Phosphatase Subfamily PPM1Z
Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1Z
Evolution
The PPM1Z subfamily is found in eumetazoa but lost from vertebrates. Its sequence is most similar to PPM1G, but it lacks the characteristic PPM1G acidic insert in the phosphatase domain. It is also similar to PPM1A, and there is some uncertainty as to whether some unicellular homologs belong to each of these subfamilies. Monosiga has an unclassified phosphatase that has a N-terminal myristoylation site but the overall sequence similarity does define it as a PPM1Z.
Domain
The PPM1Z subfamily has a N-terminal myristoylation site and a phosphatase domain. The phosphatase domain is closer to PPM1G than other PPMs in sequence, but it does not have the acidic domain inserted in catalytic domain which is common in PPM1G subfamily. C. elegans ppm-2 was shown to be myristoylated and that myristoylation was required for full function [1]
Functions
The function of PPM1Z is unclear. Drosophila has two members, CG17746 and PPM1, which is a likely retrogene copy of GC17746 [2]. CG17746 interacts with both actin (Act5C) and myosin (sqh) [3], and a number of other genes involved in cell cycle or replication. CG17746 and one of its interactors, CG8128 (a nudix hydrolase) were both found to suppress pink1-induced mitochondrial fusion [4], along with several other phosphatases and kinases. The C. elegans PP1Z, ppm-2, binds the ubiquitin ligase RPM-1, and regulates axonal outgrowth through dephosphorylation of the dlk-1 kinase [1]. dlk-1 is a JNK kinase, and Drosophila CG17746 was also reported as an enhancer of JNK signaling [5], giving a first hint of a cross-species role in DLK-JNK signaling.
References
- Baker ST, Opperman KJ, Tulgren ED, Turgeon SM, Bienvenut W, and Grill B. RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development. PLoS Genet. 2014 May;10(5):e1004297. DOI:10.1371/journal.pgen.1004297 |
- Díaz-Castillo C and Ranz JM. Nuclear chromosome dynamics in the Drosophila male germ line contribute to the nonrandom genomic distribution of retrogenes. Mol Biol Evol. 2012 Sep;29(9):2105-8. DOI:10.1093/molbev/mss096 |
- Guruharsha KG, Rual JF, Zhai B, Mintseris J, Vaidya P, Vaidya N, Beekman C, Wong C, Rhee DY, Cenaj O, McKillip E, Shah S, Stapleton M, Wan KH, Yu C, Parsa B, Carlson JW, Chen X, Kapadia B, VijayRaghavan K, Gygi SP, Celniker SE, Obar RA, and Artavanis-Tsakonas S. A protein complex network of Drosophila melanogaster. Cell. 2011 Oct 28;147(3):690-703. DOI:10.1016/j.cell.2011.08.047 |
- Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E, Mortiboys H, and Whitworth AJ. The complex I subunit NDUFA10 selectively rescues Drosophila pink1 mutants through a mechanism independent of mitophagy. PLoS Genet. 2014 Nov;10(11):e1004815. DOI:10.1371/journal.pgen.1004815 |
- Bakal C, Linding R, Llense F, Heffern E, Martin-Blanco E, Pawson T, and Perrimon N. Phosphorylation networks regulating JNK activity in diverse genetic backgrounds. Science. 2008 Oct 17;322(5900):453-6. DOI:10.1126/science.1158739 |
