Difference between revisions of "Phosphatase Subfamily FIG4"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_Sac|Family Sac]]: [[Phosphatase_Subfamily_FIG4|Subfamily FIG4]] (SAC3) | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_Sac|Family Sac]]: [[Phosphatase_Subfamily_FIG4|Subfamily FIG4]] (SAC3) | ||
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| + | FIG4 (SAC3) is 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. | ||
=== Evolution === | === Evolution === | ||
| − | The FIG4 | + | The FIG4 is found in almost all eukaryotes, including a single gene in human (FIG4/SAC3). |
=== Domain === | === Domain === | ||
| − | + | FIG4 has a single structural domain, SAC phosphatase domain. | |
=== Function === | === Function === | ||
| − | FIG4 is a phosphatidylinositol 3,5- | + | FIG4 (SAC3) is a phosphatase specificity for 5'-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2; PtdIns(3,5)P2), a rare phosphoinositide (<1% of total PI in mammalian cells) that mediates essential aspects of endocytic membrane homeostasis and coordinates fission and fusion events in the multivesicular endosomal system of mammalian cells <cite>Ikonomov09</cite>. PtdIns(3,5)P2 is found in the vacuolar membrane, and levels are regulated by FIG4, PIKfyve (the sole kinase for PtdIns(3,5)P2 synthesis) and the PIKfyve activator ArPIKfyve <cite>Zou15</cite>. The triple PIKfyve-ArPIKfyve-Sac3 (PAS) complex ensures the PtdIns(3,5)P2 homeostatic control by rapid turnover counterbalancing locally elevated PtdIns(3,5)P2 <cite>Ikonomov09</cite>. A model of domain interactions within the PAS core and their role in regulating the enzymatic activities was summarized in Figure 6 of <cite>Ikonomov09</cite>. |
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| + | Mutations in FIG4 cause neurodegeneration in patients with a form of autosomal recessive Charcot-Marie-Tooth disorder, CMT4J and in the pale tremor mouse <cite>Chow07, Ikonomov10, Nicholson11</cite>. It also causes [http://en.wikipedia.org/wiki/Yunis–Varon_syndrome Yunis-Varón syndrome] <cite>Campeau13, Nakajima13</cite>. In addition, it is also a risk factor of amyotrophic lateral sclerosis (ALS) <cite>Chow09, Kon14</cite>. | ||
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| + | FIG4 is widely expressed in different tissues (see [http://www.gtexportal.org/home/gene/FIG4 GTEx])., | ||
=== References === | === References === | ||
<biblio> | <biblio> | ||
| + | #Campeau13 pmid=23623387 | ||
| + | #Chow07 pmid=17572665 | ||
| + | #Chow09 pmid=19118816 | ||
#Ikonomov09 pmid=19840946 | #Ikonomov09 pmid=19840946 | ||
| + | #Ikonomov10 pmid=20630877 | ||
| + | #Kon14 pmid=23888880 | ||
| + | #Nakajima13 pmid=24088667 | ||
| + | #Nicholson11 pmid=21705420 | ||
| + | #Sbrissa07 pmid=17556371 | ||
| + | #Sbrissa08 pmid=18950639 | ||
| + | #Zou15 pmid=25926456 | ||
</biblio> | </biblio> | ||
Latest revision as of 18:31, 26 March 2017
Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac: Subfamily FIG4 (SAC3)
FIG4 (SAC3) is 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.
Evolution
The FIG4 is found in almost all eukaryotes, including a single gene in human (FIG4/SAC3).
Domain
FIG4 has a single structural domain, SAC phosphatase domain.
Function
FIG4 (SAC3) is a phosphatase specificity for 5'-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2; PtdIns(3,5)P2), a rare phosphoinositide (<1% of total PI in mammalian cells) that mediates essential aspects of endocytic membrane homeostasis and coordinates fission and fusion events in the multivesicular endosomal system of mammalian cells [1]. PtdIns(3,5)P2 is found in the vacuolar membrane, and levels are regulated by FIG4, PIKfyve (the sole kinase for PtdIns(3,5)P2 synthesis) and the PIKfyve activator ArPIKfyve [2]. The triple PIKfyve-ArPIKfyve-Sac3 (PAS) complex ensures the PtdIns(3,5)P2 homeostatic control by rapid turnover counterbalancing locally elevated PtdIns(3,5)P2 [1]. A model of domain interactions within the PAS core and their role in regulating the enzymatic activities was summarized in Figure 6 of [1].
Mutations in FIG4 cause neurodegeneration in patients with a form of autosomal recessive Charcot-Marie-Tooth disorder, CMT4J and in the pale tremor mouse [3, 4, 5]. It also causes Yunis-Varón syndrome [6, 7]. In addition, it is also a risk factor of amyotrophic lateral sclerosis (ALS) [8, 9].
FIG4 is widely expressed in different tissues (see GTEx).,
References
Error fetching PMID 17572665:
Error fetching PMID 19118816:
Error fetching PMID 19840946:
Error fetching PMID 20630877:
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Error fetching PMID 21705420:
Error fetching PMID 17556371:
Error fetching PMID 18950639:
Error fetching PMID 25926456:
- Error fetching PMID 19840946:
- Error fetching PMID 25926456:
- Error fetching PMID 17572665:
- Error fetching PMID 20630877:
- Error fetching PMID 21705420:
- Error fetching PMID 23623387:
- Error fetching PMID 24088667:
- Error fetching PMID 19118816:
- Error fetching PMID 23888880:
- Error fetching PMID 17556371:
- Error fetching PMID 18950639:
