ID   HMDH_CATRO              Reviewed;         601 AA.
AC   Q03163;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   25-MAY-2022, entry version 117.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34;
GN   Name=HMGR;
OS   Catharanthus roseus (Madagascar periwinkle) (Vinca rosea).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Gentianales; Apocynaceae; Rauvolfioideae; Vinceae;
OC   Catharanthinae; Catharanthus.
OX   NCBI_TaxID=4058;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=cv. Little Delicata; TISSUE=Seedling;
RX   PubMed=16653173; DOI=10.1104/pp.100.3.1613;
RA   Maldenado-Mendoza I.E., Burnett R.J., Nessler C.L.;
RT   "Nucleotide sequence of a cDNA encoding 3-hydroxy-3-methylglutaryl-CoA
RT   reductase from Catharanthus roseus.";
RL   Plant Physiol. 100:1613-1614(1992).
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; M96068; AAA33108.1; -; mRNA.
DR   PIR; T09967; T09967.
DR   AlphaFoldDB; Q03163; -.
DR   SMR; Q03163; -.
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   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Glycoprotein; Isoprene biosynthesis; Membrane; NADP;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..601
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114437"
FT   TRANSMEM        36..58
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..106
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          107..179
FT                   /note="Linker"
FT                   /evidence="ECO:0000250"
FT   REGION          180..601
FT                   /note="Catalytic"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        273
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        405
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        481
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        579
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        583
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   601 AA;  64107 MW;  D49D00D4F5DB9113 CRC64;
     MDSRRRSPTV TAKAAAGELP LAPHEGQNQQ PSIPRSSDVL PLPLYLANGV FFTLFFSVMY
     FLLTRWREKI RNATPLHVVT LSELAALASL IASVIYLVSF FGLDFVQSLI YKPNNEGWEI
     EEEILMVEDS RNGTNCTTLG CAVPPPSVPK IAPVVPQQPS KMVIIEKPAP LITPQNSEED
     EDIIKAVVAG KIPSYSLESK LGDCKRAAGI RREALQRITG KSLEGLPLEG FDYASILGQC
     CEMPVGYVQL PVGIAGPLLL DGREYMLPMA TTEGCLVAST NRGCKAILAS GGANSVLLRD
     GMTRAPVVRF GTAKRAAELK FYMEDTQNFE TISVVFNKSS RFAKLQSVQC AIAGKNLYIR
     FSCSTGDAMG MNMVSKGVQN VLEFLQTDYP DMDVLGISGN FCADKKPAAV NWIEGRGKSV
     VCEAIIKEEI VKTVLKTEVA ALIELNMVKN LAGSAIAGAL GGFNAHASNI VSAIFIATGQ
     DPAQNVESSQ CITMMEAVND GKDLHISVTM PSIEVGTVGG GTQLASQSAC LNLLGVKGAS
     KDSPGANSRL LATIVAGSVL AGELSLMSAI SAGQLVRSHM KYNRSSKDIT NIASSQLESD
     S