhibition By similarity

Sites

Active site3041Proton donor/acceptor By similarity
Metal binding2421Divalent metal cation 1 By similarity
Metal binding2441Divalent metal cation 1 By similarity
Metal binding2711Divalent metal cation 1 By similarity
Metal binding2711Divalent metal cation 2 By similarity
Metal binding3031Divalent metal cation 2 By similarity
Metal binding3521Divalent metal cation 2 By similarity
Metal binding4271Divalent metal cation 2 By similarity
Binding site2441Substrate By similarity
Binding site2751Substrate By similarity
Binding site4001Substrate By similarity
Binding site4271Substrate By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Experimental info

Sequence conflict241T → A in AAB70573. Ref.1
Sequence conflict241T → A in AAH03744. Ref.4
Sequence conflict1551D → G in AAB18613. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q60676 [UniParc].

Last modified October 16, 2013. Version 3.
Checksum: 92C5509374FD6721

FASTA49956,877
        10         20         30         40         50         60 
MAMAEGERTE CAETPRDEPP ADGTLKRAEE LKTQANDYFK AKDYENAIKF YSQAIELNPG 

        70         80         90        100        110        120 
NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY RRAASNMALG KFRAALRDYE 

       130        140        150        160        170        180 
TVVKVKPNDK DAKMKYQECS KIVKQKAFER AIAGDEHRRS VVDSLDIESM TIEDEYSGPK 

       190        200        210        220        230        240 
LEDGKVTITF MKDLMQWYKD QKKLHRKCAY QILVQVKEVL CKLSTLVETT LKETEKITVC 

       250        260        270        280        290        300 
GDTHGQFYDL LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL 

       310        320        330        340        350        360 
RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI MHGGLFSEDG 

       370        380        390        400        410        420 
VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSVSKR GVSCQFGPDV TKAFLEENQL 

       430        440        450        460        470        480 
DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP 

       490 
HPNVKPMAYA NTLLQLGMM 

« Hide

References

« Hide 'large scale' references
[1]Ollendorff V., Donoghue D.J.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_035285.2. NM_011155.2.
UniGeneMm.3294.
Mm.475000.

3D structure databases

ProteinModelPortalQ60676.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202349. 9 interactions.
IntActQ60676. 4 interactions.
MINTMINT-1353706.

PTM databases

PhosphoSiteQ60676.

Proteomic databases

PaxDbQ60676.
PRIDEQ60676.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003183; ENSMUSP00000003183; ENSMUSG00000003099.
GeneID19060.
KEGGmmu:19060.
UCSCuc009fiq.2. mouse.

Organism-specific databases

CTD5536.
MGIMGI:102666. Ppp5c.

Phylogenomic databases

eggNOGCOG0639.
GeneTreeENSGT00530000063173.
HOGENOMHOG000172698.
HOVERGENHBG000216.
InParanoidQ60676.
KOK04460.
OrthoDBEOG7V49Z3.
TreeFamTF105562.

Gene expression databases

CleanExMM_PPP5C.
GenevestigatorQ60676.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
InterProIPR004843. Calcineurin-like_PHP_apaH.
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]
PANTHERPTHR11668:SF12. PTHR11668:SF12. 1 hit.
PfamPF00149. Metallophos. 1 hit.
PF08321. PPP5. 1 hit.
PF00515. TPR_1. 1 hit.
[Graphical view]
PIRSFPIRSF033096. PPPtase_5. 1 hit.
PRINTSPR00114. STPHPHTASE.
SMARTSM00156. PP2Ac. 1 hit.
SM00028. TPR. 3 hits.
[Graphical view]
PROSITEPS00125. SER_THR_PHOSPHATASE. 1 hit.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP5C. mouse.
NextBio295562.
PROQ60676.
SOURCESearch...

Entry information

Entry namePPP5_MOUSE
AccessionPrimary (citable) accession number: Q60676
Secondary accession number(s): G5E819, O35299
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 16, 2013
Last modified: April 16, 2014
This is version 131 of the entry and version 3 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot