ID   HMDH_PYRHO              Reviewed;         413 AA.
AC   O59469;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   25-MAY-2022, entry version 127.
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=PH1805;
OS   Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS   100139 / OT-3).
OC   Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC   Pyrococcus.
OX   NCBI_TaxID=70601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX   PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA   Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA   Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA   Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA   Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA   Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT   "Complete sequence and gene organization of the genome of a hyper-
RT   thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL   DNA Res. 5:55-76(1998).
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   -!- SEQUENCE CAUTION:
CC       Sequence=BAA30924.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; BA000001; BAA30924.1; ALT_INIT; Genomic_DNA.
DR   PIR; E71191; E71191.
DR   AlphaFoldDB; O59469; -.
DR   SMR; O59469; -.
DR   STRING; 70601.3258241; -.
DR   EnsemblBacteria; BAA30924; BAA30924; BAA30924.
DR   KEGG; pho:PH1805; -.
DR   eggNOG; arCOG04260; Archaea.
DR   OMA; DDKMTRA; -.
DR   UniPathway; UPA00058; UER00103.
DR   Proteomes; UP000000752; 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.
FT   CHAIN           1..413
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114464"
FT   ACT_SITE        106
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        312
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        408
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   413 AA;  44554 MW;  3FF84B70DA984B84 CRC64;
     MGGGNLNIEE IIEKVANGEI KFYQVEKYVN GDKRLATEIR RKALEKRLGI KLHHIGYYSI
     DPNELIGRNI ENMIGVVQIP MGVAGPLKIN GEYAKGEFYI PLATTEGALV ASVNRGCSAL
     TEAGGVVTTL IDDKMTRAPL IRCPNARRAR EVAKWVEENL DYLQEKAVSK VTRHGKLRGV
     KPFIVGNNLY LRFEFETGDA MGMNMVTIAS EEIMKVIEEE FPDVRYLALS GNLCVDKKPN
     AVNFILGRGK TVIAEAVVPR KIVEKKLKTT PELIAEVNYF KNLVGSAQAG SYGFNAHFAN
     IVGAIFLATG QDEAQITEGA HGITIAEVTP DGDLYISITM PSLEIGTVGG GTRVPSQREA
     LEIMGVAGGG DPPGINAKKF AEIVAGAVLA GELSLLAAIA AKHLARAHKM LGR