ABCC_ASPFU
ID ABCC_ASPFU Reviewed; 1497 AA.
AC E9RBG1; Q4WS17; Q6MY55;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=ABC multidrug transporter C {ECO:0000303|PubMed:16622700};
GN Name=abcC {ECO:0000303|PubMed:16622700};
GN Synonyms=abcB {ECO:0000303|PubMed:24123268},
GN abcG1 {ECO:0000303|PubMed:28264842}, atrE {ECO:0000303|PubMed:14998527},
GN cdr1B {ECO:0000303|PubMed:23580559}; ORFNames=AFUA_1G14330;
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 [GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=14998527; DOI=10.1016/j.fgb.2003.12.003;
RA Pain A., Woodward J.R., Quail M.A., Anderson M.J., Clark R., Collins M.,
RA Fosker N., Fraser A., Harris D.E., Larke N., Murphy L.D., Humphray S.,
RA O'Neil S., Pertea M., Price C., Rabbinowitsch E., Rajandream M.A.,
RA Salzberg S.L., Saunders D., Seeger K., Sharp S., Warren T., Denning D.W.,
RA Barrell B.G., Hall N.;
RT "Insight into the genome of Aspergillus fumigatus: analysis of a 922 kb
RT region encompassing the nitrate assimilation gene cluster.";
RL Fungal Genet. Biol. 41:443-453(2004).
RN [2]
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 [3]
RP IDENTIFICATION, INDUCTION, AND FUNCTION.
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22509997; DOI=10.1111/j.1574-6968.2012.02575.x;
RA Bowyer P., Mosquera J., Anderson M., Birch M., Bromley M., Denning D.W.;
RT "Identification of novel genes conferring altered azole susceptibility in
RT Aspergillus fumigatus.";
RL FEMS Microbiol. Lett. 332:10-19(2012).
RN [5]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=24123268; DOI=10.1128/ec.00171-13;
RA Paul S., Diekema D., Moye-Rowley W.S.;
RT "Contributions of Aspergillus fumigatus ATP-binding cassette transporter
RT proteins to drug resistance and virulence.";
RL Eukaryot. Cell 12:1619-1628(2013).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=23580559; DOI=10.1093/jac/dkt075;
RA Fraczek M.G., Bromley M., Buied A., Moore C.B., Rajendran R., Rautemaa R.,
RA Ramage G., Denning D.W., Bowyer P.;
RT "The cdr1B efflux transporter is associated with non-cyp51a-mediated
RT itraconazole resistance in Aspergillus fumigatus.";
RL J. Antimicrob. Chemother. 68:1486-1496(2013).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28264842; DOI=10.1128/aac.02748-16;
RA Paul S., Diekema D., Moye-Rowley W.S.;
RT "Contributions of both ATP-Binding Cassette Transporter and Cyp51A Proteins
RT Are Essential for Azole Resistance in Aspergillus fumigatus.";
RL Antimicrob. Agents Chemother. 61:0-0(2017).
RN [8]
RP INDUCTION.
RX PubMed=28052140; DOI=10.1371/journal.ppat.1006096;
RA Hagiwara D., Miura D., Shimizu K., Paul S., Ohba A., Gonoi T., Watanabe A.,
RA Kamei K., Shintani T., Moye-Rowley W.S., Kawamoto S., Gomi K.;
RT "A novel Zn2-Cys6 transcription factor atrR plays a key role in an azole
RT resistance mechanism of Aspergillus fumigatus by co-regulating cyp51A and
RT cdr1B Expressions.";
RL PLoS Pathog. 13:E1006096-E1006096(2017).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP AND INDUCTION.
RX PubMed=32209680; DOI=10.1128/mbio.00338-20;
RA Esquivel B.D., Rybak J.M., Barker K.S., Fortwendel J.R., Rogers P.D.,
RA White T.C.;
RT "Characterization of the efflux capability and substrate specificity of
RT Aspergillus fumigatus PDR5-like ABC transporters expressed in Saccharomyces
RT cerevisiae.";
RL MBio 11:0-0(2020).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that shows a strong
CC substrate specificity for the azole class of drugs such as lotrimazole
CC (CLT), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC),
CC posaconazole (POS), tebuconazole (TEBZ), and voriconazole (VRC)
CC (Probable) (PubMed:22509997, PubMed:23580559, PubMed:24123268,
CC PubMed:28264842, PubMed:32209680). Is also able to transport rhodamine
CC 6G (R-6G), a known substrate for many ABC transporters
CC (PubMed:32209680). Required for normal pathogenesis in a Galleria
CC mellonella (greater wax moth) infection model (PubMed:24123268).
CC {ECO:0000269|PubMed:22509997, ECO:0000269|PubMed:23580559,
CC ECO:0000269|PubMed:24123268, ECO:0000269|PubMed:28264842,
CC ECO:0000269|PubMed:32209680, ECO:0000305|PubMed:16622700}.
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:32209680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61917;
CC Evidence={ECO:0000269|PubMed:32209680};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + itraconazole(in) = ADP + H(+) + itraconazole(out)
CC + phosphate; Xref=Rhea:RHEA:33503, ChEBI:CHEBI:6076,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:24123268, ECO:0000269|PubMed:32209680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33504;
CC Evidence={ECO:0000269|PubMed:24123268, ECO:0000269|PubMed:32209680};
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:24123268, ECO:0000269|PubMed:32209680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000269|PubMed:24123268, ECO:0000269|PubMed:32209680};
CC -!- ACTIVITY REGULATION: The efflux inhibitor FK506 impairs the transport
CC activity. {ECO:0000269|PubMed:32209680}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24123268};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the atrR transcription
CC factor (PubMed:28052140). Expression is induced upon voriconazole
CC treatment (PubMed:16622700, PubMed:24123268). Expression is increased
CC in clinical azole-resistant isolates (PubMed:23580559,
CC PubMed:32209680). In particular F20140, F18304 and F18454 show over 25-
CC fold greater basal expression levels, whereas F19980 (7.2-fold), F20063
CC (6.5-fold), F20451 (3.6-fold), F18454 (5.1-fold) and F15483 (2.1-fold)
CC also show significantly raised levels of basal expression
CC (PubMed:23580559). {ECO:0000269|PubMed:16622700,
CC ECO:0000269|PubMed:23580559, ECO:0000269|PubMed:24123268,
CC ECO:0000269|PubMed:28052140, ECO:0000269|PubMed:32209680}.
CC -!- DISRUPTION PHENOTYPE: Leads to decreased azole resistance, including
CC itraconazole, posaconazole and voriconazole.
CC {ECO:0000269|PubMed:22509997, ECO:0000269|PubMed:23580559,
CC ECO:0000269|PubMed:24123268, ECO:0000269|PubMed:28264842}.
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; BX649607; CAF32148.1; -; Genomic_DNA.
DR EMBL; AAHF01000004; EAL90765.1; -; Genomic_DNA.
DR RefSeq; XP_752803.1; XM_747710.1.
DR AlphaFoldDB; E9RBG1; -.
DR SMR; E9RBG1; -.
DR STRING; 746128.CADAFUBP00001360; -.
DR EnsemblFungi; EAL90765; EAL90765; AFUA_1G14330.
DR GeneID; 3509814; -.
DR KEGG; afm:AFUA_1G14330; -.
DR VEuPathDB; FungiDB:Afu1g14330; -.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; E9RBG1; -.
DR OMA; IAEATLC; -.
DR OrthoDB; 37708at2759; -.
DR PHI-base; PHI:4230; -.
DR PHI-base; PHI:8901; -.
DR Proteomes; UP000002530; Chromosome 1.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:AspGD.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IEA:InterPro.
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; IPR005285; Drug-R_PDR/CDR.
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 TIGRFAMs; TIGR00956; 3a01205; 1.
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; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1497
FT /note="ABC multidrug transporter C"
FT /id="PRO_0000445098"
FT TRANSMEM 523..543
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 557..577
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 599..621
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1192..1212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1226..1246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1273..1293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1313..1333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1352..1372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1464..1484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 158..412
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 853..1096
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 815..843
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 816..830
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 889..896
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 762
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1497 AA; 168184 MW; 706E5D1B5C097043 CRC64;
MSLLGTINPN INPERTVAGR GTQEEEGEIA RVEHNHHNNA ASVSTDETVL ERSKEIGDED
VAVEEVTRLA RQLTRQSTRF STSGNVENPF LETKEDSTLN PLSPNFKAKN WMKNLLALSS
RDPERYPKRV AGVAFKNLSV HGYGSPTDYQ KDVFNSVLEV GTLVRRIMGT GKQKIQILRD
FDGLVKSGEM LVVLGRPGSG CSTFLKTISG EMNGIYMDEK SYLNYQGISS KQMRKQFRGE
AIYTAETDVH FPQLTVGDTL KFAALARAPR NRLPGVSREQ YAVHMRDVVM AMLGLTHTMN
TRVGNDFVRG VSGGERKRVS IAEATLSGSP LQCWDNSTRG LDSANALEFC KTLNLMTKYA
GATVAVAIYQ ASQSAYDVFD KVTVLYEGRQ IYFGRTDEAK EFFTNMGFEC PERQTTADFL
TSLTSPAERV VKPGFEGKVP QTPDEFVRAW KSSEAYAKLM REIEEYDREF PIGGESLNQF
IESRRAMQAK NQRVKSPYTI SVWQQIELCM IRGFQRLKGD SSLTMSQLIG NFIMALVIGS
VFYNLPDDTS SFYARGALLF FAVLLNAFSS ALEILTLYAQ RPIVEKQARY AMYHPFAEAI
ASMLCDMPYK ITNAIIFNLT LYFMTNLRRE PGAFFVFLLF SFVTTLTMSM LFRTMAASSR
TLSQALVPAA ILILGLVIYT GFTIPTRNML GWSRWMNYID PIAYGFESLM VNEFHNRQFL
CPDSAFVPSS GAYDSQPLAY RVCSTVGSVS GSRYVQGDDY LNQSFQYYKS HQWRNLGIMF
GFMFFFMFTY LTATEYISES KSKGEVLLFR RGHAQPTGSH DVEKSPEVSS AAKTDEASSK
EATGAIQRQE AIFQWKDVCY DIKIKGEPRR ILDHVDGWVK PGTCTALMGV SGAGKTTLLD
VLATRVTMGV VSGEMLVDGR PRDQSFQRKT GYVQQQDLHL HTTTVREALR FSALLRQPAH
VPRQEKIDYV EEVIKLLGME SYADAVVGVP GEGLNVEQRK RLTIGVELAA KPQLLLFLDE
PTSGLDSQTS WSILDLIDTL TKHGQAILCT IHQPSAMLFQ RFDRLLFLAK GGKTVYFGEI
GEKSSTLASY FERNGAPKLP PDANPAEWML EVIGAAPGSH SDIDWPAVWR DSPERRAVHE
HLDELKRTLS QKPIDPSKAD PGSYDEFAAP FTIQLWECLL RVFSQYWRTP VYIYSKTALC
VLTALYIGFS FFNAQNSAQG LQNQMFSIFM LMTIFGNLVQ QIMPNFCTQR SLYEVRERPS
KTYSWKAFMA ANIIVELPWN TLMAFLIFVC WYYPIGLYRN AEPTDSVHER GALMFLLIWS
FLLFTSTFAH MMIAGIELAE TGGNLANLLF SLCLIFCGVL APPQSLPGFW IFMYRVSPFT
YLVSAMLSTG VSGTNAVCEP VEFLHFDPPS NMTCKDYMAD YISTRGGYLE NPSATSDCTF
CTISSTDTFL SAVSSHYSDA WRNFGIMWAY IIFNIFAAVF IYWLARVPKG KRTKGST
