MDR1_TRIRC
ID MDR1_TRIRC Reviewed; 1566 AA.
AC F2SHL1;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 3.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=ABC multidrug transporter MDR1 {ECO:0000303|PubMed:27121717};
DE AltName: Full=Multidrug resistance protein 1 {ECO:0000303|PubMed:27121717};
GN Name=MDR1 {ECO:0000303|PubMed:27121717};
GN Synonyms=pdr1 {ECO:0000303|PubMed:27121717}; ORFNames=TERG_02508;
OS Trichophyton rubrum (strain ATCC MYA-4607 / CBS 118892) (Athlete's foot
OS fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=559305;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4607 / CBS 118892;
RX PubMed=22951933; DOI=10.1128/mbio.00259-12;
RA Martinez D.A., Oliver B.G., Graeser Y., Goldberg J.M., Li W.,
RA Martinez-Rossi N.M., Monod M., Shelest E., Barton R.C., Birch E.,
RA Brakhage A.A., Chen Z., Gurr S.J., Heiman D., Heitman J., Kosti I.,
RA Rossi A., Saif S., Samalova M., Saunders C.W., Shea T., Summerbell R.C.,
RA Xu J., Young S., Zeng Q., Birren B.W., Cuomo C.A., White T.C.;
RT "Comparative genome analysis of Trichophyton rubrum and related
RT dermatophytes reveals candidate genes involved in infection.";
RL MBio 3:E259-E259(2012).
RN [2]
RP INDUCTION.
RX PubMed=27121717; DOI=10.1099/jmm.0.000268;
RA Martins M.P., Franceschini A.C.C., Jacob T.R., Rossi A.,
RA Martinez-Rossi N.M.;
RT "Compensatory expression of multidrug-resistance genes encoding ABC
RT transporters in dermatophytes.";
RL J. Med. Microbiol. 65:605-610(2016).
RN [3]
RP GENE MODEL REVISION, FUNCTION, INDUCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31501141; DOI=10.1128/aac.00863-19;
RA Monod M., Feuermann M., Salamin K., Fratti M., Makino M., Alshahni M.M.,
RA Makimura K., Yamada T.;
RT "Trichophyton rubrum azole resistance mediated by a new ABC transporter,
RT TruMDR3.";
RL Antimicrob. Agents Chemother. 0:0-0(2019).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter involved in the modulation
CC susceptibility to fluconazole, voriconazole and miconazole, 3 azoles
CC with similar molecular structure. {ECO:0000269|PubMed:31501141}.
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:31501141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61913;
CC Evidence={ECO:0000269|PubMed:31501141};
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:31501141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61917;
CC Evidence={ECO:0000269|PubMed:31501141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-miconazole(in) + ATP + H2O = (R)-miconazole(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:61928, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82894, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:31501141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61929;
CC Evidence={ECO:0000269|PubMed:31501141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-miconazole(in) + ATP + H2O = (S)-miconazole(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:61932, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82897, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:31501141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61933;
CC Evidence={ECO:0000269|PubMed:31501141};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:31501141};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced upon exposure to amphotericin B
CC (PubMed:27121717). Expression is slightly induced upon exposure to
CC voriconazole and itraconazole (PubMed:31501141). Is slightly over-
CC expressed in strain TIMM20092, and azole-resistant strain isolated in
CC Switzerland (PubMed:31501141). {ECO:0000269|PubMed:27121717,
CC ECO:0000269|PubMed:31501141}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC PDR (TC 3.A.1.205) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EGD86248.2; Type=Erroneous gene model prediction; Evidence={ECO:0000269|PubMed:31501141};
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DR EMBL; GG700649; EGD86248.2; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; F2SHL1; -.
DR SMR; F2SHL1; -.
DR STRING; 5551.XP_003237797.1; -.
DR TCDB; 3.A.1.205.27; the atp-binding cassette (abc) superfamily.
DR EnsemblFungi; EGD86248; EGD86248; TERG_02508.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; F2SHL1; -.
DR Proteomes; UP000008864; Unassembled WGS sequence.
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; 2.
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..1566
FT /note="ABC multidrug transporter MDR1"
FT /id="PRO_0000447174"
FT TRANSMEM 543..563
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 571..591
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 603..623
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..647
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..672
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 684..704
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 789..809
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1222..1242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1248..1268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1336..1356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1363..1383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1489..1509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 167..432
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 882..1125
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1168..1193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1168..1190
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 918..925
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 886
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 903
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1566 AA; 174866 MW; 2C41D7BAAE012A79 CRC64;
MASQPPQPLS GQPVTQYEEY QSEVITETTN RPTPAADIYE ITPTNDVMDD RYEHEHDDYE
SGAMYETVRT WSPQSRPELV RIASVFSRVD SHPNVTPTTE DGGQLNRRDT LAGVKIGDPV
LDPTKPEFDF YKWARMFTHV MENEGIKRNR TGVMFRNLTV LGSGSAVQYQ DTFLSPFAAP
FRPGELCGKG RNPEKVILHD FNGAIREGEL LMVLGRPGSG CSTFLKAICG ELHGLQKKKE
SIIHYNGVSQ HTFKKELRGE AVYSAEDEHH FPHLTVGQTL EFAAAARTPS KRVLGVSRKD
FSTHLARVMM SVFGLSHTYN TKVGDDYVRG VSGGERKRVS IAEIALSGAP ICCWDNSTRG
LDSATALEFT KALKIGSQVG GITQCLAIYQ ASQAIYDIFD KVIVLYEGRQ IFFGPTRIAK
QYFEEMGWYC PPRQTTADFL TSVTNPKERI AKEGYENRVP RTAVDFERYW KQSQNNKLLL
ANMDRFEAEY PPEEGHLQKL RETHGQAQAK HTTSKSPYRI SVPMQVKLCT VRAYQRLWGD
KSSTIATNIS QIMMALIIGS LFFDTPQTTD GFFAKGSVIF FAILLNGLMS ITEINGLYAQ
RPIVVKHVNF AFYHAYSEAL AGIVADIPIK FLLALVFNII IYFLGGLERS AAKFFIFFLF
TFITILTMSA IFRTLAAATK TIPQALALAG VMILALVIYT GFALQPSYMH PWFKWILYIN
PIAYAYEALL VNEVHGNRYR CATPVPPYGG GKNFACAVAG AVPGEMSVSG DAWVESSYDY
SYAHIWRNLG ILLGFLAFFY FVYLMVSELN LSSASSAEFL VFRRGHLPKS FQGSKDEEAA
AGGVMHPNDP ARLPPTNTNG AAGETAPGGS TVAVIPPQKD IFTWRNVTYD ITIKGEPRRL
LDNISGWVRP GTLTALMGVS GAGKTTLLDA LAQRTTMGVI TGDMLVNGRP LDSSFQRKTG
YVQQQDLHLE TTTVREALRF SADLRQPKSV SRKEKYEYVE DVIKMLSMED FSEAVVGNPG
EGLNVEQRKL LTIGVELAAK PQLLLFLDEP TSGLDSQSSW SIVTFLRKLA DNGQAVLSTI
HQPSGILFEQ FDRLLFLAKG GRTVYFGDIG KNSETLLNYF ETHGAEPCGP SENPAEYMLN
IVGAGPSGKS KIDWPVVWKE SEESRHVQQE LDQIQSETSK KNEGHGQSAE KEPGEFAMPF
TSQLYCVTTR VFQQYWRTPS YIWGKFLLGL ASALFIGFSF FLQNSSMAGL QNSLFSIFML
TTIFSSLVQQ IMPRFVTQRD LFEVRERPSR AYSWKVFLLA NIIVEIPYQI LLGIIAWASL
FYPTFGAHLS SERQGILLLY CVQFFIFAST FAQMIIAGLP DAETAGGIAT TMFGLMVTFN
GVLQKPNALP GFWRFMWRVS PITYTVGGLA ATSLHNREVK CAQNELAIFD PPTGATCAQY
LQKLVEAGAP GKLYNPTSTT QCQYCPLSSG DQFLGGSEIH WSDRWRNFGI GWAYIVFNIF
ATVALYYLIR VRKSSGRPNR IISVIMYHLS RAGTYCRAFI TGRKEKCPRK REQIVQTYKE
FNMLLN
