FIG4_YEAST
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 03-AUG-2022, entry version 162.
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; 123.
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; P42837; -.
DR PRIDE; P42837; -.
DR EnsemblFungi; YNL325C_mRNA; YNL325C; YNL325C.
DR GeneID; 855392; -.
DR KEGG; sce:YNL325C; -.
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 BioCyc; MetaCyc:MON3O-86; -.
DR BioCyc; YEAST:MON3O-86; -.
DR PRO; PR:P42837; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P42837; protein.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:SGD.
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; IC:ComplexPortal.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:SGD.
DR GO; GO:0010511; P:regulation of phosphatidylinositol biosynthetic process; IC:ComplexPortal.
DR InterPro; IPR043573; Fig4-like.
DR InterPro; IPR002013; SAC_dom.
DR PANTHER; PTHR45738; PTHR45738; 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 shock-
FT 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
