MDR2_ASPFU
ID MDR2_ASPFU Reviewed; 791 AA.
AC Q4WPP6;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=ABC multidrug transporter mdr2 {ECO:0000303|PubMed:9373135};
GN Name=mdr2 {ECO:0000303|PubMed:9373135}; ORFNames=AFUA_4G10000;
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 IDENTIFICATION, AND FUNCTION.
RX PubMed=9373135; DOI=10.1016/s0378-1119(97)00281-3;
RA Tobin M.B., Peery R.B., Skatrud P.L.;
RT "Genes encoding multiple drug resistance-like proteins in Aspergillus
RT fumigatus and Aspergillus flavus.";
RL Gene 200:11-23(1997).
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=21724936; DOI=10.1128/ec.05102-11;
RA Gibbons J.G., Beauvais A., Beau R., McGary K.L., Latge J.P., Rokas A.;
RT "Global transcriptome changes underlying colony growth in the opportunistic
RT human pathogen Aspergillus fumigatus.";
RL Eukaryot. Cell 11:68-78(2012).
RN [6]
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).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that may be involved in
CC A.fumigatus adaptation to azoles. {ECO:0000305|PubMed:9373135}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is up-regulated during biofilm growth
CC (PubMed:21724936). Expression is also induced upon amphotericin B
CC treatment (PubMed:18838595). Expression is down-regulated by
CC tetrandrine and posaconazole in a synergistic manner (PubMed:28080217).
CC Expression is increased in clinical azole-resistant isolates
CC (PubMed:15504870). {ECO:0000269|PubMed:15504870,
CC ECO:0000269|PubMed:18838595, ECO:0000269|PubMed:21724936,
CC ECO:0000269|PubMed:28080217}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Mitochondrial peptide exporter (TC 3.A.1.212) subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89788.1; -; Genomic_DNA.
DR RefSeq; XP_751826.1; XM_746733.1.
DR AlphaFoldDB; Q4WPP6; -.
DR SMR; Q4WPP6; -.
DR STRING; 746128.CADAFUBP00006530; -.
DR EnsemblFungi; EAL89788; EAL89788; AFUA_4G10000.
DR GeneID; 3509566; -.
DR KEGG; afm:AFUA_4G10000; -.
DR VEuPathDB; FungiDB:Afu4g10000; -.
DR eggNOG; KOG0058; Eukaryota.
DR HOGENOM; CLU_000604_84_3_1; -.
DR InParanoid; Q4WPP6; -.
DR OMA; WGTYLVK; -.
DR OrthoDB; 684058at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015421; F:ABC-type oligopeptide transporter activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0090374; P:oligopeptide export from mitochondrion; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Glycoprotein; Membrane; Nucleotide-binding;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..791
FT /note="ABC multidrug transporter mdr2"
FT /id="PRO_0000445103"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 220..240
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 307..324
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT DOMAIN 182..471
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 504..741
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 754..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 539..546
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 508
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 791 AA; 85169 MW; EAA0F7C35CC3BCF0 CRC64;
MRGIRSLPCW APGLSTKRIP PRELFADLFP NACVISARHS ARNGLIRQFS GCSGSISNSC
NPRPYRSAIT SLLSANVCSK GVSAVQPRFL STVRLFSTSQ RSLEPKSNVK STGGQVVRPE
LHQDQEHEDI EKGFELSERA AQAAQVNLSA KLAKDGAAGK KAGFKEIWRL LLIARPEAKK
LALAFLFLLV SSGITMSIPF SIGKIMDTST KATTEGGNEL FGLSLPMFYG ALAGILTLGA
AANYGRIIIL RIVGERIVAR LRSKLFRQTF VQDAEFFDAN RVGDLISRLS SDTIIVGKSI
TQNLSDGLRA AVSGAAGFGL MAYVSLKLSS ILALLLPPIG LGAFFYGRAI RNLSRQIQRN
LGTLTKIAEE RLGNVKTSQS FAGEVLEVRR YNNQVRKIFE LGKKESLISA TFFSSTGFAG
NMTILALLYV GGGMVQSGAI TIGELTSFLM YTAYAGSSMF GLSSFYSELM KGVGAASRLF
ELQDRQPTIS PTKGEKVASA RGPIRFENVT FSYPTRPAVP IFRDLNFEIP QGTNVAIVGP
SGGGKSTIAS ILLRFYSPTE GRVLIGGKDI THMNAKSLRR KIGIVSQEPV LFSGTIAENI
AYGKPQAKRS EIVAAARKAN CQFISDFPDG LDTQVGPRGA QLSGGQKQRI AIARALIKDP
DILILDEATS ALDAESETLV NSALTALLRG NNTTISIAHR LSTIKRSDTI IVLGPDGRVA
EQGSYEELSA RPDGAFTKLM EWQMSGGEVM DQLANTPANP VAQETSWDLQ SDDGTEISED
TNIPSEPRTI D
