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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 1 By similarity
Metal bindingi244 – 2441Magnesium or manganese 1 By similarity
Binding sitei244 – 2441Substrate By similarity
Metal bindingi271 – 2711Magnesium or manganese 1 By similarity
Metal bindingi271 – 2711Magnesium or manganese 2 By similarity
Binding sitei275 – 2751Substrate By similarity
Metal bindingi303 – 3031Magnesium or manganese 2 By similarity
Active sitei304 – 3041Proton donor/acceptor By similarity
Metal bindingi352 – 3521Magnesium or manganese 2 By similarity
Binding sitei400 – 4001Substrate By similarity
Metal bindingi427 – 4271Magnesium or manganese 2 By similarity
Binding sitei427 – 4271Substrate By similarity

GO - Molecular functioni

  1. RNA binding Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. phosphoprotein phosphatase activity Source: MGI
  4. protein binding Source: MGI
Complete GO annotation...

GO - Biological processi

  1. protein dephosphorylation Source: InterPro
  2. 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. Cytoplasm. Membrane By similarity
Note: Predominantly nuclear. But also present in the cytoplasm.1 Publication

GO - Cellular componenti

  1. cytosol Source: MGI
  2. membrane Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB-SubCell
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 – 11Removed By similarity
Chaini2 – 499498Serine/threonine-protein phosphatase 5
PRO_0000058895Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By 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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati28 – 6134TPR 1
Add
BLAST
Repeati62 – 9534TPR 2
Add
BLAST
Repeati96 – 12934TPR 3
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni184 – 499316Catalytic
Add
BLAST
Regioni303 – 3042Substrate binding By similarity
Regioni495 – 4995Required for autoinhibition By similarity

Sequence similaritiesi

Contains 3 TPR repeats.

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.
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

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MAMAEGERTE CAETPRDEPP ADGTLKRAEE LKTQANDYFK AKDYENAIKF    50
YSQAIELNPG NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY 100
RRAASNMALG KFRAALRDYE TVVKVKPNDK DAKMKYQECS KIVKQKAFER 150
AIAGDEHRRS VVDSLDIESM TIEDEYSGPK LEDGKVTITF MKDLMQWYKD 200
QKKLHRKCAY QILVQVKEVL CKLSTLVETT LKETEKITVC GDTHGQFYDL 250
LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL 300
RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI 350
MHGGLFSEDG VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSVSKR 400
GVSCQFGPDV TKAFLEENQL DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN 450
YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP HPNVKPMAYA NTLLQLGMM 499
Length:499
Mass (Da):56,877
Last modified:October 16, 2013 - v3
Checksum:i92C5509374FD6721
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 241T → A in AAB70573. 1 Publication
Sequence conflicti24 – 241T → A in AAH03744. 1 Publication
Sequence conflicti155 – 1551D → G in AAB18613. 1 Publication

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.