TERF_ASPTN
ID TERF_ASPTN Reviewed; 459 AA.
AC Q0D1P4;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 25-MAY-2022, entry version 60.
DE RecName: Full=Kelch-like protein terF {ECO:0000305|PubMed:24816227};
DE AltName: Full=Terrein biosynthesis cluster protein terF {ECO:0000303|PubMed:24816227};
GN Name=terF {ECO:0000303|PubMed:24816227}; ORFNames=ATEG_00140;
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: Kelch-like protein; part of the gene cluster that mediates
CC the biosynthesis of terrein, a fungal metabolite with ecological,
CC antimicrobial, antiproliferative, and antioxidative activities
CC (PubMed:24816227). The first step in the pathway is performed by the
CC polyketide synthase terA that produces 4-hydroxy-6-methylpyranon (4-
CC HMP), orsellinic acid (OA), and 2,3-dehydro-6-hydroxymellein (2,3-
CC dehydro-6-HM) by condensing acetyl-CoA with two, three, or four
CC malonyl-CoA units, respectively (PubMed:24816227). 4-HMP and OA are not
CC pathway intermediates, but are rather shunt or side products
CC (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 -!- 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}.
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DR EMBL; CH476594; EAU38786.1; -; Genomic_DNA.
DR RefSeq; XP_001210226.1; XM_001210226.1.
DR AlphaFoldDB; Q0D1P4; -.
DR SMR; Q0D1P4; -.
DR STRING; 341663.Q0D1P4; -.
DR EnsemblFungi; EAU38786; EAU38786; ATEG_00140.
DR GeneID; 4354897; -.
DR VEuPathDB; FungiDB:ATEG_00140; -.
DR eggNOG; KOG4441; Eukaryota.
DR HOGENOM; CLU_004253_10_0_1; -.
DR OMA; EMKSWTH; -.
DR OrthoDB; 1562595at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR Pfam; PF01344; Kelch_1; 1.
DR SMART; SM00612; Kelch; 5.
DR SUPFAM; SSF117281; SSF117281; 2.
PE 1: Evidence at protein level;
KW Kelch repeat; Reference proteome; Repeat.
FT CHAIN 1..459
FT /note="Kelch-like protein terF"
FT /id="PRO_0000437629"
FT REPEAT 92..144
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 145..196
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 198..248
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 251..304
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 306..354
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REPEAT 355..405
FT /note="Kelch 6"
FT /evidence="ECO:0000255"
SQ SEQUENCE 459 AA; 49873 MW; BC2865B84E9E11D5 CRC64;
MPPTISDDTT VRSFTCAQPL GRAGYELIIR QMLHRFLSDL HTTKALLDRS LQATVNHAAG
PVRSLLTIIT VGFYTLLNWC SLGSYHTTKM ISTVVTGLLL LASGCEALPT NQTPLPGKWS
TLPNITLNGV EYPRQEHAAA LVGDEIFVLG GILPWDGKEY ATTNIVQKYN MITGTWTETA
PMPAALNHAN VAVVDGKIYY LGGLEAVDET YWNATGKSAV YDPATDEWTV LPSMPEGREI
GSAATVVVDD TIYLPGGLAY TNITYDQEGT VSRFSSYNVR TQEWTTLPDL PAPRDHAGKG
IYRDMLYILG GREFGNKNVV STVFGFNLTS QQWATAFEPM PIARGGVASA TIGSLIFTAG
GEGDRRTPTA VFPEMQAYDA ATNTWVDYAD MPLPVHGSDA VVYKGEIVIP GGGIVTGATL
TPVVQTFQPP LPDSGEKSMP LMVMVYRVVF DLPWMLFKR
