ID   TCPC_CLAP2              Reviewed;         505 AA.
AC   M1W080;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2013, sequence version 1.
DT   03-AUG-2022, entry version 24.
DE   RecName: Full=Cytochrome P450 monooxygenase tcpC {ECO:0000303|PubMed:27390873};
DE            EC=1.-.-.- {ECO:0000269|PubMed:27390873};
DE   AltName: Full=Thioclapurine biosynthesis protein C {ECO:0000303|PubMed:27390873};
DE   Flags: Precursor;
GN   Name=tcpC {ECO:0000303|PubMed:27390873}; ORFNames=CPUR_02677;
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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of an unusual class of
CC       epipolythiodioxopiperazines (ETPs) lacking the reactive thiol group
CC       important for toxicity (PubMed:27390873). Firstly, L-tyrosine is
CC       prenylated by tcpD, before undergoing condensation with L-glycine in a
CC       reaction catalyzed by the NRPS tcpP leading to the diketopiperazine
CC       (DKP) backbone (PubMed:27390873). Afterwards the alpha-carbon of
CC       tyrosine is oxidized by the cytochrome P450 tcpC to form a hydroxyl
CC       group (PubMed:27390873). However, in contrast other ETP biosynthesis
CC       pathways studied so far, tcpC is not able to bishydroxylate the DKP at
CC       both alpha-carbon positions, but hydroxylates the alpha-carbon of the
CC       tyrosine part and the nitrogen of the glycine part (PubMed:27390873).
CC       The next steps involve an alpha,beta-elimination reaction catalyzed by
CC       tcpI, a methylation by the methyltransferase tcpN the action of the
CC       four enzyme cascade tcpG/K/J/I (PubMed:27390873). Due to a
CC       dysfunctional cytochrome P450 monooxygenase tcpC, the pathway leads to
CC       the biosynthesis of probable non-toxic metabolites lacking the reactive
CC       thiol group (PubMed:27390873). {ECO:0000269|PubMed:27390873}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:27390873}.
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 cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CAGA01000011; CCE28986.1; -; Genomic_DNA.
DR   AlphaFoldDB; M1W080; -.
DR   SMR; M1W080; -.
DR   STRING; 5111.M1W080; -.
DR   EnsemblFungi; CCE28986; CCE28986; CPUR_02677.
DR   VEuPathDB; FungiDB:CPUR_02677; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   HOGENOM; CLU_042557_2_0_1; -.
DR   OrthoDB; 825914at2759; -.
DR   Proteomes; UP000016801; Unassembled WGS sequence.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..505
FT                   /note="Cytochrome P450 monooxygenase tcpC"
FT                   /id="PRO_0000437709"
FT   BINDING         443
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
FT   CARBOHYD        316
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   505 AA;  57680 MW;  40988639DD66D4CA CRC64;
     MVFKMVMLKD VFPILVFLVA LRLLKSQIAQ WMIESIVTKL LQALNPVHDS LGKGISGPRW
     QYLNGQTLDK FLDGREKVQE WQKYGPVYRI WAGTTPEIVI TKPEDVRAFH VDSSRHNKAR
     SSNAGWLFHQ LLGECMGLIS GTRWIKVRSE FEPAFSHSAI TMKAAEVSND AQCYVNKLEK
     SRSSSFTVQA AEAVARFPFF CTATHLYGEL SEEERNELWE LGQRNLKMMG HVLSGGLFRF
     PIARWLYRSA VQDLESFLCD WASFNERIYK KKVGCGAKTP IVSAWKKVID GDLTREEAIH
     TLSEILFANL DVATGNLSWL VIYLAANEDI QRQVVEEISQ HRHELDHYCA RKDTLLAYCV
     LETLRLRPFT AFSIPESSPN QKVLHGFTVP GNTSVVVNTL AINYNAAFWG DKAEVFSPNR
     FHSINRLALR YNLFTFGMGT RKCLGSHFAE MMMKYFAMHL LNRFSLHIPV EKDRSKAQTE
     DTSMSTWVPI SDKEVALQKR TMGLF