Difference between revisions of "Phosphatase Subfamily FIG4"
(→Function) |
(→Evolution) |
||
| Line 5: | Line 5: | ||
=== Evolution === | === Evolution === | ||
| − | The FIG4 | + | The FIG4 is found in almost all eukaryotes, including a single gene in human (FIG4/SAC3). |
=== Domain === | === Domain === | ||
Revision as of 18:30, 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
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
Error fetching PMID 17572665:
Error fetching PMID 19118816:
Error fetching PMID 19840946:
Error fetching PMID 20630877:
Error fetching PMID 23888880:
Error fetching PMID 24088667:
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:
