Human Gene FIG4 (ENST00000230124.8) from GENCODE V44
Description: Homo sapiens FIG4 phosphoinositide 5-phosphatase (FIG4), mRNA. (from RefSeq NM_014845) RefSeq Summary (NM_014845): The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000230124.8 Gencode Gene: ENSG00000112367.12 Transcript (Including UTRs) Position: hg38 chr6:109,691,296-109,825,426 Size: 134,131 Total Exon Count: 23 Strand: + Coding Region Position: hg38 chr6:109,691,436-109,825,265 Size: 133,830 Coding Exon Count: 23
ID:FIG4_HUMAN DESCRIPTION: RecName: Full=Polyphosphoinositide phosphatase; EC=3.1.3.-; AltName: Full=Phosphatidylinositol 3,5-bisphosphate 5-phosphatase; AltName: Full=SAC domain-containing protein 3; FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide substrates in the order PtdIns(4,5)P2 > PtdIns(3,5)P2 > PtdIns(3,4,5)P3. Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. SUBUNIT: Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold. SUBCELLULAR LOCATION: Endosome membrane. Note=Localization requires VAC14 and PIKFYVE. DISEASE: Defects in FIG4 are the cause of Charcot-Marie-Tooth disease type 4J (CMT4J) [MIM:611228]. CMT4J is a recessive demyelinating, severe form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. DISEASE: Defects in FIG4 are the cause of amyotrophic lateral sclerosis type 11 (ALS11) [MIM:612577]. ALS is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10%. SIMILARITY: Contains 1 SAC domain. SEQUENCE CAUTION: Sequence=BAA13403.2; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92562
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Protein Q92562 (Reactome details) participates in the following event(s):
R-NUL-1675925 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the late endosome membrane R-NUL-1676051 PI is phosphorylated to PI5P by Pikfyve at the late endosome membrane R-HSA-1675866 PI is phosphorylated to PI5P by PIKFYVE at the late endosome membrane R-HSA-1676020 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the late endosome membrane R-HSA-1675910 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the late endosome membrane R-NUL-1675982 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the Golgi membrane R-HSA-1676005 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the Golgi membrane R-HSA-1675921 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the Golgi membrane R-HSA-1676174 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the early endosome membrane R-HSA-1676168 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the early endosome membrane R-NUL-1675886 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the early endosome membrane R-HSA-1660517 Synthesis of PIPs at the late endosome membrane R-HSA-1660514 Synthesis of PIPs at the Golgi membrane R-HSA-1660516 Synthesis of PIPs at the early endosome membrane R-HSA-1483255 PI Metabolism R-HSA-1483257 Phospholipid metabolism R-HSA-556833 Metabolism of lipids R-HSA-1430728 Metabolism