Phosphatase Subfamily PPP5C

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Phosphatase Classification: Fold PPPL: Superfamily PPPL: Family PPP: Subfamily PPP5C


The PPP5C subfamily is found throughout eukaryotes. PPP5Cs have tandem tetratricopeptide repeat (TPR) structural motifs at N-terminal, which distinguish them from other PPP subfamilies, and were used to classify PPP5C in yeast and Dictyostelium in database.


PPP5Cs typically have tandem tetratricopeptide repeats (TPRs) at N-terminal and phosphatase domain at C-terminal. Dictyostelium has an additional but partial TPR of ~30 aa residues.


PPP5C is the catalytic subunit of holoenzyme PP5, the function of which is reviewed at [1].

PPP5C also known as Protein Phospahtase 5 (PP5) is unique among PPP family members in that its catalytic and regulatory domains are contained in the same polypeptide chain. It has a tetratricopeptide repeat (TPR) domain which maintains the phosphatase in an auto-inhibited conformation that is neutralized when the heat shock protein Hsp90, or fatty acids, bind to this region. ε.

The phosphatase interacts with various proteins and participate in multiple signaling pathways. The phosphatase interacts with ATM, ATR, 53BP1, and DNA-depdent protein kianse catalytic subunits (DNA-PKc) following DNA damage. While enchance the activity of ATM and ATR, the phosphatase negatively regulates 53BP1 and DNA-PKc by dephosphorylating them. It regulates Raf-MEK-ERK pathway via inhibiting Raf-1 by dephosphorylating Serine 338. PPP5 is involved in mammalian circadian clock by activating the major clock kinae casein kinase I (CKI) ε. In addition, the elevated levels of this phosphatase may be associated with breast cancer development.

Measles virus infection inactivates Cellular PP5 with Consequent Suppression of Sp1 and c-Myc Activities [2].


  1. Zhong J, Liao J, Liu X, Wang P, Liu J, Hou W, Zhu B, Yao L, Wang J, Li J, Stark JM, Xie Y, and Xu X. Protein phosphatase PP6 is required for homology-directed repair of DNA double-strand breaks. Cell Cycle. 2011 May 1;10(9):1411-9. DOI:10.4161/cc.10.9.15479 | PubMed ID:21451261 | HubMed [zhong11]
  2. Sato H, Yoneda M, Honma R, Ikeda F, Watanabe S, and Kai C. Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities. J Virol. 2015 Oct;89(19):9709-18. DOI:10.1128/JVI.00825-15 | PubMed ID:26157124 | HubMed [Sato15]
All Medline abstracts: PubMed | HubMed