ID   FIG4_YEAST              Reviewed;         879 AA.
AC   P42837; D6W0M2;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Polyphosphoinositide phosphatase;
DE            EC=3.1.3.-;
DE   AltName: Full=Factor-induced gene 4 protein;
DE   AltName: Full=Phosphatidylinositol 3,5-bisphosphate 5-phosphatase;
GN   Name=FIG4; OrderedLocusNames=YNL325C; ORFNames=N0330;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP   MUTAGENESIS OF GLY-519.
RX   PubMed=11950935; DOI=10.1091/mbc.01-10-0498;
RA   Gary J.D., Sato T.K., Stefan C.J., Bonangelino C.J., Weisman L.S.,
RA   Emr S.D.;
RT   "Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by
RT   Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member.";
RL   Mol. Biol. Cell 13:1238-1251(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=S288c / FY1676;
RX   PubMed=7645347; DOI=10.1002/yea.320110606;
RA   Maftahi M., Nicaud J.-M., Levesque H., Gaillardin C.;
RT   "Sequencing analysis of a 15.4 kb fragment of yeast chromosome XIV
RT   identifies the RPD3, PAS8 and KRE1 loci, five new open reading frames.";
RL   Yeast 11:567-572(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH VAC14, SUBCELLULAR
RP   LOCATION, AND MUTAGENESIS OF GLY-519.
RX   PubMed=14528018; DOI=10.1091/mbc.e03-05-0297;
RA   Rudge S.A., Anderson D.M., Emr S.D.;
RT   "Vacuole size control: regulation of PtdIns(3,5)P2 levels by the vacuole-
RT   associated Vac14-Fig4 complex, a PtdIns(3,5)P2-specific phosphatase.";
RL   Mol. Biol. Cell 15:24-36(2004).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   FUNCTION, AND MUTAGENESIS OF ASP-469 AND GLY-519.
RX   PubMed=16492811; DOI=10.1083/jcb.200512105;
RA   Duex J.E., Tang F., Weisman L.S.;
RT   "The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2
RT   synthesis and turnover.";
RL   J. Cell Biol. 172:693-704(2006).
RN   [8]
RP   MUTAGENESIS OF ILE-59.
RX   PubMed=17572665; DOI=10.1038/nature05876;
RA   Chow C.Y., Zhang Y., Dowling J.J., Jin N., Adamska M., Shiga K.,
RA   Szigeti K., Shy M.E., Li J., Zhang X., Lupski J.R., Weisman L.S.,
RA   Meisler M.H.;
RT   "Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and
RT   patients with CMT4J.";
RL   Nature 448:68-72(2007).
RN   [9]
RP   IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=19037259; DOI=10.1038/emboj.2008.248;
RA   Jin N., Chow C.Y., Liu L., Zolov S.N., Bronson R., Davisson M.,
RA   Petersen J.L., Zhang Y., Park S., Duex J.E., Goldowitz D., Meisler M.H.,
RA   Weisman L.S.;
RT   "VAC14 nucleates a protein complex essential for the acute interconversion
RT   of PI3P and PI(3,5)P(2) in yeast and mouse.";
RL   EMBO J. 27:3221-3234(2008).
RN   [10]
RP   IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=18653468; DOI=10.1091/mbc.e08-04-0405;
RA   Botelho R.J., Efe J.A., Teis D., Emr S.D.;
RT   "Assembly of a Fab1 phosphoinositide kinase signaling complex requires the
RT   Fig4 phosphoinositide phosphatase.";
RL   Mol. Biol. Cell 19:4273-4286(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
CC   -!- FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis
CC       and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
CC       Major enzyme required for hyperosmotic shock-induced turnover of
CC       PtdIns(3,5)P2 and requires VAC14 for this function. In vivo, mediates
CC       turnover of PtdIns(3,5)P2 at the vacuole membrane necessary for
CC       vacuolar size control. In vitro, catalyzes the removal of phosphate
CC       from the fifth hydroxyl of the myo-inositol ring of
CC       phosphatidylinositol 3,5-bisphosphate. {ECO:0000269|PubMed:11950935,
CC       ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:16492811,
CC       ECO:0000269|PubMed:19037259}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC         bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC         inositol-3-phosphate) + phosphate; Xref=Rhea:RHEA:32955,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57923,
CC         ChEBI:CHEBI:58088; Evidence={ECO:0000269|PubMed:14528018};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:14528018};
CC   -!- SUBUNIT: Component of the PI(3,5)P2 regulatory complex, composed of
CC       ATG18, FIG4, FAB1, VAC14 and VAC7. VAC14 nucleates the assembly of the
CC       complex and serves as a scaffold. {ECO:0000269|PubMed:18653468,
CC       ECO:0000269|PubMed:19037259}.
CC   -!- INTERACTION:
CC       P42837; P34756: FAB1; NbExp=4; IntAct=EBI-28407, EBI-6754;
CC       P42837; Q06708: VAC14; NbExp=7; IntAct=EBI-28407, EBI-27189;
CC   -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:11950935,
CC       ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:18653468,
CC       ECO:0000269|PubMed:19037259}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:11950935, ECO:0000269|PubMed:14528018,
CC       ECO:0000269|PubMed:18653468, ECO:0000269|PubMed:19037259}.
CC       Note=Localized to the limiting membrane of the vacuole. Localization
CC       requires VAC14 and FAB1.
CC   -!- MISCELLANEOUS: Present with 339 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
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DR   EMBL; Z46259; CAA86373.1; -; Genomic_DNA.
DR   EMBL; Z71601; CAA96256.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10238.1; -; Genomic_DNA.
DR   PIR; S55864; S55864.
DR   RefSeq; NP_014074.1; NM_001183163.1.
DR   AlphaFoldDB; P42837; -.
DR   SMR; P42837; -.
DR   BioGRID; 35516; 127.
DR   ComplexPortal; CPX-3088; PAS complex.
DR   IntAct; P42837; 3.
DR   MINT; P42837; -.
DR   STRING; 4932.YNL325C; -.
DR   iPTMnet; P42837; -.
DR   MaxQB; P42837; -.
DR   PaxDb; 4932-YNL325C; -.
DR   PeptideAtlas; P42837; -.
DR   EnsemblFungi; YNL325C_mRNA; YNL325C; YNL325C.
DR   GeneID; 855392; -.
DR   KEGG; sce:YNL325C; -.
DR   AGR; SGD:S000005269; -.
DR   SGD; S000005269; FIG4.
DR   VEuPathDB; FungiDB:YNL325C; -.
DR   eggNOG; KOG1888; Eukaryota.
DR   GeneTree; ENSGT00550000074943; -.
DR   HOGENOM; CLU_003016_0_1_1; -.
DR   InParanoid; P42837; -.
DR   OMA; KRKCCAH; -.
DR   OrthoDB; 996872at2759; -.
DR   BioCyc; MetaCyc:MONOMER3O-86; -.
DR   BioCyc; YEAST:MONOMER3O-86; -.
DR   BioGRID-ORCS; 855392; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P42837; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P42837; Protein.
DR   GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0034399; C:nuclear periphery; IDA:SGD.
DR   GO; GO:0070772; C:PAS complex; IDA:SGD.
DR   GO; GO:0043813; F:phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; IDA:SGD.
DR   GO; GO:1903100; P:1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate metabolic process; NAS:ComplexPortal.
DR   GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:SGD.
DR   GO; GO:0010511; P:regulation of phosphatidylinositol biosynthetic process; NAS:ComplexPortal.
DR   InterPro; IPR043573; Fig4-like.
DR   InterPro; IPR002013; SAC_dom.
DR   PANTHER; PTHR45738; POLYPHOSPHOINOSITIDE PHOSPHATASE; 1.
DR   PANTHER; PTHR45738:SF5; POLYPHOSPHOINOSITIDE PHOSPHATASE; 1.
DR   Pfam; PF02383; Syja_N; 1.
DR   PROSITE; PS50275; SAC; 1.
PE   1: Evidence at protein level;
KW   Hydrolase; Membrane; Phosphoprotein; Reference proteome; Vacuole.
FT   CHAIN           1..879
FT                   /note="Polyphosphoinositide phosphatase"
FT                   /id="PRO_0000209742"
FT   DOMAIN          166..528
FT                   /note="SAC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00183"
FT   REGION          761..879
FT                   /note="Required for vacuolar localization"
FT   MOD_RES         829
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MUTAGEN         59
FT                   /note="I->T: Defective activation of FAB1."
FT                   /evidence="ECO:0000269|PubMed:17572665"
FT   MUTAGEN         469
FT                   /note="D->N: Partially defective in both hyperosmotic
FT                   shock-induced PtdIns(3,5)P2 elevation and turnover."
FT                   /evidence="ECO:0000269|PubMed:16492811"
FT   MUTAGEN         519
FT                   /note="G->R: In FIG4-1; loss of catalytic activity in
FT                   vitro. Almost 3-fold increase in PtdIns(3,5)P2 level in
FT                   vivo. Partially defective in both hyperosmotic
FT                   shock-induced PtdIns(3,5)P2 elevation and turnover."
FT                   /evidence="ECO:0000269|PubMed:11950935,
FT                   ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:16492811"
SQ   SEQUENCE   879 AA;  101746 MW;  872B3231104185FA CRC64;
     MNNDAMEHTL GGGILTTSGS KQRKTSKFVM GKYTLYETKD RMYIVGSNKR ETMFRILEID
     LTVPRGELTV LEDNVFFTRN EIMNVLASLE EATEDGLHKK ITGYGLLGFI KFTCWYYLIM
     VTKYSQVAVI GGHGIYHIDG IDIIPITNNY KKPEKSSDEA RLLNIFKDLD LTKTFYFSYT
     YDITNTLQTN ILREKLKAVD RCDITIPCGI TDYNEMFVWN NNLLSPIFAC IDTVFDWFQC
     IIHGFIDQVN VSVLGKSIYI TLIARRSHHF AGARFLKRGV NNKGHVANEV ETEQIVTDMI
     LTPFHQPGNG FFDSDRYTSF VQHRGSIPLY WTQDASNLTT KPPIRINVVD PFFSPAALHF
     DNLFQRYGGG TIQILNLIKT KEKTPRETKL LWEFEQCIDY LNEFLPTLKK LDYTSWDMSR
     ASKQDGQGVI EFLEKYAVNT VTTTGIFHNG PDFASTKIQE GICRSNCIDC LDRTNAAQFV
     IGKRALGCQL KSLGIIDNSY LEYDSDIVNI LTELFHDLGD TIALQYGGSH LVNTMETYRK
     INQWSSHSRD MIESIKRFYS NSFVDAQRQD AINLFLGHYS WREGFPSLWE MNTDFYLHNA
     YSLNMPKRSY IHWWNDYNIK SVKELINEEL IATGNDVTRE KIIKNVRGYP GAFDNYWNEY
     YLPRSVTWIR DLFAYNMNST RRYHNALSKQ DKAMSPFTSR KQSWLNNKLK MITSSKSLEK
     AEGRVVETTD LDRDTSPKQE LELYEHYLHI ISDRSQKLEE KMNSFSYSKY PIFISHESSE
     IPPMRKVIGE PLVDIAEDFT DVYDDDDDGD DENDEMTTEA LLIAPDHVSV DEKFYEKVLN
     VDDYKPALDD YSAVIHIKPD NLQLYRDLCF SKDIQLDFQ
//