Q92562Q53H49Q5TCS6FIG4_HUMANPolyphosphoinositide phosphatase3.1.3.-3.1.3.363.1.3.86Phosphatidylinositol 3,5-bisphosphate 5-phosphataseSAC domain-containing protein 3Serine-protein phosphatase FIG43.1.3.16FIG4KIAA0274SAC3Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoPrediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]VARIANT ALA-654The DNA sequence and analysis of human chromosome 6.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex.FUNCTIONSUBCELLULAR LOCATIONIDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEXMUTAGENESIS OF ASP-488ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality.IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEXInsights into Lysosomal PI(3,5)P2 Homeostasis from a Structural-Biochemical Analysis of the PIKfyve Lipid Kinase Complex.STRUCTURE BY ELECTRON MICROSCOPY (5.10 ANGSTROMS)IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEXFUNCTIONCATALYTIC ACTIVITYMUTAGENESIS OF CYS-486Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J.VARIANT CMT4J THR-41Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS.VARIANT ALS11 TYR-53VARIANTS GLY-48; GLY-388; VAL-411; CYS-647 AND THR-902Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P(2) phosphatase FIG4.VARIANTS CMT4J PRO-17; THR-41 AND LYS-302CHARACTERIZATION OF VARIANT CMT4J LYS-302Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J.CHARACTERIZATION OF VARIANT CMT4J THR-41Yunis-Varon syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase.VARIANTS YVS ASP-104 AND PRO-175CHARACTERIZATION OF VARIANTS YVS ASP-104 AND PRO-175Role of the phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria.INVOLVEMENT IN BTOPVARIANT BTOP VAL-783CHARACTERIZATION OF VARIANT BTOP VAL-783Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:17556371, PubMed:33098764). Catalyzes the dephosphorylation of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) to form phosphatidylinositol 3-phosphate (PubMed:33098764). Has serine-protein phosphatase activity acting on PIKfyve to stimulate its lipid kinase activity, its catalytically activity being required for maximal PI(3,5)P2 production (PubMed:33098764). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide and although displaying preferences for PtdIns(3,5)P2, it is capable of hydrolyzing PtdIns(3,4,5)P3 and PtdIns(4,5)P2, at least in vitro (PubMed:17556371).a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + phosphatea 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphatea 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphateH2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphateComponent 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 by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities.Q92562Q9H8Y8false3Q92562Q08AM6false5Endosome membraneLocalization requires VAC14 and PIKFYVE.Charcot-Marie-Tooth disease 4J
CMT4J
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.The disease is caused by variants affecting the gene represented in this entry.Amyotrophic lateral sclerosis 11
ALS11
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. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.The disease is caused by variants affecting the gene represented in this entry.Yunis-Varon syndrome
YVS
A severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy.The disease is caused by variants affecting the gene represented in this entry.Polymicrogyria, bilateral temporooccipital
BTOP
A disease characterized by temporo-occipital polymicrogyria, psychiatric manifestations, and epilepsy.The disease is caused by variants affecting the gene represented in this entry.Extended N-terminus.3D-structureAmyotrophic lateral sclerosisCharcot-Marie-Tooth diseaseDisease variantEndosomeHydrolaseMembraneNeurodegenerationNeuropathyReference proteomeLPITDGDYGDLPEKMLRGIVYCVADVITCSDAVASPFSMPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVIIDDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEGYYIVLITKRRKMADIGGHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQNVDLSSNFYFSYSYDLSHSLQYNLTVLRMPLEMLKSEMTQNRQESFDIFEDEGLITQGGSGVFGICSEPYMKYVWNGELLDIIKSTVHRDWLLYIIHGFCGQSKLLIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVETEQILCDASVMSFTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALHFDQMFQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPWDMAKYTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELGGCVIPTGRLQTGILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNLQFDTDAVRLFEELYEDHGDTLSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQTLSRYYSNAFSDADRQDSINLFLGVFHPTEGKPHLWELPTDFYLHHKNTMRLLPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLIVKKFHKYEEEIDIHNEFFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDETGKSVLGNKSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVKMTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQDKNSQQPCSRCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQGIMQPLGKEDSSMYREYIRNRYL
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