MDR1_ASPFU
ID MDR1_ASPFU Reviewed; 1349 AA.
AC Q4WTT9;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=ABC multidrug transporter mdr1 {ECO:0000303|PubMed:9373135};
GN Name=mdr1 {ECO:0000303|PubMed:9373135};
GN Synonyms=abcA {ECO:0000303|PubMed:16622700}; ORFNames=AFUA_5G06070;
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=16622700; DOI=10.1007/s00294-006-0073-2;
RA da Silva Ferreira M.E., Malavazi I., Savoldi M., Brakhage A.A.,
RA Goldman M.H., Kim H.S., Nierman W.C., Goldman G.H.;
RT "Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole.";
RL Curr. Genet. 50:32-44(2006).
RN [5]
RP INDUCTION.
RX PubMed=18721228; DOI=10.1111/j.1365-2958.2008.06376.x;
RA Schrettl M., Kim H.S., Eisendle M., Kragl C., Nierman W.C., Heinekamp T.,
RA Werner E.R., Jacobsen I., Illmer P., Yi H., Brakhage A.A., Haas H.;
RT "SreA-mediated iron regulation in Aspergillus fumigatus.";
RL Mol. Microbiol. 70:27-43(2008).
RN [6]
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).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that may be involved in
CC A.fumigatus adaptation to azoles such as vorizonazole.
CC {ECO:0000269|PubMed:9373135, ECO:0000305|PubMed:16622700}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + voriconazole(in) = ADP + H(+) + phosphate +
CC voriconazole(out); Xref=Rhea:RHEA:61912, ChEBI:CHEBI:10023,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:16622700};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000305|PubMed:16622700};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced upon voriconazole treatment
CC (PubMed:16622700). Expression is up-regulated in sreA deficiency
CC strains, probably in response to accumulation of toxic compounds
CC (PubMed:18721228). Expression is up-regulated during biofilm growth
CC (PubMed:21724936). Expression is increased in clinical azole-resistant
CC isolates (PubMed:15504870). {ECO:0000269|PubMed:15504870,
CC ECO:0000269|PubMed:16622700, ECO:0000269|PubMed:18721228,
CC ECO:0000269|PubMed:21724936}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000003; EAL91987.1; -; Genomic_DNA.
DR RefSeq; XP_754025.1; XM_748932.1.
DR AlphaFoldDB; Q4WTT9; -.
DR SMR; Q4WTT9; -.
DR STRING; 746128.CADAFUBP00005250; -.
DR EnsemblFungi; EAL91987; EAL91987; AFUA_5G06070.
DR GeneID; 3511130; -.
DR KEGG; afm:AFUA_5G06070; -.
DR VEuPathDB; FungiDB:Afu5g06070; -.
DR eggNOG; KOG0055; Eukaryota.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; Q4WTT9; -.
DR OMA; RSDANFW; -.
DR OrthoDB; 186078at2759; -.
DR Proteomes; UP000002530; Chromosome 5.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Glycoprotein; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1349
FT /note="ABC multidrug transporter mdr1"
FT /id="PRO_0000445102"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 779..799
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 828..848
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 896..916
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 926..948
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 1016..1036
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 1043..1063
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT DOMAIN 112..402
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 437..682
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 780..1069
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1104..1342
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..62
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 472..479
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1139..1146
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 878
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 893
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1349 AA; 147784 MW; 5C7C751A58B31043 CRC64;
MPAPETGASS REKSLEDLQV ATLEKGRSTS SFGADNEKPH DHHSLSDTIM APPDGKQKDH
GKAVDLNDDS LFAHLQEHEK EVLKRQLDAP SVKVSFFTLY RYASRKDILI ILVSAICAIA
AGAALPLFTI LFGSLASAFQ GISLGTMPYH EFYHKLTKNV LYFVYLGIAE FVTVYVSTVG
FIYTGEHLTQ KIRENYLEAI LRQNMAYFDK LGAGEVTTRI TADTNLIQDA ISEKVGLTLT
AFATFVTAFI VAYVKYWKLA LICTSTIVAL VMVMGGGSRF IVKYSKKSIE SYGAGGTVAE
EVISSIRNAT AFGTQDKLAK QYETHLAEAE KWGVKQQVIL GMMIGGMFGI MFSNYGLGFW
MGSRFVVGKE VNVGQVLTVL MSILIGSFSL GNVAPNGQAF TNGVAAAAKI YSTIDRRSPL
DPYSDEGKVL DHFEGNIEFR NVKHIYPSRP EVTVMEDVSL SMPAGKTTAL VGPSGSGKST
VVGLVERFYL PVGGQVLLDG HDIQTLNLRW LRQQISLVSQ EPVLFSTTIF RNIEHGLIGT
KFEHESKDKI RELVENAARM ANAHDFIMAL PEGYDTNVGQ RGFLLSGGQK QRIAIARAIV
SDPKILLLDE ATSALDTKSE GVVQAALDKA AEGRTTIVIA HRLSTIKTAH NIVAMVGGKI
AEQGTHDELV DRKGTYYKLV EAQRINEEKE AEALEADADM DADDFGQEGV TRIKTAVSSS
NSLDAVDEKA RLEMKRTGTQ KSVSSAVLSK KVPEQFEKYS LWTLVKFIGA FNRPELGYML
IGLTFSFLAG GGQPTQAFLY AKAISTLSLP ESMFHKLRHD ANFWSLMFFV VGIAQFISLS
INGTAFAICS ERLIRRARSQ AFRSILRQDI SFFDREENST GALTSFLSTE TKNLSGVSGV
TLGTIIMTST TLGAAMIIAL AIGWKLALVC ISVVPILLAC GFLRFYMLAQ FQQRSKSAYE
GSASYACEAT SAIRTVASLT REQDVWGVYH DQLQKQGRKS LISVLRSSLL YASSQALVFF
CVALGFWYGG TLLGHHEYSI FRFFVCFSEI LFGAQSAGTV FSFAPDMGKA KNAAAQFKKL
FDSKPTIDIW SDEGEKLESM EGEIEFRDVH FRYPTRPEQP VLRGLNLSVK PGQYIALVGP
SGCGKSTTIA LLERFYDALA GGVFVDGKDI TKLNVNSYRS FLSLVSQEPT LYQGTIKENI
LLGVDKDDVS EETLIKVCKD ANIYDFVMSL PEGFDTVVGS KGGMLSGGQK QRVAIARALL
RDPKVLLLDE ATSALDSESE KVVQAALDAA ARGRTTIAVA HRLSTIQNAD IIYVFDQGKI
VESGTHHELI RNKGRYYELV NLQSLGKTH
