ABCA2_ASPFU
ID ABCA2_ASPFU Reviewed; 1499 AA.
AC Q4X006;
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 A-2 {ECO:0000305};
GN Name=abcA {ECO:0000303|PubMed:24123268}; ORFNames=AFUA_2G15130;
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 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 [3]
RP FUNCTION.
RX PubMed=23796749; DOI=10.1016/j.fgb.2013.06.004;
RA Paul S., Moye-Rowley W.S.;
RT "Functional analysis of an ATP-binding cassette transporter protein from
RT Aspergillus fumigatus by heterologous expression in Saccharomyces
RT cerevisiae.";
RL Fungal Genet. Biol. 57:85-91(2013).
RN [4]
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 confers resistance to
CC structurally and functionally unrelated compounds including azoles such
CC as itraconazole, posaconazole, and voriconazole.
CC {ECO:0000269|PubMed:23796749, ECO:0000269|PubMed:24123268,
CC 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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33504;
CC Evidence={ECO:0000269|PubMed:24123268};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000269|PubMed:24123268};
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 induced upon voriconazole treatment
CC (PubMed:24123268). Expression is also induced in triazole-resistant
CC isolates (PubMed:32209680). {ECO:0000269|PubMed:24123268,
CC ECO:0000269|PubMed:32209680}.
CC -!- DISRUPTION PHENOTYPE: Leads to decreased azole resistance, including
CC itraconazole, posaconazole and voriconazole.
CC {ECO:0000269|PubMed:24123268}.
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; AAHF01000001; EAL93809.1; -; Genomic_DNA.
DR RefSeq; XP_755847.1; XM_750754.1.
DR AlphaFoldDB; Q4X006; -.
DR SMR; Q4X006; -.
DR STRING; 746128.CADAFUBP00003017; -.
DR EnsemblFungi; EAL93809; EAL93809; AFUA_2G15130.
DR GeneID; 3512747; -.
DR KEGG; afm:AFUA_2G15130; -.
DR VEuPathDB; FungiDB:Afu2g15130; -.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; Q4X006; -.
DR OMA; SIFHWQD; -.
DR OrthoDB; 37708at2759; -.
DR PHI-base; PHI:4229; -.
DR Proteomes; UP000002530; Chromosome 2.
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..1499
FT /note="ABC multidrug transporter A-2"
FT /id="PRO_0000445096"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 561..581
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 606..626
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 635..655
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 669..689
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 778..798
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1193..1213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1227..1247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1268..1288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1317..1337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1353..1373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1466..1486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 166..415
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 857..1100
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 80..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 893..900
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 763
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1499 AA; 168667 MW; F83716A62AFBE896 CRC64;
MAMQPSYPAP FGAAAISSSA GQEVASTIRR QFTDADADRI VETPLGEKAD SSDTAGPDSE
DGIDQEGHDK ITALARSLSQ ISQKSAGPTN TFLDPSSDPE LDPNSDKFSS RKWMKNLLHI
KTRDPDRYPR RTAGVSFRNL NAYGYGTAAD YQADVANMWL KGFGWLRSIL GCRNRVQIDI
LRNFEGFVRS GEMLVVLGRP GSGCSTFLKT IAGETHGLWL DEGTHIQYEG ISWDEMHSRF
RGEVIYQAET EIHFPQLTAG ETLLFAAQAR TPANRFPGVS REQYATHMRD VVMTMLGLSH
TVNTRIGNEY IRGVSGGERK RVSIAETILC GCPLQCWDNS TRGLDSSTAL EFVKNLRLST
DYTGSTAIVA IYQASQAIYD IFDKVIVLYE GRQIYFGKAS DAKRFFIDMG FDCPDRQTTG
DFLTSLTSPS ERLVRKGYEA LVPRTPDEFA ARWRESAERQ RLLADIEAFE NESPLGGSKY
KEFTVSRAAE KAKGTRAPSP YTLSYPMQIR LCLRRGFLRL KGDMSMTLAT VIGNSIMAFI
VSSVFYNLDQ TTNSFFSRGA LLFFAILLNA FASSLEILTL WQQRPIVEKH DKYALYHPSA
EAISSMIVDL PSKFLVSVVF NLILYFMTNL RRTPGHFFVF YLFSVTITLT MSNIFRWIGA
ISRSMAQAMV PSSIFMMILV IYTGFTIPVR DMHPWFKWLN YLNPIGYAFE SLMINEFSDR
RFPCAQYVPA GPGYEDVPLS SKICSQKGAV AGQDYVDGDA FINTSYRYFS SHLWRNYGII
LGFFFFFLAA YIICSELVRA KPSKGEILVF PRGKIPAFVK KSRRDGDLEG APTFEKQQLD
NAGHDSTAAI VKQTSIFHWQ DVCYDIKVKG ETRRILDHID GWVKPGTLTA LMGVTGAGKT
SLLDVLANRV TMGVITGEML VDGRMRDDSF QRKTGYVQQQ DLHLETSTVR EALIFSATLR
QPASTPHKEK LAYVEEVIKM LNMEEYAEAV VGVLGEGLNV EQRKRLTIGV ELAAKPALLC
FFDEPTSGLD SQTAWSICTL MRKLADHGQA ILCTIHQPSA ILMQQFDRLL FLAKGGKTVY
FGELGPNMET LIKYFENKGS SKCPKNANPA EWMLEVIGAA PGSHADQDWP EVWNNSPERA
QVRAELARMK EELLQRPPPP RTKEYGEFAM PLWAQFLVCL QRMFQQYWRS PSYIYSKAAT
SIIPPLFIGF TFWREPTSLQ GLQNQMFAIF MLLVIFPNLV QQMMPYFVTQ RALYEVRERP
SKAYSWKAFM LASILVELPW NILMAVPAYF CWYYPIGLYR NAYPTDSVTE RGGTMFLLIL
IFMMFTSTFS SMIIAGIEQP ETGGNIAQLL FSLCLIFNGV LASPSALPGF WIFMYRVSPF
TYLVSAVLSV GLAGTSVKCS DIEILHVPPP QGQNCSSFLD AYVQMSHGRL LNPEATSDCQ
VCPVADTDTF LAQVSISYSD RWRNVGLLFV YIVFNIFAAI FLYWLIRVPK KRSRKIKEE
