VAC14_YEAST
ID VAC14_YEAST Reviewed; 880 AA.
AC Q06708; D6VZ21;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Vacuole morphology and inheritance protein 14;
DE AltName: Full=Swollen vacuole phenotype 2 protein;
GN Name=VAC14; Synonyms=SVP2; OrderedLocusNames=YLR386W; ORFNames=L3502.1;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [2]
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 [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11889142; DOI=10.1083/jcb.200201002;
RA Bonangelino C.J., Nau J.J., Duex J.E., Brinkman M., Wurmser A.E.,
RA Gary J.D., Emr S.D., Weisman L.S.;
RT "Osmotic stress-induced increase of phosphatidylinositol 3,5-bisphosphate
RT requires Vac14p, an activator of the lipid kinase Fab1p.";
RL J. Cell Biol. 156:1015-1028(2002).
RN [4]
RP FUNCTION, AND INTERACTION WITH YDR466W; YGR241C; YLR093C; VAC14; FIG4 AND
RP YPR029C.
RX PubMed=12062051; DOI=10.1016/s0960-9822(02)00891-6;
RA Dove S.K., McEwen R.K., Mayes A., Hughes D.C., Beggs J.D., Michell R.H.;
RT "Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein
RT trafficking to the multivesicular body.";
RL Curr. Biol. 12:885-893(2002).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
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, INTERACTION WITH FIG4, AND SUBCELLULAR LOCATION.
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 [8]
RP FUNCTION.
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 [9]
RP IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, SUBCELLULAR
RP LOCATION, DOMAIN, AND MUTAGENESIS OF HIS-56; ARG-61; GLN-101 AND LEU-149.
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-867, 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).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-767 AND SER-805, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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 Regulates the synthesis of PtdIns(3,5)P2 by positive activation of FAB1
CC and by controlling FIG4 localization. Required for FIG4-mediated
CC turnover of PtdIns(3,5)P2 after hyperosmotic shock. Essential for the
CC control of trafficking of some proteins to the vacuole lumen via the
CC multivesicular body (MVB), and for maintenance of vacuole size and
CC acidity. {ECO:0000269|PubMed:11889142, ECO:0000269|PubMed:12062051,
CC ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:16492811,
CC ECO:0000269|PubMed:19037259}.
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 Q06708; P43601: ATG18; NbExp=5; IntAct=EBI-27189, EBI-22968;
CC Q06708; P34756: FAB1; NbExp=9; IntAct=EBI-27189, EBI-6754;
CC Q06708; P42837: FIG4; NbExp=7; IntAct=EBI-27189, EBI-28407;
CC Q06708; Q06708: VAC14; NbExp=4; IntAct=EBI-27189, EBI-27189;
CC Q06708; P53950: VAC7; NbExp=4; IntAct=EBI-27189, EBI-28714;
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:11889142,
CC ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:18653468, ECO:0000269|PubMed:19037259}; Peripheral
CC membrane protein {ECO:0000269|PubMed:11889142,
CC ECO:0000269|PubMed:14528018, ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:18653468, ECO:0000269|PubMed:19037259}.
CC Note=Limiting membrane of the vacuole. Localization requires FAB1 and
CC FIG4.
CC -!- DOMAIN: The N-terminal domain mediates interaction with FAB1 and VAC7
CC while the C-terminal domain mediates interaction with FIG4.
CC {ECO:0000269|PubMed:19037259}.
CC -!- MISCELLANEOUS: Present with 12388 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the VAC14 family. {ECO:0000305}.
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DR EMBL; U19104; AAB67272.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09687.1; -; Genomic_DNA.
DR PIR; S51473; S51473.
DR RefSeq; NP_013490.3; NM_001182275.3.
DR AlphaFoldDB; Q06708; -.
DR BioGRID; 31645; 354.
DR ComplexPortal; CPX-3088; PAS complex.
DR DIP; DIP-1176N; -.
DR IntAct; Q06708; 26.
DR MINT; Q06708; -.
DR STRING; 4932.YLR386W; -.
DR iPTMnet; Q06708; -.
DR MaxQB; Q06708; -.
DR PaxDb; Q06708; -.
DR PRIDE; Q06708; -.
DR EnsemblFungi; YLR386W_mRNA; YLR386W; YLR386W.
DR GeneID; 851102; -.
DR KEGG; sce:YLR386W; -.
DR SGD; S000004378; VAC14.
DR VEuPathDB; FungiDB:YLR386W; -.
DR eggNOG; KOG0212; Eukaryota.
DR GeneTree; ENSGT00390000008385; -.
DR HOGENOM; CLU_007740_0_0_1; -.
DR InParanoid; Q06708; -.
DR OMA; TYLRMQL; -.
DR BioCyc; MetaCyc:G3O-32452-MON; -.
DR BioCyc; YEAST:G3O-32452-MON; -.
DR PRO; PR:Q06708; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q06708; protein.
DR GO; GO:0010008; C:endosome membrane; IBA:GO_Central.
DR GO; GO:0000306; C:extrinsic component of vacuolar membrane; IDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0070772; C:PAS complex; IDA:SGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060090; F:molecular adaptor activity; IPI:SGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:SGD.
DR GO; GO:1903100; P:1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate metabolic process; IC:ComplexPortal.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:SGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0090218; P:positive regulation of lipid kinase activity; IMP:SGD.
DR GO; GO:1903778; P:protein localization to vacuolar membrane; IMP:SGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010511; P:regulation of phosphatidylinositol biosynthetic process; IC:ComplexPortal.
DR Gene3D; 1.25.10.10; -; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR026825; Vac14.
DR InterPro; IPR021841; VAC14_Fig4p-bd.
DR PANTHER; PTHR16023; PTHR16023; 1.
DR Pfam; PF11916; Vac14_Fig4_bd; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
PE 1: Evidence at protein level;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Repeat;
KW Transport; Vacuole.
FT CHAIN 1..880
FT /note="Vacuole morphology and inheritance protein 14"
FT /id="PRO_0000065756"
FT REPEAT 82..119
FT /note="HEAT 1"
FT REPEAT 243..280
FT /note="HEAT 2"
FT REPEAT 388..425
FT /note="HEAT 3"
FT REPEAT 429..466
FT /note="HEAT 4"
FT REPEAT 517..554
FT /note="HEAT 5"
FT REGION 333..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..880
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..361
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 850..872
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 767
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 805
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 867
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 56
FT /note="H->Y: Loss of interaction with ATG18 and VAC7."
FT /evidence="ECO:0000269|PubMed:19037259"
FT MUTAGEN 61
FT /note="R->K: Loss of interaction with ATG18 and VAC7."
FT /evidence="ECO:0000269|PubMed:19037259"
FT MUTAGEN 101
FT /note="Q->R: Loss of interaction with ATG18 and VAC7."
FT /evidence="ECO:0000269|PubMed:19037259"
FT MUTAGEN 149
FT /note="L->R: Loss of interaction with ATG18, FAB1 and VAC7.
FT No loss of interaction with FIG4."
FT /evidence="ECO:0000269|PubMed:19037259"
SQ SEQUENCE 880 AA; 99773 MW; E625AB6F032D2E1B CRC64;
MEKSIAKGLS DKLYEKRKAA ALELEKLVKQ CVLEGDYDRI DKIIDELCRD YAYALHQPMA
RNAGLMGLAA TAIALGINDV GRYLRNILPP VLACFGDQND QVRFYACESL YNIAKIAKGE
ILVYFNEIFD VLCKISADTE NSVRGAAELL DRLIKDIVAE RASNYISIVN NGSHGLLPAI
KTDPISGDVY QEEYEQDNQL AFSLPKFIPL LTERIYAINP DTRVFLVDWL KVLLNTPGLE
LISYLPSFLG GLFTFLGDSH KDVRTVTHTL MDSLLHEVDR ISKLQTEIKM KRLERLKMLE
DKYNNSSTPT KKADGALIAE KKKTLMTALG GLSKPLSMET DDTKLSNTNE TDDERHLTSQ
EQLLDSEATS QEPLRDGEEY IPGQDINLNF PEVITVLVNN LASSEAEIQL IALHWIQVIL
SISPNVFIPF LSKILSVLLK LLSDSDPHIT EIAQLVNGQL LSLCSSYVGK ETDGKIAYGP
IVNSLTLQFF DSRIDAKIAC LDWLILIYHK APNQILKHND SMFLTLLKSL SNRDSVLIEK
ALSLLQSLCS DSNDNYLRQF LQDLLTLFKR DTKLVKTRAN FIMRQISSRL SPERVYKVIS
SILDNYNDTT FVKMMIQILS TNLITSPEMS SLRNKLRTCE DGMFFNSLFK SWCPNPVSVI
SLCFVAENYE LAYTVLQTYA NYELKLNDLV QLDILIQLFE SPVFTRMRLQ LLEQQKHPFL
HKCLFGILMI IPQSKAFETL NRRLNSLNIW TSQSYVMNNY IRQRENSNFC DSNSDISQRS
VSQSKLHFQE LINHFKAVSE EDEYSSDMIR LDHGANNKSL LLGSFLDGID EDKQEIVTPI
SPMNEAINEE MESPNDNSSV ILKDSGSLPF NRNVSDKLKK
