Protein phosphatase catalytic subunits

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Protein phosphatase catalytic subunits

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

3263

protein phosphatase 1 catalytic subunit alpha Show summary »« Hide summary

Target Id

3264

Nomenclature

protein phosphatase 1 catalytic subunit alpha

Previous and unofficial names

dism2 | PP1A | PP1alpha | Ppp1c | protein phosphatase 1, catalytic subunit, alpha isoform

Genes

PPP1CA (Hs), Ppp1ca (Mm), Ppp1ca (Rn)

Ensembl ID

ENSG00000172531 (Hs), ENSMUSG00000040385 (Mm), ENSRNOG00000018708 (Rn)

UniProtKB AC

P62136 (Hs), P62137 (Mm), P62138 (Rn)

EC number

3.1.3.16

Inhibitors

microcystin-LR pIC₅₀ 10.0 [10]

calyculin A pIC₅₀ 9.0 [8]

okadaic acid pIC₅₀ 7.2 [8]

cantharidin pIC₅₀ 6.8 [8]

Comment

Component of the protein phosphatase type 1 complex which dephosphorylates numerous substrate proteins [9,11]. Notably it is important for cell division, the regulation of glycogen metabolism and synaptic plasticity.

protein phosphatase 2 catalytic subunit alpha Show summary »« Hide summary

Target Id

3263

Nomenclature

protein phosphatase 2 catalytic subunit alpha

Previous and unofficial names

PP2A | PP2Ac | PP2Calpha | protein phosphatase 2A catalytic subunit, alpha isoform

Genes

PPP2CA (Hs), Ppp2ca (Mm), Ppp2ca (Rn)

Ensembl ID

ENSG00000113575 (Hs), ENSMUSG00000020349 (Mm), ENSRNOG00000005389 (Rn)

UniProtKB AC

P67775 (Hs), O88591 (Mm), P63331 (Rn)

EC number

3.1.3.16

Inhibitors

microcystin-LR pIC₅₀ 9.0 – 10.0 [10]

okadaic acid pIC₅₀ 9.0 [8]

calyculin A pIC₅₀ 8.7 [8]

cantharidin pIC₅₀ 6.7 [1]

Comment

PP2A phosphatases are holoenzymes, constituting of at least two subunits, a scaffolding subunit (A) and and a catalytic subunit (C). The AC core dimer can form heterotrimers with a range of regulatory B-type subunits (B55, B56, PR48 and PR93) [4]. Endogenous proteins have been identified as PP2A phosphatase inhibitors [4-5]. PP2A phosphatases mediate dephosphorylation of a range of substrate proteins [2-3,6-7]. PP2A is particularly important for regulating microtubule-associated protein (MAP) phosphorylation and stability during the cell cyle [12].

References

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1. Bajsa J, McCluskey A, Gordon CP, Stewart SG, Hill TA, Sahu R, Duke SO, Tekwani BL. (2010) The antiplasmodial activity of norcantharidin analogs. Bioorg Med Chem Lett, 20 (22): 6688-95. [PMID:20888768]

2. Becher J, Simula L, Volpe E, Procaccini C, La Rocca C, D'Acunzo P, Cianfanelli V, Strappazzon F, Caruana I, Nazio F et al.. (2018) AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis. Dev Cell, 47 (5): 592-607.e6. [PMID:30513302]

3. Cianfanelli V, Fuoco C, Lorente M, Salazar M, Quondamatteo F, Gherardini PF, De Zio D, Nazio F, Antonioli M, D'Orazio M et al.. (2015) AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol, 17 (1): 20-30. [PMID:25438055]

4. Fan L, Liu MH, Guo M, Hu CX, Yan ZW, Chen J, Chen GQ, Huang Y. (2016) FAM122A, a new endogenous inhibitor of protein phosphatase 2A. Oncotarget, 7 (39): 63887-63900. [PMID:27588481]

5. Labbé JC, Vigneron S, Méchali F, Robert P, Roque S, Genoud C, Goguet-Rubio P, Barthe P, Labesse G, Cohen-Gonsaud M et al.. (2021) The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop. Nat Commun, 12 (1): 3565. [PMID:34117214]

6. Li F, Kozono D, Deraska P, Branigan T, Dunn C, Zheng XF, Parmar K, Nguyen H, DeCaprio J, Shapiro GI et al.. (2020) CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol Cell, 80 (3): 410-422.e6. [PMID:33108758]

7. Li HH, Cai X, Shouse GP, Piluso LG, Liu X. (2007) A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J, 26 (2): 402-11. [PMID:17245430]

8. McCluskey A, Keane MA, Walkom CC, Bowyer MC, Sim AT, Young DJ, Sakoff JA. (2002) The first two cantharidin analogues displaying PP1 selectivity. Bioorg Med Chem Lett, 12 (3): 391-3. [PMID:11814804]

9. Nie H, Zheng Y, Li R, Guo TB, He D, Fang L, Liu X, Xiao L, Chen X, Wan B et al.. (2013) Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis. Nat Med, 19 (3): 322-8. [PMID:23396208]

10. Sheppeck 2nd JE, Gauss CM, Chamberlin AR. (1997) Inhibition of the Ser-Thr phosphatases PP1 and PP2A by naturally occurring toxins. Bioorg Med Chem, 5 (9): 1739-50. [PMID:9354230]

11. Song H, Pu J, Wang L, Wu L, Xiao J, Liu Q, Chen J, Zhang M, Liu Y, Ni M et al.. (2015) ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation. Autophagy, 11 (8): 1308-25. [PMID:26083323]

12. Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE. (2012) Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit α4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem, 287 (29): 24207-15. [PMID:22613722]

How to cite this family page

Database page citation:

Protein phosphatase catalytic subunits. Accessed on 06/07/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1092.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.