LIPID MAPS

LMPD ID

LMP012350

Gene ID

9896

Species

Homo sapiens (Human)

Gene Name

FIG4 phosphoinositide 5-phosphatase

Gene Symbol

FIG4

Synonyms

YVS; BTOP; SAC3; ALS11; CMT4J; KIAA0274; dJ249I4.1;

Chromosome

6

Map Location

6q21

EC Number

3.1.3.-

Summary

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]

Orthologs

View orthologs and multiple alignments for FIG4

polyphosphoinositide phosphatase
Refseq ID	NP_055660
Protein GI	7662034
UniProt ID	Q92562
mRNA ID	NM_014845
Length	907
MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVIIDDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEGYYIVLITKRRKMADIGGHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQNVDLSSNFYFSYSYDLSHSLQYNLTVLRMPLEMLKSEMTQNRQESFDIFEDEGLITQGGSGVFGICSEPYMKYVWNGELLDIIKSTVHRDWLLYIIHGFCGQSKLLIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVETEQILCDASVMSFTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALHFDQMFQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPWDMAKYTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELGGCVIPTGRLQTGILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNLQFDTDAVRLFEELYEDHGDTLSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQTLSRYYSNAFSDADRQDSINLFLGVFHPTEGKPHLWELPTDFYLHHKNTMRLLPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLIVKKFHKYEEEIDIHNEFFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDETGKSVLGNKSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVKMTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQDKNSQQPCSRCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQGIMQPLGKEDSSMYREYIRNRYL

Entrez Gene ID

9896

Gene Name

FIG4 phosphoinositide 5-phosphatase

Gene Symbol

FIG4

Species

Homo sapiens

Gene Ontology (GO Annotations)

GO ID	Source	Type	Description
GO:0000139	TAS:Reactome	C	Golgi membrane
GO:0031901	TAS:Reactome	C	early endosome membrane
GO:0010008	IDA:UniProtKB	C	endosome membrane
GO:0031902	TAS:Reactome	C	late endosome membrane
GO:0043813	TAS:Reactome	F	phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity
GO:0004438	IEA:Ensembl	F	phosphatidylinositol-3-phosphatase activity
GO:0043812	IEA:Ensembl	F	phosphatidylinositol-4-phosphate phosphatase activity
GO:0008219	IEA:UniProtKB-KW	P	cell death
GO:0007626	IEA:Ensembl	P	locomotory behavior
GO:0032288	IEA:Ensembl	P	myelin assembly
GO:0031642	IEA:Ensembl	P	negative regulation of myelination
GO:0048666	IEA:Ensembl	P	neuron development
GO:0006661	TAS:Reactome	P	phosphatidylinositol biosynthetic process
GO:0036092	TAS:GOC	P	phosphatidylinositol-3-phosphate biosynthetic process
GO:0006644	TAS:Reactome	P	phospholipid metabolic process
GO:0043473	IEA:Ensembl	P	pigmentation
GO:0010976	IEA:Ensembl	P	positive regulation of neuron projection development
GO:0044281	TAS:Reactome	P	small molecule metabolic process
GO:0007033	IEA:Ensembl	P	vacuole organization

BIOCYC Pathway Links

BIOCYC Pathway ID	Description
PWY-6352	3-phosphoinositide biosynthesis
PWY-6352	3-phosphoinositide biosynthesis
PWY-6371	superpathway of inositol phosphate compounds

REACTOME Pathway Links

REACTOME Pathway ID	Description
REACT_111217	Metabolism
REACT_22258	Metabolism of lipids and lipoproteins
REACT_121175	PI Metabolism
REACT_120870	Phospholipid metabolism
REACT_120836	Synthesis of PIPs at the Golgi membrane
REACT_120756	Synthesis of PIPs at the early endosome membrane
REACT_120918	Synthesis of PIPs at the late endosome membrane

InterPro Annotations

Accession	Description
IPR002013	SAC domain

Entry Information

Gene Name

FIG4 phosphoinositide 5-phosphatase

UniProt ID

Q92562

Species

Human

Comments

Comment Type	Description
Disease	Amyotrophic lateral sclerosis 11 (ALS11) [MIM:612577]: 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 Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Charcot-Marie-Tooth disease 4J (CMT4J) [MIM:611228]: 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 Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Yunis-Varon syndrome (YVS) [MIM:216340]: 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 Note=The disease is caused by mutations affecting the gene represented in this entry.
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
Sequence Caution	Sequence=BAA13403.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
Similarity	Contains 1 SAC domain. {ECO:0000255\|PROSITE- ProRule:PRU00183}.
Subcellular Location	Endosome membrane Note=Localization requires VAC14 and PIKFYVE.
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