Phosphatase Subfamily PPP6C

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Phosphatase Classification: Fold PPPL: Superfamily PPPL: Family PPP: Subfamily PPP6C

Evolution

PPP6C is found throughout eukaryotes, including opisthokonta, amoebazoa, plants and etc.

Domain

PPP6C has a single domain - phosphatase domain.

Functions

PPP6C, catalytic subunit of Protein Phosphatase 6 (PP6) holoenzyme.

The PP6 holoenzyme in yeast has been proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS (SIT4 phosphatase-associated proteins) domain-containing sub- unit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS).

PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL-2 receptor stimulation. Its N-terminal domain restricts G to S phase progression in cancer cells, in part through control of cyclin D1. PP6 is akso required for efficient activation of DNA-PK,21 which is essential for NHEJ-mediated repair of DSBs (reviewed in the introduction of [1]).

Human PPP6C is involved in autophagy but the underlying mechanism is unclear as April, 2015 [2].


References

  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. Wengrod J, Wang D, Weiss S, Zhong H, Osman I, and Gardner LB. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma. Sci Signal. 2015 Mar 10;8(367):ra27. DOI:10.1126/scisignal.aaa0899 | PubMed ID:25759478 | HubMed [Wengrod15]
All Medline abstracts: PubMed | HubMed