ID   ATD_ASPTN               Reviewed;         350 AA.
AC   Q0CJ58;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   25-MAY-2022, entry version 51.
DE   RecName: Full=Terreic acid biosynthesis cluster protein D {ECO:0000303|PubMed:25265334};
GN   Name=atD {ECO:0000303|PubMed:25265334}; ORFNames=ATEG_06276;
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   FUNCTION.
RX   PubMed=9003280; DOI=10.1007/s004380050289;
RA   Fujii I., Ono Y., Tada H., Gomi K., Ebizuka Y., Sankawa U.;
RT   "Cloning of the polyketide synthase gene atX from Aspergillus terreus and
RT   its identification as the 6-methylsalicylic acid synthase gene by
RT   heterologous expression.";
RL   Mol. Gen. Genet. 253:1-10(1996).
RN   [3]
RP   FUNCTION.
RX   PubMed=9438344; DOI=10.1007/bf02826548;
RA   Pazoutova S., Linka M., Storkova S., Schwab H.;
RT   "Polyketide synthase gene pksM from Aspergillus terreus expressed during
RT   growth phase.";
RL   Folia Microbiol. (Praha) 42:419-430(1997).
RN   [4]
RP   BIOTECHNOLOGY.
RX   PubMed=10051623; DOI=10.1073/pnas.96.5.2227;
RA   Kawakami Y., Hartman S.E., Kinoshita E., Suzuki H., Kitaura J., Yao L.,
RA   Inagaki N., Franco A., Hata D., Maeda-Yamamoto M., Fukamachi H., Nagai H.,
RA   Kawakami T.;
RT   "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:2227-2232(1999).
RN   [5]
RP   BIOTECHNOLOGY.
RX   PubMed=23686727; DOI=10.1002/jobm.201200617;
RA   Olesen S.H., Ingles D.J., Yang Y., Schoenbrunn E.;
RT   "Differential antibacterial properties of the MurA inhibitors terreic acid
RT   and fosfomycin.";
RL   J. Basic Microbiol. 54:322-326(2014).
RN   [6]
RP   FUNCTION.
RX   PubMed=24534845; DOI=10.1016/j.jbiotec.2014.01.038;
RA   Boruta T., Bizukojc M.;
RT   "Culture-based and sequence-based insights into biosynthesis of secondary
RT   metabolites by Aspergillus terreus ATCC 20542.";
RL   J. Biotechnol. 175:53-62(2014).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=25265334; DOI=10.1021/ol502242a;
RA   Guo C.J., Sun W.W., Bruno K.S., Wang C.C.;
RT   "Molecular genetic characterization of terreic acid pathway in Aspergillus
RT   terreus.";
RL   Org. Lett. 16:5250-5253(2014).
CC   -!- FUNCTION: part of the gene cluster that mediates the biosynthesis of
CC       terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase
CC       (PubMed:24534845, PubMed:25265334). The first step of the pathway is
CC       the synthesis of 6-methylsalicylic acid (6-MSA) by the 6-
CC       methylsalicylic acid synthase atX (PubMed:9003280, PubMed:9438344,
CC       PubMed:25265334). In the biosynthesis of 6-MSA, atX utilizes one
CC       acetyl-CoA and three malonyl-CoAs as its substrates and catalyzes a
CC       series of programmed reactions including Claisen condensation,
CC       dehydration, reduction, and cyclization to yield 6-MSA (PubMed:9003280,
CC       PubMed:9438344, PubMed:25265334). The 6-methylsalicylic acid
CC       decarboxylase atA then catalyzes the decarboxylative hydroxylation of
CC       6-MSA to 3-methylcatechol (PubMed:25265334). The next step is the
CC       conversion of 3-methylcatechol to terremutin via several oxidation
CC       steps involving the cytochrome P450 monooxygenase atE and probably also
CC       the cytochrome P450 monooxygenase atG (PubMed:25265334). Lastly, atC is
CC       required for the oxidation of terremutin to terreic acid
CC       (PubMed:25265334). No function could be assigned to atD yet, although
CC       it is involved in the biosynthesis of terreic acid (PubMed:25265334).
CC       {ECO:0000269|PubMed:25265334, ECO:0000269|PubMed:9003280,
CC       ECO:0000269|PubMed:9438344, ECO:0000305|PubMed:24534845}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25265334}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of terreic acid
CC       (PubMed:25265334). {ECO:0000269|PubMed:25265334}.
CC   -!- BIOTECHNOLOGY: Terreic acid is a metabolite with antibiotic properties
CC       (PubMed:23686727). Terric acid acts also as a selective inhibitor of
CC       human Bruton's tyrosine kinase in mast cells and other immune cells
CC       (PubMed:10051623). {ECO:0000269|PubMed:10051623,
CC       ECO:0000269|PubMed:23686727}.
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DR   EMBL; CH476602; EAU32820.1; -; Genomic_DNA.
DR   RefSeq; XP_001215454.1; XM_001215454.1.
DR   AlphaFoldDB; Q0CJ58; -.
DR   EnsemblFungi; EAU32820; EAU32820; ATEG_06276.
DR   GeneID; 4322100; -.
DR   VEuPathDB; FungiDB:ATEG_06276; -.
DR   eggNOG; ENOG502S24I; Eukaryota.
DR   HOGENOM; CLU_068080_0_0_1; -.
DR   OMA; GYKPFFR; -.
DR   OrthoDB; 1423082at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.10; -; 1.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   SUPFAM; SSF51182; SSF51182; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..350
FT                   /note="Terreic acid biosynthesis cluster protein D"
FT                   /id="PRO_0000437640"
FT   TRANSMEM        201..221
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        327..347
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        249
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   350 AA;  40886 MW;  C74F7EFBAD0E4E3F CRC64;
     MSSSSMGHGW YSSATFWTLW DLVRSRTEDD RFGGLLTCEF LPPPPGRSFM MRQTYRHSVE
     GPIPENLRKL IESDHRPDGP PMHFHQWQTE YFKVEEGICV VEVNGKQTML TPDDEEISCK
     AGNIHRFFIH PDSRERMTVI LSASDSGVDY QLDRVFFENW YGYWHDALLY QGGLDFIQTL
     CIHDAGDHYT PGPAWLPFRR FIGYWMCVVI GRWIGGLLGY KPFFREYTTD WDFAVTKMKA
     NPWTRRLVND SYANKKSWDE QVELSSRPKA QNADYELLVT DITEENRRKK AQWSYEWTCE
     IGEWHRYRCG SRGEGEWGGA PKALLRGEGL LLSYVLLVCL FLLSAYCDMR