MDR3_ASPFU
ID MDR3_ASPFU Reviewed; 528 AA.
AC Q4WF45;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 90.
DE RecName: Full=Major facilitator superfamily multidrug transporter mdr3 {ECO:0000303|PubMed:12709346};
GN Name=mdr3 {ECO:0000303|PubMed:12709346}; ORFNames=AFUA_3G03500;
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, AND FUNCTION.
RX PubMed=12709346; DOI=10.1128/aac.47.5.1719-1726.2003;
RA Nascimento A.M., Goldman G.H., Park S., Marras S.A., Delmas G., Oza U.,
RA Lolans K., Dudley M.N., Mann P.A., Perlin D.S.;
RT "Multiple resistance mechanisms among Aspergillus fumigatus mutants with
RT high-level resistance to itraconazole.";
RL Antimicrob. Agents Chemother. 47:1719-1726(2003).
RN [3]
RP INDUCTION.
RX PubMed=15504870; DOI=10.1128/aac.48.11.4405-4413.2004;
RA da Silva Ferreira M.E., Capellaro J.L., dos Reis Marques E., Malavazi I.,
RA Perlin D., Park S., Anderson J.B., Colombo A.L., Arthington-Skaggs B.A.,
RA Goldman M.H., Goldman G.H.;
RT "In vitro evolution of itraconazole resistance in Aspergillus fumigatus
RT involves multiple mechanisms of resistance.";
RL Antimicrob. Agents Chemother. 48:4405-4413(2004).
RN [4]
RP INDUCTION.
RX PubMed=18838595; DOI=10.1128/aac.01431-07;
RA Gautam P., Shankar J., Madan T., Sirdeshmukh R., Sundaram C.S., Gade W.N.,
RA Basir S.F., Sarma P.U.;
RT "Proteomic and transcriptomic analysis of Aspergillus fumigatus on exposure
RT to amphotericin B.";
RL Antimicrob. Agents Chemother. 52:4220-4227(2008).
RN [5]
RP INDUCTION.
RX PubMed=28080217; DOI=10.1089/mdr.2016.0217;
RA Li S.X., Song Y.J., Jiang L., Zhao Y.J., Guo H., Li D.M., Zhu K.J.,
RA Zhang H.;
RT "Synergistic effects of tetrandrine with posaconazole against Aspergillus
RT fumigatus.";
RL Microb. Drug Resist. 23:674-681(2017).
RN [6]
RP INDUCTION.
RX PubMed=29124846; DOI=10.1111/1462-2920.13988;
RA Wang H.C., Huang J.C., Lin Y.H., Chen Y.H., Hsieh M.I., Choi P.C., Lo H.J.,
RA Liu W.L., Hsu C.S., Shih H.I., Wu C.J., Chen Y.C.;
RT "Prevalence, mechanisms and genetic relatedness of the human pathogenic
RT fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the
RT environment of Taiwan.";
RL Environ. Microbiol. 20:270-280(2018).
CC -!- FUNCTION: Major facilitator superfamily transporter that confers
CC resistance to azoles such as itraconazole.
CC {ECO:0000269|PubMed:12709346}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is increased in clinical azole-resistant isolates
CC and by the presence of itraconazole (PubMed:12709346, PubMed:15504870,
CC PubMed:29124846). Expression is down-regulated by tetrandrine and
CC posaconazole in a synergistic manner (PubMed:28080217). Expression is
CC also induced upon amphotericin B treatment (PubMed:18838595).
CC {ECO:0000269|PubMed:12709346, ECO:0000269|PubMed:15504870,
CC ECO:0000269|PubMed:18838595, ECO:0000269|PubMed:28080217,
CC ECO:0000269|PubMed:29124846}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000010; EAL86632.1; -; Genomic_DNA.
DR RefSeq; XP_748670.1; XM_743577.1.
DR AlphaFoldDB; Q4WF45; -.
DR SMR; Q4WF45; -.
DR STRING; 746128.CADAFUBP00004388; -.
DR EnsemblFungi; EAL86632; EAL86632; AFUA_3G03500.
DR GeneID; 3506162; -.
DR KEGG; afm:AFUA_3G03500; -.
DR VEuPathDB; FungiDB:Afu3g03500; -.
DR eggNOG; KOG0254; Eukaryota.
DR HOGENOM; CLU_000960_27_4_1; -.
DR InParanoid; Q4WF45; -.
DR OMA; FTICSAQ; -.
DR OrthoDB; 595536at2759; -.
DR Proteomes; UP000002530; Chromosome 3.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 2.
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..528
FT /note="Major facilitator superfamily multidrug transporter
FT mdr3"
FT /id="PRO_0000445107"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 528 AA; 57042 MW; 648B5A92103A0869 CRC64;
MLAMAASAEE TNRQSNAGRR SVISPSEAPP EAEQSDVYQA PPPGLKEWLF ILILCSTQLF
VQGAFGYILI PLHIVGQTFG QGPSEATRMT WHVGGYSLTV GTFILIAGKL GDLYGSKRIL
VLGWAWFGVW SVIGGCSAFT HSPVFFDTAR ALQGIGPALL LPNALAIAGR TYPPGKKKNM
IFSAFAVAAP LGCFTAGVVG SVFAQYVWWP WVMWTYSIGC FIIAAVGLWV IPSDYPRCQK
AATLQFDYIG SVLGVAGLLL LNISWNQAPI DGWSTPYVYV LLIGGFLVLG LFELQERRAP
GIRSWINFAM CLLWIQQCSS RQGPSQGILP ALATPYLMAV ITSGWLMAIA CAAFLGGCIL
QSTAPVEQSY WMNTFWSFVI MAWGMDISFP ASTTILSDAV PVKHQGASAS LVNTVINYSI
AIGLGIAGTV EAEVSHQGVN QLRGYRAALW SSVGLAALAF GIALVFAVCT FQEQRSSRKS
SQEREQRACI EGCILGLTLT PDREWERVEL GRLLSHVSQT GGLRSQSV
