ID   HMDH_AERPE              Reviewed;         421 AA.
AC   Q9YAS4;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   25-MAY-2022, entry version 123.
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=APE_1869;
OS   Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 /
OS   K1).
OC   Archaea; Crenarchaeota; Thermoprotei; Desulfurococcales;
OC   Desulfurococcaceae; Aeropyrum.
OX   NCBI_TaxID=272557;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1;
RX   PubMed=10382966; DOI=10.1093/dnares/6.2.83;
RA   Kawarabayasi Y., Hino Y., Horikawa H., Yamazaki S., Haikawa Y., Jin-no K.,
RA   Takahashi M., Sekine M., Baba S., Ankai A., Kosugi H., Hosoyama A.,
RA   Fukui S., Nagai Y., Nishijima K., Nakazawa H., Takamiya M., Masuda S.,
RA   Funahashi T., Tanaka T., Kudoh Y., Yamazaki J., Kushida N., Oguchi A.,
RA   Aoki K., Kubota K., Nakamura Y., Nomura N., Sako Y., Kikuchi H.;
RT   "Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon,
RT   Aeropyrum pernix K1.";
RL   DNA Res. 6:83-101(1999).
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}.
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DR   EMBL; BA000002; BAA80874.1; -; Genomic_DNA.
DR   PIR; E72573; E72573.
DR   AlphaFoldDB; Q9YAS4; -.
DR   SMR; Q9YAS4; -.
DR   STRING; 272557.APE_1869; -.
DR   EnsemblBacteria; BAA80874; BAA80874; APE_1869.
DR   KEGG; ape:APE_1869; -.
DR   PATRIC; fig|272557.25.peg.1254; -.
DR   eggNOG; arCOG04260; Archaea.
DR   OMA; DDKMTRA; -.
DR   UniPathway; UPA00058; UER00103.
DR   Proteomes; UP000002518; Chromosome.
DR   GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR   CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR   Gene3D; 1.10.3270.10; -; 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; IPR023282; HMG_CoA_Rdtase_N.
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..421
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114458"
FT   ACT_SITE        109
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        240
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        315
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        410
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   421 AA;  44625 MW;  9F67AF57FA651822 CRC64;
     MGSSSGQKPR RLEDLVDKLA SGSLSHSRLE KELGNANEAA LVRRLYLERL TGASLSSVAS
     TILDFQELYG RNIENPIGAV QVPVGVAGPL RINGDYARGD FYIPLATTEG ALVASVNRGA
     KAITLSGGAR AKVIKDGMTR APLLWTPSVY EAHRLAMWVE DRIEDLRSVV AGVTRHGRLQ
     HIYPYIIGNL VWLRLSFSTG DAMGMNMVTI SSDRICRYIE ENYDGDAKCI ALSGNMCTDK
     KPAAINKILG RGKYVVAEAV IKGEVVKNVL KTTPQNINLV NVTKNLLGSA AAGSHSFNAH
     FANIIAAIFI ATGQDAAQVV ESSMGYTWTE VRGEDLYISV TLPSLEVGTV GGGTRLPTQR
     ELLALLGVAG GGNPPGSNAL KLAEIIASAV LAGELNLLSA IAAGQLARAH ELLGRGGLKI
     S