Phosphatase Subfamily PTC7

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PTC7

Evolution

The PTC7 subfamily is found throughout eukaryotes. It is single copy in most opisthokonts.

Domain Architecture

PTC7 proteins typically consist of a single structural domain: a PPM-fold phosphatase domain. A PLAT domain is found N-terminal of the phosphatase domain in Monosiga, some algae and scattered other organisms, and Monosiga also encodes an uncertain C-terminal LIM domain.

Functions

Yeast Ptc7p, dephosphorylates and activates the mitochondrial hydroxylase Coq7p (Cat5p) and so activates coenzyme Q6 biosynthesis. Ptc7 may reverse the action of the Coq8 kinase (ABC1/YGL119W) (see, e.g. [1]), and in humans, ABC1 kinases ADCK3 and ACDK4 have been implicated in the related coenzyme Q10 biosynthesis [2]. COQ7 is found in most eukaryotes, except plants and excavates [3]. COQ7 in humans is targeted to mitochondria, cleaved to become trapped in these organelles, and then function in the biosynthesis of ubiquinone, a cofactor in the electron transport chain. It is suggested that S114 in human COQ7 is phosphorylated and controls its activity [4]. The uncleaved form of these proteins in the nucleus [5].

Subcellular localization

Human PPTC7 is reported as a mitochondrial protein by multiple datasets summarized in Mitominer, and knockdown in human cells has an effect on mitochondrial respiration [6], though PPTC7 lacks a mitochondrial targeting signal TargetP 1.1.

References

1. He CH, Xie LX, Allan CM, Tran UC, and Clarke CF. Coenzyme Q supplementation or over-expression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants. Biochim Biophys Acta. 2014 Apr 4;1841(4):630-44. DOI:10.1016/j.bbalip.2013.12.017 |
2. Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, Fang H, Song X, Cattran DC, Avila-Casado C, Paterson AD, Nitschké P, Bole-Feysot C, Cochat P, Esteve-Rudd J, Haberberger B, Allen SJ, Zhou W, Airik R, Otto EA, Barua M, Al-Hamed MH, Kari JA, Evans J, Bierzynska A, Saleem MA, Böckenhauer D, Kleta R, El Desoky S, Hacihamdioglu DO, Gok F, Washburn J, Wiggins RC, Choi M, Lifton RP, Levy S, Han Z, Salviati L, Prokisch H, Williams DS, Pollak M, Clarke CF, Pei Y, Antignac C, and Hildebrandt F. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest. 2013 Dec;123(12):5179-89. DOI:10.1172/JCI69000 |
3. Martín-Montalvo A, González-Mariscal I, Pomares-Viciana T, Padilla-López S, Ballesteros M, Vazquez-Fonseca L, Gandolfo P, Brautigan DL, Navas P, and Santos-Ocaña C. The phosphatase Ptc7 induces coenzyme Q biosynthesis by activating the hydroxylase Coq7 in yeast. J Biol Chem. 2013 Sep 27;288(39):28126-37. DOI:10.1074/jbc.M113.474494 |
5. Monaghan RM, Barnes RG, Fisher K, Andreou T, Rooney N, Poulin GB, and Whitmarsh AJ. A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity. Nat Cell Biol. 2015 Jun;17(6):782-92. DOI:10.1038/ncb3170 |
6. Lanning NJ, Looyenga BD, Kauffman AL, Niemi NM, Sudderth J, DeBerardinis RJ, and MacKeigan JP. A mitochondrial RNAi screen defines cellular bioenergetic determinants and identifies an adenylate kinase as a key regulator of ATP levels. Cell Rep. 2014 May 8;7(3):907-17. DOI:10.1016/j.celrep.2014.03.065 |

Technical notes

Accessory PLAT domain is found in a small number of single cellular eukaryotes

The combination of PLAT and PPM domain is found in sparsely, by BLASTing monosiga PTC7, both full sequence and the region containing PLAT and PPM, against eukaryotes NR dataset. domain (1-400). Below are the organisms and their genes that have the domain combination of PLAT and PPM:

• Algae: Monoraphidium neglectum (KIY99478.1), Micromonas sp. RCC299 (XP_002499745.1), Bathycoccus prasinos (XP_007509274.1)
• Eudicot: Capsella rubella (XP_006283668.1)
• Cryptomonad: Guillardia theta (XP_005819750.1)
• Fungus: Blastocystis hominis (CBK25361.2)