MVD1_YEAST
ID MVD1_YEAST Reviewed; 396 AA.
AC P32377; D6W1L8; Q6B1C8;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Diphosphomevalonate decarboxylase {ECO:0000303|PubMed:9244250};
DE EC=4.1.1.33 {ECO:0000269|PubMed:8626466};
DE AltName: Full=Ergosterol biosynthesis protein 19 {ECO:0000303|PubMed:9244250};
DE AltName: Full=Mevalonate pyrophosphate decarboxylase {ECO:0000303|PubMed:8626466};
DE Short=MPD {ECO:0000303|PubMed:8626466};
DE AltName: Full=Mevalonate-5-diphosphate decarboxylase {ECO:0000303|PubMed:11698677};
DE Short=MDD {ECO:0000303|PubMed:11698677};
DE Short=MDDase {ECO:0000303|PubMed:11698677};
GN Name=MVD1 {ECO:0000303|PubMed:11698677};
GN Synonyms=ERG19 {ECO:0000303|PubMed:9244250},
GN MPD {ECO:0000303|PubMed:8626466}; OrderedLocusNames=YNR043W;
GN ORFNames=N3427;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=8626466; DOI=10.1074/jbc.271.14.7895;
RA Toth M.J., Huwyler L.;
RT "Molecular cloning and expression of the cDNAs encoding human and yeast
RT mevalonate pyrophosphate decarboxylase.";
RL J. Biol. Chem. 271:7895-7898(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF LEU-79.
RX PubMed=9244250; DOI=10.1128/jb.179.15.4664-4670.1997;
RA Berges T., Guyonnet D., Karst F.;
RT "The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is
RT essential for viability, and a single Leu-to-Pro mutation in a conserved
RT sequence leads to thermosensitivity.";
RL J. Bacteriol. 179:4664-4670(1997).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-194.
RX PubMed=1740455; DOI=10.1016/s0021-9258(19)50638-x;
RA Ashby M.N., Kutsunai S.Y., Ackerman S., Tzagoloff A., Edwards P.A.;
RT "COQ2 is a candidate for the structural gene encoding para-
RT hydroxybenzoate:polyprenyltransferase.";
RL J. Biol. Chem. 267:4128-4136(1992).
RN [7]
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 [8]
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS), AND SUBUNIT.
RX PubMed=11698677; DOI=10.1073/pnas.181466998;
RA Bonanno J.B., Edo C., Eswar N., Pieper U., Romanowski M.J., Ilyin V.,
RA Gerchman S.E., Kycia H., Studier F.W., Sali A., Burley S.K.;
RT "Structural genomics of enzymes involved in sterol/isoprenoid
RT biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12896-12901(2001).
CC -!- FUNCTION: Diphosphomevalonate decarboxylase; part of the second module
CC of ergosterol biosynthesis pathway that includes the middle steps of
CC the pathway (PubMed:8626466, PubMed:9244250). MVD1/ERG19 converts
CC diphosphomevalonate into isopentenyl diphosphate (PubMed:8626466). The
CC second module is carried out in the vacuole and involves the formation
CC of 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:8626466,
CC ECO:0000269|PubMed:9244250, ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-5-diphosphomevalonate + ATP = ADP + CO2 + isopentenyl
CC diphosphate + phosphate; Xref=Rhea:RHEA:23732, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57557,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:456216; EC=4.1.1.33;
CC Evidence={ECO:0000269|PubMed:8626466};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23733;
CC Evidence={ECO:0000269|PubMed:8626466};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 3/3. {ECO:0000269|PubMed:8626466}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11698677}.
CC -!- MISCELLANEOUS: Present with 13700 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the diphosphomevalonate decarboxylase family.
CC {ECO:0000305}.
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DR EMBL; U49261; AAC49252.1; -; mRNA.
DR EMBL; X97557; CAA66158.1; -; Genomic_DNA.
DR EMBL; Z71658; CAA96324.1; -; Genomic_DNA.
DR EMBL; AY693152; AAT93171.1; -; Genomic_DNA.
DR EMBL; M81698; AAA34506.2; -; Genomic_DNA.
DR EMBL; BK006947; DAA10584.1; -; Genomic_DNA.
DR PIR; S63374; S63374.
DR RefSeq; NP_014441.1; NM_001183220.1.
DR PDB; 1FI4; X-ray; 2.27 A; A=1-396.
DR PDBsum; 1FI4; -.
DR AlphaFoldDB; P32377; -.
DR SMR; P32377; -.
DR BioGRID; 35868; 268.
DR DIP; DIP-6729N; -.
DR IntAct; P32377; 2.
DR MINT; P32377; -.
DR STRING; 4932.YNR043W; -.
DR iPTMnet; P32377; -.
DR MaxQB; P32377; -.
DR PaxDb; P32377; -.
DR PRIDE; P32377; -.
DR EnsemblFungi; YNR043W_mRNA; YNR043W; YNR043W.
DR GeneID; 855779; -.
DR KEGG; sce:YNR043W; -.
DR SGD; S000005326; MVD1.
DR VEuPathDB; FungiDB:YNR043W; -.
DR eggNOG; KOG2833; Eukaryota.
DR GeneTree; ENSGT00390000015359; -.
DR HOGENOM; CLU_040369_4_2_1; -.
DR InParanoid; P32377; -.
DR OMA; LTLHAMM; -.
DR BioCyc; MetaCyc:MON-653; -.
DR BioCyc; YEAST:MON-653; -.
DR BioCyc; YEAST:YNR043W-MON; -.
DR BRENDA; 4.1.1.33; 984.
DR Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR Reactome; R-SCE-446199; Synthesis of Dolichyl-phosphate.
DR SABIO-RK; P32377; -.
DR UniPathway; UPA00057; UER00100.
DR EvolutionaryTrace; P32377; -.
DR PRO; PR:P32377; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P32377; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004163; F:diphosphomevalonate decarboxylase activity; IDA:SGD.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IMP:SGD.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; -; 1.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR005935; Mev_decarb.
DR InterPro; IPR029765; Mev_diP_decarb.
DR InterPro; IPR041431; Mvd1_C.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR Pfam; PF18376; MDD_C; 1.
DR PIRSF; PIRSF015950; Mev_P_decrbx; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
DR TIGRFAMs; TIGR01240; mevDPdecarb; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Nucleotide-binding; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..396
FT /note="Diphosphomevalonate decarboxylase"
FT /id="PRO_0000087015"
FT BINDING 19..22
FT /ligand="(R)-5-diphosphomevalonate"
FT /ligand_id="ChEBI:CHEBI:57557"
FT /evidence="ECO:0000250|UniProtKB:O23722"
FT BINDING 74
FT /ligand="(R)-5-diphosphomevalonate"
FT /ligand_id="ChEBI:CHEBI:57557"
FT /evidence="ECO:0000250|UniProtKB:O23722"
FT BINDING 153..158
FT /ligand="(R)-5-diphosphomevalonate"
FT /ligand_id="ChEBI:CHEBI:57557"
FT /evidence="ECO:0000250|UniProtKB:O23722"
FT BINDING 209
FT /ligand="(R)-5-diphosphomevalonate"
FT /ligand_id="ChEBI:CHEBI:57557"
FT /evidence="ECO:0000250|UniProtKB:O23722"
FT MUTAGEN 79
FT /note="L->P: Leads to thermosensitivity."
FT /evidence="ECO:0000269|PubMed:9244250"
FT CONFLICT 160
FT /note="L -> S (in Ref. 5; AAT93171)"
FT /evidence="ECO:0000305"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1FI4"
FT TURN 25..28
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:1FI4"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1FI4"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 75..90
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 120..135
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 142..153
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 154..160
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 161..168
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 192..199
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 221..227
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 246..265
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 276..292
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 297..301
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 316..327
FT /evidence="ECO:0007829|PDB:1FI4"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 339..350
FT /evidence="ECO:0007829|PDB:1FI4"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 367..375
FT /evidence="ECO:0007829|PDB:1FI4"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:1FI4"
SQ SEQUENCE 396 AA; 44116 MW; 6DDFCC72F1BB6430 CRC64;
MTVYTASVTA PVNIATLKYW GKRDTKLNLP TNSSISVTLS QDDLRTLTSA ATAPEFERDT
LWLNGEPHSI DNERTQNCLR DLRQLRKEME SKDASLPTLS QWKLHIVSEN NFPTAAGLAS
SAAGFAALVS AIAKLYQLPQ STSEISRIAR KGSGSACRSL FGGYVAWEMG KAEDGHDSMA
VQIADSSDWP QMKACVLVVS DIKKDVSSTQ GMQLTVATSE LFKERIEHVV PKRFEVMRKA
IVEKDFATFA KETMMDSNSF HATCLDSFPP IFYMNDTSKR IISWCHTINQ FYGETIVAYT
FDAGPNAVLY YLAENESKLF AFIYKLFGSV PGWDKKFTTE QLEAFNHQFE SSNFTARELD
LELQKDVARV ILTQVGSGPQ ETNESLIDAK TGLPKE
