Serine/threonine-protein phosphatase 5

UniProt P53041 Organism Homo sapiens Gene PPP5, PPP5C EC 3.1.3.16

Also known as: PPP5, PPP5C

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 (By similarity). Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1 (By similarity). 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 (By similarity). Dephosphorylate FNIP1, disrupting interaction with HSP90AA1/Hsp90.

Classification

Family (Pfam): PF00149 Metallophos, PF08321 PPP5, PF00515 TPR_1
InterPro: Calcineurin-like_PHP, Metallo-depent_PP-like, PP5_C, PPP_dom, PPP_phosphatase, Ser/Thr-sp_prot-phosphatase, TPR-like_helical_dom_sf, TPR_rpt
Functional cluster: Protein Serine/Threonine Kinases

Experimental structures · PDB · 22

1A17 X-ray 2.45A
1S95 X-ray 1.60A
1WAO X-ray 2.90A
2BUG NMR
3H60 X-ray 2.00A
3H61 X-ray 1.45A
3H62 X-ray 1.40A
3H63 X-ray 1.30A
3H64 X-ray 1.90A
3H66 X-ray 2.59A
3H67 X-ray 1.65A
3H68 X-ray 1.50A
… and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 38

Drugs targeting this protein · 1

LB-100 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Serine/threonine-protein phosphatase 5 2 shared papers
Serine/threonine-protein phosphatase 5 3 shared papers
Heat shock protein HSP 90-alpha 5 shared papers
Cell division cycle protein 16 homolog 1 shared papers
Serine/threonine-protein phosphatase T 1 shared papers
TP53-binding protein 1 2 shared papers
Serine/threonine-protein kinase ATR 2 shared papers
Kelch domain-containing protein 10 homolog 1 shared papers
Kelch domain-containing protein 10 1 shared papers
Folliculin-interacting protein 1 2 shared papers
DNA-dependent protein kinase catalytic subunit 1 shared papers
Estrogen receptor 1 shared papers

Literature · 32 cited papers

Post-translational regulation of FNIP1 creates a rheostat for the molecular chaperone Hsp90. Cell Rep. · 2019
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients. EMBO J. · 2017
The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat. Commun. · 2016
The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol. Cell · 2012
Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-beta pathway. Cell. Signal. · 2012
S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation. J. Biol. Chem. · 2012
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Protein phosphatase 5 is necessary for ATR-mediated DNA repair. Biochem. Biophys. Res. Commun. · 2011
Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro. J. Biol. Chem. · 2010
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin. J. Med. Chem. · 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
… and 20 more in the literature graph

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