Phosphatase Family Sac

Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac

Subfamilies

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.

Phosphatase domain

Based upon the crystal structure of yeast SAC1 (1-, the yeast SAC1 has two structure domains: SacN and catalytic phosphatase domain (PD) [1]). 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 [2]. Yeast Sac1p has phosphatase activity towards PtdIns4P. The region of 451-511 has been shown to be required for PtdIns4P phosphatase activity [2], even though it was described as disordered in first crystal paper and not included in the study solving the structure [1]. We include the region in our profile of Sac PD. See HMM profile of SacN and catalytic domain.

References

1. 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 |
2. 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 |