ID   INPC_EMENI              Reviewed;         583 AA.
AC   Q5B7J0; C8V551;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=Acyl-CoA ligase inpC {ECO:0000250|UniProtKB:Q5BA81};
DE            EC=6.2.1.- {ECO:0000250|UniProtKB:Q5BA81};
DE   AltName: Full=Fellutamide B biosynthesis cluster protein C {ECO:0000303|PubMed:27294372};
DE   AltName: Full=Inp cluster protein C {ECO:0000303|PubMed:20952652};
GN   Name=inpC {ECO:0000303|PubMed:20952652}; ORFNames=ANIA_03490;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
RN   [3]
RP   IDENTIFICATION, AND INDUCTION.
RX   PubMed=20952652; DOI=10.1128/aem.00683-10;
RA   Bergmann S., Funk A.N., Scherlach K., Schroeckh V., Shelest E., Horn U.,
RA   Hertweck C., Brakhage A.A.;
RT   "Activation of a silent fungal polyketide biosynthesis pathway through
RT   regulatory cross talk with a cryptic nonribosomal peptide synthetase gene
RT   cluster.";
RL   Appl. Environ. Microbiol. 76:8143-8149(2010).
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=27294372; DOI=10.1021/acschembio.6b00213;
RA   Yeh H.H., Ahuja M., Chiang Y.M., Oakley C.E., Moore S., Yoon O.,
RA   Hajovsky H., Bok J.W., Keller N.P., Wang C.C., Oakley B.R.;
RT   "Resistance gene-guided genome mining: serial promoter exchanges in
RT   Aspergillus nidulans reveal the biosynthetic pathway for fellutamide B, a
RT   proteasome inhibitor.";
RL   ACS Chem. Biol. 11:2275-2284(2016).
CC   -!- FUNCTION: Acyl-CoA ligase; part of the inp gene cluster that mediates
CC       the biosynthesis of fellutamide B, a mycotoxin that acts as a
CC       proteasome inhibitor (PubMed:20952652, PubMed:27294372). In the first
CC       step of fellutabmide B biosynthesis inpC activates 3-hydroxydodecanoic
CC       acid to generate 3-hydroxydodecanoyl-AMP that is then loaded onto the
CC       T0 domain of inpB (PubMed:27294372). The 3-hydroxydodecanoyl-S-
CC       phosphopantetheinyl-T0 is sequentially extended with L-Asn and L-Gln by
CC       the two CAT modules of inpB (PubMed:27294372). The linear lipodipeptide
CC       from inpB is then transferred onto inpA for the addition of the third
CC       amino acid, L-Leu (PubMed:27294372). Reductive releasing of the
CC       lipotripeptide by the TE domain of inpA produces (2S)-fellutamide B
CC       (PubMed:27294372). InpF might be involved in the release and transfer
CC       of the lipodipeptide from inpB to inpA (PubMed:27294372). The inp
CC       cluster-encoded proteasome subunit inpE confers resistance to
CC       internally produced fellutamides (PubMed:27294372). The MFS efflux
CC       transporter inpD may contribute to fellutamide resistance as well
CC       (PubMed:27294372). {ECO:0000269|PubMed:27294372,
CC       ECO:0000305|PubMed:20952652}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:27294372}.
CC   -!- INDUCTION: Expression is positively regulated by the secondary
CC       metabolism cross-pathway regulator scpR (PubMed:20952652).
CC       {ECO:0000269|PubMed:20952652}.
CC   -!- DOMAIN: Both substrate-binding domains (SBD1 and SBD2) are involved in
CC       the substrate recognition, and are sufficient to confer the substrate
CC       specificity. {ECO:0000250|UniProtKB:Q42524}.
CC   -!- DISRUPTION PHENOTYPE: Eliminates the production of fellutamides
CC       (PubMed:27294372). {ECO:0000269|PubMed:27294372}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; BN001302; CBF76048.1; -; Genomic_DNA.
DR   RefSeq; XP_661094.1; XM_656002.1.
DR   AlphaFoldDB; Q5B7J0; -.
DR   SMR; Q5B7J0; -.
DR   STRING; 162425.CADANIAP00005267; -.
DR   EnsemblFungi; CBF76048; CBF76048; ANIA_03490.
DR   EnsemblFungi; EAA59051; EAA59051; AN3490.2.
DR   GeneID; 2872911; -.
DR   KEGG; ani:AN3490.2; -.
DR   eggNOG; KOG1176; Eukaryota.
DR   HOGENOM; CLU_000022_59_2_1; -.
DR   InParanoid; Q5B7J0; -.
DR   OMA; LAMITHY; -.
DR   OrthoDB; 683933at2759; -.
DR   Proteomes; UP000000560; Chromosome II.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016405; F:CoA-ligase activity; IBA:GO_Central.
DR   GO; GO:0019748; P:secondary metabolic process; IBA:GO_Central.
DR   Gene3D; 3.30.300.30; -; 1.
DR   InterPro; IPR025110; AMP-bd_C.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding; Ligase; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..583
FT                   /note="Acyl-CoA ligase inpC"
FT                   /id="PRO_0000444110"
FT   REGION          280..350
FT                   /note="SBD1"
FT                   /evidence="ECO:0000250|UniProtKB:Q42524"
FT   REGION          351..413
FT                   /note="SBD2"
FT                   /evidence="ECO:0000250|UniProtKB:Q42524"
FT   BINDING         202..217
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         350..355
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         434
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         456
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         554
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
SQ   SEQUENCE   583 AA;  64205 MW;  5800D00D2046BE70 CRC64;
     MIFTPPVWGP EMMAIPASRP IHEFLVERDS RHLYDWSEEK PALTIADRVD ALARSLGREL
     GWSPNTGSPW SKVVGIFSFN TLDFLVASWA IHRIGGICML MHPTSSAAEI KRHIELTECR
     VLFTCRSLLP TANEVLVASK VQDPRAYLLD LPEELGRKPS LPDQGQQTVE QLISAGATLP
     LIEALDWAEG QGKEQVAYLC PTSGTSGLQE SALTVKKLAM ITHYNIIANI IQATTFEAGP
     KKGRTEVALG FLPLSHSYGL ILAHLTAWRG DTYILHARFD MQAALASIEK YRIERLYLVP
     PIISALVNNP FLLDLCDTSS VTSVVTGSGP FGPRLAEALS RVRPSWQVLP GYGLTETAVI
     ISITDPNITY PGADGCLVPG VEARLINSNG NEVEAYNEPG ELLLKSPSIM KGYLGQETAT
     REVFDEQGWL RTGDIAVFRL TGQDGKVTPH LDIVDRKKDI MKVKGLQVAP VEIESHLAAH
     PAVAEVAVVG VRDEDAGERP YAFIVRSPRT MADLDEEALK ADLNRHVEAT LSEPHWLRKN
     IRFVEEFPKS SNGKPLKYKL KESLATSYAR KTSPAIPNNT RNR