VTC2_YEAST
ID VTC2_YEAST Reviewed; 828 AA.
AC P43585; D6VTM5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Vacuolar transporter chaperone 2;
DE AltName: Full=Phosphate metabolism protein 1;
GN Name=VTC2; Synonyms=PHM1; OrderedLocusNames=YFL004W;
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].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8789262;
RX DOI=10.1002/(sici)1097-0061(199601)12:1<77::aid-yea887>3.0.co;2-5;
RA Naitou M., Ozawa M., Sasanuma S., Kobayashi M., Hagiwara H., Shibata T.,
RA Hanaoka F., Watanabe K., Ono A., Yamazaki M., Tashiro H., Eki T.,
RA Murakami Y.;
RT "Sequencing of a 23 kb fragment from Saccharomyces cerevisiae chromosome
RT VI.";
RL Yeast 12:77-84(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 7-27; 72-93; 103-127; 152-175; 208-219; 308-322;
RP 324-340; 347-358; 448-477 AND 500-515, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (JUN-2005) to UniProtKB.
RN [5]
RP INDUCTION.
RX PubMed=11102525; DOI=10.1091/mbc.11.12.4309;
RA Ogawa N., DeRisi J.L., Brown P.O.;
RT "New components of a system for phosphate accumulation and polyphosphate
RT metabolism in Saccharomyces cerevisiae revealed by genomic expression
RT analysis.";
RL Mol. Biol. Cell 11:4309-4321(2000).
RN [6]
RP FUNCTION, IDENTIFICATION IN VTC COMPLEX, SUBUNIT, AND INTERACTION WITH NYV1
RP AND VPH1.
RX PubMed=11823419; DOI=10.1093/emboj/21.3.259;
RA Mueller O., Bayer M.J., Peters C., Andersen J.S., Mann M., Mayer A.;
RT "The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-
RT complex formation.";
RL EMBO J. 21:259-269(2002).
RN [7]
RP TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=12584253; DOI=10.1242/jcs.00328;
RA Mueller O., Neumann H., Bayer M.J., Mayer A.;
RT "Role of the Vtc proteins in V-ATPase stability and membrane trafficking.";
RL J. Cell Sci. 116:1107-1115(2003).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-657, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=YAL6B;
RX PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA Jensen O.N.;
RT "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT pathway.";
RL Mol. Cell. Proteomics 4:310-327(2005).
RN [10]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-196; SER-264;
RP SER-583; SER-615; SER-616 AND SER-657, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-583 AND SER-657, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-187; SER-615;
RP SER-616 AND SER-657, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-187; SER-196;
RP SER-583; SER-615; SER-616; THR-620; SER-626 AND SER-657, AND IDENTIFICATION
RP 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 [15]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF TYR-22; LYS-26; LYS-127; LYS-130;
RP LYS-131 AND LYS-134.
RX PubMed=27080106; DOI=10.1126/science.aad9858;
RA Wild R., Gerasimaite R., Jung J.Y., Truffault V., Pavlovic I., Schmidt A.,
RA Saiardi A., Jessen H.J., Poirier Y., Hothorn M., Mayer A.;
RT "Control of eukaryotic phosphate homeostasis by inositol polyphosphate
RT sensor domains.";
RL Science 352:986-990(2016).
CC -!- FUNCTION: Component of the vacuolar transporter chaperone (VTC)
CC complex, which plays a role in vacuolar membrane fusion
CC (PubMed:11823419). Binds inositol hexakisphosphate (Ins6P) and similar
CC inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate
CC (5-InsP7); these are important intracellular signaling molecules
CC (PubMed:27080106). Inositol polyphosphate binding promotes vacuolar
CC polyphosphate synthesis (PubMed:27080106).
CC {ECO:0000269|PubMed:11823419, ECO:0000269|PubMed:27080106}.
CC -!- SUBUNIT: The VTC complex is an integral membrane heterooligomer
CC composed of VTC1, VTC2, VTC3 and VTC4. The complex interacts with the
CC v-SNARE NYV1 and with the V(0) subunit of V-ATPase VPH1.
CC {ECO:0000269|PubMed:11823419}.
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:12584253};
CC Multi-pass membrane protein {ECO:0000269|PubMed:12584253}.
CC -!- INDUCTION: By low phosphate. {ECO:0000269|PubMed:11102525}.
CC -!- DOMAIN: The SPX domain has very high affinity for inositol
CC polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-
CC myo-inositol pentakisphosphate (5-InsP7), and moderate affinity for
CC inorganic pyrophosphate. Its affinity for inorganic phosphate is tow to
CC three orders of magnitude lower. {ECO:0000269|PubMed:27080106}.
CC -!- MISCELLANEOUS: Present with 2915 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the VTC2/3 family. {ECO:0000305}.
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DR EMBL; D50617; BAA09234.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12435.1; -; Genomic_DNA.
DR PIR; S56250; S56250.
DR RefSeq; NP_116651.1; NM_001179962.1.
DR PDB; 3G3O; X-ray; 2.10 A; A=183-553.
DR PDBsum; 3G3O; -.
DR AlphaFoldDB; P43585; -.
DR SMR; P43585; -.
DR BioGRID; 31142; 61.
DR ComplexPortal; CPX-784; Vacuolar transporter chaperone complex.
DR DIP; DIP-7596N; -.
DR IntAct; P43585; 8.
DR MINT; P43585; -.
DR STRING; 4932.YFL004W; -.
DR TCDB; 4.E.1.1.1; the vacuolar (acidocalcisome) polyphosphate polymerase (v-ppp) family.
DR iPTMnet; P43585; -.
DR MaxQB; P43585; -.
DR PaxDb; P43585; -.
DR PRIDE; P43585; -.
DR EnsemblFungi; YFL004W_mRNA; YFL004W; YFL004W.
DR GeneID; 850544; -.
DR KEGG; sce:YFL004W; -.
DR SGD; S000001890; VTC2.
DR VEuPathDB; FungiDB:YFL004W; -.
DR eggNOG; KOG1161; Eukaryota.
DR eggNOG; KOG4580; Eukaryota.
DR GeneTree; ENSGT00940000176481; -.
DR HOGENOM; CLU_009308_2_0_1; -.
DR InParanoid; P43585; -.
DR OMA; SFKFWIH; -.
DR BioCyc; YEAST:YFL004W-MON; -.
DR EvolutionaryTrace; P43585; -.
DR PRO; PR:P43585; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P43585; protein.
DR GO; GO:0000421; C:autophagosome membrane; IC:ComplexPortal.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IC:ComplexPortal.
DR GO; GO:0033254; C:vacuolar transporter chaperone complex; IPI:SGD.
DR GO; GO:0005516; F:calmodulin binding; IDA:SGD.
DR GO; GO:0000822; F:inositol hexakisphosphate binding; IDA:UniProtKB.
DR GO; GO:0061736; P:engulfment of target by autophagosome; IC:ComplexPortal.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; IMP:UniProtKB.
DR GO; GO:0016237; P:lysosomal microautophagy; IDA:SGD.
DR GO; GO:0006799; P:polyphosphate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006797; P:polyphosphate metabolic process; IMP:SGD.
DR GO; GO:0008104; P:protein localization; IMP:SGD.
DR GO; GO:0007034; P:vacuolar transport; IDA:SGD.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IMP:SGD.
DR Gene3D; 3.20.100.30; -; 1.
DR InterPro; IPR003807; DUF202.
DR InterPro; IPR004331; SPX_dom.
DR InterPro; IPR018966; VTC_domain.
DR InterPro; IPR042267; VTC_sf.
DR Pfam; PF02656; DUF202; 1.
DR Pfam; PF09359; VTC; 1.
DR PROSITE; PS51382; SPX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Vacuole.
FT CHAIN 1..828
FT /note="Vacuolar transporter chaperone 2"
FT /id="PRO_0000065935"
FT TOPO_DOM 1..693
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 694..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 717..727
FT /note="Vacuolar"
FT /evidence="ECO:0000250"
FT TRANSMEM 728..748
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 749..766
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 767..787
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 788..828
FT /note="Vacuolar"
FT /evidence="ECO:0000250"
FT DOMAIN 1..146
FT /note="SPX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00714"
FT REGION 127..134
FT /note="Important for inositol polyphosphate binding"
FT /evidence="ECO:0000269|PubMed:27080106"
FT REGION 580..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..611
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 22
FT /note="Important for inositol polyphosphate binding"
FT /evidence="ECO:0000269|PubMed:27080106"
FT SITE 26
FT /note="Important for inositol polyphosphate binding"
FT /evidence="ECO:0000269|PubMed:27080106"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 620
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 626
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15665377,
FT ECO:0007744|PubMed:17287358, ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MUTAGEN 22
FT /note="Y->F: Decreases affinity for inositol polyphosphate.
FT Strongly decreases affinity for inositol polyphosphate;
FT when associated with A-26 and A-131."
FT /evidence="ECO:0000269|PubMed:27080106"
FT MUTAGEN 26
FT /note="K->A: Decreases affinity for inositol polyphosphate.
FT Strongly decreases affinity for inositol polyphosphate;
FT when associated with F-22 and A-131."
FT /evidence="ECO:0000269|PubMed:27080106"
FT MUTAGEN 127
FT /note="K->A: Abolishes inositol polyphosphate binding; when
FT associated with A-130 and A-134."
FT /evidence="ECO:0000269|PubMed:27080106"
FT MUTAGEN 130
FT /note="K->A: Abolishes inositol polyphosphate binding; when
FT associated with A-127 and A-134."
FT /evidence="ECO:0000269|PubMed:27080106"
FT MUTAGEN 131
FT /note="K->A: Decreases affinity for inositol polyphosphate.
FT Strongly decreases affinity for inositol polyphosphate;
FT when associated with F-22 and A-26."
FT /evidence="ECO:0000269|PubMed:27080106"
FT MUTAGEN 134
FT /note="K->A: Abolishes inositol polyphosphate binding; when
FT associated with A-127 and A-130."
FT /evidence="ECO:0000269|PubMed:27080106"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 212..223
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 303..310
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 318..325
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 336..343
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 348..353
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 358..370
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 374..393
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 397..409
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 416..429
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 434..437
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:3G3O"
FT TURN 457..460
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:3G3O"
FT STRAND 471..478
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 503..509
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 522..531
FT /evidence="ECO:0007829|PDB:3G3O"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:3G3O"
SQ SEQUENCE 828 AA; 95441 MW; BCEF34FDB2012ABD CRC64;
MLFGVKLANE VYPPWKGSYI NYEGLKKFLK EDSVKDGSND KKARWDDSDE SKFVEELDKE
LEKVYGFQLK KYNNLMERLS HLEKQTDTEA AIKALDADAF QRVLEELLSE STELDNFKRL
NFTGFAKIVK KHDKLYPKYP SVKSLLEVRL KELPSHSEEY SPLLYRISFL YNILRSNFNT
ASEPLASASK FSSIVSNDID MNFRSFKFWV HNDNLMEVKT RILRHLPVLV YANVPSENDD
LVNRFESDIS NNDEIVGSSS STSSVEHGLG ARSFDPLINT LYFDNEHFEL YNDKLLKLNS
APTLRLRWTG QLSDKPDIFL EKKTLIEDEA TGKSEFDLTK LQLKQKFING FIFEGDKKFK
EQTLKKLKES GTAGRDLERL EEDFSEIQNF IIKNELQPVF RTVYTRTAFQ IPGDDKIRVT
IDSNIVFIKE DSFDRERPIR DPNTWHRTDI DANVANPLKF LRGGEYAKFP YSVMEIKVKS
SLDSSMSASS MISNVKLPKK HGQWLNDLTN SHLVKEIPKF SIFVQGVASL YGDDEKLDIL
PFWLPDLETD IRQDPKQAYE EEKKKLLKQK EIQKKIDGMR RLSNLKEPQH QAAVPVSQEE
NERITSQGDL EADGSSDEET EQEPHSKRSK KVRRRKPKAT FLRILAGRDP KLMGVDSEEE
EIELPPGVKK PLNLLKNAGP VNVEAKVWLA NERTFNRWLS VTSLLSVLTF SIYNSVKKAE
YPTLANYMAY VYFGLTIFCA LWSYSIYMKR VDIIQQRSGQ HLDAPLGPVL VSIVLFVTLV
VNFVMAFRNA AKSRQELQIQ NLEVPERIPE VLRPLQNYLF KLMGPSSD
