Difference between revisions of "Phosphatase Family Sac"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_Sac|Family Sac]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_Sac|Family Sac]] | ||
| − | The Sac family has four subfamilies: | + | === Subfamilies === |
| − | * [[Phosphatase_Subfamily_SAC1|SAC1]] - an integral membrane phosphoinositide phosphatase located in endoplasmic reticulum (ER) and golgi apparatus. Its substrate in vivo is phosphatidylinositol 4-phosphate ( | + | |
| + | The Sac family is found across eukaryotic genomes. It has four subfamilies, all of which are phosphoinositide phosphatases, involved in vesicular trafficking: | ||
| + | * [[Phosphatase_Subfamily_SAC1|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. | ||
* [[Phosphatase_Subfamily_INPP5F|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. | * [[Phosphatase_Subfamily_INPP5F|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. | ||
| − | * [[Phosphatase_Subfamily_FIG4|FIG4]] (SAC3) - a phosphatidylinositol 3,5-bisphosphate ( | + | * [[Phosphatase_Subfamily_FIG4|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. |
| − | * [[Phosphatase_Subfamily_Synaptojanin|Synaptojanin]] - a | + | * [[Phosphatase_Subfamily_Synaptojanin|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) <cite>Manford10</cite>). 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 <cite>Cai14</cite>. Yeast Sac1p has phosphatase activity towards PtdIns4P. The region of 451-511 has been shown to be required for PtdIns4P phosphatase activity <cite>Cai14</cite>, even though it was described as disordered in first crystal paper and not included in the study solving the structure <cite>Manford10</cite>. We include the region in our profile of Sac PD. See [[HMM_PD00008|HMM profile of SacN and catalytic domain]]. | ||
| + | |||
| + | === References === | ||
| + | <biblio> | ||
| + | #Cai14 pmid=25113029 | ||
| + | #Manford10 pmid=20389282 | ||
| + | </biblio> | ||
Latest revision as of 18:20, 26 March 2017
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
- 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 |
