PPP5_RABIT
ID PPP5_RABIT Reviewed; 42 AA.
AC P55739;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Serine/threonine-protein phosphatase 5;
DE Short=PP5;
DE EC=3.1.3.16 {ECO:0000269|PubMed:9000529};
DE AltName: Full=Protein phosphatase T;
DE Short=PPT;
DE Flags: Fragment;
GN Name=PPP5C; Synonyms=PPP5;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Liver;
RX PubMed=7925273; DOI=10.1002/j.1460-2075.1994.tb06748.x;
RA Chen M.X., McPartlin A.E., Brown L., Chen Y.H., Barker H.M., Cohen P.T.W.;
RT "A novel human protein serine/threonine phosphatase, which possesses four
RT tetratricopeptide repeat motifs and localizes to the nucleus.";
RL EMBO J. 13:4278-4290(1994).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, LIPID-BINDING, AND
RP CLEAVAGE.
RX PubMed=9000529; DOI=10.1016/s0014-5793(96)01427-5;
RA Chen M.X., Cohen P.T.;
RT "Activation of protein phosphatase 5 by limited proteolysis or the binding
RT of polyunsaturated fatty acids to the TPR domain.";
RL FEBS Lett. 400:136-140(1997).
RN [3]
RP IDENTIFICATION IN A COMPLEX WITH HSP90AA1 AND NR3C1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
CC -!- FUNCTION: Serine/threonine-protein phosphatase that dephosphorylates a
CC myriad of proteins involved in different signaling pathways including
CC the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors
CC NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT
CC (PubMed:9000529). Implicated in wide ranging cellular processes,
CC including apoptosis, differentiation, DNA damage response, cell
CC survival, regulation of ion channels or circadian rhythms, in response
CC to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well
CC as oxidative and genotoxic stresses. Participates in the control of DNA
CC damage response mechanisms such as checkpoint activation and DNA damage
CC repair through, for instance, the regulation ATM/ATR-signaling and
CC dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated
CC apoptosis induced by oxidative stress (By similarity). Plays a positive
CC role in adipogenesis, mainly through the dephosphorylation and
CC activation of PPARG transactivation function. Also dephosphorylates and
CC inhibits the anti-adipogenic effect of NR3C1 (By similarity). Regulates
CC the circadian rhythms, through the dephosphorylation and activation of
CC CSNK1E. May modulate TGF-beta signaling pathway by the regulation of
CC SMAD3 phosphorylation and protein expression levels. Dephosphorylates
CC and may play a role in the regulation of TAU/MAPT (By similarity).
CC Through their dephosphorylation, may play a role in the regulation of
CC ions channels such as KCNH2 (By similarity). Dephosphorylate FNIP1,
CC disrupting interaction with HSP90AA1/Hsp90 (By similarity).
CC {ECO:0000250|UniProtKB:P53041, ECO:0000250|UniProtKB:P53042,
CC ECO:0000250|UniProtKB:Q60676, ECO:0000269|PubMed:9000529}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:9000529};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630;
CC Evidence={ECO:0000269|PubMed:9000529};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:9000529};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000269|PubMed:9000529};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Autoinhibited. In the autoinhibited state, the TPR
CC domain interacts with the catalytic region and prevents substrate
CC access to the catalytic pocket. Allosterically activated by various
CC polyunsaturated fatty acids, free long-chain fatty-acids and long-chain
CC fatty acyl-CoA esters, arachidonic acid being the most effective
CC activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release
CC the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and
CC GNA13 is synergistic with the one produced by fatty acids binding.
CC Inhibited by okadaic acid. {ECO:0000269|PubMed:9000529}.
CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and
CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and
CC client protein TSC2 (By similarity). Probably forms a complex composed
CC of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and
CC client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not
CC contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Part of
CC a complex with HSP90/HSP90AA1 and steroid receptors (PubMed:9195923).
CC Interacts (via TPR repeats) with HSP90AA1 (via TPR repeat-binding
CC motif) or HSPA1A/HSPA1B; the interaction is direct and activates the
CC phosphatase activity (By similarity). Dissociates from HSPA1A/HSPA1B
CC and HSP90AA1 in response to arachidonic acid (By similarity). Interacts
CC with CPNE1 (via VWFA domain) (By similarity). Interacts with CDC16,
CC CDC27 (By similarity). Interacts with KLHDC10 (via the 6 Kelch
CC repeats); inhibits the phosphatase activity on MAP3K5 (By similarity).
CC Interacts with ATM and ATR; both interactions are induced by DNA damage
CC and enhance ATM and ATR kinase activity (By similarity). Interacts with
CC RAD17; reduced by DNA damage. Interacts with nuclear receptors such as
CC NR3C1/GCR and PPARG (activated by agonist); regulates their
CC transactivation activities (By similarity). Interacts (via TPR repeats)
CC with S100 proteins S100A1, S100A2, S100A6, S100B and S100P; the
CC interactions are calcium-dependent, strongly activate PPP5C phosphatase
CC activity and compete with HSP90AA1 and MAP3K5 interactions (By
CC similarity). Interacts with SMAD2 and SMAD3 but not with SMAD1;
CC decreases SMAD3 phosphorylation and protein levels (By similarity).
CC Interacts (via TPR repeats) with CRY1 and CRY2; the interaction with
CC CRY2 down-regulates the phosphatase activity on CSNK1E (By similarity).
CC Interacts (via TPR repeats) with the active form of RAC1, GNA12 or
CC GNA13; these interactions activate the phosphatase activity and
CC translocate PPP5C to the cell membrane (By similarity). Interacts with
CC FLCN (By similarity). {ECO:0000250|UniProtKB:P53041,
CC ECO:0000250|UniProtKB:Q60676, ECO:0000269|PubMed:9195923}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P53041}. Cytoplasm
CC {ECO:0000250|UniProtKB:P53041}. Cell membrane
CC {ECO:0000250|UniProtKB:P53041}. Note=Predominantly nuclear. But also
CC present in the cytoplasm. Translocates from the cytoplasm to the plasma
CC membrane in a RAC1-dependent manner. {ECO:0000250|UniProtKB:P53041}.
CC -!- PTM: Activated by at least two different proteolytic cleavages
CC producing a 56 kDa and a 50 kDa form. {ECO:0000269|PubMed:9000529}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; P55739; -.
DR SMR; P55739; -.
DR STRING; 9986.ENSOCUP00000018147; -.
DR eggNOG; KOG0376; Eukaryota.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISS:UniProtKB.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR029052; Metallo-depent_PP-like.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Hydrolase; Magnesium; Manganese; Membrane;
KW Metal-binding; Nucleus; Protein phosphatase; Reference proteome.
FT CHAIN <1..42
FT /note="Serine/threonine-protein phosphatase 5"
FT /id="PRO_0000058896"
FT REGION 38..42
FT /note="Required for autoinhibition"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 42 AA; 4719 MW; 5B85BC402EF4692F CRC64;
KASYIHLRGS DLRPQFHQFT AVPHPNVKPM AYANALLQLG VM
