MOKH_MONPI
ID MOKH_MONPI Reviewed; 455 AA.
AC Q3S2U4;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 25-MAY-2022, entry version 60.
DE RecName: Full=Transcription factor mokH {ECO:0000303|PubMed:18578535};
DE AltName: Full=Monacolin K biosynthesis protein H {ECO:0000303|PubMed:18578535};
GN Name=mokH {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:ABA02246.1};
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 FUNCTION.
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: Transcription factor that regulates the gene cluster that
CC mediates the biosynthesis of monakolin K, also known as lovastatin, and
CC which acts as a potent competitive inhibitor of HMG-CoA reductase
CC (PubMed:18578535, PubMed:19693441, PubMed:19968298). Monakolin K
CC biosynthesis is performed in two stages (PubMed:19693441). The first
CC stage is catalyzed by the nonaketide synthase mokA, which belongs to
CC type I polyketide synthases and catalyzes the iterative nine-step
CC formation of the polyketide (PubMed:18578535, PubMed:19693441). This
CC PKS stage is completed by the action of dehydrogenase mokE, which
CC catalyzes the NADPH-dependent reduction of the unsaturated tetra-,
CC penta- and heptaketide intermediates that arise during the mokA-
CC mediated biosynthesis of the nonaketide chain and leads to
CC dihydromonacolin L (PubMed:19693441). Covalently bound dihydromonacolin
CC L is released from mokA by the mokD esterase (By similarity).
CC Conversion of dihydromonacolin L into monacolin L and then monacolin J
CC is subsequently performed with the participation of molecular oxygen
CC and P450 monoogygenase mokC (PubMed:19693441). Finally, mokF performs
CC the conversion of monacoline J to monacoline K through the addition of
CC the side-chain diketide moiety (2R)-2-methylbutanoate produced by the
CC diketide synthase mokB (PubMed:19693441). HMG-CoA reductase mokG may
CC act as a down-regulator of monacolin K production (PubMed:18578535).
CC {ECO:0000250|UniProtKB:Q0C8M2, ECO:0000269|PubMed:19968298,
CC ECO:0000303|PubMed:18578535}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00227}.
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}.
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DR EMBL; DQ176595; ABA02246.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U4; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR CDD; cd00067; GAL4; 1.
DR Gene3D; 4.10.240.10; -; 1.
DR InterPro; IPR001138; Zn2-C6_fun-type_DNA-bd.
DR InterPro; IPR036864; Zn2-C6_fun-type_DNA-bd_sf.
DR Pfam; PF00172; Zn_clus; 1.
DR SMART; SM00066; GAL4; 1.
DR SUPFAM; SSF57701; SSF57701; 1.
DR PROSITE; PS00463; ZN2_CY6_FUNGAL_1; 1.
DR PROSITE; PS50048; ZN2_CY6_FUNGAL_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Metal-binding; Nucleus; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..455
FT /note="Transcription factor mokH"
FT /id="PRO_0000436291"
FT DNA_BIND 26..58
FT /note="Zn(2)-C6 fungal-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 296..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..97
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 455 AA; 49306 MW; 5B0328BF4EFB41F0 CRC64;
MALSPVQDPP SHTDKTMPRR AFRRSCDRCH AQKIKCIGSE GAVARASCQR CQQAGLRCVY
SERCPKRKLP KPNPAESSPA SSTAGLHTSS SDSSPPVPSD GLPLDLPGPD SSGVSLQFLD
PSADCDWPWS SIGVDETVVN NCLDLSHGHG HGDLSCQLEL PMPDLPSPFE FSAEKSPSPS
VSGSIAGAVS AQRELFDGLS TVSQELEAIL LAVAVEWPKQ EIWTYPIGTF FNASRRLLVY
LQQQSNTRSD QGMLNECLRT KNLFMAVHCY MLIVKIFTSL SELLLSQIRH SQAGQLTPLE
GHQFEPPPSS SRDRSSVDTM PIFNPNLHIG GLFSYLNPFM HALSSACTTL RVGVQLLREN
ESALGIPPAQ GVAASVSMGK EEWADGEDVA SAVTTADEDL RQPASRILSM VWSDEVGDQK
AKSADAAGPR SRTLAVLRRC NREIFSLARQ HNLAS
