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Protein

Serine/threonine-protein phosphatase 5

Gene

Ppp5c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

Mg2+By similarity, Mn2+By similarityNote: Binds 2 Mg2+ or Mn2+ cations 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)DescriptionActionsGraphical viewLength
Metal bindingi242Manganese 1By similarity1
Metal bindingi244Manganese 1; via tele nitrogenBy similarity1
Binding sitei244SubstrateBy similarity1
Metal bindingi271Manganese 1By similarity1
Metal bindingi271Manganese 2By similarity1
Binding sitei275SubstrateBy similarity1
Metal bindingi303Manganese 2By similarity1
Active sitei304Proton donor/acceptorBy similarity1
Metal bindingi352Manganese 2; via tele nitrogenBy similarity1
Binding sitei400SubstrateBy similarity1
Metal bindingi427Manganese 2; via pros nitrogenBy similarity1
Binding sitei427SubstrateBy similarity1

GO - Molecular functioni

  • ADP binding Source: MGI
  • ATP binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • phosphoprotein phosphatase activity Source: MGI
  • RNA binding Source: MGI
  • signal transducer activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:102666. Ppp5c.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, 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)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000588952 – 499Serine/threonine-protein phosphatase 5Add BLAST498

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1

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

EPDiQ60676.
MaxQBiQ60676.
PaxDbiQ60676.
PeptideAtlasiQ60676.
PRIDEiQ60676.

PTM databases

PhosphoSitePlusiQ60676.

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

BgeeiENSMUSG00000003099.
CleanExiMM_PPP5C.
ExpressionAtlasiQ60676. baseline and differential.
GenevisibleiQ60676. MM.

Interactioni

Subunit structurei

Interacts with CPNE1 (via VWFA domain) (PubMed:12522145). 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. Interacts with FLCN (By similarity).By similarity3 Publications

Protein-protein interaction databases

BioGridi202349. 9 interactors.
IntActiQ60676. 4 interactors.
MINTiMINT-1353706.
STRINGi10090.ENSMUSP00000003183.

Structurei

3D structure databases

ProteinModelPortaliQ60676.
SMRiQ60676.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati28 – 61TPR 1Add BLAST34
Repeati62 – 95TPR 2Add BLAST34
Repeati96 – 129TPR 3Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni184 – 499CatalyticAdd BLAST316
Regioni303 – 304Substrate bindingBy similarity2
Regioni495 – 499Required for autoinhibitionBy similarity5

Sequence similaritiesi

Contains 3 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0376. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00530000063173.
HOGENOMiHOG000172698.
HOVERGENiHBG000216.
InParanoidiQ60676.
KOiK04460.
OMAiWMGRGPS.
OrthoDBiEOG091G0589.
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:SF21. PTHR11668:SF21. 2 hits.
PfamiPF00149. Metallophos. 1 hit.
PF08321. PPP5. 1 hit.
PF00515. TPR_1. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
SM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF56300. 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)DescriptionActionsGraphical viewLength
Sequence conflicti24T → A in AAB70573 (Ref. 1) Curated1
Sequence conflicti24T → A in AAH03744 (PubMed:15489334).Curated1
Sequence conflicti155D → G in AAB18613 (PubMed:7972012).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ60676.
SMRiQ60676.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202349. 9 interactors.
IntActiQ60676. 4 interactors.
MINTiMINT-1353706.
STRINGi10090.ENSMUSP00000003183.

PTM databases

PhosphoSitePlusiQ60676.

Proteomic databases

EPDiQ60676.
MaxQBiQ60676.
PaxDbiQ60676.
PeptideAtlasiQ60676.
PRIDEiQ60676.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003183; ENSMUSP00000003183; ENSMUSG00000003099.
GeneIDi19060.
KEGGimmu:19060.
UCSCiuc009fiq.2. mouse.

Organism-specific databases

CTDi5536.
MGIiMGI:102666. Ppp5c.

Phylogenomic databases

eggNOGiKOG0376. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00530000063173.
HOGENOMiHOG000172698.
HOVERGENiHBG000216.
InParanoidiQ60676.
KOiK04460.
OMAiWMGRGPS.
OrthoDBiEOG091G0589.
TreeFamiTF105562.

Enzyme and pathway databases

ReactomeiR-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

Miscellaneous databases

ChiTaRSiPpp5c. mouse.
PROiQ60676.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003099.
CleanExiMM_PPP5C.
ExpressionAtlasiQ60676. baseline and differential.
GenevisibleiQ60676. MM.

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:SF21. PTHR11668:SF21. 2 hits.
PfamiPF00149. Metallophos. 1 hit.
PF08321. PPP5. 1 hit.
PF00515. TPR_1. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
SM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF56300. SSF56300. 1 hit.
PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 158 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.