CTVD_ASPTN
ID CTVD_ASPTN Reviewed; 348 AA.
AC Q0C9L5;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=Terpene cyclase ctvD {ECO:0000303|PubMed:26954888};
DE EC=5.4.99.- {ECO:0000269|PubMed:26954888};
DE AltName: Full=Citreoviridin biosynthesis protein D {ECO:0000303|PubMed:26954888};
GN Name=ctvD {ECO:0000303|PubMed:26954888}; ORFNames=ATEG_09619;
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=2523213; DOI=10.1016/0003-9861(89)90554-7;
RA Sayood S.F., Suh H., Wilcox C.S., Schuster S.M.;
RT "Effect of citreoviridin and isocitreoviridin on beef heart mitochondrial
RT ATPase.";
RL Arch. Biochem. Biophys. 270:714-721(1989).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=22753871; DOI=10.1182/blood-2011-12-399063;
RA Yavlovich A., Viard M., Zhou M., Veenstra T.D., Wang J.M., Gong W.,
RA Heldman E., Blumenthal R., Raviv Y.;
RT "Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting
RT cells to CD4(+) target cells.";
RL Blood 120:1246-1253(2012).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=22822083; DOI=10.1158/0008-5472.can-12-0567;
RA Chang H.Y., Huang H.C., Huang T.C., Yang P.C., Wang Y.C., Juan H.F.;
RT "Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by
RT activating the unfolded protein response.";
RL Cancer Res. 72:4696-4706(2012).
RN [5]
RP FUNCTION, AND PATHWAY.
RX PubMed=26954888; DOI=10.1021/acs.orglett.6b00299;
RA Lin T.S., Chiang Y.M., Wang C.C.;
RT "Biosynthetic pathway of the reduced polyketide product citreoviridin in
RT Aspergillus terreus var. aureus revealed by heterologous expression in
RT Aspergillus nidulans.";
RL Org. Lett. 18:1366-1369(2016).
CC -!- FUNCTION: Hydrolase; part of the gene cluster that mediates the
CC biosynthesis of citreoviridin, an inhibitor of the of F1-ATPase beta-
CC subunit (PubMed:26954888). The HR-PKS ctvA accepts acetyl-CoA as the
CC starter unit and catalyzes eight iterations of malonyl-CoA extension
CC and four iterations of SAM-dependent methylation at C4, C12, C14, and
CC C16 (PubMed:26954888). The KR and DH domains selectively act on the
CC first six iterations to generate the hexaene chain (PubMed:26954888).
CC In the last three iterations, the KR and DH domains terminate their
CC functions to yield a beta,delta-diketo ester moiety, which then
CC undergoes intramolecular cyclization to yield an alpha-pyrone
CC intermediate (PubMed:26954888). Subsequently, ctvB methylates the
CC alpha-pyrone hydroxyl group to generate citreomontanin
CC (PubMed:26954888). In order to form the tetrahydrofuran ring with the
CC correct stereochemistry, the terminal alkenes of citreomontanin need to
CC undergo isomerization to yield a (17Z)-hexaene, a step that could be
CC catalyzed by ctvC (PubMed:26954888). The (17Z)-hexaene then undergoes
CC bisepoxidation by ctvC to form a (17R,16R,15S,14R)-bisepoxide moiety
CC (PubMed:26954888). Lastly, ctvD acts as a regioselective hydrolase to
CC form the tetrahydrofuran ring with the substituents in the correct
CC absolute configuration, completing the biosynthesis of citreoviridin
CC (PubMed:26954888). {ECO:0000269|PubMed:26954888}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954888}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Citreoviridin inhibits mitochondrial oxidative
CC phosphorylation by binding to the beta-subunit of F1-ATPase
CC (PubMed:2523213). Ectopic mitochondrial ATP synthase is a factor that
CC mediates HIV-1 transfer between antigen-presenting cells (APCs) and
CC CD4+ target cells, and citreoviridin can completely block antigen-
CC presenting cell (APC)-mediated transfer of HIV-1 at the APC-target
CC cells (PubMed:22753871). Inhibition of Ectopic mitochondrial ATP
CC synthase by citreoviridin can also lead to suppression of cancer growth
CC by activating the unfolded protein response (PubMed:22822083).
CC {ECO:0000269|PubMed:22753871, ECO:0000269|PubMed:22822083,
CC ECO:0000269|PubMed:2523213}.
CC -!- SIMILARITY: Belongs to the membrane-bound ascI terpene cyclase family.
CC {ECO:0000305}.
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DR EMBL; CH476608; EAU29810.1; -; Genomic_DNA.
DR RefSeq; XP_001218241.1; XM_001218240.1.
DR AlphaFoldDB; Q0C9L5; -.
DR EnsemblFungi; EAU29810; EAU29810; ATEG_09619.
DR GeneID; 4354537; -.
DR VEuPathDB; FungiDB:ATEG_09619; -.
DR eggNOG; ENOG502SHVK; Eukaryota.
DR HOGENOM; CLU_038717_0_0_1; -.
DR OMA; LWFLQWD; -.
DR OrthoDB; 1036136at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Glycoprotein; Isomerase; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..348
FT /note="Terpene cyclase ctvD"
FT /id="PRO_0000437744"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..255
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 348 AA; 38405 MW; B4921226CAFBF284 CRC64;
MALSAYFLLC LSVLGLDAIY GFGFRNGFLE LMANSYRERK LSGTAEPLQG NITGTGLDEL
LGNLIVFYWP VLDGNHPGLS LQAFHFLGAI VAVWVAIQVQ SWRSPNRNSL LRSPTLFAML
SQVVAIAVIV PLWCAISIWS SSSPRPITRA VSASAAHSIR LIPISMVLGF GIPTIGMLLP
ESTHQNLFSK QIAIAVWQIW PIYVALWHWG LRVLFRSRLK EGISVRTACR TACSFAFVCA
IIPHAVSWGL SLTLIPTNLL ADVLPWQFAG GGTVQVQSMA QGGLWFLQWD HLIGMGSFLL
WAMHMRWTVE QQSSFLQTCY LALKVGVLCL ISGPCGAAVW LLWEESQF
