ID   ICCH_TALVA              Reviewed;         365 AA.
AC   A0A482ND39;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Short-chain dehydrogenase iccH {ECO:0000303|PubMed:30905148};
DE            EC=1.1.1.- {ECO:0000305|PubMed:30905148};
DE   AltName: Full=Ilicicolin H biosynthesis cluster protein H {ECO:0000303|PubMed:30905148};
GN   Name=iccH {ECO:0000303|PubMed:30905148};
OS   Talaromyces variabilis (Penicillium variabile).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX   NCBI_TaxID=28576;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=HXQ-H-1;
RX   PubMed=30905148; DOI=10.1021/jacs.9b02204;
RA   Zhang Z., Jamieson C.S., Zhao Y.L., Li D., Ohashi M., Houk K.N., Tang Y.;
RT   "Enzyme-catalyzed inverse-electron demand Diels-Alder reaction in the
RT   biosynthesis of antifungal ilicicolin H.";
RL   J. Am. Chem. Soc. 141:5659-5663(2019).
CC   -!- FUNCTION: NADH-dependent flavin oxidoreductase; part of the gene
CC       cluster that mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-
CC       pyridonealkaloid that has potent and broad antifungal activities by
CC       inhibiting the mitochondrial respiration chain (PubMed:30905148). IccA
CC       to iccE are sufficient for ilicicolin H biosynthesis and the roles of
CC       the remaining enzymes, iccF, iccG and iccH within the pathway have
CC       still to be determined (PubMed:30905148). The biosynthesis of
CC       ilicicolin H starts with formation of the tetramic acid by the hybrid
CC       PKS-NRPS synthetase iccA with the partnering trans-enoyl reductase iccB
CC       since iccA lacks a designated enoylreductase (ER) domain. The
CC       cytochrome P450 monooxygenase iccC then catalyzes the ring expansion of
CC       the tetramate to the acyclic 2-pyridone. The pericyclase iccD further
CC       converts the acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the
CC       epimerase iccE converts 8-epi-ilicicolin H into ilicicolin H via
CC       epimerizationd (PubMed:30905148) (Probable).
CC       {ECO:0000269|PubMed:30905148, ECO:0000305|PubMed:30905148}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:30905148}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; MK539848; QBQ83706.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A482ND39; -.
DR   SMR; A0A482ND39; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Membrane; NADP; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..365
FT                   /note="Short-chain dehydrogenase iccH"
FT                   /id="PRO_0000449006"
FT   TRANSMEM        267..287
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         11..17
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         36..42
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         44..46
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         70..71
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         99..100
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         102
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         181
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   BINDING         258..263
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KES3"
FT   CARBOHYD        90
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        324
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   365 AA;  40621 MW;  9EB44A35FCC0CCA4 CRC64;
     MNQQGTVIVT GANGGLGNAI VSHILDRQDL NTNYYGIYTV RDTVRGARTV LRTLEWAKSV
     KHSHELLAID LGSLDSVRRA ARDINSRVAN GTIPPIRALI LNAGWGEQTT HSFTNDGFDM
     SFQVNYLSHF LLTLLLLQSM DKKHGRIEVL GSWTHEYLIP GVSTCSTTDP NNKKGPSASM
     YTPKRYQQIF NYPINTEDLA KGKWSSEREH PGDLNAGLRR YGAAKLCEIM MFRELSNRIE
     KDPELSAISV VAVDPGAMPS ELNRRSIWVM FLLMKFVLPL LAPLAVWLQP NGTIRTTTKS
     ARDVVRAAFD TATLGDHPNG IYLNGSEIAD VGPEAKDAEK SRTLWHDSLV YARLEKGDTI
     LKAWE