Phosphatase Family Sac
The Sac family is found across eukaryotic genomes. It has four subfamilies, all of which are phosphoinositide phosphatases, involved in vesicular trafficking:
- SAC1 - an integral membrane phosphoinositide phosphatase located in endoplasmic reticulum (ER) and golgi apparatus. Its substrate in vivo is phosphatidylinositol 4-phosphate (PI4P), and it is also able to dephosphorylate other phosphoinositides in vitro. SAC1 is conserved in eukaryotes.
- INPP5F (SAC2) - a phosphoinositide phosphatase in the endocytic pathway. It is conserved in metazoa and fungi and is also found in a few plants and basal eukaryotes.
- FIG4 (SAC3) - a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) phosphatase located in the vacuolar membrane. It is associated with a form of Charcot-Marie-Tooth disorder CMT4J, Yunis-Varón syndrome, and amyotrophic lateral sclerosis (ALS). FIG4 is found in most if not all eukaryotes.
- Synaptojanin - a PI(3,5)P2 phosphatase in the endocytic pathway. It has two phosphatase domains dephosphorylate 3-position and 5-position of PtdIns(3,5)P2, respectively. It is found throughout eukaryotes except excavates and some chromalveolates. Human has two members (SYNJ1/INPP5G and SYNJ2/INPP5H) which originated from a duplication event in tetrapods.
Based upon the crystal structure of yeast SAC1 (1-, the yeast SAC1 has two structure domains: SacN and catalytic phosphatase domain (PD) ). The SacN ranges approximately from 1-181; the catalytic PD ranges approximately from 182-504. The SacN domain mediates the interaction with VPS74, which is proposed to mediate packaging of medial Golgi glycosyltransferases into coatomer (also called COP1)-coated vesicles, thereby maintaining Golgi residence . Yeast Sac1p has phosphatase activity towards PtdIns4P. The region of 451-511 has been shown to be required for PtdIns4P phosphatase activity , even though it was described as disordered in first crystal paper and not included in the study solving the structure . We include the region in our profile of Sac PD. See HMM profile of SacN and catalytic domain.
- Manford A, Xia T, Saxena AK, Stefan C, Hu F, Emr SD, and Mao Y. Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function. EMBO J. 2010 May 5;29(9):1489-98. DOI:10.1038/emboj.2010.57 |
- Cai Y, Deng Y, Horenkamp F, Reinisch KM, and Burd CG. Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. J Cell Biol. 2014 Aug 18;206(4):485-91. DOI:10.1083/jcb.201404041 |