LOVE_ASPTN
ID LOVE_ASPTN Reviewed; 503 AA.
AC Q0C8L8;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, 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}; ORFNames=ATEG_09966;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION, PATHWAY, AND PROBABLE FUNCTION.
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 [3]
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 [4]
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 [5]
RP IDENTIFICATION.
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 [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; CH476609; EAU29415.1; -; Genomic_DNA.
DR RefSeq; XP_001209268.1; XM_001209268.1.
DR AlphaFoldDB; Q0C8L8; -.
DR EnsemblFungi; EAU29415; EAU29415; ATEG_09966.
DR GeneID; 4319612; -.
DR VEuPathDB; FungiDB:ATEG_09966; -.
DR HOGENOM; CLU_639350_0_0_1; -.
DR OMA; TNSARCE; -.
DR OrthoDB; 1097078at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
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; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..503
FT /note="Transcriptional regulator LovE"
FT /id="PRO_0000449661"
FT DNA_BIND 35..67
FT /note="Zn(2)-C6 fungal-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 331..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 503 AA; 55410 MW; 1919FBB1441121D4 CRC64;
MAADQGTFTT SVTLSPVEGS RTGGILPRRA FRRSCDRCHA QKIKCTGNKE VTARAPCQRC
QQAGLRCVYS ERCPKRKLRP SRAADLVSAD PDPCLHMSSP PVPSQSLPLD VSESHSSNTS
RQFLDPPDSY DWSWTSIGTD EAIDTDCWGL SQCDGGFSCQ LEPTLPDLPS PFESTVEKAP
LPPVSSDIAR AASAQRELFD DLSAVSQELE AILLAVTVEW PKQEIWTRAS PHSPTAFPER
ITQRRHNMWA NWLTDLHVFS LDPIGMFFNA SRRLLTVLRQ QAHADCHQGT LDECLRTKNL
FTAVHCYILN VRILTSISEL LLSQIRRTQN SHMNPWEGSR SESPSRDDTS STSGHSSVDT
IPDFSEDLPI GELFSYVDPL THALFSACTT LHVGVQLLRE NEITLGVHSA QGIAASISMS
GGPGEDIART GATNSARCEE QPTTPAARVL FMFLSDEGAS QEVKSAGSRG RTIAALRRCY
EDIFSLARKH KYGMLRDLNN IPP
