P42837 (FIG4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Polyphosphoinositide phosphatase
EC=3.1.3.-

Alternative name(s):
Factor-induced gene 4 protein
Phosphatidylinositol 3,5-bisphosphate 5-phosphatase

Gene names

Name:	FIG4
Ordered Locus Names:	YNL325C
ORF Names:	N0330

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	879 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Major enzyme required for hyperosmotic shock-induced turnover of PtdIns(3,5)P2 and requires VAC14 for this function. In vivo, mediates turnover of PtdIns(3,5)P2 at the vacuole membrane necessary for vacuolar size control. In vitro, catalyzes the removal of phosphate from the fifth hydroxyl of the myo-inositol ring of phosphatidylinositol 3,5-bisphosphate. Ref.1 Ref.5 Ref.7 Ref.9
Catalytic activity	1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate. Ref.5
Cofactor	Magnesium. Ref.5
Subunit structure	Component of the PI(3,5)P2 regulatory complex, composed of ATG18, FIG4, FAB1, VAC14 and VAC7. VAC14 nucleates the assembly of the complex and serves as a scaffold. Ref.9 Ref.10
Subcellular location	Vacuole membrane; Peripheral membrane protein. Note: Localized to the limiting membrane of the vacuole. Localization requires VAC14 and FAB1. Ref.1 Ref.5 Ref.9 Ref.10
Miscellaneous	Present with 339 molecules/cell in log phase SD medium.
Sequence similarities	Contains 1 SAC domain.

Ontologies

Keywords
Cellular component	Membrane Vacuole
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phosphatidylinositol dephosphorylation Inferred from direct assay Ref.5. Source: SGD
Cellular_component	PAS complex Inferred from direct assay Ref.9. Source: SGD extrinsic to membrane Inferred from direct assay Ref.1. Source: SGD fungal-type vacuole membrane Inferred from direct assay Ref.5. Source: SGD
Molecular_function	phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity Inferred from direct assay Ref.5. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VAC14	Q06708	3	EBI-28407,EBI-27189

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 879	879	Polyphosphoinositide phosphatase		PRO_0000209742
Regions
	Domain	166 – 528	363	SAC
	Region	761 – 879	119	Required for vacuolar localization
Amino acid modifications
	Modified residue	829	1	Phosphoserine Ref.11
Experimental info
	Mutagenesis	59	1	I → T: Defective activation of FAB1. Ref.8
	Mutagenesis	469	1	D → N: Partially defective in both hyperosmotic shock-induced PtdIns(3,5)P2 elevation and turnover. Ref.7
	Mutagenesis	519	1	G → R in FIG4-1; loss of catalytic activity in vitro. Almost 3-fold increase in PtdIns(3,5)P2 level in vivo. Partially defective in both hyperosmotic shock-induced PtdIns(3,5)P2 elevation and turnover. Ref.1 Ref.5 Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P42837 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 872B3231104185FA	FASTA	879	101,746
	10 20 30 40 50 60 MNNDAMEHTL GGGILTTSGS KQRKTSKFVM GKYTLYETKD RMYIVGSNKR ETMFRILEID 70 80 90 100 110 120 LTVPRGELTV LEDNVFFTRN EIMNVLASLE EATEDGLHKK ITGYGLLGFI KFTCWYYLIM 130 140 150 160 170 180 VTKYSQVAVI GGHGIYHIDG IDIIPITNNY KKPEKSSDEA RLLNIFKDLD LTKTFYFSYT 190 200 210 220 230 240 YDITNTLQTN ILREKLKAVD RCDITIPCGI TDYNEMFVWN NNLLSPIFAC IDTVFDWFQC 250 260 270 280 290 300 IIHGFIDQVN VSVLGKSIYI TLIARRSHHF AGARFLKRGV NNKGHVANEV ETEQIVTDMI 310 320 330 340 350 360 LTPFHQPGNG FFDSDRYTSF VQHRGSIPLY WTQDASNLTT KPPIRINVVD PFFSPAALHF 370 380 390 400 410 420 DNLFQRYGGG TIQILNLIKT KEKTPRETKL LWEFEQCIDY LNEFLPTLKK LDYTSWDMSR 430 440 450 460 470 480 ASKQDGQGVI EFLEKYAVNT VTTTGIFHNG PDFASTKIQE GICRSNCIDC LDRTNAAQFV 490 500 510 520 530 540 IGKRALGCQL KSLGIIDNSY LEYDSDIVNI LTELFHDLGD TIALQYGGSH LVNTMETYRK 550 560 570 580 590 600 INQWSSHSRD MIESIKRFYS NSFVDAQRQD AINLFLGHYS WREGFPSLWE MNTDFYLHNA 610 620 630 640 650 660 YSLNMPKRSY IHWWNDYNIK SVKELINEEL IATGNDVTRE KIIKNVRGYP GAFDNYWNEY 670 680 690 700 710 720 YLPRSVTWIR DLFAYNMNST RRYHNALSKQ DKAMSPFTSR KQSWLNNKLK MITSSKSLEK 730 740 750 760 770 780 AEGRVVETTD LDRDTSPKQE LELYEHYLHI ISDRSQKLEE KMNSFSYSKY PIFISHESSE 790 800 810 820 830 840 IPPMRKVIGE PLVDIAEDFT DVYDDDDDGD DENDEMTTEA LLIAPDHVSV DEKFYEKVLN 850 860 870 VDDYKPALDD YSAVIHIKPD NLQLYRDLCF SKDIQLDFQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member." Gary J.D., Sato T.K., Stefan C.J., Bonangelino C.J., Weisman L.S., Emr S.D. Mol. Biol. Cell 13:1238-1251(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-519.
[2]	"Sequencing analysis of a 15.4 kb fragment of yeast chromosome XIV identifies the RPD3, PAS8 and KRE1 loci, five new open reading frames." Maftahi M., Nicaud J.-M., Levesque H., Gaillardin C. Yeast 11:567-572(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: S288c / FY1676.
[3]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications." Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., Beinhauer J.D., Boskovic J., Buitrago M.J. , Bussereau F., Coster F., Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J. Nature 387:93-98(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"Vacuole size control: regulation of PtdIns(3,5)P2 levels by the vacuole-associated Vac14-Fig4 complex, a PtdIns(3,5)P2-specific phosphatase." Rudge S.A., Anderson D.M., Emr S.D. Mol. Biol. Cell 15:24-36(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH VAC14, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-519.
[6]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[7]	"The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover." Duex J.E., Tang F., Weisman L.S. J. Cell Biol. 172:693-704(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-469 AND GLY-519.
[8]	"Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J." Chow C.Y., Zhang Y., Dowling J.J., Jin N., Adamska M., Shiga K., Szigeti K., Shy M.E., Li J., Zhang X., Lupski J.R., Weisman L.S., Meisler M.H. Nature 448:68-72(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ILE-59.
[9]	"VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse." Jin N., Chow C.Y., Liu L., Zolov S.N., Bronson R., Davisson M., Petersen J.L., Zhang Y., Park S., Duex J.E., Goldowitz D., Meisler M.H., Weisman L.S. EMBO J. 27:3221-3234(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, SUBCELLULAR LOCATION.
[10]	"Assembly of a Fab1 phosphoinositide kinase signaling complex requires the Fig4 phosphoinositide phosphatase." Botelho R.J., Efe J.A., Teis D., Emr S.D. Mol. Biol. Cell 19:4273-4286(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, SUBCELLULAR LOCATION.
[11]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z46259 Genomic DNA. Translation: CAA86373.1. Z71601 Genomic DNA. Translation: CAA96256.1. BK006947 Genomic DNA. Translation: DAA10238.1.
PIR	S55864.
RefSeq	NP_014074.1. NM_001183163.1.
3D structure databases
ProteinModelPortal	P42837.
SMR	P42837. Positions 106-529.
ModBase	Search...
Protein-protein interaction databases
IntAct	P42837. 1 interaction.
MINT	MINT-2781314.
STRING	4932.YNL325C.
Proteomic databases
PaxDb	P42837.
PRIDE	P42837.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YNL325C; YNL325C; YNL325C.
GeneID	855392.
KEGG	sce:YNL325C.
Organism-specific databases
CYGD	YNL325c.
SGD	S000005269. FIG4.
Phylogenomic databases
eggNOG	COG5329.
GeneTree	ENSGT00550000074943.
HOGENOM	HOG000168063.
OMA	DISKMVP.
OrthoDB	EOG4KSSSV.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-15183.
Gene expression databases
Genevestigator	P42837.
GermOnline	YNL325C. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR002013. Syja_N. [Graphical view]
Pfam	PF02383. Syja_N. 1 hit. [Graphical view]
PROSITE	PS50275. SAC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	979202.

Entry information

Entry name

FIG4_YEAST

Accession

Primary (citable) accession number: P42837
Secondary accession number(s): D6W0M2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program