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P53042 (PPP5_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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.2 Ref.3 Ref.4 Ref.5 Ref.6

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. Ref.2 Ref.6

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 Ref.6 Ref.7

Subcellular location

Nucleus. Cytoplasm. Membrane By similarity. Note: Predominantly nuclear. But also present in the cytoplasm. Ref.3

Tissue specificity

Predominantly found in brain and, in lower levels, in testis, but was nearly undetectable in spleen, lung, skeletal muscle, kidney and liver. Ref.4

Post-translational modification

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

Sequence similarities

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

Contains 3 TPR repeats.

Biophysicochemical properties

Kinetic parameters:

KM=12.1 µM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius) Ref.4

Ontologies

Keywords
   Cellular componentCytoplasm
Membrane
Nucleus
   DomainRepeat
TPR repeat
   LigandIron
Manganese
Metal-binding
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpositive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

protein dephosphorylation

Inferred from electronic annotation. Source: InterPro

protein heterooligomerization

Inferred from physical interaction PubMed 12786973. Source: RGD

response to morphine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 12786973. Source: RGD

cytosol

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuron projection

Inferred from direct assay PubMed 12786973. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 12786973. Source: RGD

nucleus

Inferred from direct assay PubMed 12786973. Source: RGD

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphoprotein phosphatase activity

Inferred from direct assay PubMed 9383998. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 499498Serine/threonine-protein phosphatase 5
PRO_0000058897

Regions

Repeat28 – 6134TPR 1
Repeat62 – 9534TPR 2
Repeat96 – 12934TPR 3
Region200 – 499300Catalytic
Region303 – 3042Substrate binding By similarity
Region495 – 4995Required for autoinhibition

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

Mutagenesis291E → A: No effect on phosphatase activity. Ref.2
Mutagenesis321K → A: No effect on phosphatase activity. Ref.2
Mutagenesis401K → A: Slightly reduces activation by arachidonic acid.
Mutagenesis561E → A: No effect on phosphatase activity. Ref.2
Mutagenesis631I → A: No effect on phosphatase activity. Ref.2
Mutagenesis741R → A: No effect on phosphatase activity. Ref.2
Mutagenesis761E → A: Increases basal phosphatase activity. Ref.2
Mutagenesis771C → A: No effect on phosphatase activity. Ref.2
Mutagenesis801Y → A: No effect on phosphatase activity. Ref.2
Mutagenesis931K → E: Loss of inhibition of KCNH2 channel stimulation. Ref.6
Mutagenesis971K → A: No effect on phosphatase activity. Ref.2
Mutagenesis1011R → A: No effect on phosphatase activity. Ref.2
Mutagenesis1261K → A: Loss of inhibition of KCNH2 channel stimulation. Ref.6
Mutagenesis4511Y → A: Insensitive to okadaic acid. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P53042 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 720A7FB7AFC701D2

FASTA49956,917
        10         20         30         40         50         60 
MAMAEGERTE CAEPPRDEPP AEGTLKRAEE LKTQANDYFK AKDYENAIKF YSQAIELNPS 

        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

[1]"Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain."
Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G.
J. Biol. Chem. 269:22586-22592(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Testis.
[2]"Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation."
Kang H., Sayner S.L., Gross K.L., Russell L.C., Chinkers M.
Biochemistry 40:10485-10490(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS PHOSPHATASE, ENZYME REGULATION, MUTAGENESIS OF GLU-29; LYS-32; GLU-56; ILE-63; ARG-74; GLU-76; CYS-77; TYR-80; LYS-97 AND ARG-101.
[3]"Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity."
Yamaguchi Y., Katoh H., Mori K., Negishi M.
Curr. Biol. 12:1353-1358(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS PHOSPHATASE, INTERACTION WITH GNA12 AND GNA13, SUBCELLULAR LOCATION.
[4]"Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease."
Liu F., Iqbal K., Grundke-Iqbal I., Rossie S., Gong C.X.
J. Biol. Chem. 280:1790-1796(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEPHOSPHORYLATING MAPT, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[5]"Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5."
von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.
Nat. Cell Biol. 8:1011-1016(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MAPK SIGNALING.
[6]"Rac GTPase signaling through the PP5 protein phosphatase."
Gentile S., Darden T., Erxleben C., Romeo C., Russo A., Martin N., Rossie S., Armstrong D.L.
Proc. Natl. Acad. Sci. U.S.A. 103:5202-5206(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RAC1 SIGNALING, ENZYME REGULATION, INTERACTION WITH RAC1, MUTAGENESIS OF LYS-93; LYS-126 AND TYR-451.
[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: INTERACTION WITH CRY1 AND CRY2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X77237 mRNA. Translation: CAA54454.1.
PIRA55346.
RefSeqNP_113917.1. NM_031729.1.
UniGeneRn.6107.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JA7X-ray2.00A16-499[»]
4JA9X-ray2.30A16-499[»]
ProteinModelPortalP53042.
SMRP53042. Positions 23-499.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEP53042.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000023078; ENSRNOP00000023078; ENSRNOG00000016907.
GeneID65179.
KEGGrno:65179.
UCSCRGD:68415. rat.

Organism-specific databases

CTD5536.
RGD68415. Ppp5c.

Phylogenomic databases

eggNOGCOG0639.
GeneTreeENSGT00530000063173.
HOGENOMHOG000172698.
HOVERGENHBG000216.
InParanoidP53042.
KOK04460.
OMAFKLLYPN.
OrthoDBEOG7V49Z3.
PhylomeDBP53042.
TreeFamTF105562.

Enzyme and pathway databases

BRENDA3.1.3.16. 5301.

Gene expression databases

ArrayExpressP53042.
GenevestigatorP53042.

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. 2 hits.
[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

NextBio614076.
PROP53042.

Entry information

Entry namePPP5_RAT
AccessionPrimary (citable) accession number: P53042
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 117 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references