MDR2_TRIIM
ID MDR2_TRIIM Reviewed; 1331 AA.
AC A0A059JJ46;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
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=H109_00372;
OS Trichophyton interdigitale (strain MR816).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=1215338;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MR816;
RX PubMed=29467168; DOI=10.1534/genetics.117.300573;
RA Persinoti G.F., Martinez D.A., Li W., Doegen A., Billmyre R.B.,
RA Averette A., Goldberg J.M., Shea T., Young S., Zeng Q., Oliver B.G.,
RA Barton R., Metin B., Hilmioglu-Polat S., Ilkit M., Graeser Y.,
RA Martinez-Rossi N.M., White T.C., Heitman J., Cuomo C.A.;
RT "Whole-genome analysis illustrates global clonal population structure of
RT the ubiquitous dermatophyte pathogen Trichophyton rubrum.";
RL Genetics 208:1657-1669(2018).
RN [2]
RP IDENTIFICATION, FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16849730; DOI=10.1099/jmm.0.46522-0;
RA Fachin A.L., Ferreira-Nozawa M.S., Maccheroni W. Jr., Martinez-Rossi N.M.;
RT "Role of the ABC transporter TruMDR2 in terbinafine, 4-nitroquinoline N-
RT oxide and ethidium bromide susceptibility in Trichophyton rubrum.";
RL J. Med. Microbiol. 55:1093-1099(2006).
RN [3]
RP INDUCTION.
RX PubMed=17425668; DOI=10.1111/j.1574-6968.2007.00710.x;
RA Paiao F.G., Segato F., Cursino-Santos J.R., Peres N.T.,
RA Martinez-Rossi N.M.;
RT "Analysis of Trichophyton rubrum gene expression in response to cytotoxic
RT drugs.";
RL FEMS Microbiol. Lett. 271:180-186(2007).
RN [4]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19141731; DOI=10.1099/jmm.0.002907-0;
RA Maranhao F.C., Paiao F.G., Fachin A.L., Martinez-Rossi N.M.;
RT "Membrane transporter proteins are involved in Trichophyton rubrum
RT pathogenesis.";
RL J. Med. Microbiol. 58:163-168(2009).
RN [5]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that may be involved in
CC the modulation susceptibility to a wide range of unrelated cytotoxic
CC compounds, including terbinafine, 4-nitroquinoline N-oxide, and
CC ethidium bromide (PubMed:16849730). May play a role in pathogenicity
CC (PubMed:19141731). {ECO:0000269|PubMed:16849730,
CC ECO:0000269|PubMed:19141731}.
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:0000250|UniProtKB:F2T1C4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33504;
CC Evidence={ECO:0000250|UniProtKB:F2T1C4};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced upon exposure to a wide range of
CC unrelated cytotoxic compounds, including acriflavine, benomyl, ethidium
CC bromide, ketoconazole, chloramphenicol, griseofulvin, fluconazole,
CC imazalil, itraconazole, methotrexate, 4-nitroquinoline N-oxide,
CC tioconazolethe, or the allylamine terbinafine (PubMed:16849730,
CC PubMed:17425668, PubMed:27121717). Expression in up-regulated in the
CC presence of keratin (PubMed:19141731). {ECO:0000269|PubMed:16849730,
CC ECO:0000269|PubMed:17425668, ECO:0000269|PubMed:19141731,
CC ECO:0000269|PubMed:27121717}.
CC -!- DISRUPTION PHENOTYPE: Leads to increased sensitivity to terbinafine, 4-
CC nitroquinoline N-oxide, and ethidium bromide (PubMed:16849730). Leads
CC to a reduction in infecting activity, characterized by low growth on
CC human nails (PubMed:19141731). Impairs the MDR4 induction when the
CC fungus is challenged with amphotericin B or terbinafine
CC (PubMed:27121717). {ECO:0000269|PubMed:16849730,
CC ECO:0000269|PubMed:19141731, ECO:0000269|PubMed:27121717}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
CC -!- CAUTION: This protein was first identified as a Trichophyton rubrum
CC transporter and called TruMDR2, but it was further realized that the
CC isolate used for the identification was a Trichophyton interdigitale
CC isolate. {ECO:0000305|PubMed:16849730}.
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DR EMBL; AOKY01000033; KDB27804.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A059JJ46; -.
DR SMR; A0A059JJ46; -.
DR STRING; 1215338.A0A059JJ46; -.
DR DrugBank; DB00857; Terbinafine.
DR EnsemblFungi; KDB27804; KDB27804; H109_00372.
DR HOGENOM; CLU_000604_17_2_1; -.
DR OMA; RSDANFW; -.
DR Proteomes; UP000024533; 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 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 2: Evidence at transcript 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_0000447179"
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 810..830
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..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..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; 145280 MW; E35AD73CE307EA60 CRC64;
MVEVSEKPNT QDDGVSKQEN RNPASSSSST SDKEKVAKKG NSDATKSSTP EDLDAQLAHL
PEHEREILKQ QLFIPDAKAT YGTLFRYATR NDMIFLAIVS LASIAAGAAL PLFTVLFGSL
AGTFRDIALH RITYDEFNSI LTRNSLYFVY LGIAQFILLY VSTVGFIYVG EHITQKIRAK
YLHAILRQNI GFFDKLGAGE VTTRITADTN LIQDGISEKV GLTLTALSTF FSAFIIGYVR
YWKLALICSS TIVAMILVMG GISRFVVKSG RMTLVSYGEG GTVAEEVISS IRNATAFGTQ
EKLARQYEVH LKEARKWGRR LQMMLGIMFG SMMAIMYSNY GLGFWMGSRF LVGGETDLSA
IVNILLAIVI GSFSIGNVAP NTQAFASAIS AGAKIFSTID RVSAIDPGSD EGDTIENVEG
TIEFRGIKHI YPSRPEVVVM EDINLVVPKG KTTALVGPSG SGKSTVVGLL ERFYNPVSGS
VLLDGRDIKT LNLRWLRQQI SLVSQEPTLF GTTIFENIRL GLIGSPMENE SEEQIKERIV
SAAKEANAHD FIMGLPDGYA TDVGQRGFLL SGGQKQRIAI ARAIVSDPKI LLLDEATSAL
DTKSEGVVQA ALDAASRGRT TIVIAHRLST IKSADNIVVI VGGRIAEQGT HDELVDKKGT
YLQLVEAQKI NEERGEESED EAVLEKEKEI SRQISVPAKS VNSGKYPDED VEANLGRIDT
KKSLSSVILS QKRSQEKETE YSLGTLIRFI AGFNKPERLI MLCGFFFAVL SGAGQPVQSV
FFAKGITTLS LPPSLYGKLR EDANFWSLMF LMLGLVQLVT QSAQGVIFAI CSESLIYRAR
SKSFRAMLRQ DIAFFDLPEN STGALTSFLS TETKHLSGVS GATLGTILMV STTLIVALTV
ALAFGWKLAL VCISTVPVLL LCGFYRFWIL AQFQTRAKKA YESSASYACE ATSSIRTVAS
LTREQGVMEI YEGQLNDQAK KSLRSVAKSS LLYAASQSFS FFCLALGFWY GGGLLGKGEY
NAFQFFLCIS CVIFGSQSAG IVFSFSPDMG KAKSAAADFK RLFDRVPTID IESPDGEKLE
TVEGTIEFRD VHFRYPTRPE QPVLRGLNLT VKPGQYIALV GPSGCGKSTT IALVERFYDT
LSGGVYIDGK DISRLNVNSY RSHLALVSQE PTLYQGTIRD NVLLGVDRDD VPDEQVFAAC
KAANIYDFIM SLPDGFGTVV GSKGSMLSGG QKQRIAIARA LIRDPKVLLL DEATSALDSE
SEKVVQAALD AAAKGRTTIA VAHRLSTIQK ADIIYVFDQG RIVESGTHHE LLQNKGRYYE
LVHMQSLEKT Q
