MDR1_CRYGR
ID MDR1_CRYGR Reviewed; 1408 AA.
AC A0A095C325;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=ABC multidrug transporter MDR1 {ECO:0000303|PubMed:25630649};
GN Name=MDR1 {ECO:0000303|PubMed:25630649}; ORFNames=CNBG_1138;
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),
CC nocodazole and 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=0.31 uM for fluconazole transport {ECO:0000269|PubMed:25630649};
CC Vmax=23.40 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 not induced in the presence of fluconazole
CC (FLC). {ECO:0000269|PubMed:25630649, ECO:0000269|PubMed:29378705}.
CC -!- DISRUPTION PHENOTYPE: Caused higher susceptibility to nocodazole and
CC rhodamine 6G (R-6G) but higher resistance to cycloheximid (CHX)
CC (PubMed:29378705). Causes further increase in susceptibility toward
CC fluconazole and itraconazole, when AFR1 and AFR2 are also deleted
CC (PubMed:29378705). {ECO:0000269|PubMed:29378705}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
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DR EMBL; KQ410559; KGB75300.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A095C325; -.
DR SMR; A0A095C325; -.
DR STRING; 552467.XP_003191799.1; -.
DR EnsemblFungi; KGB75300; KGB75300; CNBG_1138.
DR VEuPathDB; FungiDB:CNBG_1138; -.
DR HOGENOM; CLU_000604_17_0_1; -.
DR OMA; LFMLPMT; -.
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 Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Glycoprotein; Membrane; Nucleotide-binding;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1408
FT /note="ABC multidrug transporter MDR1"
FT /id="PRO_0000452668"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 436..456
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 838..858
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 882..902
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 952..972
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 973..993
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 1072..1092
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 1099..1119
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT DOMAIN 157..464
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 499..744
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 838..1125
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1162..1402
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 534..541
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1197..1204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1408 AA; 152284 MW; 3B060916FA47FDDB CRC64;
MSASPSPIGA AAGLDHLQAR RDEEVVDSEK DALAHDSHAV NSGIPHPTAT APTIGIPIVP
ISAGRESSAP EEKISRSSIA ASSDILHNPP SEKSISSAVP KSHRYKKSKF NFLKSRKKKE
EEEKKNKEKE KEASVLPPVS FFALFKFAAP LEIVAMVFGL LLAIAAGSCQ PLMTLIFGRL
TTSFTNYAVI VNQISQGGLT PETAAALQAA KDDLKTQSGH NALYLMAIGI GMFLATWLYM
FIWNVTGELN SKRIRERYLA AVLRQEIAYF DDLGAGEVAT RIQTDCHLVQ EGTSEKVALV
FQYAGTFVCG FVLAFVRSPR LAGALISILP VIMICGGIMM TAMAKFGTAA LDHIAKAGSL
AEEVIGSIRT VQAFGKEKIL GNKFADHIEK SKVIGRKGSI FEGFGLSIMF FAIYAAYALA
FYYGGILVSH GDANSGIVIN VFMSILIGSF SMAMLAPELA AVTKARGAAA KLFATIDRVP
AIDSANKEGL KPDSLHGEIS FENVRFHYPS RPSVPILKGF TTTFEAGKTF ALVGASGSGK
STVVSLIERF YDPVSGVVKL DGRDIRSLNL NWLRQQIGLV SQEPTLFGTT VRGNVEHGLI
GSIYENASPE EKFELVKKAC IDANAHGFIM KLPQGYDTMV GERGMLLSGG QKQRVAIARA
IVSDPRILLL DEATSALDTQ SEGIVQDALD KASRGRTTIT IAHRLSTIRD ADRIYVMGAG
EVIEQGSHNE LLNNENGPYA QLVNNQKLAQ EAAAEALQED DDIDDLDDTV LGGASSPMQE
KNGQLYRAVT GRSLASIAMD DIQAKRAEDL AAEDKIPSSF ALYARLLRMN SADKLIYIFA
FIAAICAGMV YPSLAILFGK ALSDFEIQDP NELRQALSRK ALWYFITALA AAIVIFFQSA
GFSRAGWDLN GVLRKKLFTA TLRHDIEWFD EDRNSTGAVT SNLADQPQKV QGLFGPTLGT
VVQSCATLIG GCIIGLCYGP LLSLIGIACI PILVSGGYIR LKVVVLKDQR MKKLHAASAH
LASEAAGAVR TVASLTREED VRRIYSEALK GPMKLNFRTS IKSQCLFAAS QGLTFCIIAL
VFYIGALWII DGKYSTASFY TVLNSIVFAS IQAGNVFTFV PDASKANSSA ASIFRTIDNE
PAINAESTEG KMLDHEHVVG HVRIEGVHFR YPTRPGVRVL RNLTIDVPAG TYVALVGPSG
CGKSTTIQML ERFYDPLAGR VTLDGIDIKE LNLANYRSQI SLVSQEPTLY AGTIRFNILL
GANKPMEEVT QDEIDAACKD ANIYDFIISL PDGFDTEVGG KGSQLSGGQK QRIAIARALI
RNPKVLLLDE ATSALDSQSE KVVQEALDKA AKGRTTIAIA HRLSSIQHSD QIYYFSEGKV
AEHGTHQELL AKKGGYYDLV QMQNLSRQ
