ID   HMDH_METJA              Reviewed;         405 AA.
AC   Q58116;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   25-MAY-2022, entry version 128.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34;
GN   Name=hmgA; OrderedLocusNames=MJ0705;
OS   Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS   10045 / NBRC 100440) (Methanococcus jannaschii).
OC   Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC   Methanocaldococcaceae; Methanocaldococcus.
OX   NCBI_TaxID=243232;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX   PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA   Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA   Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA   Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA   Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA   Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA   Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA   Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA   Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT   "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT   jannaschii.";
RL   Science 273:1058-1073(1996).
CC   -!- FUNCTION: Converts HMG-CoA to mevalonate. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC         methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L77117; AAB98699.1; -; Genomic_DNA.
DR   PIR; A64388; A64388.
DR   RefSeq; WP_010870211.1; NC_000909.1.
DR   AlphaFoldDB; Q58116; -.
DR   SMR; Q58116; -.
DR   STRING; 243232.MJ_0705; -.
DR   EnsemblBacteria; AAB98699; AAB98699; MJ_0705.
DR   GeneID; 1451573; -.
DR   KEGG; mja:MJ_0705; -.
DR   eggNOG; arCOG04260; Archaea.
DR   HOGENOM; CLU_001734_2_2_2; -.
DR   InParanoid; Q58116; -.
DR   OMA; DDKMTRA; -.
DR   OrthoDB; 26445at2157; -.
DR   PhylomeDB; Q58116; -.
DR   UniPathway; UPA00058; UER00103.
DR   Proteomes; UP000000805; Chromosome.
DR   GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IBA:GO_Central.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR   CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR   Gene3D; 3.30.70.420; -; 1.
DR   Gene3D; 3.90.770.10; -; 1.
DR   InterPro; IPR002202; HMG_CoA_Rdtase.
DR   InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR   InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR   InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR   InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR   InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR   PANTHER; PTHR10572; PTHR10572; 1.
DR   Pfam; PF00368; HMG-CoA_red; 1.
DR   PRINTS; PR00071; HMGCOARDTASE.
DR   SUPFAM; SSF55035; SSF55035; 1.
DR   SUPFAM; SSF56542; SSF56542; 1.
DR   TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR   PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR   PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR   PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
PE   3: Inferred from homology;
KW   Isoprene biosynthesis; NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..405
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114461"
FT   ACT_SITE        100
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        310
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        400
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   405 AA;  44128 MW;  F8F8E4729A77DFC9 CRC64;
     MENYNDILEK MLNGEIKPYQ LDKMFGSKIA TEIRRKFIEK KVGIEFKHIC NYSIDEEMAM
     KKNIENMIGA IQIPLGFAGP LKINGEYAKG EFYIPLATTE GALVASVNRG CSIITKCGGA
     TVRVIDDKMT RAPCLKTKSV VDAIKVRDWI RENFERIKEV AESTTRHGKL IKIEPILIVG
     RNLYPRFVFK TGDAMGMNMV TIATEKACNF IEGELKKEGI FVKTVAVSGN ACVDKKPSGM
     NLINGRGKSI VAEVFLTEKE VNKYLKTTSQ AIAEVNRLKN YIGSAISNSM GFNAHYANII
     GAIFLATGQD EAHIVEGSLG ITMAEVEDDG LYFSVTLPDV PIGTVGGGTR VETQKECLEM
     LGCYGDNKAL KFAEIVGAAV LAGELSLLGA LAAGHLGKAH QELGR