ID   CCTR_TALIS              Reviewed;         261 AA.
AC   A0A0U1LR74;
DT   18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT   17-FEB-2016, sequence version 1.
DT   25-MAY-2022, entry version 19.
DE   RecName: Full=Cyclochlorotine biosynthesis protein R {ECO:0000303|PubMed:26954535};
GN   Name=cctR {ECO:0000303|PubMed:26954535}; ORFNames=PISL3812_02623;
OS   Talaromyces islandicus (Penicillium islandicum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC   Talaromyces sect. Islandici.
OX   NCBI_TaxID=28573;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 26535 / WF-38-12;
RX   PubMed=26197417; DOI=10.1016/j.jbiotec.2015.07.004;
RA   Schafhauser T., Wibberg D., Rueckert C., Winkler A., Flor L., van Pee K.H.,
RA   Fewer D.P., Sivonen K., Jahn L., Ludwig-Mueller J., Caradec T., Jacques P.,
RA   Huijbers M.M., van Berkel W.J., Weber T., Wohlleben W., Kalinowski J.;
RT   "Draft genome sequence of Talaromyces islandicus ('Penicillium islandicum')
RT   WF-38-12, a neglected mold with significant biotechnological potential.";
RL   J. Biotechnol. 211:101-102(2015).
RN   [2]
RP   FUNCTION.
RX   PubMed=26954535; DOI=10.1111/1462-2920.13294;
RA   Schafhauser T., Kirchner N., Kulik A., Huijbers M.M., Flor L., Caradec T.,
RA   Fewer D.P., Gross H., Jacques P., Jahn L., Jokela J., Leclere V.,
RA   Ludwig-Mueller J., Sivonen K., van Berkel W.J., Weber T., Wohlleben W.,
RA   van Pee K.H.;
RT   "The cyclochlorotine mycotoxin is produced by the nonribosomal peptide
RT   synthetase CctN in Talaromyces islandicus ('Penicillium islandicum').";
RL   Environ. Microbiol. 18:3728-3741(2016).
CC   -!- FUNCTION: Part of the gene cluster that mediates the biosynthesis of
CC       the mycotoxin cyclochlorotine, a hepatotoxic and carcinogenic cyclic
CC       chlorinated pentapeptide (PubMed:26954535). Cyclochlorotine is formed
CC       by the nonproteinogenic amino acids L-2-aminobutyrate (2Abu), L-beta-
CC       phenylalanine (beta-Phe), the unique L-cis-3,4-dichloroproline
CC       Pro(Cl(2)) and two L-serines (Ser) (PubMed:26954535). The condensation
CC       of the 5 building blocks is performed by the cyclochlorotine synthetase
CC       cctN, a nonribosomal peptide synthetase (PubMed:26954535). The
CC       assembled linear pentapeptide is then assumed to be released through
CC       cyclization by the terminal condensation-like domain of cctN
CC       (PubMed:26954535). Incorporation of the alternative substrates allo-
CC       threonine or alanine by the domains A3 or A1 respectively may lead to
CC       the production of the variants hydroxy-cyclochlorotine and deoxy-
CC       cyclochlorotine, respectively (PubMed:26954535). CctP probably acts as
CC       a phenylalanine aminomutase and provides the uncommon building block
CC       beta-Phe (PubMed:26954535). Furthermore, 2Abu can be synthesized from
CC       threonine by one of the threonine dehydratases and transaminases
CC       localized outside of the cluster (PubMed:26954535). The biosynthesis of
CC       the unusual dichloroproline moiety remains elusive since the actual
CC       halogenase still awaits to be detected, with the possibility that
CC       proline halogenation is accomplished by a so far unknown type of
CC       halogenase (PubMed:26954535). Finally, the cluster encoded transporters
CC       cctQ and cctS are most likely responsible for cyclochlorotine secretion
CC       and thereby may contribute to intrinsic resistance (PubMed:26954535).
CC       The functions of the remaining proteins encoded by the cluster (cctM,
CC       cctO, cctR and cctG) have not been identified yet (PubMed:26954535).
CC       {ECO:0000269|PubMed:26954535}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954535}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
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DR   EMBL; CVMT01000002; CRG85576.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0U1LR74; -.
DR   EnsemblFungi; CRG85576; CRG85576; PISL3812_02623.
DR   OMA; CIRITIY; -.
DR   OrthoDB; 1162942at2759; -.
DR   Proteomes; UP000054383; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043386; P:mycotoxin biosynthetic process; IEA:InterPro.
DR   InterPro; IPR021765; UstYa-like.
DR   PANTHER; PTHR33365; PTHR33365; 1.
DR   Pfam; PF11807; UstYa; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..261
FT                   /note="Cyclochlorotine biosynthesis protein R"
FT                   /id="PRO_0000438668"
FT   TRANSMEM        38..58
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        95
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   261 AA;  29537 MW;  DE006B6C1AFA6A22 CRC64;
     MEEELEPLNR PTLDPDESYA EEKIYGSSHR EPNSRIRVFV SLLILSNTIS FGLLGWIGLS
     STQASLAIPE DYAIPPRIAT QYKRFWWTTE YSSKNQSQQD ELWNSIVWTY GMIGVDHEWS
     KSQHWPDTMS LPQDKTKAVY LLQAYHEIHC LGVLRRLMSQ SLAGVDFSES EHTHAHIAHC
     FDSLLQSTIC RADSTPLYTF GGTIVGSGQQ HECRDWNALR DYATQNSACY TEESGFGGQC
     SDGDGLVPAT PMETQQDGFW L