ID   LOVE_ASPTE              Reviewed;         503 AA.
AC   Q9Y7D3;
DT   01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   25-MAY-2022, entry version 69.
DE   RecName: Full=Transcriptional regulator LovE {ECO:0000303|PubMed:10334994};
DE   AltName: Full=Lovastatin biosynthesis cluster protein E {ECO:0000303|PubMed:10334994};
GN   Name=lovE {ECO:0000303|PubMed:10334994};
OS   Aspergillus terreus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=33178;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, PATHWAY, AND PROBABLE
RP   FUNCTION.
RC   STRAIN=ATCC 20542 / MF4845;
RX   PubMed=10334994; DOI=10.1126/science.284.5418.1368;
RA   Kennedy J., Auclair K., Kendrew S.G., Park C., Vederas J.C.,
RA   Hutchinson C.R.;
RT   "Modulation of polyketide synthase activity by accessory proteins during
RT   lovastatin biosynthesis.";
RL   Science 284:1368-1372(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND IDENTIFICATION.
RC   STRAIN=CCTCC AF93208;
RX   PubMed=19781329;
RA   Huang X., Li H.M.;
RT   "Cloning and bioinformatic analysis of lovastatin biosynthesis regulatory
RT   gene lovE.";
RL   Chin. Med. J. 122:1800-1805(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Sasirekhamani M., Ebenezer P., Devakumar K.M.;
RT   "Molecular characterization and bioinformatic analysis of lovastatin
RT   biosynthetic regulatory gene lovE in Aspergillus terreus PEMS 01.";
RL   Submitted (JUN-2014) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   BIOTECHNOLOGY.
RX   PubMed=6933445; DOI=10.1073/pnas.77.7.3957;
RA   Alberts A.W., Chen J., Kuron G., Hunt V., Huff J., Hoffman C., Rothrock J.,
RA   Lopez M., Joshua H., Harris E., Patchett A., Monaghan R., Currie S.,
RA   Stapley E., Albers-Schonberg G., Hensens O., Hirshfield J., Hoogsteen K.,
RA   Liesch J., Springer J.;
RT   "Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-
RT   coenzyme A reductase and a cholesterol-lowering agent.";
RL   Proc. Natl. Acad. Sci. U.S.A. 77:3957-3961(1980).
RN   [5]
RP   INDUCTION, AND PROBABLE FUNCTION.
RX   PubMed=18414850; DOI=10.1007/s00253-008-1409-2;
RA   Barrios-Gonzalez J., Banos J.G., Covarrubias A.A., Garay-Arroyo A.;
RT   "Lovastatin biosynthetic genes of Aspergillus terreus are expressed
RT   differentially in solid-state and in liquid submerged fermentation.";
RL   Appl. Microbiol. Biotechnol. 79:179-186(2008).
RN   [6]
RP   BIOTECHNOLOGY.
RX   PubMed=29236027; DOI=10.3390/ijms18122690;
RA   Chen M.C., Tsai Y.C., Tseng J.H., Liou J.J., Horng S., Wen H.C., Fan Y.C.,
RA   Zhong W.B., Hsu S.P.;
RT   "Simvastatin inhibits cell proliferation and migration in human anaplastic
RT   thyroid cancer.";
RL   Int. J. Mol. Sci. 18:0-0(2017).
RN   [7]
RP   BIOTECHNOLOGY.
RX   PubMed=29932104; DOI=10.3390/ijms19071834;
RA   Zhong W.B., Tsai Y.C., Chin L.H., Tseng J.H., Tang L.W., Horng S.,
RA   Fan Y.C., Hsu S.P.;
RT   "A synergistic anti-cancer effect of troglitazone and lovastatin in a human
RT   anaplastic thyroid cancer cell line and in a mouse xenograft model.";
RL   Int. J. Mol. Sci. 19:0-0(2018).
CC   -!- FUNCTION: Transcription factor that regulates the expression of the he
CC       gene cluster that mediates the biosynthesis of lovastatin (also known
CC       as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of
CC       (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR).
CC       {ECO:0000305|PubMed:18414850}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00227}.
CC   -!- INDUCTION: Highly expressed during the first day of culture on solid
CC       medium; thereafter levels decrease but remain high. Expressed at much
CC       lower levels in liquid culture. {ECO:0000269|PubMed:18414850}.
CC   -!- BIOTECHNOLOGY: Lovastatin acts as a hypolipidemic agent that works as
CC       inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase
CC       (HMGR) which reduces HMG-CoA to mevalonate and is the key step in
CC       cholesterol biosynthesis (PubMed:6933445). Lovastatin, simvastatin and
CC       related compounds are widely used to treat hypercholesteremia and
CC       reduce the risk of cardiovascular disease (PubMed:6933445).
CC       Furthermore, statins such as lovastatin were found to be anticancer
CC       agents (PubMed:29236027, PubMed:29932104).
CC       {ECO:0000269|PubMed:29236027, ECO:0000269|PubMed:29932104,
CC       ECO:0000269|PubMed:6933445}.
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DR   EMBL; AF141925; AAD34557.1; -; Genomic_DNA.
DR   EMBL; KJ201024; AIC76506.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9Y7D3; -.
DR   SMR; Q9Y7D3; -.
DR   VEuPathDB; FungiDB:ATEG_09966; -.
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..503
FT                   /note="Transcriptional regulator LovE"
FT                   /id="PRO_0000430275"
FT   DNA_BIND        35..67
FT                   /note="Zn(2)-C6 fungal-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT   REGION          89..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          331..358
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        99..124
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   503 AA;  55427 MW;  E07AA77AD1B92BD2 CRC64;
     MAADQGIFTN SVTLSPVEGS RTGGTLPRRA FRRSCDRCHA QKIKCTGNKE VTGRAPCQRC
     QQAGLRCVYS ERCPKRKLRQ SRAADLVSAD PDPCLHMSSP PVPSQSLPLD VSESHSSNTS
     RQFLDPPDSY DWSWTSIGTD EAIDTDCWGL SQCDGGFSCQ LEPTLPDLPS PFESTVEKAP
     LPPVSSDIAR AASAQRELFD DLSAVSQELE EILLAVTVEW PKQEIWTRAS PHSPTASRER
     IAQRRQNVWA NWLTDLHMFS LDPIGMFFNA SRRLLTVLRQ QAQADCHQGT LDECLRTKNL
     FTAVHCYILN VRILTAISEL LLSQIRRTQN SHMSPLEGSR SQSPSRDDTS SSSGHSSVDT
     IPFFSENLPI GELFSYVDPL THALFSACTT LHVGVQLLRE NEITLGVHSA QGIAASISMS
     GEPGEDIART GATNSARCEE QPTTPAARVL FMFLSDEGAF QEAKSAGSRG RTIAALRRCY
     EDIFSLARKH KHGMLRDLNN IPP