ID   ATRR_ASPFU              Reviewed;         895 AA.
AC   Q4WI89;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 2.
DT   25-MAY-2022, entry version 68.
DE   RecName: Full=ABC-transporter-regulating transcription factor {ECO:0000303|PubMed:28052140};
GN   Name=atrR {ECO:0000303|PubMed:28052140}; ORFNames=AFUA_2G02690;
OS   Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS   A1100) (Aspergillus fumigatus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=330879;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX   PubMed=16372009; DOI=10.1038/nature04332;
RA   Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA   Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA   Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA   Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA   Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA   Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA   Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA   Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA   Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA   Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA   O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA   Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA   Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA   Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA   Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA   Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA   Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA   Barrell B.G., Denning D.W.;
RT   "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT   Aspergillus fumigatus.";
RL   Nature 438:1151-1156(2005).
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=28052140; DOI=10.1371/journal.ppat.1006096;
RA   Hagiwara D., Miura D., Shimizu K., Paul S., Ohba A., Gonoi T., Watanabe A.,
RA   Kamei K., Shintani T., Moye-Rowley W.S., Kawamoto S., Gomi K.;
RT   "A novel Zn2-Cys6 transcription factor atrR plays a key role in an azole
RT   resistance mechanism of Aspergillus fumigatus by co-regulating cyp51A and
RT   cdr1B Expressions.";
RL   PLoS Pathog. 13:E1006096-E1006096(2017).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=30862750; DOI=10.1128/mbio.02563-18;
RA   Paul S., Stamnes M., Thomas G.H., Liu H., Hagiwara D., Gomi K.,
RA   Filler S.G., Moye-Rowley W.S.;
RT   "AtrR is an essential determinant of azole resistance in Aspergillus
RT   fumigatus.";
RL   MBio 10:0-0(2019).
CC   -!- FUNCTION: Transcription factor that regulates expression of the genes
CC       related to ergosterol biosynthesis, including erg3B, erg24A, erg25A, as
CC       well as cyp51A that encodes a target protein of azoles
CC       (PubMed:30862750, PubMed:28052140). Responsible for the expression of
CC       the ABC transporter abcC/cdr1B/abcG1 related to azole resistance
CC       (PubMed:28052140, PubMed:30862750). Directly binds both the cyp51A and
CC       abcC/cdr1B/abcG1 promoters at a conserved 34 bp region called the atrR
CC       response element (ATRE) (PubMed:30862750, PubMed:28052140). AtrR also
CC       binds to the promoter regions of both the sterol response transcription
CC       factor srbA and atrR genes themselves, the latter suggesting the
CC       possibility that atrR is autoregulated (PubMed:30862750). AtrR is
CC       necessary for hypoxia adaptation and virulence (PubMed:28052140).
CC       {ECO:0000269|PubMed:28052140, ECO:0000269|PubMed:30862750}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00227}.
CC       Membrane {ECO:0000255}; Single-pass membrane protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Results in a hypersensitivity to the azole drugs
CC       fluconazole, miconazole, and itraconazole (PubMed:28052140). In
CC       addition to the medical azoles, shows also hypersensitivity to widely
CC       used azole fungicides, bromuconazole, tebuconazole, difenoconazole, and
CC       propiconazole (PubMed:28052140). Impairs growth under hypoxic
CC       conditions and attenuation of virulence in murine infection model for
CC       aspergillosis (PubMed:28052140). Cures azole resistant phenotype in a
CC       clinical strain with cyp51A G54E mutation (PubMed:28052140).
CC       {ECO:0000269|PubMed:28052140}.
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DR   EMBL; AAHF01000008; EAL87366.1; -; Genomic_DNA.
DR   RefSeq; XP_749404.1; XM_744311.1.
DR   AlphaFoldDB; Q4WI89; -.
DR   STRING; 330879.Q4WI89; -.
DR   EnsemblFungi; EAL87366; EAL87366; AFUA_2G02690.
DR   GeneID; 3506650; -.
DR   KEGG; afm:AFUA_2G02690; -.
DR   VEuPathDB; FungiDB:Afu2g02690; -.
DR   eggNOG; ENOG502QZJZ; Eukaryota.
DR   HOGENOM; CLU_011099_0_0_1; -.
DR   InParanoid; Q4WI89; -.
DR   OrthoDB; 1013000at2759; -.
DR   Proteomes; UP000002530; Chromosome 2.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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   3: Inferred from homology;
KW   DNA-binding; Membrane; Metal-binding; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation; Transmembrane;
KW   Transmembrane helix; Virulence; Zinc.
FT   CHAIN           1..895
FT                   /note="ABC-transporter-regulating transcription factor"
FT                   /id="PRO_0000448724"
FT   TRANSMEM        648..668
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DNA_BIND        69..96
FT                   /note="Zn(2)-C6 fungal-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT   REGION          156..218
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          726..813
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        158..209
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   895 AA;  99861 MW;  BEAC2E1989F1C505 CRC64;
     MDGIGDGTES MGFDMPMLMN QQPHLFGSYG HDGSPVAPIF SNPTFQDEPS IGAADDNSDA
     KRRRIARACD MCRKKKIKCD GKMPKCSHCT NYKTDCVFTQ VEKKRNPPKG AKYIEGLENR
     LGRMESLLRL SGLLSEDDGG KTDLGTLEKR LADRYHASGS NTPHNPQKIN IPSQSQIAMS
     QQNSSSHYST PRLESQSSPR TAATSPESQK ESETEVEGLS DMMCSLVTNN CGETRYIGSS
     SGFSIFSPKG IQWVNEKTGD NSFQEMISSA YVDDNKWMYW KPEIFSDIFA RRVFKPLPPK
     DEAMSLFKDF FDNFNCMFPL YHEPTFMHLV ERQYSRDPYE GSGWWASINV VLAIAHRLRV
     MSNLVPQEED RKAWLYLKNA MGVLTELTMR NTDLLSVQAL LGMSLFLQGT PNPQPSFFLV
     AAAIRLSHSI GLHKRGSGFG LNPVEVEQRK RVFWIAYLLD KDICLRSGRP PVQDDDDMNV
     ELPSDDPPDN IGNVPLSDGR SKFNLFRSMC RFATIESKVY KRLYSAKASK QSDGELLNTI
     GELDKELEDW KDSIPLDFRP EHEIKASHTP LILHVVVLHF AYYNCLTTIH RMSVHHGYWT
     SRLSNYAIQG LNARPLNPRV FLSAVLCVTA ARASINLIKY IPQGDFACVW LILYYPVSAL
     VTLFANILQN PSDARARSDV KLMNVVVNFL STLVSDESNG SIKRMLGLCG EFERIAKVVL
     DKAEKESYSK KKRKSPEEPV NLQQSTPEEH PAPSPSTTQP TQAPSRNVPM SSPLFAENPG
     DPGGNTMADD AGGFASSREI PGTTGVSTNI PPNIQAMPGI AQDYQDMLSP DPLEGVSFAD
     QPPYSATANT PLSSFQQPFV PQDLWQMPMT IEWDWADMST NFPVFDTNGP PHGGL