Difference between revisions of "Phosphatase Subfamily SAC1"

Revision as of 18:24, 15 April 2015

Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac: Subfamily SAC1

SAC1 is an integral membrane phosphoinositide phosphatase located in endoplasmic reticulum (ER) and golgi apparatus. SAC1 is conserved in eukaryotes.

Evolution

The SAC1 subfamily is conserved in eukaryotes. It is present in almost all the 203 eukaryotic genomes in gOrtholog database (internal).

Domain

The SAC1 subfamily has a single structural domain, SAC phosphatase domain. It also has a tail which contains localization signal and motifs interacting with other proteins (e.g. coatomer I complex [1]).

Function

The members of the SAC1 subfamily are integral membrane phosphoinositide phosphatases that play evolutionary conserved roles in eukaryotic cell physiology [2]. It locates in the endoplasmic reticulum (ER) and the Golgi apparatus in yeast and mammals.

SAC1 is best characterized in Saccharomyces cerevisiae [3, 4]. Yeast SAC1 mutants display a wide array of phenotypes including inositol auxotrophy, cold sensitivity, secretory defects, disturbed ATP transport into the ER, or suppression of actin gene mutations. Sac1p is able to dephosphorylate PtdIns[3]P, PtdIns[4]P, and PtdIns[3,5]P2 in vitro, the role of Sac1p in processes involving PtdIns[4]P has been the primary focus of in vivo studies (see SGD).

In mammals, it regulates Golgi membrane morphology and mitotic spindle organization [5]. The human SAC1 is widely expressed in different tissues (see GTEx). It interacts with the coatomer I complex via a putative COPI interaction motif (KXKXX) at its C terminus in a manner dependent on its catalytic activity [1].

References

1. Rohde HM, Cheong FY, Konrad G, Paiha K, Mayinger P, and Boehmelt G. The human phosphatidylinositol phosphatase SAC1 interacts with the coatomer I complex. J Biol Chem. 2003 Dec 26;278(52):52689-99. DOI:10.1074/jbc.M307983200 | PubMed ID:14527956 | HubMed [Rohde03]
2. Nemoto Y, Kearns BG, Wenk MR, Chen H, Mori K, Alb JG Jr, De Camilli P, and Bankaitis VA. Functional characterization of a mammalian Sac1 and mutants exhibiting substrate-specific defects in phosphoinositide phosphatase activity. J Biol Chem. 2000 Nov 3;275(44):34293-305. DOI:10.1074/jbc.M003923200 | PubMed ID:10887188 | HubMed [Nemoto00]
3. Cleves AE, Novick PJ, and Bankaitis VA. Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function. J Cell Biol. 1989 Dec;109(6 Pt 1):2939-50. DOI:10.1083/jcb.109.6.2939 | PubMed ID:2687291 | HubMed [Cleves89]
4. 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 | PubMed ID:25113029 | HubMed [Cai14]
5. Liu Y, Boukhelifa M, Tribble E, Morin-Kensicki E, Uetrecht A, Bear JE, and Bankaitis VA. The Sac1 phosphoinositide phosphatase regulates Golgi membrane morphology and mitotic spindle organization in mammals. Mol Biol Cell. 2008 Jul;19(7):3080-96. DOI:10.1091/mbc.e07-12-1290 | PubMed ID:18480408 | HubMed [Liu08]