MDR2_TRIRC
ID MDR2_TRIRC Reviewed; 1331 AA.
AC F2T1C4;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=ABC multidrug transporter MDR2 {ECO:0000303|PubMed:27121717};
DE AltName: Full=Multidrug resistance protein 2 {ECO:0000303|PubMed:27121717};
GN Name=MDR2 {ECO:0000303|PubMed:27121717}; ORFNames=TERG_08613;
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 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).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=33896045; DOI=10.1111/myc.13286;
RA Yamada T., Yaguchi T., Tamura T., Pich C., Salamin K., Feuermann M.,
RA Monod M.;
RT "Itraconazole resistance of Trichophyton rubrum mediated by the ABC
RT transporter TruMDR2.";
RL Mycoses 64:936-946(2021).
CC -!- FUNCTION: ABC-type efflux transporter involved in the modulation
CC susceptibility to itraconazole. {ECO:0000269|PubMed:31501141,
CC ECO:0000269|PubMed:33896045}.
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:31501141, ECO:0000269|PubMed:33896045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33504;
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, the
CC allylamine terbinafine, and itraconazole (PubMed:27121717,
CC PubMed:31501141). Is highly over-expressed in strain TIMM20092, and
CC azole-resistant strain isolated in Switzerland (PubMed:31501141).
CC {ECO:0000269|PubMed:27121717, ECO:0000269|PubMed:31501141}.
CC -!- DISRUPTION PHENOTYPE: Impairs the resistance to itraconazole of the
CC azole-resistant strain TIMM20092. {ECO:0000269|PubMed:33896045}.
CC -!- MISCELLANEOUS: Dermatophytes showing reduced sensitivity to antifungal
CC agents have emerged in several countries and, in particular, up-
CC regulation of MDR2 expression in some clinical isolates such as strain
CC TIMM20092 leads to increased resistance to itraconazole during clinical
CC treatments. {ECO:0000269|PubMed:31501141, ECO:0000269|PubMed:33896045}.
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; GG700664; EGD92396.1; -; Genomic_DNA.
DR RefSeq; XP_003230907.1; XM_003230859.1.
DR AlphaFoldDB; F2T1C4; -.
DR SMR; F2T1C4; -.
DR STRING; 559305.F2T1C4; -.
DR EnsemblFungi; EGD92396; EGD92396; TERG_08613.
DR GeneID; 10376855; -.
DR VEuPathDB; FungiDB:TERG_08613; -.
DR eggNOG; KOG0055; Eukaryota.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; F2T1C4; -.
DR Proteomes; UP000008864; Unassembled WGS sequence.
DR GO; GO:0000324; C:fungal-type vacuole; IEA:EnsemblFungi.
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:0008559; F:ABC-type xenobiotic transporter activity; IEA:EnsemblFungi.
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:EnsemblFungi.
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 Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1331
FT /note="ABC multidrug transporter MDR2"
FT /id="PRO_0000447178"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 325..345
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 358..378
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 762..782
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 808..828
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 884..904
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 910..930
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 995..1015
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TRANSMEM 1025..1045
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT DOMAIN 97..387
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 422..667
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 764..1051
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1086..1324
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 457..464
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1121..1128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 860
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1331 AA; 145439 MW; 178E62AD8B740EF5 CRC64;
MVEPSEKPNT QNDDVSKQEI RNPVSSSSST SDKEKVAKKG NSDATKSLTP EDLDAQLAHL
PEHEREILKQ QLFIPEVKAT YGTLFRYATR NDMILLAIVS LASIAAGAAL PLFTVLFGSL
AGTFRDIALH RITYDEFNSI LTRNSLYFVY LGIAQFILLY VSTVGFIYVG EHITQKIRAR
YLHAILRQNI GFFDKLGAGE VTTRITADTN LIQDGISEKV GLTLTALSTF FSAFIIGYVR
YWKLALICTS TIVAMVLVMG GISRFVVKSG RMTLVSYGEG GTVAEEVISS IRNATAFGTQ
EKLARQYEVH LREARKWGRR LQMMLGIMFG SMMAIMYSNY GLGFWMGSRF LVGGETDLSA
IVNILLAIVI GSFSIGNVAP NTQAFASAIS AGAKIFSTID RVSAIDPGSD EGDTIENVEG
TIEFRGIKHI YPSRPEVVVM EDINLVVPKG KTTALVGPSG SGKSTVVGLL ERFYNPVAGS
VFLDGRDIKT LNLRWLRQQI SLVSQEPTLF GTTIFENIRL GLIGSPMENE SEEQIKERIV
SAAKEANAHD FVMGLPDGYA TDVGQRGFLL SGGQKQRIAI ARAIVSDPKI LLLDEATSAL
DTKSEGVVQA ALDAASRGRT TIVIAHRLST IKSADNIVVI VGGRIAEQGT HDELVDKKGT
YLQLVEAQKI NEERGEESED EAVLEKEKEI SRQISVPAKS VNSGKYPDED VEANLGRIDT
KKSLSSVILS QKRGQEKETE YSLGTLIRFI AGFNKPERLI MLCGFFFAVL SGAGQPVQSV
FFAKGITTLS LPPSLYGKLR EDANFWSLMF LMLGLVQLIT QSAQGVIFAL CSESLIYRAR
SKSFRAMLRQ DIAFFDLSEN STGALTSFLS TETKHLSGVS GATLGTILMV STTLIVALTV
ALAFGWKLAL VCISTVPVLL LCGFYRFWIL AQFQTRAKKA YESSASYACE ATSSIRTVAS
LTRENGVMEI YEGQLNDQAK KSLRSVAKSS LLYAASQSFS FFCLALGFWY GGGLLGKGEY
NAFQFFLCIS CVIFGSQSAG IVFSFSPDMG KAKSAAADFK RLFDRVPTID IESPDGEKLE
TVEGTIEFRD VHFRYPTRPE QPVLRGLNLT VKPGQYIALV GPSGCGKSTT IALVERFYDT
LSGGVYIDGK DISRLNVNSY RSHLALVSQE PTLYQGTIRD NVLLGVDRDD VPDEQVFAAC
KAANIYDFIM SLPDGFATVV GSKGSMLSGG QKQRIAIARA LIRDPKVLLL DEATSALDSE
SEKVVQAALD AAAKGRTTIA VAHRLSTIQK ADIIYVFDQG RIVESGTHHE LLQNKGRYYE
LVHMQSLEKT H
