AFR2_CRYGR
ID AFR2_CRYGR Reviewed; 1529 AA.
AC P9WEU3;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=ABC multidrug transporter AFR2 {ECO:0000303|PubMed:25630649};
GN Name=AFR2 {ECO:0000303|PubMed:25630649}; ORFNames=CNBG_6088;
OS Cryptococcus gattii serotype B (strain R265) (Filobasidiella gattii)
OS (Cryptococcus bacillisporus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus gattii species complex.
OX NCBI_TaxID=294750;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=R265;
RX PubMed=21304167; DOI=10.1128/mbio.00342-10;
RA D'Souza C.A., Kronstad J.W., Taylor G., Warren R., Yuen M., Hu G.,
RA Jung W.H., Sham A., Kidd S.E., Tangen K., Lee N., Zeilmaker T., Sawkins J.,
RA McVicker G., Shah S., Gnerre S., Griggs A., Zeng Q., Bartlett K., Li W.,
RA Wang X., Heitman J., Stajich J.E., Fraser J.A., Meyer W., Carter D.,
RA Schein J., Krzywinski M., Kwon-Chung K.J., Varma A., Wang J., Brunham R.,
RA Fyfe M., Ouellette B.F.F., Siddiqui A., Marra M., Jones S., Holt R.,
RA Birren B.W., Galagan J.E., Cuomo C.A.;
RT "Genome variation in Cryptococcus gattii, an emerging pathogen of
RT immunocompetent hosts.";
RL MBio 2:E342-E342(2011).
RN [2]
RP FUNCTION, INDUCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=25630649; DOI=10.1093/jac/dku554;
RA Basso L.R. Jr., Gast C.E., Bruzual I., Wong B.;
RT "Identification and properties of plasma membrane azole efflux pumps from
RT the pathogenic fungi Cryptococcus gattii and Cryptococcus neoformans.";
RL J. Antimicrob. Chemother. 70:1396-1407(2015).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=29378705; DOI=10.1128/aac.01751-17;
RA Chang M., Sionov E., Khanal Lamichhane A., Kwon-Chung K.J., Chang Y.C.;
RT "Roles of three Cryptococcus neoformans and Cryptococcus gattii efflux
RT pump-coding genes in response to drug treatment.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that confers resistance to
CC structurally and functionally unrelated compounds including azoles such
CC as fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and
CC voriconazole (VRC). {ECO:0000269|PubMed:25630649,
CC ECO:0000269|PubMed:29378705}.
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:25630649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33504;
CC Evidence={ECO:0000269|PubMed:25630649};
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:25630649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000269|PubMed:25630649};
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:25630649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61917;
CC Evidence={ECO:0000269|PubMed:25630649};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.36 uM for fluconazole transport {ECO:0000269|PubMed:25630649};
CC Vmax=33.98 pmol/min/mg enzyme for fluconazole transport
CC {ECO:0000269|PubMed:25630649};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25630649};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced in the presence of fluconazole (FLC).
CC {ECO:0000269|PubMed:25630649, ECO:0000269|PubMed:29378705}.
CC -!- DISRUPTION PHENOTYPE: Does not affect the susceptibility to azoles, but
CC displays slightly lower minimum inhibitory concentrations (MICs) to
CC cycloheximide and higher MICs to rhodamine 6G (R-6G) (PubMed:29378705).
CC Causes further increase in susceptibility toward fluconazole and
CC itraconazole, when AFR1 and MDR1 are also deleted (PubMed:29378705).
CC {ECO:0000269|PubMed:29378705}.
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; CP025772; KGB80250.2; -; Genomic_DNA.
DR AlphaFoldDB; P9WEU3; -.
DR SMR; P9WEU3; -.
DR Proteomes; UP000029445; Chromosome 14.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; 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; 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; 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; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1529
FT /note="ABC multidrug transporter AFR2"
FT /id="PRO_0000452666"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 589..609
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 614..634
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 648..668
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1193..1213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1229..1249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1268..1288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1314..1334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1353..1373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1465..1485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 144..394
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 845..1087
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1493..1529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1505..1529
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 881..888
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 742
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1529 AA; 170343 MW; 891521079693C369 CRC64;
MAFAGVGQGI GTYDRTEQAS GAPLGRVTSR AHFTDIHPSD DLPAQTEENR AREVGHLARQ
LTRQSVTVTD DSTDVFSYQE GSDLDPFSDK FNAKKWTKLM FEAVQTCGPA RKAGLSFRNL
GVHGFGSDAD YQKTVGNLPL VGIGSLRDLI GNRKRKVQIL NSMDGVLEAG EMLVVLGPPG
SGCTTMLKTI AGEMNGIYLD ESSSLNYRGI TPKEIYGQFR GEAIYTAEVD IHFPNLTVGQ
TLSFAAEARA PRNPPGGISK KEYAKHMRDV VMSVFGISHT LNTIVGNDFV RGVSGGERKR
VTIAEASLAG APLQCWDNST RGLDSANAIE FCKNLRLNAD YMGISSAVAI YQAPQSAYDC
FDKVSVLYEG EQIFFGKTTD AKQFFVDMGF HCPSQQTVPD FLTSLTSPSE RRPREGFEGK
VPTTPQEFAA RWKQSDKYQE LLAQIAEFEN KYPVHGEKYR EFLESRRAQQ SKHLRSKSPY
TLSYGGQVEL CLRRGFDRLR ADPSLTLTQL FGNFIMALII GSVFYNLPVT TSSFYSRGAL
LFFAILMSAF GSALEILILY AQRGIVEKHS RYAFYHPSAE AVASALTDIP YKVMNCIIFN
LTLYFMTNLR REPGAYFFFM LISFTLTMVM SMLFRSIASL SRSLTQALAP AALLILGLVM
YTGFAVNVAN MRGWARWMNW LDPIAYGFES LMINEFHGRE YECSTFVPMG PGYEDATGQQ
HVCSTAGAVA GSSVVNGDAY INLSYEYYHA HKWRNFGILI GFFLFFTAIY LTATEFITAK
KSKGEILVFP RGKIPHALLA QSTHSHGSSD DVEGGKFAGG SNMKKEITGA DRANAGIIQK
QTAIFSWKDV VYDIKIKKEP RRILDHVDGW VKPGTLTALM GVSGAGKTTL LDVLATRVTM
GVVTGEMLVD GKQRDLSFQR KTGYVQQQDL HLETSTVREA LRFSAILRQP NTVSIKEKYE
YVEEVLKLLE MDGYADAVVG VPGTGLNVEQ RKRLTIGVEL VAKPALLLFL DEPTSGLDSQ
TSWNILLLLR KLTEHGQAIL CTIHQPSAML FEQFDRLLFL ARGGKTVYFG EVGKGSRILI
DYFEKNGASK CPEGENPAEW MLAAIGAAPG SHSEVDWHQT WINSPERIEV RSELARIKET
QGGKGEAALQ NKDYEKSKAE VKAEYAEFAS PLWKQFIVVL MRVWQQHWRT PSYIWAKVAL
CSLSGLFIGF SFFKAGTSQQ GLQNQLFSVF MMFTIFGQLT QQIMPNFVTQ RSLYEVRERP
SKTYSWKIFI LSNIVSEIPW AILMGVIIYF TWYYPIGYYR NAIPEDAVHL RGALMFLYIE
MFLLFNATFS IMIVAGIATA ETAGNIANLL FSMCLIFCGV LASGSSLPGF WVFMYRVSPF
TYLVEGMLSV AVANTDVVCS DIEFLTFNPP SGQSCGDYMS TFITNYGGYL VDENATTACE
FCSMSKTNTF LAQFDIYYSN KWRDFGLLWV YVVFNVIAAI GIYWLARVPK NTGKERASEP
EDVQEKQVPA QSTEKKYQSI SRSSESTVA
