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Protein

Polyphosphoinositide phosphatase

Gene

FIG4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS12771-MONOMER.
ZFISH:HS12771-MONOMER.
ReactomeiR-HSA-1660514. Synthesis of PIPs at the Golgi membrane.
R-HSA-1660516. Synthesis of PIPs at the early endosome membrane.
R-HSA-1660517. Synthesis of PIPs at the late endosome membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Polyphosphoinositide phosphatase (EC:3.1.3.-)
Alternative name(s):
Phosphatidylinositol 3,5-bisphosphate 5-phosphatase
SAC domain-containing protein 3
Gene namesi
Name:FIG4
Synonyms:KIAA0274, SAC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:16873. FIG4.

Subcellular locationi

  • Endosome membrane 1 Publication

  • Note: Localization requires VAC14 and PIKFYVE.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 4J (CMT4J)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:611228
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07195717L → P in CMT4J. 1 PublicationCorresponds to variant rs587777713dbSNPEnsembl.1
Natural variantiVAR_03697441I → T in CMT4J; the mutant protein is unstable; low levels of the protein results from impaired interaction with VAC14. 3 PublicationsCorresponds to variant rs121908287dbSNPEnsembl.1
Natural variantiVAR_071958302E → K in CMT4J; loss of function. 1 PublicationCorresponds to variant rs587777714dbSNPEnsembl.1
Amyotrophic lateral sclerosis 11 (ALS11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612577
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05483253D → Y in ALS11. 1 PublicationCorresponds to variant rs121908290dbSNPEnsembl.1
Yunis-Varon syndrome (YVS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:216340
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070051104G → D in YVS; complete loss of function mutation. 1 PublicationCorresponds to variant rs397509395dbSNPEnsembl.1
Natural variantiVAR_070052175L → P in YVS; complete loss of function mutation. 1 PublicationCorresponds to variant rs397514707dbSNPEnsembl.1
Polymicrogyria, bilateral temporooccipital (BTOP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by temporo-occipital polymicrogyria, psychiatric manifestations, and epilepsy.
See also OMIM:612691
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071959783D → V in BTOP; partial loss of function. 1 PublicationCorresponds to variant rs587777716dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi488D → A: Loss of activity. 1 Publication1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi9896.
MalaCardsiFIG4.
MIMi216340. phenotype.
611228. phenotype.
612577. phenotype.
612691. phenotype.
OpenTargetsiENSG00000112367.
Orphaneti803. Amyotrophic lateral sclerosis.
208441. Bilateral parasagittal parieto-occipital polymicrogyria.
139515. Charcot-Marie-Tooth disease type 4J.
35689. Primary lateral sclerosis.
3472. Yunis-Varon syndrome.
PharmGKBiPA162388528.

Polymorphism and mutation databases

BioMutaiFIG4.
DMDMi2497367.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002097431 – 907Polyphosphoinositide phosphataseAdd BLAST907

Proteomic databases

EPDiQ92562.
MaxQBiQ92562.
PaxDbiQ92562.
PeptideAtlasiQ92562.
PRIDEiQ92562.
TopDownProteomicsiQ92562.

PTM databases

DEPODiQ92562.
iPTMnetiQ92562.
PhosphoSitePlusiQ92562.
SwissPalmiQ92562.

Expressioni

Gene expression databases

BgeeiENSG00000112367.
CleanExiHS_FIG4.
ExpressionAtlasiQ92562. baseline and differential.
GenevisibleiQ92562. HS.

Organism-specific databases

HPAiCAB017823.
HPA068859.

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VAC14Q08AM63EBI-4290773,EBI-2107455

Protein-protein interaction databases

BioGridi115225. 7 interactors.
IntActiQ92562. 1 interactor.
MINTiMINT-2812974.
STRINGi9606.ENSP00000230124.

Structurei

3D structure databases

ProteinModelPortaliQ92562.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini154 – 547SACPROSITE-ProRule annotationAdd BLAST394

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi746 – 749Poly-Pro4
Compositional biasi755 – 758Poly-Ser4

Sequence similaritiesi

Contains 1 SAC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1888. Eukaryota.
COG5329. LUCA.
GeneTreeiENSGT00550000074943.
HOGENOMiHOG000168063.
InParanoidiQ92562.
OMAiHKQDKNS.
OrthoDBiEOG091G01F4.
PhylomeDBiQ92562.
TreeFamiTF105702.

Family and domain databases

InterProiIPR002013. SAC_dom.
[Graphical view]
PfamiPF02383. Syja_N. 1 hit.
[Graphical view]
PROSITEiPS50275. SAC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q92562-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTAAAPIIS SVQKLVLYET RARYFLVGSN NAETKYRVLK IDRTEPKDLV
60 70 80 90 100
IIDDRHVYTQ QEVRELLGRL DLGNRTKMGQ KGSSGLFRAV SAFGVVGFVR
110 120 130 140 150
FLEGYYIVLI TKRRKMADIG GHAIYKVEDT NMIYIPNDSV RVTHPDEARY
160 170 180 190 200
LRIFQNVDLS SNFYFSYSYD LSHSLQYNLT VLRMPLEMLK SEMTQNRQES
210 220 230 240 250
FDIFEDEGLI TQGGSGVFGI CSEPYMKYVW NGELLDIIKS TVHRDWLLYI
260 270 280 290 300
IHGFCGQSKL LIYGRPVYVT LIARRSSKFA GTRFLKRGAN CEGDVANEVE
310 320 330 340 350
TEQILCDASV MSFTAGSYSS YVQVRGSVPL YWSQDISTMM PKPPITLDQA
360 370 380 390 400
DPFAHVAALH FDQMFQRFGS PIIILNLVKE REKRKHERIL SEELVAAVTY
410 420 430 440 450
LNQFLPPEHT IVYIPWDMAK YTKSKLCNVL DRLNVIAESV VKKTGFFVNR
460 470 480 490 500
PDSYCSILRP DEKWNELGGC VIPTGRLQTG ILRTNCVDCL DRTNTAQFMV
510 520 530 540 550
GKCALAYQLY SLGLIDKPNL QFDTDAVRLF EELYEDHGDT LSLQYGGSQL
560 570 580 590 600
VHRVKTYRKI APWTQHSKDI MQTLSRYYSN AFSDADRQDS INLFLGVFHP
610 620 630 640 650
TEGKPHLWEL PTDFYLHHKN TMRLLPTRRS YTYWWTPEVI KHLPLPYDEV
660 670 680 690 700
ICAVNLKKLI VKKFHKYEEE IDIHNEFFRP YELSSFDDTF CLAMTSSARD
710 720 730 740 750
FMPKTVGIDP SPFTVRKPDE TGKSVLGNKS NREEAVLQRK TAASAPPPPS
760 770 780 790 800
EEAVSSSSED DSGTDREEEG SVSQRSTPVK MTDAGDSAKV TENVVQPMKE
810 820 830 840 850
LYGINLSDGL SEEDFSIYSR FVQLGQSQHK QDKNSQQPCS RCSDGVIKLT
860 870 880 890 900
PISAFSQDNI YEVQPPRVDR KSTEIFQAHI QASQGIMQPL GKEDSSMYRE

YIRNRYL
Length:907
Mass (Da):103,635
Last modified:February 1, 1997 - v1
Checksum:i7B6F115C095EC332
GO

Sequence cautioni

The sequence BAA13403 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti310V → A in BAD96452 (Ref. 2) Curated1
Sequence conflicti453S → P in BAD96452 (Ref. 2) Curated1
Sequence conflicti598F → S in BAD96452 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07195717L → P in CMT4J. 1 PublicationCorresponds to variant rs587777713dbSNPEnsembl.1
Natural variantiVAR_03697441I → T in CMT4J; the mutant protein is unstable; low levels of the protein results from impaired interaction with VAC14. 3 PublicationsCorresponds to variant rs121908287dbSNPEnsembl.1
Natural variantiVAR_05483148D → G.1 Publication1
Natural variantiVAR_05483253D → Y in ALS11. 1 PublicationCorresponds to variant rs121908290dbSNPEnsembl.1
Natural variantiVAR_070051104G → D in YVS; complete loss of function mutation. 1 PublicationCorresponds to variant rs397509395dbSNPEnsembl.1
Natural variantiVAR_070052175L → P in YVS; complete loss of function mutation. 1 PublicationCorresponds to variant rs397514707dbSNPEnsembl.1
Natural variantiVAR_071958302E → K in CMT4J; loss of function. 1 PublicationCorresponds to variant rs587777714dbSNPEnsembl.1
Natural variantiVAR_020378364M → L.Corresponds to variant rs2295837dbSNPEnsembl.1
Natural variantiVAR_054833388R → G.1 Publication1
Natural variantiVAR_054834411I → V.1 Publication1
Natural variantiVAR_054835647Y → C.1 PublicationCorresponds to variant rs150301327dbSNPEnsembl.1
Natural variantiVAR_022826654V → A.1 PublicationCorresponds to variant rs9885672dbSNPEnsembl.1
Natural variantiVAR_071959783D → V in BTOP; partial loss of function. 1 PublicationCorresponds to variant rs587777716dbSNPEnsembl.1
Natural variantiVAR_054836902I → T.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87464 mRNA. Translation: BAA13403.2. Different initiation.
AK222732 mRNA. Translation: BAD96452.1.
AL133472, AL512303 Genomic DNA. Translation: CAI19669.1.
AL512303, AL133472 Genomic DNA. Translation: CAI42494.1.
BC041338 mRNA. Translation: AAH41338.1.
CCDSiCCDS5078.1.
RefSeqiNP_055660.1. NM_014845.5.
UniGeneiHs.529959.

Genome annotation databases

EnsembliENST00000230124; ENSP00000230124; ENSG00000112367.
GeneIDi9896.
KEGGihsa:9896.
UCSCiuc003ptt.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87464 mRNA. Translation: BAA13403.2. Different initiation.
AK222732 mRNA. Translation: BAD96452.1.
AL133472, AL512303 Genomic DNA. Translation: CAI19669.1.
AL512303, AL133472 Genomic DNA. Translation: CAI42494.1.
BC041338 mRNA. Translation: AAH41338.1.
CCDSiCCDS5078.1.
RefSeqiNP_055660.1. NM_014845.5.
UniGeneiHs.529959.

3D structure databases

ProteinModelPortaliQ92562.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115225. 7 interactors.
IntActiQ92562. 1 interactor.
MINTiMINT-2812974.
STRINGi9606.ENSP00000230124.

PTM databases

DEPODiQ92562.
iPTMnetiQ92562.
PhosphoSitePlusiQ92562.
SwissPalmiQ92562.

Polymorphism and mutation databases

BioMutaiFIG4.
DMDMi2497367.

Proteomic databases

EPDiQ92562.
MaxQBiQ92562.
PaxDbiQ92562.
PeptideAtlasiQ92562.
PRIDEiQ92562.
TopDownProteomicsiQ92562.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230124; ENSP00000230124; ENSG00000112367.
GeneIDi9896.
KEGGihsa:9896.
UCSCiuc003ptt.3. human.

Organism-specific databases

CTDi9896.
DisGeNETi9896.
GeneCardsiFIG4.
GeneReviewsiFIG4.
HGNCiHGNC:16873. FIG4.
HPAiCAB017823.
HPA068859.
MalaCardsiFIG4.
MIMi216340. phenotype.
609390. gene.
611228. phenotype.
612577. phenotype.
612691. phenotype.
neXtProtiNX_Q92562.
OpenTargetsiENSG00000112367.
Orphaneti803. Amyotrophic lateral sclerosis.
208441. Bilateral parasagittal parieto-occipital polymicrogyria.
139515. Charcot-Marie-Tooth disease type 4J.
35689. Primary lateral sclerosis.
3472. Yunis-Varon syndrome.
PharmGKBiPA162388528.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1888. Eukaryota.
COG5329. LUCA.
GeneTreeiENSGT00550000074943.
HOGENOMiHOG000168063.
InParanoidiQ92562.
OMAiHKQDKNS.
OrthoDBiEOG091G01F4.
PhylomeDBiQ92562.
TreeFamiTF105702.

Enzyme and pathway databases

BioCyciMetaCyc:HS12771-MONOMER.
ZFISH:HS12771-MONOMER.
ReactomeiR-HSA-1660514. Synthesis of PIPs at the Golgi membrane.
R-HSA-1660516. Synthesis of PIPs at the early endosome membrane.
R-HSA-1660517. Synthesis of PIPs at the late endosome membrane.

Miscellaneous databases

GeneWikiiFig4.
GenomeRNAii9896.
PROiQ92562.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112367.
CleanExiHS_FIG4.
ExpressionAtlasiQ92562. baseline and differential.
GenevisibleiQ92562. HS.

Family and domain databases

InterProiIPR002013. SAC_dom.
[Graphical view]
PfamiPF02383. Syja_N. 1 hit.
[Graphical view]
PROSITEiPS50275. SAC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFIG4_HUMAN
AccessioniPrimary (citable) accession number: Q92562
Secondary accession number(s): Q53H49, Q5TCS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.