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Q60676

- PPP5_MOUSE

UniProt

Q60676 - PPP5_MOUSE

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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

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. RNA binding Source: MGI
  4. signal transducer activity Source: Ensembl

GO - Biological processi

  1. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  2. protein dephosphorylation Source: InterPro
  3. protein heterooligomerization Source: Ensembl
  4. response to morphine Source: MGI
Complete GO annotation...

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-KW
  3. neuronal cell body Source: Ensembl
  4. neuron projection Source: Ensembl
  5. nucleus Source: UniProtKB-KW
Complete GO annotation...

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_dom.
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

        10         20         30         40         50
MAMAEGERTE CAETPRDEPP ADGTLKRAEE LKTQANDYFK AKDYENAIKF
60 70 80 90 100
YSQAIELNPG NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY
110 120 130 140 150
RRAASNMALG KFRAALRDYE TVVKVKPNDK DAKMKYQECS KIVKQKAFER
160 170 180 190 200
AIAGDEHRRS VVDSLDIESM TIEDEYSGPK LEDGKVTITF MKDLMQWYKD
210 220 230 240 250
QKKLHRKCAY QILVQVKEVL CKLSTLVETT LKETEKITVC GDTHGQFYDL
260 270 280 290 300
LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL
310 320 330 340 350
RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI
360 370 380 390 400
MHGGLFSEDG VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSVSKR
410 420 430 440 450
GVSCQFGPDV TKAFLEENQL DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN
460 470 480 490
YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP HPNVKPMAYA NTLLQLGMM
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_dom.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 136 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