Q60676 (PPP5_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified December 11, 2013. Version 128. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein phosphatase 5
Protein phosphatase T
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||499 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
A phosphoprotein + H2O = a protein + phosphate.
Binds 2 divalent metal cation per subutnit By similarity.
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.
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
Exressed in liver (at protein level) and brain, enriched in suprachiasmatic nuclei. Ref.7
Does not show circadian oscillation. Ref.7
May be proteocally activated by at least two different cleavages which leads to products of 56 and 50 kDa By similarity.
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
Contains 3 TPR repeats.
|Technical term||Complete proteome|
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: InterProresponse to morphine
Inferred from electronic annotation. Source: UniProtKB-SubCellnucleus
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Molecular_function||RNA bindingmetal ion binding|
Inferred from electronic annotation. Source: UniProtKB-KWphosphoprotein phosphatase activity
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 499||498||Serine/threonine-protein phosphatase 5||PRO_0000058895|
|Repeat||28 – 61||34||TPR 1|
|Repeat||62 – 95||34||TPR 2|
|Repeat||96 – 129||34||TPR 3|
|Region||184 – 499||316||Catalytic|
|Region||303 – 304||2||Substrate binding By similarity|
|Region||495 – 499||5||Required for autoinhibition By similarity|
|Active site||304||1||Proton donor/acceptor By similarity|
|Metal binding||242||1||Divalent metal cation 1 By similarity|
|Metal binding||244||1||Divalent metal cation 1 By similarity|
|Metal binding||271||1||Divalent metal cation 1 By similarity|
|Metal binding||271||1||Divalent metal cation 2 By similarity|
|Metal binding||303||1||Divalent metal cation 2 By similarity|
|Metal binding||352||1||Divalent metal cation 2 By similarity|
|Metal binding||427||1||Divalent metal cation 2 By similarity|
|Binding site||244||1||Substrate By similarity|
|Binding site||275||1||Substrate By similarity|
|Binding site||400||1||Substrate By similarity|
|Binding site||427||1||Substrate By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Sequence conflict||24||1||T → A in AAB70573. Ref.1|
|Sequence conflict||24||1||T → A in AAH03744. Ref.4|
|Sequence conflict||155||1||D → G in AAB18613. Ref.5|
|||Ollendorff V., Donoghue D.J.|
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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. Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||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].
|||"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].
|||"Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor."|
Proc. Natl. Acad. Sci. U.S.A. 91:11075-11079(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-155.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.|
|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.
|RefSeq||NP_035285.2. NM_011155.2. |
3D structure databases
Protein-protein interaction databases
|IntAct||Q60676. 5 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000003183; ENSMUSP00000003183; ENSMUSG00000003099. |
|UCSC||uc009fiq.2. mouse. |
|MGI||MGI:102666. Ppp5c. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
|InterPro||IPR004843. PEstase_dom. |
|PANTHER||PTHR11668:SF12. PTHR11668:SF12. 1 hit. |
|Pfam||PF00149. Metallophos. 1 hit. |
PF08321. PPP5. 1 hit.
PF00515. TPR_1. 1 hit.
|PIRSF||PIRSF033096. PPPtase_5. 1 hit. |
|PRINTS||PR00114. STPHPHTASE. |
|SMART||SM00156. PP2Ac. 1 hit. |
SM00028. TPR. 3 hits.
|PROSITE||PS00125. SER_THR_PHOSPHATASE. 1 hit. |
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
|ChiTaRS||PPP5C. mouse. |
|Accession||Primary (citable) accession number: Q60676|
Secondary accession number(s): G5E819, O35299
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|