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:

• 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 excavate and some chromalveolate. 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, the yeast SAC1 has two structure domains: SacN and catalytic domain [1]). The SacN ranges approximately from 1-181; the catalytic phosphatase domain 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]. The catalytic domain 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 structure [1]. See HMM profile of SacN and catalytic domain.

References

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