INPD_EMENI
ID INPD_EMENI Reviewed; 517 AA.
AC Q5B7I9; C8V550;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 93.
DE RecName: Full=MFS efflux transporter inpD {ECO:0000305};
DE AltName: Full=Fellutamide B biosynthesis cluster protein D {ECO:0000303|PubMed:27294372};
DE AltName: Full=Inp cluster protein D {ECO:0000303|PubMed:20952652};
GN Name=inpD {ECO:0000303|PubMed:20952652}; ORFNames=ANIA_03491;
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, AND DISRUPTION PHENOTYPE.
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: MFS efflux transporter; part of the inp gene cluster that
CC mediates 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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the secondary
CC metabolism cross-pathway regulator scpR (PubMed:20952652).
CC {ECO:0000269|PubMed:20952652}.
CC -!- DISRUPTION PHENOTYPE: Does not affect production of fellutamides
CC (PubMed:27294372). {ECO:0000269|PubMed:27294372}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; BN001302; CBF76046.1; -; Genomic_DNA.
DR RefSeq; XP_661095.1; XM_656003.1.
DR AlphaFoldDB; Q5B7I9; -.
DR SMR; Q5B7I9; -.
DR EnsemblFungi; CBF76046; CBF76046; ANIA_03491.
DR EnsemblFungi; EAA59052; EAA59052; AN3491.2.
DR GeneID; 2872912; -.
DR KEGG; ani:AN3491.2; -.
DR eggNOG; KOG0254; Eukaryota.
DR HOGENOM; CLU_000960_22_1_1; -.
DR InParanoid; Q5B7I9; -.
DR OMA; TILPMND; -.
DR OrthoDB; 627633at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..517
FT /note="MFS efflux transporter inpD"
FT /id="PRO_0000444111"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 517 AA; 56019 MW; 321B7A1BAEA1A4E0 CRC64;
MEKTQTPSLT PDELSARSST PFEEREEEEE VHYVGHLKFS FIFVGLCLSV FQVALSLQDI
GWYGSAYLFT DCAFQLVFGR LYSMLPVKIV YLGALLLFEI GSIICATAPN SIALILGRTI
AGIGAGGILS GALTILSQSV PRAKVAVFNG ILGAVNGIAF ICGPLLAGGI INGTTWRWIF
YINPIISAPT FFITVFLLKL DPPKTNVKTW RGRIAMLDLP AFTLFLGSIL CLILALLWGG
KEYSWKNARI IVLFILFGVI MLAFMLVQKR KGDDALVPMR ILCQRSIAFG MFFSFCTSGT
GFILEYYLPI WLQVIKDLSV ISSAVKLLPI IAAAVVFTTL CGILTPVIGH YVPFMIIATM
LLSVGMGLLS TLEYTSPIRH VLGFQVPAGV GLGCALQQTL VAAQTILPMN DIPIGVSLIV
LAQTLGGTIA LSAADTIYTG TLSSSISSRF PQINRETVLT TGNREIRNLV PAESLSVIMD
LCNKAIVKTW YLSIGLAAAS IIGVLGMEWR RVTPPKK
