MDRA_ASPFU
ID MDRA_ASPFU Reviewed; 607 AA.
AC Q4WS70;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 81.
DE RecName: Full=Major facilitator superfamily multidrug transporter mdrA {ECO:0000303|PubMed:26933209};
GN Name=mdrA {ECO:0000303|PubMed:26933209}; ORFNames=AFUA_1G13800;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP INDUCTION.
RX PubMed=21264256; DOI=10.1371/journal.pone.0016016;
RA Morton C.O., Varga J.J., Hornbach A., Mezger M., Sennefelder H., Kneitz S.,
RA Kurzai O., Krappmann S., Einsele H., Nierman W.C., Rogers T.R.,
RA Loeffler J.;
RT "The temporal dynamics of differential gene expression in Aspergillus
RT fumigatus interacting with human immature dendritic cells in vitro.";
RL PLoS ONE 6:E16016-E16016(2011).
RN [3]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26933209; DOI=10.1093/mmy/myw005;
RA Meneau I., Coste A.T., Sanglard D.;
RT "Identification of Aspergillus fumigatus multidrug transporter genes and
RT their potential involvement in antifungal resistance.";
RL Med. Mycol. 54:616-627(2016).
CC -!- FUNCTION: MFS transporter involved in the basal level of azole
CC susceptibility (PubMed:26933209). Confers resistance to voriconazole
CC and, to a lesser extent, to fluconazole (PubMed:26933209).
CC {ECO:0000269|PubMed:26933209}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is up-regulated by exposure to human monocyte-
CC derived immature dendritic cells (PubMed:21264256). Expression is
CC increased in clinical azole-resistant isolates (PubMed:26933209).
CC {ECO:0000269|PubMed:21264256, ECO:0000269|PubMed:26933209}.
CC -!- DISRUPTION PHENOTYPE: Exhibits enhanced susceptibility to voriconazole,
CC however itraconazole susceptibility is less affected.
CC {ECO:0000269|PubMed:26933209}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. DHA1 family.
CC Polyamines/proton antiporter (TC 2.A.1.2.16) subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000004; EAL90712.1; -; Genomic_DNA.
DR RefSeq; XP_752750.1; XM_747657.1.
DR AlphaFoldDB; Q4WS70; -.
DR SMR; Q4WS70; -.
DR STRING; 746128.CADAFUBP00001307; -.
DR EnsemblFungi; EAL90712; EAL90712; AFUA_1G13800.
DR GeneID; 3510614; -.
DR KEGG; afm:AFUA_1G13800; -.
DR VEuPathDB; FungiDB:Afu1g13800; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_6_1; -.
DR InParanoid; Q4WS70; -.
DR OMA; FGRQIIF; -.
DR OrthoDB; 540452at2759; -.
DR Proteomes; UP000002530; Chromosome 1.
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; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..607
FT /note="Major facilitator superfamily multidrug transporter
FT mdrA"
FT /id="PRO_0000445106"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 523..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 607 AA; 67431 MW; 1DB58E23AA0F09C0 CRC64;
MATEKGDQNA EKIEQSLPQK IPYWRLVVDQ GVLTQQIIDY PYKGSGTEED PYEVVWMEND
PRNPMTWTQL RKWSLTMTVA VSTLAVALVS SAYTGGVREI EAEFHIGSEV ATLGVSLFVL
GFAIGPLLWA PLSEMFGRQI IFTVTYCALT AFNAGSAGAQ NSWTLIILRF FAGAFGASPL
TNAGGVIADM FHAKQRGIAM SLFAAAPFLG PVLGPIIGGF LGMNAGWRWV MGFLGAFSGA
VWIICTIFVP ETYAPVLLRR RAEKLSKHTG KVYVSKIDID QGRVTLKDAF KTALSRPWIL
LFKEPIVFLL SLYMAIIYGT LYMLFSAYPI VFQGVRHWNQ GVSSLPFLGI MVGMMFAVTY
SVWDNKRYVQ VQAKHGGFAP PEARLPPTLI ASVAIPIGLF WFAWTNYPSI HWIVCILAGA
PFGFGMVLVF LGIMNYLIDA YTIFAASVLA ANSVLRSIFG AVFPLFTTYM YEDLGIHWAS
SIPAFLALAC VPFPFLFYKY GATIRKRCEY AAKSDAFMRK LAEQMKQAPE PESEETEEPV
FDRTEAPAPD VSDVSETESN VEELPDVRQM RSRASTRTAS SLRRVVSYEG NPYDIDRVNT
RESFTKK
