MOKG_MONPI
ID MOKG_MONPI Reviewed; 1052 AA.
AC Q3S2U3;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 25-MAY-2022, entry version 76.
DE RecName: Full=3-hydroxy-3-methylglutaryl coenzyme A reductase mokG {ECO:0000305};
DE Short=HMG-CoA reductase {ECO:0000303|PubMed:18578535};
DE EC=1.1.1.34;
DE AltName: Full=Monacolin K biosynthesis protein G {ECO:0000303|PubMed:18578535};
GN Name=mokG {ECO:0000303|PubMed:18578535};
OS Monascus pilosus (Red mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Monascus.
OX NCBI_TaxID=89488 {ECO:0000312|EMBL:ABA02245.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=18578535; DOI=10.1021/jf800595k;
RA Chen Y.P., Tseng C.P., Liaw L.L., Wang C.L., Chen I.C., Wu W.J., Wu M.D.,
RA Yuan G.F.;
RT "Cloning and characterization of monacolin K biosynthetic gene cluster from
RT Monascus pilosus.";
RL J. Agric. Food Chem. 56:5639-5646(2008).
RN [2]
RP FUNCTION.
RX PubMed=19693441; DOI=10.1007/s10529-009-0093-3;
RA Sakai K., Kinoshita H., Nihira T.;
RT "Identification of mokB involved in monacolin K biosynthesis in Monascus
RT pilosus.";
RL Biotechnol. Lett. 31:1911-1916(2009).
RN [3]
RP INDUCTION.
RX PubMed=19968298; DOI=10.1021/jf903139x;
RA Chen Y.-P., Yuan G.-F., Hsieh S.-Y., Lin Y.-S., Wang W.-Y., Liaw L.-L.,
RA Tseng C.-P.;
RT "Identification of the mokH gene encoding transcription factor for the
RT upregulation of monacolin K biosynthesis in Monascus pilosus.";
RL J. Agric. Food Chem. 58:287-293(2010).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=21821946; DOI=10.1271/bbb.110195;
RA Hong S.Y., Oh J.H., Lee I.;
RT "Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in
RT red ginseng by fermentation with Monascus pilosus.";
RL Biosci. Biotechnol. Biochem. 75:1490-1495(2011).
CC -!- FUNCTION: HMG-CoA reductase; part of the gene cluster that mediates the
CC biosynthesis of monakolin K, also known as lovastatin, and which acts
CC as a potent competitive inhibitor of HMG-CoA reductase
CC (PubMed:18578535). Monakolin K biosynthesis is performed in two stages
CC (PubMed:19693441). The first stage is catalyzed by the nonaketide
CC synthase mokA, which belongs to type I polyketide synthases and
CC catalyzes the iterative nine-step formation of the polyketide
CC (PubMed:18578535, PubMed:19693441). This PKS stage is completed by the
CC action of dehydrogenase mokE, which catalyzes the NADPH-dependent
CC reduction of the unsaturated tetra-, penta- and heptaketide
CC intermediates that arise during the mokA-mediated biosynthesis of the
CC nonaketide chain and leads to dihydromonacolin L (PubMed:19693441).
CC Covalently bound dihydromonacolin L is released from mokA by the mokD
CC esterase (By similarity). Conversion of dihydromonacolin L into
CC monacolin L and then monacolin J is subsequently performed with the
CC participation of molecular oxygen and P450 monoogygenase mokC
CC (PubMed:19693441). Finally, mokF performs the conversion of monacoline
CC J to monacoline K through the addition of the side-chain diketide
CC moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB
CC (PubMed:19693441). HMG-CoA reductase mokG may act as a down-regulator
CC of monacolin K production (PubMed:18578535).
CC {ECO:0000250|UniProtKB:Q0C8M2, ECO:0000303|PubMed:18578535,
CC ECO:0000303|PubMed:19693441}.
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: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000303|PubMed:18578535}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Expression is controlled by the monacolin K cluster
CC transcription regulator mokH (PubMed:19968298).
CC {ECO:0000269|PubMed:19968298}.
CC -!- BIOTECHNOLOGY: Monacoline K acts as an inhibitor of HMG-CoA reductase
CC involved in cholesterogenesis (PubMed:21821946). Its
CC hypocholesterolemic activity might be useful for lowering cholesterol
CC levels in the blood and reduce artherosclerosis and coronary heart
CC disease (PubMed:21821946). {ECO:0000269|PubMed:21821946}.
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; DQ176595; ABA02245.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U3; -.
DR SMR; Q3S2U3; -.
DR UniPathway; UPA00875; -.
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:InterPro.
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; IPR025583; HMG-CoA_N_dom.
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 InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF13323; HPIH; 1.
DR Pfam; PF12349; Sterol-sensing; 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.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Membrane; NADP; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1052
FT /note="3-hydroxy-3-methylglutaryl coenzyme A reductase
FT mokG"
FT /id="PRO_0000436289"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 224..403
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 461..617
FT /note="Linker"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT REGION 571..594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..1044
FT /note="Catalytic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT COMPBIAS 574..591
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 734
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 867
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 943
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1039
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 798
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1043
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1052 AA; 112803 MW; 6BC49D73EC37A298 CRC64;
MASAAVTPKL GWVQHQVTNG LHAVVGQVCR HPIHTLLVTA LIAATTYLHV LEGTFRAANL
GPGSKTDAAP FDVQSFLWGS RSLRLGETSS WRWQVGDLSE ATGDGQVNHH WALVTLSFPG
ASVDDRSPAF LWNALPDSVG AEPITPTSNF FTSISNEFSL AFRVPYTQLS DFLEAVEFVA
SDKEDRSWAI RFPHGEGKPI SLGRWLGNSW LSFLHRAKHA ETVDMAIIGL GYLALNMTLV
SLFRAMRQLG SRFWLAASVL LSGAFAFVFG LGVTTACGVP VDMLLLSEGI PFLVLTVGFE
KPIRFTRAVL YASNQLRRGL QQRDVADKHD SRQRHMIPNA MLFAINREGW SIVQSYLLEI
GALALGAVFR PRERFGQFCF LAAWMVLFDA ILLFTFYATI LCVKLEVTRM QNPGTLDLAD
DQHGPRIFGY KVNPTSLARW KLIMVGGFVL FNVLQLSSFF YRIMGGFMTN AALTPTTVSP
FKVAANGLND IYLAARAGGV ETWVTVLPPI RYVMEASGLE MSAGRRPVFD GVLAGLESPL
GRLCLMGALV FSLYLNNHLI PAARWHFSPG APKESAAPAP PSSPASVPSA VPVPAPSSRS
FEEIEALFKA NQAESLTDDE LAELCLRGKI AGYSLEKTLE SIASAGSSST ATTRLEAFTR
AVRIRRAAVS RTPSTRDLSG GIQESLLPYR NYNYELVHGA CCENVIGYLP LPLGLAGPMV
IDGQAYFIPM ATTEGVLVAS ASRGCKAINT GGGAVTMLKG DGMTRGPCLG FPSAKRAAEA
QRWVESPVGH QVLTDAFNAT SRFARLQTLT VAQAGTYLYI RFRTTTGDAM GMNMISKGVE
KALQAMTAHG FPDMNTITLS GNFCADKKSA AINWIGGRGK SVIAEATIPA DTVRKVLKTD
IDALVELNTA KNLVGSAMAG SMGGFNAHAS NLVQAVFLAT GQDPAQNVES SSCITTMKKI
DGNLHIAVSM PSMEVGTIGG GTILEAQGAM LDLLGVRGAH PTDPGANARR LARIVAAAVL
AGELSTCSAL AAGHLVNAHM RHNRSAASSE KK
