TERD_ASPTN
ID TERD_ASPTN Reviewed; 614 AA.
AC Q0D1P2;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=FAD-dependent monooxygenase terD {ECO:0000305|PubMed:24816227};
DE EC=1.-.-.- {ECO:0000305|PubMed:24816227};
DE AltName: Full=Terrein biosynthesis cluster protein terD {ECO:0000303|PubMed:24816227};
DE Flags: Precursor;
GN Name=terD {ECO:0000303|PubMed:24816227}; ORFNames=ATEG_00142;
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 BIOTECHNOLOGY.
RX PubMed=15558216; DOI=10.1007/s00018-004-4341-3;
RA Park S.H., Kim D.S., Kim W.G., Ryoo I.J., Lee D.H., Huh C.H., Youn S.W.,
RA Yoo I.D., Park K.C.;
RT "Terrein: a new melanogenesis inhibitor and its mechanism.";
RL Cell. Mol. Life Sci. 61:2878-2885(2004).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=15603975; DOI=10.1016/j.bmcl.2004.10.057;
RA Lee S., Kim W.G., Kim E., Ryoo I.J., Lee H.K., Kim J.N., Jung S.H.,
RA Yoo I.D.;
RT "Synthesis and melanin biosynthesis inhibitory activity of (+/-)-terrein
RT produced by Penicillium sp. 20135.";
RL Bioorg. Med. Chem. Lett. 15:471-473(2005).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=18776656; DOI=10.1038/ja.2008.60;
RA Arakawa M., Someno T., Kawada M., Ikeda D.;
RT "A new terrein glucoside, a novel inhibitor of angiogenin secretion in
RT tumor angiogenesis.";
RL J. Antibiot. 61:442-448(2008).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=18358890; DOI=10.1016/j.joen.2008.01.015;
RA Lee J.C., Yu M.K., Lee R., Lee Y.H., Jeon J.G., Lee M.H., Jhee E.C.,
RA Yoo I.D., Yi H.K.;
RT "Terrein reduces pulpal inflammation in human dental pulp cells.";
RL J. Endod. 34:433-437(2008).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=19493001; DOI=10.1111/j.1600-0625.2009.00847.x;
RA Park S.H., Kim D.S., Lee H.K., Kwon S.B., Lee S., Ryoo I.J., Kim W.G.,
RA Yoo I.D., Park K.C.;
RT "Long-term suppression of tyrosinase by terrein via tyrosinase degradation
RT and its decreased expression.";
RL Exp. Dermatol. 18:562-566(2009).
RN [7]
RP BIOTECHNOLOGY.
RX PubMed=21104936; DOI=10.1002/cbf.1708;
RA Lee Y.H., Lee N.H., Bhattarai G., Oh Y.T., Yu M.K., Yoo I.D., Jhee E.C.,
RA Yi H.K.;
RT "Enhancement of osteoblast biocompatibility on titanium surface with
RT Terrein treatment.";
RL Cell Biochem. Funct. 28:678-685(2010).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=23417151; DOI=10.3892/or.2013.2288;
RA Porameesanaporn Y., Uthaisang-Tanechpongtamb W., Jarintanan F.,
RA Jongrungruangchok S., Thanomsub Wongsatayanon B.;
RT "Terrein induces apoptosis in HeLa human cervical carcinoma cells through
RT p53 and ERK regulation.";
RL Oncol. Rep. 29:1600-1608(2013).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24816227; DOI=10.1016/j.chembiol.2014.03.010;
RA Zaehle C., Gressler M., Shelest E., Geib E., Hertweck C., Brock M.;
RT "Terrein biosynthesis in Aspergillus terreus and its impact on
RT phytotoxicity.";
RL Chem. Biol. 21:719-731(2014).
RN [10]
RP BIOTECHNOLOGY.
RX PubMed=25318762; DOI=10.3892/ijmm.2014.1964;
RA Chen Y.F., Wang S.Y., Shen H., Yao X.F., Zhang F.L., Lai D.;
RT "The marine-derived fungal metabolite, terrein, inhibits cell proliferation
RT and induces cell cycle arrest in human ovarian cancer cells.";
RL Int. J. Mol. Med. 34:1591-1598(2014).
RN [11]
RP BIOTECHNOLOGY.
RX PubMed=26416516; DOI=10.1002/cbf.3145;
RA Lee Y.H., Lee S.J., Jung J.E., Kim J.S., Lee N.H., Yi H.K.;
RT "Terrein reduces age-related inflammation induced by oxidative stress
RT through Nrf2/ERK1/2/HO-1 signalling in aged HDF cells.";
RL Cell Biochem. Funct. 33:479-486(2015).
RN [12]
RP INDUCTION.
RX PubMed=25852654; DOI=10.3389/fmicb.2015.00184;
RA Gressler M., Hortschansky P., Geib E., Brock M.;
RT "A new high-performance heterologous fungal expression system based on
RT regulatory elements from the Aspergillus terreus terrein gene cluster.";
RL Front. Microbiol. 6:184-184(2015).
RN [13]
RP BIOTECHNOLOGY.
RX PubMed=25592371; DOI=10.3892/or.2015.3719;
RA Zhang F., Mijiti M., Ding W., Song J., Yin Y., Sun W., Li Z.;
RT "(+)-Terrein inhibits human hepatoma Bel-7402 proliferation through cell
RT cycle arrest.";
RL Oncol. Rep. 33:1191-1200(2015).
RN [14]
RP BIOTECHNOLOGY.
RX PubMed=27127118;
RA Shibata A., Ibaragi S., Mandai H., Tsumura T., Kishimoto K., Okui T.,
RA Hassan N.M., Shimo T., Omori K., Hu G.F., Takashiba S., Suga S., Sasaki A.;
RT "Synthetic terrein inhibits progression of head and neck cancer by
RT suppressing angiogenin production.";
RL Anticancer Res. 36:2161-2168(2016).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of terrein, a fungal metabolite with
CC ecological, antimicrobial, antiproliferative, and antioxidative
CC activities (PubMed:24816227). The first step in the pathway is
CC performed by the polyketide synthase terA that produces 4-hydroxy-6-
CC methylpyranon (4-HMP), orsellinic acid (OA), and 2,3-dehydro-6-
CC hydroxymellein (2,3-dehydro-6-HM) by condensing acetyl-CoA with two,
CC three, or four malonyl-CoA units, respectively (PubMed:24816227). 4-HMP
CC and OA are not pathway intermediates, but are rather shunt or side
CC products (PubMed:24816227). 2,3-dehydro-6-HM is further converted to 6-
CC hydroxymellein (6-HM) by the 6-hydroxymellein synthase terB
CC (PubMed:24816227). The monooxygenases terC and terD, the multicopper
CC oxidase terE and the Kelch-like protein terF are then involved in the
CC transformation of 6-HM to terrein (PubMed:24816227). Even if they are
CC co-regulated with the other terrein cluster genes, terH and terI seem
CC to be dispensable for terrein production; whereas one or both of the 2
CC transporters terG and terJ are probably required for efficient
CC secretion of metabolites (PubMed:24816227).
CC {ECO:0000269|PubMed:24816227}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24816227}.
CC -!- INDUCTION: Expression is under the control of the terrein cluster-
CC specific transcription factor terR (PubMed:25852654).
CC {ECO:0000269|PubMed:25852654}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of terrein
CC (PubMed:24816227). {ECO:0000269|PubMed:24816227}.
CC -!- BIOTECHNOLOGY: Terrein shows anticancer activity on various tumors
CC including cervical carcinoma, ovarian cancer, and head and neck cancer
CC (PubMed:23417151, PubMed:25318762, PubMed:27127118, PubMed:25592371).
CC The secondary metabolite acts as angiogenesis inhibitors through the
CC inhibition of angiogenin secretion (PubMed:18776656, PubMed:27127118).
CC Terrein has also anti-inflammatory activity (PubMed:18358890). It shows
CC an alleviative function of age-related inflammation characterized as an
CC anti-oxidant and might therefore be a useful nutraceutical compound for
CC anti-aging (PubMed:26416516). Terrein may enhance osseointegration by
CC decreasing the level of ROS and has a potentially synergistic effect on
CC osteoblast differentiation (PubMed:21104936). Terrein has also been
CC shown to act as a melanogenesis inhibitor (PubMed:15558216,
CC PubMed:15603975, PubMed:19493001). {ECO:0000269|PubMed:15558216,
CC ECO:0000269|PubMed:15603975, ECO:0000269|PubMed:18358890,
CC ECO:0000269|PubMed:18776656, ECO:0000269|PubMed:19493001,
CC ECO:0000269|PubMed:21104936, ECO:0000269|PubMed:23417151,
CC ECO:0000269|PubMed:25318762, ECO:0000269|PubMed:25592371,
CC ECO:0000269|PubMed:26416516, ECO:0000269|PubMed:27127118}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CH476594; EAU38788.1; -; Genomic_DNA.
DR RefSeq; XP_001210228.1; XM_001210228.1.
DR AlphaFoldDB; Q0D1P2; -.
DR SMR; Q0D1P2; -.
DR STRING; 33178.CADATEAP00005732; -.
DR EnsemblFungi; EAU38788; EAU38788; ATEG_00142.
DR GeneID; 4354899; -.
DR VEuPathDB; FungiDB:ATEG_00142; -.
DR eggNOG; KOG3855; Eukaryota.
DR HOGENOM; CLU_009665_9_2_1; -.
DR OMA; DFICAAD; -.
DR OrthoDB; 366744at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.40.30.20; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012941; Phe_hydrox_C_dim_dom.
DR InterPro; IPR038220; PHOX_C_sf.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR Pfam; PF07976; Phe_hydrox_dim; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..614
FT /note="FAD-dependent monooxygenase terD"
FT /evidence="ECO:0000255"
FT /id="PRO_0000437616"
FT BINDING 6..35
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 137
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 239..241
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 282
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 303
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 614 AA; 67859 MW; D4FEEF87E069F651 CRC64;
MSSKFDVVIC GSGTAGLAAA TWLAQYGVDC KILESRSGPL DVGQADGIQV RSVEIFESFG
MAEELLREAY HNIEVAFWGS NPTSSGMGIV RKRSAHATTP GLSHMPRVIL NQARFNEMWL
EAMRRRNGQE VDYGHKVTKV TVDEEKATDP DAYPVTIVAQ KDGQEQVFEA KYCLASDGAH
SAVRKSLGFN MVGETSDSVW GVMDVFPRTN FPDIRKQCII QSDAGSIITI PREGGSMVRV
YVELAAGTNA KEVTLEQIQN ASRQVFHPYA LDVADVWWWS AYPIGQRIAD HFSKANRVFL
TGDACHTHSP KAGQGMNVSL QDGYNIGWKL ASVLKGHAGP ELLETYVLER QKVADVLINW
DKVWAKQMCS IAKEDGGVVD ANGKIDFSEV FVKAEAFTAG LTVTYGDSII TQAGDSNQQA
ATNLKVGMRL PAAQVVRFCD AKVMKTVNAL PSDGRWRIMI FPGDIRQPSA STRLAQLGTY
LFSNHGPIRK YLPPGADIDS LIEVIVILSG ERLEIQQDQI PDAFWPTTGK YRMRDLHKIY
IDDETYHNGH GHAYDFYGID PERGAVAIVR PDQYISKVLD MKNHEGISAF FEKFLQKKGQ
ANGSLNSHDE WTLA
