AFR1_CRYGR
ID AFR1_CRYGR Reviewed; 1542 AA.
AC P9WEU4;
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 AFR1 {ECO:0000303|PubMed:25630649};
GN Name=AFR1 {ECO:0000303|PubMed:25630649}; ORFNames=CNBG_1200;
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: Major pleiotropic ABC efflux transporter that confers
CC resistance to structurally and functionally unrelated compounds
CC including azoles such as fluconazole (FLC), itraconazole (ITC),
CC posaconazole (POS), and voriconazole (VRC) (PubMed:25630649,
CC PubMed:29378705). Is also able to efflux the eukaryote protein
CC synthesis inhibitor cycloheximide (CHX) (PubMed:29378705).
CC {ECO:0000269|PubMed:25630649, 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=0.65 uM for fluconazole transport {ECO:0000269|PubMed:25630649};
CC Vmax=65.60 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: Results in drastically higher susceptibility to
CC fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), as well as
CC to the eukaryote protein synthesis inhibitor cycloheximide (CHX).
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; CP025761; KGB75362.3; -; Genomic_DNA.
DR AlphaFoldDB; P9WEU4; -.
DR SMR; P9WEU4; -.
DR Proteomes; UP000029445; Chromosome 3.
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 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; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
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..1542
FT /note="ABC multidrug transporter AFR1"
FT /id="PRO_0000452665"
FT TRANSMEM 584..604
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 618..638
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 669..689
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 694..714
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 844..864
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1253..1273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1284..1304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1335..1355
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1365..1385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1390..1410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1516..1536
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 221..473
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 917..1159
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..84
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 125..141
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 953..960
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 822
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 923
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1542 AA; 172927 MW; EB7BCB78694937BF CRC64;
MSAAGVPAEL NNLGAPITAT TQNPSGLANS QVTSDPVPSA TQHDEHRSSA GNTLADEEGD
KSVDAEKVEA MYTGDSKQKR LPADSSEDIV AELEPHHVSV HRGKEEFAAL ERKYSTLSQQ
SQHELHRPTT RHSIRSSFSR KDRVVSRLTQ DEAEKAKEGE GEFNLVQVLR SSRENQDEAG
IKRKAVGVIW EDHEVIGAGG MRINIRNFSS AIIEQFMMPA LKVLGIFGVN PFAPKPKNIL
YPSSGLLKPG EMCLVLGRPE AGCTTFLKTI TNQRAGYMEI KGNVEYAGVG WKEMRKRYGG
EVVYNQEDDD HLPTLTVAQT IRFALATKTP KKKIPGVSAK QFQDDMLDLL LSMLNIKHTA
NTIVGNAFVR GVSGGERKRV SIAEMFCSGA TVCSWDNSTR GLDASTALDY AKSLRLLTDI
MGQTTFVSLY QAGEGIYDQF DKVLVLNEGH VAYFGPAKEA RQYMIGLGYR DLPRQTTADY
LSGCTDVNER RFADGRDETN VPATPEEMGK AYRESEICAR MNREREEYKQ LMAEDATIRE
DFKQAVLEQK HKGVSKKSSY TVSFFQQIFI IFKRQLRLKF QDHFGISTGY ATSIIIALIV
GSVYFRLPET ASGAFTRGGL LFLGLLFNAL TSFSELPSQM LGRSVLYRQN EYRFYRPAAF
AVASVLADVP YNASVIFLFS IVLYFMGGLY SSGGAFFIFY LFVFLTFMVM SAFFRTLGVA
TSDYNVAARL ASVLISFMVT YTGYMIPVQQ MKRWLFWIFY LNPLSYGYEA IFANEFSRID
LTCDSSYTIP RNVPQAGITG YPDTLGPNQM CSIFGSTPGN PNVSGSDYMA VGYSYYKTHI
WRNFGILVGF FAFFMFLQMM FIEYLEQGAK HFSINVYKKE DKDLKAKNER LAERREAFRA
GQLEQDLSEL KMRPEPFTWE GLNYTVPIPG GHRQLLNDIY GYVKPGSLTA LMGASGAGKT
TLLDVLASRK NIGVIEGDIL MNGRPIGTDF QRGCAYAEQQ DTHEWTTTVR EALQYSAYLR
QPQHVPKQEK DDYVEDIIEL LELQELADAM IGFPGYGLSV EARKRVTIGV ELAAKPELLL
FLDEPTSGLD GQSAYNIVRF LKKLCAAGQK ILCTIHQPNA LLFQSFDRLL LLQRGGECVY
FGDIGPDSKV LIDYLERNGA KVPHDANPAE FMLEAIGAGS RKRIGSDWGE KWRNSPEFAE
VKREIQELKA EALAKPVEEK SSRTEYATSF LFQLKTVLHR TNVALWRNAD YQWTRLFAHL
AIGLIVTLTF LQLDNSVQSL QYRVFAIFFA TVLPALILAQ IEPQYIMSRM TFNREASSKM
YSSTVFALTQ LLAEMPYSLG CAVSFFLLLY YGVGFPHASS RAGYFFLMIL VTEIYAVTLG
QAVAALSPTI LIAALFNPFL LVLFSIFCGV TAPPPTLPYF WRKWMWPLDP FTRLISGLVS
TVLQDQEVVC KDGEYQVFPA PSGQTCQQWA GAFAEAVGGY INNPDSTDDC QFCQYRTGQA
FFIPLEISFS TRWRDFGIFI CYVVFNILVL LIAARFLKWQ RR
