TCPT_CLAP2
ID TCPT_CLAP2 Reviewed; 321 AA.
AC M1W428;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Thioredoxin reductase tcpT {ECO:0000303|PubMed:27390873};
DE EC=1.8.1.- {ECO:0000305|PubMed:27390873};
DE AltName: Full=Thioclapurine biosynthesis protein T {ECO:0000303|PubMed:27390873};
GN Name=tcpT {ECO:0000303|PubMed:27390873}; ORFNames=CPUR_02681;
OS Claviceps purpurea (strain 20.1) (Ergot fungus) (Sphacelia segetum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX NCBI_TaxID=1111077;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=20.1;
RX PubMed=23468653; DOI=10.1371/journal.pgen.1003323;
RA Schardl C.L., Young C.A., Hesse U., Amyotte S.G., Andreeva K., Calie P.J.,
RA Fleetwood D.J., Haws D.C., Moore N., Oeser B., Panaccione D.G.,
RA Schweri K.K., Voisey C.R., Farman M.L., Jaromczyk J.W., Roe B.A.,
RA O'Sullivan D.M., Scott B., Tudzynski P., An Z., Arnaoudova E.G.,
RA Bullock C.T., Charlton N.D., Chen L., Cox M., Dinkins R.D., Florea S.,
RA Glenn A.E., Gordon A., Gueldener U., Harris D.R., Hollin W., Jaromczyk J.,
RA Johnson R.D., Khan A.K., Leistner E., Leuchtmann A., Li C., Liu J., Liu J.,
RA Liu M., Mace W., Machado C., Nagabhyru P., Pan J., Schmid J., Sugawara K.,
RA Steiner U., Takach J.E., Tanaka E., Webb J.S., Wilson E.V., Wiseman J.L.,
RA Yoshida R., Zeng Z.;
RT "Plant-symbiotic fungi as chemical engineers: Multi-genome analysis of the
RT Clavicipitaceae reveals dynamics of alkaloid loci.";
RL PLoS Genet. 9:E1003323-E1003323(2013).
RN [2]
RP FUNCTION, AND INDUCTION.
RX PubMed=27390873; DOI=10.1371/journal.pone.0158945;
RA Dopstadt J., Neubauer L., Tudzynski P., Humpf H.U.;
RT "The epipolythiodiketopiperazine gene cluster in Claviceps purpurea:
RT dysfunctional cytochrome P450 enzyme prevents formation of the previously
RT unknown clapurines.";
RL PLoS ONE 11:E0158945-E0158945(2016).
CC -!- FUNCTION: Thioredoxin reductase; part of the gene cluster that mediates
CC the biosynthesis of an unusual class of epipolythiodioxopiperazines
CC (ETPs) lacking the reactive thiol group important for toxicity
CC (PubMed:27390873). Firstly, L-tyrosine is prenylated by tcpD, before
CC undergoing condensation with L-glycine in a reaction catalyzed by the
CC NRPS tcpP leading to the diketopiperazine (DKP) backbone
CC (PubMed:27390873). Afterwards the alpha-carbon of tyrosine is oxidized
CC by the cytochrome P450 tcpC to form a hydroxyl group (PubMed:27390873).
CC However, in contrast other ETP biosynthesis pathways studied so far,
CC tcpC is not able to bishydroxylate the DKP at both alpha-carbon
CC positions, but hydroxylates the alpha-carbon of the tyrosine part and
CC the nitrogen of the glycine part (PubMed:27390873). The next steps
CC involve an alpha,beta-elimination reaction catalyzed by tcpI, a
CC methylation by the methyltransferase tcpN the action of the four enzyme
CC cascade tcpG/K/J/I (PubMed:27390873). Due to a dysfunctional cytochrome
CC P450 monooxygenase tcpC, the pathway leads to the biosynthesis of
CC probable non-toxic metabolites lacking the reactive thiol group
CC (PubMed:27390873). {ECO:0000269|PubMed:27390873}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E9RAH5};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:E9RAH5};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:27390873}.
CC -!- SUBUNIT: Homodimer (By similarity). {ECO:0000250|UniProtKB:E9RAH5}.
CC -!- INDUCTION: Expression is positively regulated by the thioclapurine
CC cluster-specific transcription factor tcpZ (PubMed:27390873).
CC {ECO:0000269|PubMed:27390873}.
CC -!- SIMILARITY: Belongs to the class-II pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; CAGA01000011; CCE28990.1; -; Genomic_DNA.
DR AlphaFoldDB; M1W428; -.
DR SMR; M1W428; -.
DR STRING; 1111077.M1W428; -.
DR EnsemblFungi; CCE28990; CCE28990; CPUR_02681.
DR VEuPathDB; FungiDB:CPUR_02681; -.
DR eggNOG; ENOG502S1DJ; Eukaryota.
DR HOGENOM; CLU_031864_5_0_1; -.
DR OrthoDB; 1133476at2759; -.
DR PhylomeDB; M1W428; -.
DR Proteomes; UP000016801; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; FAD; Flavoprotein; NADP; Oxidoreductase;
KW Redox-active center; Reference proteome.
FT CHAIN 1..321
FT /note="Thioredoxin reductase tcpT"
FT /id="PRO_0000437712"
FT BINDING 14..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 36..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 49
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 114
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 282
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 289..290
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT DISULFID 138..141
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
SQ SEQUENCE 321 AA; 33910 MW; 721688F7678B2799 CRC64;
MSTSNIVDAL IIGGGPAGLS AALAFARQNQ SAIVFDSGRY RNAATDYMHL IPGLDHKAPA
EFRATARSQI TDRYDKIRIL EGVDIVAAKK TDADSFELSD EAGQTWNGRK LILATGVEDV
MLDIPGYAEL WGKSIVHCLY CKGYEQRGGS AGVLAVGPLG NVNMALHIAR QETALSKRVT
LYSNGNESLA GELVSAFGSA TAMRTDARKI KEFVAGADGK GVAIRFEDGS EVVEDYLAHQ
APVKAREGLA DLLGLEKGPN GEVKVSSPFQ QASVRGVFAA GDNGAMLKNV PNAVFSGHVA
GQMASTQLLA DLNGQKSIFP I
