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:
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=== 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 (PtdIns4P), and it is also able to dephosphorylate other phosphoinositides in vitro. SAC1 is conserved in eukaryotes.  
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* [[Phosphatase_Subfamily_INPP5F|INPP5F]]
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The Sac family is found across eukaryotic genomes. It has four subfamilies, all of which are phosphoinositide phosphatases, involved in vesicular trafficking:  
* [[Phosphatase_Subfamily_FIG4|FIG4]] (SAC3) - a phosphatidylinositol 3,5-bisphosphate (PtdIns(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.
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* [[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_Synaptojanin|Synaptojanin]]
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* [[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.
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* [[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.
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* [[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.
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=== Phosphatase domain ===
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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]].
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=== References ===
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<biblio>
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#Cai14 pmid=25113029
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#Manford10 pmid=20389282
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</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

Error fetching PMID 25113029:
Error fetching PMID 20389282:
  1. Error fetching PMID 20389282: [Manford10]
  2. Error fetching PMID 25113029: [Cai14]
All Medline abstracts: PubMed | HubMed