MRR1_CANAL
ID MRR1_CANAL Reviewed; 1108 AA.
AC Q5A4G2; A0A1D8PKF0;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 117.
DE RecName: Full=Multidrug resistance regulator 1 {ECO:0000303|PubMed:17983269};
GN Name=MRR1 {ECO:0000303|PubMed:17983269}; Synonyms=HAP1;
GN OrderedLocusNames=CAALFM_C305920WA; ORFNames=CaO19.7372;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP IDENTIFICATION.
RX PubMed=18629206; DOI=10.1002/cfg.492;
RA Maicas S., Moreno I., Nieto A., Gomez M., Sentandreu R., Valentin E.;
RT "In silico analysis for transcription factors with Zn(II)(2)C(6) binuclear
RT cluster DNA-binding domains in Candida albicans.";
RL Comp. Funct. Genomics 6:345-356(2005).
RN [5]
RP INDUCTION, DISRUPTION PHENOTYPE, FUNCTION, AND MUTAGENESIS OF PRO-683 AND
RP GLY-997.
RX PubMed=17983269; DOI=10.1371/journal.ppat.0030164;
RA Morschhauser J., Barker K.S., Liu T.T., Blass-Warmuth J., Homayouni R.,
RA Rogers P.D.;
RT "The transcription factor Mrr1p controls expression of the MDR1 efflux pump
RT and mediates multidrug resistance in Candida albicans.";
RL PLoS Pathog. 3:E164-E164(2007).
RN [6]
RP FUNCTION.
RX PubMed=18577180; DOI=10.1111/j.1365-2958.2008.06309.x;
RA Dunkel N., Blass J., Rogers P.D., Morschhauser J.;
RT "Mutations in the multi-drug resistance regulator MRR1, followed by loss of
RT heterozygosity, are the main cause of MDR1 overexpression in fluconazole-
RT resistant Candida albicans strains.";
RL Mol. Microbiol. 69:827-840(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19527793; DOI=10.1016/j.fgb.2009.06.003;
RA Chen C.G., Yang Y.L., Tseng K.Y., Shih H.I., Liou C.H., Lin C.C., Lo H.J.;
RT "Rep1p negatively regulating MDR1 efflux pump involved in drug resistance
RT in Candida albicans.";
RL Fungal Genet. Biol. 46:714-720(2009).
RN [8]
RP FUNCTION, AND PROMOTER-BINDING.
RX PubMed=19279142; DOI=10.1091/mbc.e08-11-1093;
RA Sellam A., Askew C., Epp E., Lavoie H., Whiteway M., Nantel A.;
RT "Genome-wide mapping of the coactivator Ada2p yields insight into the
RT functional roles of SAGA/ADA complex in Candida albicans.";
RL Mol. Biol. Cell 20:2389-2400(2009).
RN [9]
RP FUNCTION.
RX PubMed=21136999; DOI=10.1002/prca.200800252;
RA Hoehamer C.F., Cummings E.D., Hilliard G.M., Morschhaeuser J., Rogers P.D.;
RT "Proteomic analysis of Mrr1p- and Tac1p-associated differential protein
RT expression in azole-resistant clinical isolates of Candida albicans.";
RL Proteomics Clin. Appl. 3:968-978(2009).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF PRO-683.
RX PubMed=21343453; DOI=10.1128/aac.01467-10;
RA Mogavero S., Tavanti A., Senesi S., Rogers P.D., Morschhaeuser J.;
RT "Differential requirement of the transcription factor Mcm1 for activation
RT of the Candida albicans multidrug efflux pump MDR1 by its regulators Mrr1
RT and Cap1.";
RL Antimicrob. Agents Chemother. 55:2061-2066(2011).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF PRO-683.
RX PubMed=21402859; DOI=10.1128/aac.01343-10;
RA Schubert S., Barker K.S., Znaidi S., Schneider S., Dierolf F., Dunkel N.,
RA Aid M., Boucher G., Rogers P.D., Raymond M., Morschhaeuser J.;
RT "Regulation of efflux pump expression and drug resistance by the
RT transcription factors Mrr1, Upc2, and Cap1 in Candida albicans.";
RL Antimicrob. Agents Chemother. 55:2212-2223(2011).
RN [12]
RP INDUCTION.
RX PubMed=21592964; DOI=10.1074/jbc.m111.233569;
RA Singh R.P., Prasad H.K., Sinha I., Agarwal N., Natarajan K.;
RT "Cap2-HAP complex is a critical transcriptional regulator that has dual but
RT contrasting roles in regulation of iron homeostasis in Candida albicans.";
RL J. Biol. Chem. 286:25154-25170(2011).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF PRO-683.
RX PubMed=22924823; DOI=10.1111/j.1365-2958.2012.08210.x;
RA Sasse C., Dunkel N., Schaefer T., Schneider S., Dierolf F., Ohlsen K.,
RA Morschhaeuser J.;
RT "The stepwise acquisition of fluconazole resistance mutations causes a
RT gradual loss of fitness in Candida albicans.";
RL Mol. Microbiol. 86:539-556(2012).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24041896; DOI=10.1128/aac.01504-13;
RA Sun N., Li D., Fonzi W., Li X., Zhang L., Calderone R.;
RT "Multidrug-resistant transporter mdr1p-mediated uptake of a novel
RT antifungal compound.";
RL Antimicrob. Agents Chemother. 57:5931-5939(2013).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF PRO-683.
RX PubMed=23844834; DOI=10.1111/mmi.12327;
RA Schillig R., Morschhauser J.;
RT "Analysis of a fungus-specific transcription factor family, the Candida
RT albicans zinc cluster proteins, by artificial activation.";
RL Mol. Microbiol. 89:1003-1017(2013).
RN [16]
RP FUNCTION.
RX PubMed=24243794; DOI=10.1128/ec.00245-13;
RA Lohberger A., Coste A.T., Sanglard D.;
RT "Distinct roles of Candida albicans drug resistance transcription factors
RT TAC1, MRR1, and UPC2 in virulence.";
RL Eukaryot. Cell 13:127-142(2014).
CC -!- FUNCTION: Transcription factor that acts as the central regulator of
CC the MDR1 efflux pump. Other target genes include those encoding
CC oxidoreductases, whose up-regulation in fluconazole-resistant isolates
CC may help to prevent cell damage resulting from the generation of toxic
CC molecules in the presence of fluconazole and thereby contribute to drug
CC resistance. {ECO:0000269|PubMed:17983269, ECO:0000269|PubMed:18577180,
CC ECO:0000269|PubMed:19279142, ECO:0000269|PubMed:19527793,
CC ECO:0000269|PubMed:21136999, ECO:0000269|PubMed:21343453,
CC ECO:0000269|PubMed:21402859, ECO:0000269|PubMed:22924823,
CC ECO:0000269|PubMed:23844834, ECO:0000269|PubMed:24041896,
CC ECO:0000269|PubMed:24243794}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- INDUCTION: Expression is coordinately up-regulated with MDR1 in drug-
CC resistant, clinical isolates. Expression is induced by HAP43.
CC {ECO:0000269|PubMed:17983269, ECO:0000269|PubMed:21592964}.
CC -!- DISRUPTION PHENOTYPE: Decreases MDR1 expression and leads to greater
CC fluconazole and cerulenin susceptibility. {ECO:0000269|PubMed:17983269,
CC ECO:0000269|PubMed:19527793, ECO:0000269|PubMed:24041896}.
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DR EMBL; CP017625; AOW28600.1; -; Genomic_DNA.
DR RefSeq; XP_716613.1; XM_711520.1.
DR AlphaFoldDB; Q5A4G2; -.
DR SMR; Q5A4G2; -.
DR STRING; 237561.Q5A4G2; -.
DR PRIDE; Q5A4G2; -.
DR EnsemblFungi; KHC79130; KHC79130; W5Q_03099.
DR EnsemblFungi; KHC87354; KHC87354; I503_03093.
DR GeneID; 3641741; -.
DR KEGG; cal:CAALFM_C305920WA; -.
DR CGD; CAL0000179436; MRR1.
DR VEuPathDB; FungiDB:C3_05920W_A; -.
DR eggNOG; ENOG502QRPQ; Eukaryota.
DR HOGENOM; CLU_005934_0_0_1; -.
DR InParanoid; Q5A4G2; -.
DR OMA; SCLTRCA; -.
DR OrthoDB; 473654at2759; -.
DR Proteomes; UP000000559; Chromosome 3.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:CGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:CGD.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR CDD; cd00067; GAL4; 1.
DR Gene3D; 4.10.240.10; -; 1.
DR InterPro; IPR007219; Transcription_factor_dom_fun.
DR InterPro; IPR001138; Zn2-C6_fun-type_DNA-bd.
DR InterPro; IPR036864; Zn2-C6_fun-type_DNA-bd_sf.
DR Pfam; PF04082; Fungal_trans; 1.
DR Pfam; PF00172; Zn_clus; 1.
DR SMART; SM00906; Fungal_trans; 1.
DR SMART; SM00066; GAL4; 1.
DR SUPFAM; SSF57701; SSF57701; 1.
DR PROSITE; PS00463; ZN2_CY6_FUNGAL_1; 1.
DR PROSITE; PS50048; ZN2_CY6_FUNGAL_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; DNA-binding; Metal-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Zinc.
FT CHAIN 1..1108
FT /note="Multidrug resistance regulator 1"
FT /id="PRO_0000431799"
FT DNA_BIND 31..59
FT /note="Zn(2)-C6 fungal-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 968..990
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1021..1064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 134..165
FT /evidence="ECO:0000255"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..84
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..122
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..138
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 968..987
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1021..1051
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 683
FT /note="P->S: Leads to constitutive MDR1 overexpression and
FT multidrug resistance."
FT /evidence="ECO:0000269|PubMed:17983269,
FT ECO:0000269|PubMed:21343453, ECO:0000269|PubMed:21402859,
FT ECO:0000269|PubMed:22924823, ECO:0000269|PubMed:23844834"
FT MUTAGEN 997
FT /note="G->V: Leads to constitutive MDR1 overexpression and
FT multidrug resistance."
FT /evidence="ECO:0000269|PubMed:17983269"
SQ SEQUENCE 1108 AA; 126669 MW; 1624BF1AF6A22A03 CRC64;
MSIATTPIET PKSPKSTEPQ VRKRKKVSTV CTNCRKRKIR CDRQHPCNNC IKSKKHNACV
YDDGQVSPAN FSTNGSSHGN TVPESRPYEE SARIPIRFDA EAPRKKSKPN TPNNERKNSK
KSPDNTVANN QQTASENEVT ITLSELNMLK QRLQNIEANI NAQSNPQSNP SYVPQTPAYP
TQPNILPPPV SFNSWSPKQS NERVMFSPQQ RLTTNYNVSH TRGQSPSIQL PPLSFKDTPR
ASIDSAPLYS EMSPPRSDLI ASSLTSPESI QMSVSGDVVG VNPYLNETET INFYDGYTSI
CVRDFRRVNH GPFAWSSLMR KDKALSSLWN HILKKKEKKN VASQTFVFGQ DVHEISQENT
QLVASESNES ETKFKKKTLE TFGFNDVVPY DILKKKLQTQ INKTTSPLGL TLYEEQVNME
LQLVDRIHQQ LPKKKVLWKL IDRFFSLLYP FMPFLDEIDF RESVTKIIGE TEYKDEKIKE
LKVEKRLDLA VIGVLLIILR MSYLSLFCNK ESVNEMRLKT TDPSPEAQDM KYLLQNPIGI
SLIDSAQNCL QYFDIFRKTS MPVLQCAYFL QLYHIFAPED GDDGDGADTY ALNSMVVRMA
YSMGLNREPD NFKDVLNDKR QNHLGRKIWH FLVIGDVHNS YAFGTPKLIG DDFYDTKVPF
IEEGNENLID KSLDQYVTKS VFPGYFSIYN SVDQILKLIL SVSRRSKVSE ICKILNQFEI
GIAEQYGTLS DCLKPKENLI HIFARNMPVK MYISLKSFLV SVYFHLFLYY EHKNDSLSFF
YLRKILKTGA GDIMPHYFEL LGNSEVVCDM VINPKLIQII HKANQINIAL IIRVNMSIYR
MKNSQHHAEN CKKDDFYYSY YKELCKFSSC LTRCAEVGIA AVSKLSTRYY YAWKITKGHN
FLLKTITSME FYEKESTNAQ EITLPKYKLE QIADLENICE VALNKLGKTS VMGDEFCSNV
NYKKYKGDQT YSTSSESSST PNKDSPLDSR KYTNDFGLDL VNNQEIDKIW LQMLSLKSEE
AQQQRQQESQ PFTSSQSQSQ SPLTSANQGY MPRPESRRGS YYGNTPFALE NLNFDGFGGQ
SKSSNNGEAD LSSFDFFVDL PFDQLFTN
