ID   MLCR_PENCI              Reviewed;         459 AA.
AC   Q8J0F2;
DT   11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   25-MAY-2022, entry version 64.
DE   RecName: Full=Transcription factor mlcR {ECO:0000303|PubMed:12172803};
DE   AltName: Full=Compactin biosynthesis protein R {ECO:0000303|PubMed:12172803};
GN   Name=mlcR {ECO:0000303|PubMed:12172803};
OS   Penicillium citrinum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5077;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RX   PubMed=12172803; DOI=10.1007/s00438-002-0697-y;
RA   Abe Y., Suzuki T., Ono C., Iwamoto K., Hosobuchi M., Yoshikawa H.;
RT   "Molecular cloning and characterization of an ML-236B (compactin)
RT   biosynthetic gene cluster in Penicillium citrinum.";
RL   Mol. Genet. Genomics 267:636-646(2002).
RN   [2]
RP   FUNCTION.
RX   PubMed=12242508; DOI=10.1007/s00438-002-0736-8;
RA   Abe Y., Suzuki T., Mizuno T., Ono C., Iwamoto K., Hosobuchi M.,
RA   Yoshikawa H.;
RT   "Effect of increased dosage of the ML-236B (compactin) biosynthetic gene
RT   cluster on ML-236B production in Penicillium citrinum.";
RL   Mol. Genet. Genomics 268:130-137(2002).
RN   [3]
RP   BIOTECHNOLOGY.
RX   PubMed=1010803; DOI=10.7164/antibiotics.29.1346;
RA   Endo A., Kuroda M., Tsujita Y.;
RT   "ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis
RT   produced by Penicillium citrinium.";
RL   J. Antibiot. 29:1346-1348(1976).
RN   [4]
RP   FUNCTION.
RX   PubMed=12436257; DOI=10.1007/s00438-002-0755-5;
RA   Abe Y., Ono C., Hosobuchi M., Yoshikawa H.;
RT   "Functional analysis of mlcR, a regulatory gene for ML-236B (compactin)
RT   biosynthesis in Penicillium citrinum.";
RL   Mol. Genet. Genomics 268:352-361(2002).
RN   [5]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=18667169; DOI=10.1016/j.fgb.2008.07.002;
RA   Baba S., Nihira T., Hosobuchi M.;
RT   "Identification of the specific sequence recognized by Penicillium citrinum
RT   MlcR, a GAL4-type transcriptional activator of ML-236B (compactin)
RT   biosynthetic genes.";
RL   Fungal Genet. Biol. 45:1277-1283(2008).
RN   [6]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=19266218; DOI=10.1007/s00438-009-0435-9;
RA   Baba S., Kinoshita H., Hosobuchi M., Nihira T.;
RT   "MlcR, a zinc cluster activator protein, is able to bind to a single
RT   (A/T)CGG site of cognate asymmetric motifs in the ML-236B (compactin)
RT   biosynthetic gene cluster.";
RL   Mol. Genet. Genomics 281:627-634(2009).
CC   -!- FUNCTION: Transcription factor that regulates the gene cluster that
CC       mediates the biosynthesis of compactin, also known as mevastatin or ML-
CC       236B, and which acts as a potent competitive inhibitor of HMG-CoA
CC       reductase (PubMed:12172803, PubMed:12242508, PubMed:12436257). Binds to
CC       the consensus-binding motif 5'-WCGG-N(6)-TCGG-3' of target genes
CC       (PubMed:18667169). {ECO:0000269|PubMed:12436257,
CC       ECO:0000269|PubMed:18667169, ECO:0000303|PubMed:12172803,
CC       ECO:0000303|PubMed:12242508}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00227}.
CC   -!- BIOTECHNOLOGY: Compactin (also known as mevastatin or ML-236B) and the
CC       intermediary metabolites Ml-236C and ML-236A are inhibitors of HMG-CoA
CC       reductase involved in cholesterogenesis (PubMed:1010803). Their
CC       hypocholesterolemic activity might be useful for lowering cholesterol
CC       levels in the blood and reduce artherosclerosis and coronary heart
CC       disease (PubMed:1010803). {ECO:0000269|PubMed:1010803}.
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; AB072893; BAC20569.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q8J0F2; -.
DR   SMR; Q8J0F2; -.
DR   PRIDE; Q8J0F2; -.
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..459
FT                   /note="Transcription factor mlcR"
FT                   /id="PRO_0000436292"
FT   DNA_BIND        21..53
FT                   /note="Zn(2)-C6 fungal-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT   REGION          64..84
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          135..170
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   459 AA;  50357 MW;  4D2D1B3307EF46C1 CRC64;
     MSLPHATIPT NLRRRAFRRS CDRCHAQKLK CTGSNANLVR AQCQRCQQAG LRCVYSERLP
     KRNLHKEAAA GTTRATETSQ PMTATSSTVF SSLAETPPPY CSPPTHIGTS ALKETLSEPS
     AATLQFYDTS INFDDPESFP GGWPQPNTFR DDANSNESSG IPDLGYDFEG PLDATAPVSP
     SLFDLEVEGN SSSGQSNTSN TQRDLFESLS DVSQDLEVIL HGVTVEWPKQ KILSYPIGDF
     LNAFGRLLLH LQERVITSSN SSMLDGCLQT KNLFMAVHCY MLSVKIMTSL SQLLLSEVMK
     AQPCGQKQST RMDWYWSGST TRNDNGRAEA LPSFHSNLHI GELISHLDPF MHALSSACTT
     LRVSLRLLSE IETALGIAQE HGAAASIRLV LSDMPSTSWQ ILGAENKTIT PASRLLSVLW
     SDEAGDEEPK STKASGKTIN VLRRCYKEIF ALAKKHNIA