ID   HMDH_CAMAC              Reviewed;         593 AA.
AC   P48021;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   25-MAY-2022, entry version 109.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34;
OS   Camptotheca acuminata (Happy tree).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; Cornales; Nyssaceae; Camptotheca.
OX   NCBI_TaxID=16922;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8208857; DOI=10.1104/pp.103.1.41;
RA   Burnett R.J., Maldonado-Mendoza I.E., McKnight T.D., Nessler C.L.;
RT   "Expression of a 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from
RT   Camptotheca acuminata is differentially regulated by wounding and methyl
RT   jasmonate.";
RL   Plant Physiol. 103:41-48(1993).
CC   -!- FUNCTION: Catalyzes the synthesis of mevalonate. The specific precursor
CC       of all isoprenoid compounds present in plants.
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         Evidence={ECO:0000255|PROSITE-ProRule:PRU10003};
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC       membrane protein.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR   EMBL; L10390; AAA33040.1; -; Genomic_DNA.
DR   AlphaFoldDB; P48021; -.
DR   SMR; P48021; -.
DR   UniPathway; UPA00058; UER00103.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; PS01192; HMG_COA_REDUCTASE_3; 1.
DR   PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
PE   3: Inferred from homology;
KW   Endoplasmic reticulum; Glycoprotein; Isoprene biosynthesis; Membrane; NADP;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..593
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114435"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        94..114
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..36
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          115..177
FT                   /note="Linker"
FT                   /evidence="ECO:0000250"
FT   REGION          178..593
FT                   /note="Catalytic"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        272
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        404
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        480
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        578
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        449
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        582
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   593 AA;  63278 MW;  F22CB55B2E4944A7 CRC64;
     MDVRRRSINS IHQIPSVGGT APPMLKPKQP TKVDAVDLPD SPKASDALPL PLYITNGVFF
     TLFFTVVYYL LVRWREKIRN STPLHVVTLS EIAAIFTFVA SFIYLLGFFG IGLVQPFTSR
     SSHDDVWGVD DDEDVDEIVL KEDTRTVPCA AAPVDCPLPP IKPKVVDPVP ISPPSSEEDE
     EIIKSVVEGT TPSYALESKL GDSHRAAAIR REALQRMTKK SLAGLPLDGF DYDSILGQCC
     EMPVGYVQIP VGIAGPLLLD GREYSVPMAT TEGCLVASTN RGCKAIFACG GATSVLLRDA
     MTRAPVVRFG SAKRAADLKF FLENPLNFET LAAVFNSSSR FGKLQNIKCA IAGKNLYMRY
     SCSTGDAMGM NMISKGVQNV LDFLQDDFPD MDVIGISGNY CSDKKPAAVN WIEGRGKSVV
     CEAVIKEEVV KKVLKTNVAS LVELNMLKNL TGSAMAGALG GFNAHASNIV SAVYLATGQD
     PAQNVESSHC ITMMEAINDG KDLHVSVTMP SIEVGTVGGG TQLASQSACL NLLGVKGASK
     EAPGSNARLL ATIVAGSVLA GELSLMSAIA AGQLVNSHMK YNRSNKDVTK ASS