Difference between revisions of "Phosphatase Subfamily FIG4"
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=== Function === | === Function === | ||
| − | FIG4 (SAC3) is a phosphatase | + | 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>. |
| − | FIG4 | + | 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>. |
| − | FIG4 | + | FIG4 is widely expressed in different tissues (see [http://www.gtexportal.org/home/gene/FIG4 GTEx])., |
=== References === | === References === | ||
Revision as of 18:28, 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 (SAC3) subfamily is conserved in eukaryotes. It is present in almost all the 203 eukaryotic genomes in gOrtholog database (internal).
Domain
The FIG4 (SAC3) subfamily 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
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- 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:
