ID   IDI1_YEAST              Reviewed;         288 AA.
AC   P15496; D6W3Q1;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 205.
DE   RecName: Full=Isopentenyl-diphosphate delta-isomerase {ECO:0000305};
DE            EC=5.3.3.2 {ECO:0000269|PubMed:2223785, ECO:0000269|PubMed:2681212, ECO:0000269|PubMed:7908830};
DE   AltName: Full=Isopentenyl pyrophosphate isomerase {ECO:0000303|PubMed:2681212};
DE            Short=IPP isomerase {ECO:0000303|PubMed:2681212};
GN   Name=IDI1 {ECO:0000303|PubMed:2681212}; Synonyms=BOT2;
GN   OrderedLocusNames=YPL117C; ORFNames=LPH10C;
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], PROTEIN SEQUENCE OF 2-36, FUNCTION,
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX   PubMed=2681212; DOI=10.1016/s0021-9258(19)47283-9;
RA   Anderson M.S., Muehlbacher M., Street I.P., Proffitt J., Poulter C.D.;
RT   "Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved
RT   purification of the enzyme and isolation of the gene from Saccharomyces
RT   cerevisiae.";
RL   J. Biol. Chem. 264:19169-19175(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169875;
RA   Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA   Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA   Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA   Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA   DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA   Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA   Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA   Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA   Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA   Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA   Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA   Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA   Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA   Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA   Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA   Vo D.H., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL   Nature 387:103-105(1997).
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 124-154, ACTIVE SITE, FUNCTION, CATALYTIC ACTIVITY, AND
RP   ACTIVITY REGULATION.
RX   PubMed=2223785; DOI=10.1021/bi00484a023;
RA   Street I.P., Poulter C.D.;
RT   "Isopentenyldiphosphate:dimethylallyldiphosphate isomerase: construction of
RT   a high-level heterologous expression system for the gene from Saccharomyces
RT   cerevisiae and identification of an active-site nucleophile.";
RL   Biochemistry 29:7531-7538(1990).
RN   [5]
RP   PROTEIN SEQUENCE OF 196-215, CATALYTIC ACTIVITY, FUNCTION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, AND MUTAGENESIS OF CYS-138;
RP   CYS-139 AND GLU-207.
RX   PubMed=7908830; DOI=10.1021/bi00180a014;
RA   Street I.P., Coffman H.R., Baker J.A., Poulter C.D.;
RT   "Identification of Cys139 and Glu207 as catalytically important groups in
RT   the active site of isopentenyl diphosphate:dimethylallyl diphosphate
RT   isomerase.";
RL   Biochemistry 33:4212-4217(1994).
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   IDENTIFICATION BY MASS 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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP   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   [9]
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   [10]
RP   REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX   PubMed=32679672; DOI=10.3390/genes11070795;
RA   Jorda T., Puig S.;
RT   "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL   Genes (Basel) 11:0-0(2020).
CC   -!- FUNCTION: Isopentenyl-diphosphate delta-isomerase; part of the second
CC       module of ergosterol biosynthesis pathway that includes the middle
CC       steps of the pathway (PubMed:2223785, PubMed:2681212, PubMed:7908830).
CC       IDI1 catalyzes the 1,3-allylic rearrangement of isopentenyl (IPP) to
CC       its highly electrophilic allylic isomer, dimethylallyl diphosphate
CC       (DMAPP) (PubMed:2223785, PubMed:2681212, PubMed:7908830). The second
CC       module is carried out in the vacuole and involves the formation of
CC       farnesyl diphosphate, which is also an important intermediate in the
CC       biosynthesis of ubiquinone, dolichol, heme and prenylated proteins.
CC       Activity by the mevalonate kinase ERG12 first converts mevalonate into
CC       5-phosphomevalonate. 5-phosphomevalonate is then further converted to
CC       5-diphosphomevalonate by the phosphomevalonate kinase ERG8. The
CC       diphosphomevalonate decarboxylase MVD1/ERG19 then produces isopentenyl
CC       diphosphate. The isopentenyl-diphosphate delta-isomerase IDI1 then
CC       catalyzes the 1,3-allylic rearrangement of the homoallylic substrate
CC       isopentenyl (IPP) to its highly electrophilic allylic isomer,
CC       dimethylallyl diphosphate (DMAPP). Finally the farnesyl diphosphate
CC       synthase ERG20 catalyzes the sequential condensation of isopentenyl
CC       pyrophosphate with dimethylallyl pyrophosphate, and then with the
CC       resultant geranylpyrophosphate to the ultimate product farnesyl
CC       pyrophosphate (PubMed:32679672). {ECO:0000269|PubMed:2223785,
CC       ECO:0000269|PubMed:2681212, ECO:0000269|PubMed:7908830,
CC       ECO:0000303|PubMed:32679672}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=isopentenyl diphosphate = dimethylallyl diphosphate;
CC         Xref=Rhea:RHEA:23284, ChEBI:CHEBI:57623, ChEBI:CHEBI:128769;
CC         EC=5.3.3.2; Evidence={ECO:0000269|PubMed:2223785,
CC         ECO:0000269|PubMed:2681212, ECO:0000269|PubMed:7908830};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23285;
CC         Evidence={ECO:0000269|PubMed:2223785, ECO:0000269|PubMed:2681212,
CC         ECO:0000269|PubMed:7908830};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q46822};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q46822};
CC   -!- ACTIVITY REGULATION: 3,4-epoxy-l-butenyl diphosphate and 3-
CC       (fluoromethyl)-3-butenyl diphosphate (FIPP) act as specific active
CC       site-directed inhibitors of IP Pisomerase. {ECO:0000269|PubMed:2223785,
CC       ECO:0000269|PubMed:2681212}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=43 uM for isopentenyl-diphosphate {ECO:0000269|PubMed:7908830};
CC         Vmax=20 umol/min/mg enzyme {ECO:0000269|PubMed:7908830};
CC   -!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
CC       biosynthesis; dimethylallyl diphosphate from isopentenyl diphosphate:
CC       step 1/1. {ECO:0000269|PubMed:2223785, ECO:0000269|PubMed:2681212,
CC       ECO:0000269|PubMed:7908830}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- MISCELLANEOUS: Present with 25500 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the IPP isomerase type 1 family. {ECO:0000305}.
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DR   EMBL; J05090; AAA34708.1; -; Genomic_DNA.
DR   EMBL; U43503; AAB68245.1; -; Genomic_DNA.
DR   EMBL; BK006949; DAA11317.1; -; Genomic_DNA.
DR   PIR; A34440; A34440.
DR   RefSeq; NP_015208.1; NM_001183931.1.
DR   AlphaFoldDB; P15496; -.
DR   SMR; P15496; -.
DR   BioGRID; 36064; 152.
DR   IntAct; P15496; 14.
DR   MINT; P15496; -.
DR   STRING; 4932.YPL117C; -.
DR   iPTMnet; P15496; -.
DR   MaxQB; P15496; -.
DR   PaxDb; 4932-YPL117C; -.
DR   PeptideAtlas; P15496; -.
DR   EnsemblFungi; YPL117C_mRNA; YPL117C; YPL117C.
DR   GeneID; 855986; -.
DR   KEGG; sce:YPL117C; -.
DR   AGR; SGD:S000006038; -.
DR   SGD; S000006038; IDI1.
DR   VEuPathDB; FungiDB:YPL117C; -.
DR   eggNOG; KOG0142; Eukaryota.
DR   GeneTree; ENSGT00390000008527; -.
DR   HOGENOM; CLU_060552_0_2_1; -.
DR   InParanoid; P15496; -.
DR   OMA; LRLCPWF; -.
DR   OrthoDB; 777305at2759; -.
DR   BioCyc; MetaCyc:YPL117C-MONOMER; -.
DR   BioCyc; YEAST:YPL117C-MONOMER; -.
DR   BRENDA; 5.3.3.2; 984.
DR   Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR   UniPathway; UPA00059; UER00104.
DR   BioGRID-ORCS; 855986; 1 hit in 10 CRISPR screens.
DR   PRO; PR:P15496; -.
DR   Proteomes; UP000002311; Chromosome XVI.
DR   RNAct; P15496; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0005773; C:vacuole; NAS:UniProt.
DR   GO; GO:0004452; F:isopentenyl-diphosphate delta-isomerase activity; IDA:SGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0050992; P:dimethylallyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IDA:UniProt.
DR   GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; IDA:SGD.
DR   GO; GO:0009240; P:isopentenyl diphosphate biosynthetic process; IBA:GO_Central.
DR   CDD; cd02885; IPP_Isomerase; 1.
DR   Gene3D; 3.90.79.10; Nucleoside Triphosphate Pyrophosphohydrolase; 1.
DR   InterPro; IPR011876; IsopentenylPP_isomerase_typ1.
DR   InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR   InterPro; IPR000086; NUDIX_hydrolase_dom.
DR   NCBIfam; TIGR02150; IPP_isom_1; 1.
DR   PANTHER; PTHR10885; ISOPENTENYL-DIPHOSPHATE DELTA-ISOMERASE; 1.
DR   PANTHER; PTHR10885:SF0; ISOPENTENYL-DIPHOSPHATE DELTA-ISOMERASE; 1.
DR   Pfam; PF00293; NUDIX; 1.
DR   SUPFAM; SSF55811; Nudix; 1.
DR   PROSITE; PS51462; NUDIX; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Isomerase; Isoprene biosynthesis;
KW   Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW   Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:2681212"
FT   CHAIN           2..288
FT                   /note="Isopentenyl-diphosphate delta-isomerase"
FT                   /id="PRO_0000205231"
FT   DOMAIN          102..259
FT                   /note="Nudix hydrolase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT   REGION          33..58
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        39..56
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        139
FT                   /evidence="ECO:0000269|PubMed:2223785"
FT   ACT_SITE        207
FT                   /evidence="ECO:0000269|PubMed:7908830"
FT   BINDING         89
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13907"
FT   BINDING         93
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q46822"
FT   BINDING         104
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q46822"
FT   BINDING         123
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13907"
FT   BINDING         127
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13907"
FT   BINDING         140
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13907"
FT   BINDING         205
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q46822"
FT   BINDING         207
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q46822"
FT   MOD_RES         7
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MUTAGEN         138
FT                   /note="C->S,V: 10-fold reduction in activity."
FT                   /evidence="ECO:0000269|PubMed:7908830"
FT   MUTAGEN         139
FT                   /note="C->A,V: Inactive."
FT                   /evidence="ECO:0000269|PubMed:7908830"
FT   MUTAGEN         139
FT                   /note="C->S: Reduces activity over 100000-fold."
FT                   /evidence="ECO:0000269|PubMed:7908830"
FT   MUTAGEN         207
FT                   /note="E->Q,V: Inactive."
FT                   /evidence="ECO:0000269|PubMed:7908830"
SQ   SEQUENCE   288 AA;  33352 MW;  44A373A62EAE1C70 CRC64;
     MTADNNSMPH GAVSSYAKLV QNQTPEDILE EFPEIIPLQQ RPNTRSSETS NDESGETCFS
     GHDEEQIKLM NENCIVLDWD DNAIGAGTKK VCHLMENIEK GLLHRAFSVF IFNEQGELLL
     QQRATEKITF PDLWTNTCCS HPLCIDDELG LKGKLDDKIK GAITAAVRKL DHELGIPEDE
     TKTRGKFHFL NRIHYMAPSN EPWGEHEIDY ILFYKINAKE NLTVNPNVNE VRDFKWVSPN
     DLKTMFADPS YKFTPWFKII CENYLFNWWE QLDDLSEVEN DRQIHRML
//