ATRF_ASPFU
ID ATRF_ASPFU Reviewed; 1547 AA.
AC Q4WDD4;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=ABC multidrug transporter atrF;
GN Name=atrF {ECO:0000303|PubMed:12135575}; ORFNames=AFUA_6G04360;
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 INDUCTION.
RX PubMed=12135575; DOI=10.1016/s1087-1845(02)00016-6;
RA Slaven J.W., Anderson M.J., Sanglard D., Dixon G.K., Bille J.,
RA Roberts I.S., Denning D.W.;
RT "Increased expression of a novel Aspergillus fumigatus ABC transporter
RT gene, atrF, in the presence of itraconazole in an itraconazole resistant
RT clinical isolate.";
RL Fungal Genet. Biol. 36:199-206(2002).
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 FUNCTION, INDUCTION, AND CATALYTIC ACTIVITY.
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).
RN [5]
RP FUNCTION, AND 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: Pleiotropic ABC efflux transporter involved in the basal
CC level of azole susceptibility (PubMed:26933209, PubMed:28080217).
CC Confers resistance to fluconazole and voriconazole (PubMed:26933209).
CC {ECO:0000269|PubMed:26933209, ECO:0000269|PubMed:28080217}.
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:0000269|PubMed:26933209};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000269|PubMed:26933209};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + fluconazole(in) + H2O = ADP + fluconazole(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:61916, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:46081, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26933209};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced upon voriconazole treatment
CC (PubMed:12135575, PubMed:15504870). Expression is increased in clinical
CC azole-resistant isolates (PubMed:26933209, PubMed:28080217,
CC PubMed:29124846). Expression is down-regulated by tetrandrine and
CC posaconazole in a synergistic manner (PubMed:28080217).
CC {ECO:0000269|PubMed:12135575, ECO:0000269|PubMed:15504870,
CC ECO:0000269|PubMed:26933209, ECO:0000269|PubMed:28080217,
CC ECO:0000269|PubMed:29124846}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC PDR (TC 3.A.1.205) subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000012; EAL85604.1; -; Genomic_DNA.
DR RefSeq; XP_747642.1; XM_742549.1.
DR AlphaFoldDB; Q4WDD4; -.
DR SMR; Q4WDD4; -.
DR STRING; 330879.Q4WDD4; -.
DR TCDB; 3.A.1.205.30; the atp-binding cassette (abc) superfamily.
DR EnsemblFungi; EAL85604; EAL85604; AFUA_6G04360.
DR GeneID; 3505316; -.
DR KEGG; afm:AFUA_6G04360; -.
DR VEuPathDB; FungiDB:Afu6g04360; -.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; Q4WDD4; -.
DR OMA; SSWGQWI; -.
DR OrthoDB; 1022017at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR CDD; cd03233; ABCG_PDR_domain1; 1.
DR CDD; cd03232; ABCG_PDR_domain2; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR013525; ABC_2_trans.
DR InterPro; IPR029481; ABC_trans_N.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR043926; ABCG_dom.
DR InterPro; IPR034001; ABCG_PDR_1.
DR InterPro; IPR034003; ABCG_PDR_2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR010929; PDR_CDR_ABC.
DR Pfam; PF01061; ABC2_membrane; 2.
DR Pfam; PF19055; ABC2_membrane_7; 1.
DR Pfam; PF00005; ABC_tran; 2.
DR Pfam; PF14510; ABC_trans_N; 1.
DR Pfam; PF06422; PDR_CDR; 1.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Glycoprotein; Hydrolase; Membrane;
KW Nucleotide-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1547
FT /note="ABC multidrug transporter atrF"
FT /id="PRO_0000445100"
FT TRANSMEM 552..572
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 586..606
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 635..655
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 657..677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 698..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 722..742
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 804..824
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1230..1250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1260..1280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1309..1329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1334..1354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1356..1376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1397..1417
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1491..1511
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1520..1540
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 197..439
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 892..1130
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 85..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..66
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 928..935
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 905
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 980
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 999
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1547 AA; 173257 MW; D8CD0F561E5CD226 CRC64;
MADGSRLPES ATSTTMETNT NEHAKVLSPD AETVPSSSMT ATSSELSLDG RWGERDQGEP
VSRRGAMEDF EEMRRELTQL SLRRTRSVGK DAHRLRSRAS GRASQVHDEE KAIDEEDSTI
DGDGDGYQGG FDLGEFLMGG HLERRTTTGE PAKKVGVLFK HLTVKGVETG ASFVRTLPDA
VVGTFGPDLY RIVCSFIPQL RFGKQPPVRE LLHDFTGLVR EGEMMLVLGR PGAGCSTFLK
TIANDRGAFA GVEGEVRYGG LSAEEQLKHF RGEVNYNPED DQHFPSLTVW QTLKFSLINK
TKKHDKNSIP IIIDALLKMF GITHTKNTLV GNEYVRGVSG GERKRVSIAE TLATKSSVVC
WDNSTRGLDA STALDYAKSL RIMTDVSKRT TFVTLYQAGE SIYELMDKVL VIDSGRMLYQ
GPANKAREYF VNLGFHCPEK STTADFLTSI CDPNARQFQP GREASTPKTP EELEAVFRNS
ETYKTICDEV ASYEKKLQDT DQEDTRRFQK TVAQSKSRTV SKKSSYTVSF ARQVLACVQR
EFWLLWGDKT SLYTKYFIII SNALIVSSLF YGESLDTSGA FSRGGALFFS ILFLGWLQLT
ELMPAVTGRG IVARHKEYAF YRPSAVSIAR VVMDFPAIFC MVVPFTIIMY FMTGLDVTAS
KFFIYFLFVY TTTFSITSLY RMFAALSPTI DDAVRFSGIA LNILVIFVGY VIPKQGLIDG
SIWFGWLFYV NPIAYSYEAV LTNEFSDRIM DCAPSQLVPQ GPGVDPRYQG CALPGSELGR
RGVSGSRYLE ESFQFTRSHL WRNFGVVIAF TVLYLIVTVL AAEFLSFVGG GGGALVFKRS
KRAKKLATQT TQGNDEEKVQ DVGDKAALSR GEAMSASNGE SFKRISSSDR IFTWSNVEYT
VPYGNGTRKL LNGVNGYAKP GVMIALMGAS GAGKTTLLNT LAQRQKMGVV TGDFLVDGRP
LGADFQRGTG FCEQMDLHDN TSTIREALEF SALLRQDRNV SKQEKLDYVD QIIDLLELND
IQDAIIGSLN VEQKKRVTIG VELAAKPSLL LFLDEPTSGL DSQAAFSIVR FLKKLSLAGQ
AILCTIHQPS SMLIQQFDMI LALNPGGNTF YFGPVGHDGG DVIKYFADRG VVCPPSKNVA
EFILETAAKA TTTKDGKKID WNEEWRNSEQ NQRVLDEIQQ IREERSKIPV TETGSPYEFA
ASTMTQTLLL TKRIFRQYWR DPSYYYGKLF VSVIIGIFNG FTFWMLGNSI ANMQDRMFSI
FLIIMIPPVV LNSIVPKFYI NRALWEAREY PSRIYGWFAF CTANIVCEIP MAIVSSLIYW
LLWYYPVGFP TDSSTAGYVF LMSMLFFLFM SSWGQWICAF APSFTVISNV LPFFFVMCNL
FNGIVRPYRD YPVFWKYWMY YVNPVTWWLR GVISSIFPTV QIDCSPSETT HFNPPPGQTC
ANYAGNFITN IAKNGYLLNP DASADCQYCP YSNGAEYMAT LNVHDGDKWR CFGIFLAFVI
INWLLVYFFI YTVRVRGWSF GMGYLFGGMG LVIDKVKGVF KRKSEKA
