NRG1_CANAL
ID NRG1_CANAL Reviewed; 310 AA.
AC Q5A0E5; A0A1D8PRJ2; Q3MNT7;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Transcriptional regulator NRG1;
GN Name=NRG1; OrderedLocusNames=CAALFM_C704230WA; ORFNames=CaO19.7150;
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 FUNCTION.
RX PubMed=11532938; DOI=10.1093/emboj/20.17.4742;
RA Murad A.M., Leng P., Straffon M., Wishart J., Macaskill S., MacCallum D.,
RA Schnell N., Talibi D., Marechal D., Tekaia F., d'Enfert C., Gaillardin C.,
RA Odds F.C., Brown A.J.;
RT "NRG1 represses yeast-hypha morphogenesis and hypha-specific gene
RT expression in Candida albicans.";
RL EMBO J. 20:4742-4752(2001).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=11532939; DOI=10.1093/emboj/20.17.4753;
RA Braun B.R., Kadosh D., Johnson A.D.;
RT "NRG1, a repressor of filamentous growth in C.albicans, is down-regulated
RT during filament induction.";
RL EMBO J. 20:4753-4761(2001).
RN [6]
RP FUNCTION.
RX PubMed=11737641; DOI=10.1046/j.1365-2958.2001.02713.x;
RA Murad A.M., d'Enfert C., Gaillardin C., Tournu H., Tekaia F., Talibi D.,
RA Marechal D., Marchais V., Cottin J., Brown A.J.;
RT "Transcript profiling in Candida albicans reveals new cellular functions
RT for the transcriptional repressors CaTup1, CaMig1 and CaNrg1.";
RL Mol. Microbiol. 42:981-993(2001).
RN [7]
RP INDUCTION.
RX PubMed=12388749; DOI=10.1091/mbc.e02-05-0272;
RA Nantel A., Dignard D., Bachewich C., Harcus D., Marcil A., Bouin A.P.,
RA Sensen C.W., Hogues H., van het Hoog M., Gordon P., Rigby T., Benoit F.,
RA Tessier D.C., Thomas D.Y., Whiteway M.;
RT "Transcription profiling of Candida albicans cells undergoing the yeast-to-
RT hyphal transition.";
RL Mol. Biol. Cell 13:3452-3465(2002).
RN [8]
RP FUNCTION.
RX PubMed=14555488; DOI=10.1128/ec.2.5.1053-1060.2003;
RA Saville S.P., Lazzell A.L., Monteagudo C., Lopez-Ribot J.L.;
RT "Engineered control of cell morphology in vivo reveals distinct roles for
RT yeast and filamentous forms of Candida albicans during infection.";
RL Eukaryot. Cell 2:1053-1060(2003).
RN [9]
RP FUNCTION.
RX PubMed=12940995; DOI=10.1046/j.1365-2958.2003.03646.x;
RA Zheng X.D., Wang Y.M., Wang Y.;
RT "CaSPA2 is important for polarity establishment and maintenance in Candida
RT albicans.";
RL Mol. Microbiol. 49:1391-1405(2003).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=15189998; DOI=10.1128/ec.3.3.776-784.2004;
RA Lotz H., Sohn K., Brunner H., Muhlschlegel F.A., Rupp S.;
RT "RBR1, a novel pH-regulated cell wall gene of Candida albicans, is
RT repressed by RIM101 and activated by NRG1.";
RL Eukaryot. Cell 3:776-784(2004).
RN [11]
RP INDUCTION.
RX PubMed=15556091; DOI=10.1016/j.femsyr.2004.08.004;
RA Toyoda M., Cho T., Kaminishi H., Sudoh M., Chibana H.;
RT "Transcriptional profiling of the early stages of germination in Candida
RT albicans by real-time RT-PCR.";
RL FEMS Yeast Res. 5:287-296(2004).
RN [12]
RP INDUCTION.
RX PubMed=15554973; DOI=10.1111/j.1365-2958.2004.04350.x;
RA Bensen E.S., Martin S.J., Li M., Berman J., Davis D.A.;
RT "Transcriptional profiling in Candida albicans reveals new adaptive
RT responses to extracellular pH and functions for Rim101p.";
RL Mol. Microbiol. 54:1335-1351(2004).
RN [13]
RP FUNCTION.
RX PubMed=15946869; DOI=10.1016/j.fgb.2005.04.008;
RA Russell C.L., Brown A.J.;
RT "Expression of one-hybrid fusions with Staphylococcus aureus lexA in
RT Candida albicans confirms that Nrg1 is a transcriptional repressor and that
RT Gcn4 is a transcriptional activator.";
RL Fungal Genet. Biol. 42:676-683(2005).
RN [14]
RP FUNCTION.
RX PubMed=15659176; DOI=10.1111/j.1365-2958.2004.04414.x;
RA Staib P., Morschhauser J.;
RT "Differential expression of the NRG1 repressor controls species-specific
RT regulation of chlamydospore development in Candida albicans and Candida
RT dubliniensis.";
RL Mol. Microbiol. 55:637-652(2005).
RN [15]
RP INDUCTION.
RX PubMed=16710830; DOI=10.1002/yea.1373;
RA Umeyama T., Kaneko A., Niimi M., Uehara Y.;
RT "Repression of CDC28 reduces the expression of the morphology-related
RT transcription factors, Efg1p, Nrg1p, Rbf1p, Rim101p, Fkh2p and Tec1p and
RT induces cell elongation in Candida albicans.";
RL Yeast 23:537-552(2006).
RN [16]
RP FUNCTION.
RX PubMed=17005810; DOI=10.1128/aac.00628-06;
RA Saville S.P., Lazzell A.L., Bryant A.P., Fretzen A., Monreal A.,
RA Solberg E.O., Monteagudo C., Lopez-Ribot J.L., Milne G.T.;
RT "Inhibition of filamentation can be used to treat disseminated
RT candidiasis.";
RL Antimicrob. Agents Chemother. 50:3312-3316(2006).
RN [17]
RP FUNCTION.
RX PubMed=16518764; DOI=10.1086/500950;
RA Chamilos G., Lionakis M.S., Lewis R.E., Lopez-Ribot J.L., Saville S.P.,
RA Albert N.D., Halder G., Kontoyiannis D.P.;
RT "Drosophila melanogaster as a facile model for large-scale studies of
RT virulence mechanisms and antifungal drug efficacy in Candida species.";
RL J. Infect. Dis. 193:1014-1022(2006).
RN [18]
RP FUNCTION.
RX PubMed=18627379; DOI=10.1111/j.1462-5822.2008.01198.x;
RA Nobile C.J., Solis N., Myers C.L., Fay A.J., Deneault J.S., Nantel A.,
RA Mitchell A.P., Filler S.G.;
RT "Candida albicans transcription factor Rim101 mediates pathogenic
RT interactions through cell wall functions.";
RL Cell. Microbiol. 10:2180-2196(2008).
RN [19]
RP FUNCTION.
RX PubMed=17967861; DOI=10.1128/iai.00982-07;
RA Saville S.P., Lazzell A.L., Chaturvedi A.K., Monteagudo C.,
RA Lopez-Ribot J.L.;
RT "Use of a genetically engineered strain to evaluate the pathogenic
RT potential of yeast cell and filamentous forms during Candida albicans
RT systemic infection in immunodeficient mice.";
RL Infect. Immun. 76:97-102(2008).
RN [20]
RP INDUCTION.
RX PubMed=18216277; DOI=10.1091/mbc.e07-11-1110;
RA Banerjee M., Thompson D.S., Lazzell A., Carlisle P.L., Pierce C.,
RA Monteagudo C., Lopez-Ribot J.L., Kadosh D.;
RT "UME6, a novel filament-specific regulator of Candida albicans hyphal
RT extension and virulence.";
RL Mol. Biol. Cell 19:1354-1365(2008).
RN [21]
RP FUNCTION.
RX PubMed=18653474; DOI=10.1091/mbc.e07-09-0946;
RA Ramsdale M., Selway L., Stead D., Walker J., Yin Z., Nicholls S.M.,
RA Crowe J., Sheils E.M., Brown A.J.;
RT "MNL1 regulates weak acid-induced stress responses of the fungal pathogen
RT Candida albicans.";
RL Mol. Biol. Cell 19:4393-4403(2008).
RN [22]
RP FUNCTION.
RX PubMed=19144791; DOI=10.1128/cvi.00480-08;
RA Saville S.P., Lazzell A.L., Chaturvedi A.K., Monteagudo C.,
RA Lopez-Ribot J.L.;
RT "Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as
RT an experimental live attenuated vaccine against hematogenously disseminated
RT candidiasis.";
RL Clin. Vaccine Immunol. 16:430-432(2009).
RN [23]
RP FUNCTION.
RX PubMed=20709787; DOI=10.1128/ec.00111-10;
RA Uppuluri P., Pierce C.G., Thomas D.P., Bubeck S.S., Saville S.P.,
RA Lopez-Ribot J.L.;
RT "The transcriptional regulator Nrg1p controls Candida albicans biofilm
RT formation and dispersion.";
RL Eukaryot. Cell 9:1531-1537(2010).
RN [24]
RP FUNCTION.
RX PubMed=20232156; DOI=10.1007/s11046-010-9297-2;
RA Cleary I.A., Saville S.P.;
RT "An analysis of the impact of NRG1 overexpression on the Candida albicans
RT response to specific environmental stimuli.";
RL Mycopathologia 170:1-10(2010).
RN [25]
RP INDUCTION.
RX PubMed=22726313; DOI=10.1111/j.1365-2672.2012.05372.x;
RA Oh S., Go G.W., Mylonakis E., Kim Y.;
RT "The bacterial signalling molecule indole attenuates the virulence of the
RT fungal pathogen Candida albicans.";
RL J. Appl. Microbiol. 113:622-628(2012).
CC -!- FUNCTION: Transcriptional repressor that binds NRG1 response elements
CC (NRE) of target promoters. Involved in regulation of chlamydospore
CC formation, hyphal growth, virulence, and stress response. Plays a key
CC role in regulating true hyphal growth, but does not regulate
CC pseudohyphal growth in the same fashion. Directs transcriptional
CC repression of a subset of filament-specific genes such as HWP1, HYR1,
CC ALS8, HWP1, or ECE1; via the TUP1 pathway. Functions with UME6 in a
CC negative feedback loop to control the level and duration of filament-
CC specific gene expression in response to inducing conditions. Plays a
CC key role in biofilm formation and dispersion. Also plays the role of a
CC negative regulator of virulence in mice models. Required for the
CC expression of the cell wall genes RBR1. {ECO:0000269|PubMed:11532938,
CC ECO:0000269|PubMed:11532939, ECO:0000269|PubMed:11737641,
CC ECO:0000269|PubMed:12940995, ECO:0000269|PubMed:14555488,
CC ECO:0000269|PubMed:15189998, ECO:0000269|PubMed:15659176,
CC ECO:0000269|PubMed:15946869, ECO:0000269|PubMed:16518764,
CC ECO:0000269|PubMed:17005810, ECO:0000269|PubMed:17967861,
CC ECO:0000269|PubMed:18627379, ECO:0000269|PubMed:18653474,
CC ECO:0000269|PubMed:19144791, ECO:0000269|PubMed:20232156,
CC ECO:0000269|PubMed:20709787}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- INDUCTION: Down-regulated during filament induction and in response to
CC serum at 37 degrees Celsius. Expression of NRG1 is also repressed by
CC RIM101 and under conditions that repress CDC28 expression. The
CC bacterial signaling molecules indole and its derivate indole-3-
CC acetonitrile (IAN) increase NRG1 expression.
CC {ECO:0000269|PubMed:11532939, ECO:0000269|PubMed:12388749,
CC ECO:0000269|PubMed:15189998, ECO:0000269|PubMed:15554973,
CC ECO:0000269|PubMed:15556091, ECO:0000269|PubMed:16710830,
CC ECO:0000269|PubMed:18216277, ECO:0000269|PubMed:22726313}.
CC -!- DISRUPTION PHENOTYPE: Exhibits a high degree of filamentous growth and
CC leads to avirulence in a mouse model. {ECO:0000269|PubMed:11532939}.
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DR EMBL; CP017629; AOW30760.1; -; Genomic_DNA.
DR RefSeq; XP_715199.1; XM_710106.1.
DR AlphaFoldDB; Q5A0E5; -.
DR SMR; Q5A0E5; -.
DR BioGRID; 1226260; 1.
DR STRING; 237561.Q5A0E5; -.
DR PRIDE; Q5A0E5; -.
DR GeneID; 3643166; -.
DR KEGG; cal:CAALFM_C704230WA; -.
DR CGD; CAL0000186831; NRG1.
DR VEuPathDB; FungiDB:C7_04230W_A; -.
DR eggNOG; KOG1721; Eukaryota.
DR HOGENOM; CLU_069169_0_0_1; -.
DR InParanoid; Q5A0E5; -.
DR OMA; PNPSAYW; -.
DR OrthoDB; 1620043at2759; -.
DR Proteomes; UP000000559; Chromosome 7.
DR GO; GO:0031519; C:PcG protein complex; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:CGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:CGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0097316; P:cellular response to N-acetyl-D-glucosamine; IMP:CGD.
DR GO; GO:0036244; P:cellular response to neutral pH; IMP:CGD.
DR GO; GO:0009267; P:cellular response to starvation; IMP:CGD.
DR GO; GO:0001410; P:chlamydospore formation; IMP:CGD.
DR GO; GO:0044114; P:development of symbiont in host; IMP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0060258; P:negative regulation of filamentous growth; IMP:CGD.
DR GO; GO:0045827; P:negative regulation of isoprenoid metabolic process; IMP:CGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:CGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CGD.
DR GO; GO:0009372; P:quorum sensing; IMP:CGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 2.
DR SUPFAM; SSF57667; SSF57667; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE 2: Evidence at transcript level;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Repressor;
KW Stress response; Virulence; Zinc; Zinc-finger.
FT CHAIN 1..310
FT /note="Transcriptional regulator NRG1"
FT /id="PRO_0000424609"
FT ZN_FING 228..250
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 256..280
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 85..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 310 AA; 34299 MW; FC798E706E6CE147 CRC64;
MLYQQSYPIT NKLLNASAAG STSTASIIDG GCTLSKPGSG KTKSTTSLPS FNELLTSIPL
PNEFKPSTKN TNQAAAATAT SPYNYYMGPP AQHRLPTPPP YPMSSPTTAT AATPLSQQSP
HLQPQQTLQQ PQPYHQQYYN YQYAAPPYPH PSQVPPPASY QQRHQQPMYQ NTNGVPIIIR
PSPGLITPTS TTFDHAKIRS NSTGDLSANS LALSSNNNTQ SKDPRRKHVC KVCSRSFTTS
GHLARHNRIH TGERKHQCPW PTCEARFARQ DNCNQHYKTH TNGKNKRNRQ QHRTLEASHV
GTKYNTKSLV
