BCR1_CANAL
ID BCR1_CANAL Reviewed; 740 AA.
AC Q59U10; A0A1D8PT78; Q59U34;
DT 28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Biofilm and cell wall regulator 1 {ECO:0000303|PubMed:17030992};
GN Name=BCR1 {ECO:0000303|PubMed:17030992}; Synonyms=USV1;
GN OrderedLocusNames=CAALFM_CR06440CA; ORFNames=CaO19.723, CaO19.8342;
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, AND INDUCTION.
RX PubMed=15964282; DOI=10.1016/j.cub.2005.05.047;
RA Nobile C.J., Mitchell A.P.;
RT "Regulation of cell-surface genes and biofilm formation by the C. albicans
RT transcription factor Bcr1p.";
RL Curr. Biol. 15:1150-1155(2005).
RN [5]
RP INDUCTION.
RX PubMed=15814840; DOI=10.1091/mbc.e05-01-0073;
RA Kadosh D., Johnson A.D.;
RT "Induction of the Candida albicans filamentous growth program by relief of
RT transcriptional repression: a genome-wide analysis.";
RL Mol. Biol. Cell 16:2903-2912(2005).
RN [6]
RP FUNCTION.
RX PubMed=17030992; DOI=10.1128/ec.00194-06;
RA Nobile C.J., Nett J.E., Andes D.R., Mitchell A.P.;
RT "Function of Candida albicans adhesin Hwp1 in biofilm formation.";
RL Eukaryot. Cell 5:1604-1610(2006).
RN [7]
RP FUNCTION.
RX PubMed=16839200; DOI=10.1371/journal.ppat.0020063;
RA Nobile C.J., Andes D.R., Nett J.E., Smith F.J., Yue F., Phan Q.T.,
RA Edwards J.E., Filler S.G., Mitchell A.P.;
RT "Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation
RT in vitro and in vivo.";
RL PLoS Pathog. 2:E63-E63(2006).
RN [8]
RP FUNCTION.
RX PubMed=17277173; DOI=10.1128/ec.00340-06;
RA Argimon S., Wishart J.A., Leng R., Macaskill S., Mavor A., Alexandris T.,
RA Nicholls S., Knight A.W., Enjalbert B., Walmsley R., Odds F.C., Gow N.A.,
RA Brown A.J.;
RT "Developmental regulation of an adhesin gene during cellular morphogenesis
RT in the fungal pathogen Candida albicans.";
RL Eukaryot. Cell 6:682-692(2007).
RN [9]
RP INDUCTION.
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 [10]
RP FUNCTION.
RX PubMed=19197361; DOI=10.1371/journal.ppat.1000294;
RA Bastidas R.J., Heitman J., Cardenas M.E.;
RT "The protein kinase Tor1 regulates adhesin gene expression in Candida
RT albicans.";
RL PLoS Pathog. 5:E1000294-E1000294(2009).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=20605982; DOI=10.1128/iai.00480-10;
RA Nett J.E., Marchillo K., Spiegel C.A., Andes D.R.;
RT "Development and validation of an in vivo Candida albicans biofilm denture
RT model.";
RL Infect. Immun. 78:3650-3659(2010).
RN [12]
RP FUNCTION.
RX PubMed=20415594; DOI=10.1086/652407;
RA Luo G., Ibrahim A.S., Spellberg B., Nobile C.J., Mitchell A.P., Fu Y.;
RT "Candida albicans Hyr1p confers resistance to neutrophil killing and is a
RT potential vaccine target.";
RL J. Infect. Dis. 201:1718-1728(2010).
RN [13]
RP FUNCTION.
RX PubMed=20223293; DOI=10.1016/j.micinf.2010.03.001;
RA Fuchs B.B., Eby J., Nobile C.J., El Khoury J.B., Mitchell A.P.,
RA Mylonakis E.;
RT "Role of filamentation in Galleria mellonella killing by Candida
RT albicans.";
RL Microbes Infect. 12:488-496(2010).
RN [14]
RP FUNCTION.
RX PubMed=19959578; DOI=10.1099/mic.0.033530-0;
RA Ricicova M., Kucharikova S., Tournu H., Hendrix J., Bujdakova H.,
RA Van Eldere J., Lagrou K., Van Dijck P.;
RT "Candida albicans biofilm formation in a new in vivo rat model.";
RL Microbiology 156:909-919(2010).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20705667; DOI=10.1099/mic.0.039354-0;
RA Harriott M.M., Lilly E.A., Rodriguez T.E., Fidel P.L. Jr., Noverr M.C.;
RT "Candida albicans forms biofilms on the vaginal mucosa.";
RL Microbiology 156:3635-3644(2010).
RN [16]
RP FUNCTION.
RX PubMed=21829325; DOI=10.1371/journal.pbio.1001117;
RA Yi S., Sahni N., Daniels K.J., Lu K.L., Srikantha T., Huang G.,
RA Garnaas A.M., Soll D.R.;
RT "Alternative mating type configurations (a/alpha versus a/a or alpha/alpha)
RT of Candida albicans result in alternative biofilms regulated by different
RT pathways.";
RL PLoS Biol. 9:E1001117-E1001117(2011).
RN [17]
RP FUNCTION.
RX PubMed=21283544; DOI=10.1371/journal.pone.0016218;
RA Dwivedi P., Thompson A., Xie Z., Kashleva H., Ganguly S., Mitchell A.P.,
RA Dongari-Bagtzoglou A.;
RT "Role of Bcr1-activated genes Hwp1 and Hyr1 in Candida albicans oral
RT mucosal biofilms and neutrophil evasion.";
RL PLoS ONE 6:E16218-E16218(2011).
RN [18]
RP FUNCTION.
RX PubMed=21407800; DOI=10.1371/journal.pone.0017046;
RA Wachtler B., Wilson D., Haedicke K., Dalle F., Hube B.;
RT "From attachment to damage: defined genes of Candida albicans mediate
RT adhesion, invasion and damage during interaction with oral epithelial
RT cells.";
RL PLoS ONE 6:E17046-E17046(2011).
RN [19]
RP FUNCTION.
RX PubMed=22145027; DOI=10.1371/journal.pone.0028151;
RA Ding C., Vidanes G.M., Maguire S.L., Guida A., Synnott J.M., Andes D.R.,
RA Butler G.;
RT "Conserved and divergent roles of Bcr1 and CFEM proteins in Candida
RT parapsilosis and Candida albicans.";
RL PLoS ONE 6:E28151-E28151(2011).
RN [20]
RP FUNCTION.
RX PubMed=22544909; DOI=10.1128/ec.00103-12;
RA Fanning S., Xu W., Solis N., Woolford C.A., Filler S.G., Mitchell A.P.;
RT "Divergent targets of Candida albicans biofilm regulator Bcr1 in vitro and
RT in vivo.";
RL Eukaryot. Cell 11:896-904(2012).
RN [21]
RP FUNCTION.
RX PubMed=22265407; DOI=10.1016/j.cell.2011.10.048;
RA Nobile C.J., Fox E.P., Nett J.E., Sorrells T.R., Mitrovich Q.M.,
RA Hernday A.D., Tuch B.B., Andes D.R., Johnson A.D.;
RT "A recently evolved transcriptional network controls biofilm development in
RT Candida albicans.";
RL Cell 148:126-138(2012).
RN [22]
RP FUNCTION.
RX PubMed=22882910; DOI=10.1111/j.1365-2958.2012.08193.x;
RA Fanning S., Xu W., Beaurepaire C., Suhan J.P., Nantel A., Mitchell A.P.;
RT "Functional control of the Candida albicans cell wall by catalytic protein
RT kinase A subunit Tpk1.";
RL Mol. Microbiol. 86:284-302(2012).
RN [23]
RP FUNCTION.
RX PubMed=22359502; DOI=10.1371/journal.ppat.1002525;
RA Finkel J.S., Xu W., Huang D., Hill E.M., Desai J.V., Woolford C.A.,
RA Nett J.E., Taff H., Norice C.T., Andes D.R., Lanni F., Mitchell A.P.;
RT "Portrait of Candida albicans adherence regulators.";
RL PLoS Pathog. 8:E1002525-E1002525(2012).
RN [24]
RP FUNCTION, INTERACTION WITH CBK1, PHOSPHORYLATION AT THR-191 AND SER-556,
RP AND MUTAGENESIS OF THR-191 AND SER-556.
RX PubMed=22589718; DOI=10.1371/journal.ppat.1002683;
RA Gutierrez-Escribano P., Zeidler U., Suarez M.B., Bachellier-Bassi S.,
RA Clemente-Blanco A., Bonhomme J., Vazquez de Aldana C.R., d'Enfert C.,
RA Correa-Bordes J.;
RT "The NDR/LATS kinase Cbk1 controls the activity of the transcriptional
RT regulator Bcr1 during biofilm formation in Candida albicans.";
RL PLoS Pathog. 8:E1002683-E1002683(2012).
RN [25]
RP DISRUPTION PHENOTYPE.
RX PubMed=34986357; DOI=10.1016/j.celrep.2021.110183;
RA Kumwenda P., Cottier F., Hendry A.C., Kneafsey D., Keevan B., Gallagher H.,
RA Tsai H.J., Hall R.A.;
RT "Estrogen promotes innate immune evasion of Candida albicans through
RT inactivation of the alternative complement system.";
RL Cell Rep. 38:110183-110183(2022).
CC -!- FUNCTION: Transcription factor which acts as a master regulator of
CC biofilm formation (PubMed:15964282, PubMed:17030992, PubMed:16839200,
CC PubMed:20223293, PubMed:19959578, PubMed:20705667, PubMed:21829325,
CC PubMed:21283544, PubMed:21407800, PubMed:22145027, PubMed:22265407,
CC PubMed:22882910, PubMed:22589718). Biofilms play an important role in
CC pathogenesis and produce many infections such as oropharyngeal
CC candidiasis or vulvovaginal candidiasis (PubMed:20705667,
CC PubMed:21283544, PubMed:21407800, PubMed:22544909, PubMed:22265407).
CC Controls the expression of genes that govern cell-surface properties
CC such as ALS1, ALS3, HWP1 AND HYR1 (PubMed:16839200, PubMed:17277173,
CC PubMed:19197361, PubMed:20415594, PubMed:22145027, PubMed:22544909,
CC PubMed:22589718). Down-stream component of the hyphal regulatory
CC network that couples expression of cell-surface genes to hyphal
CC differentiation (PubMed:20223293, PubMed:21407800, PubMed:22359502).
CC {ECO:0000269|PubMed:15964282, ECO:0000269|PubMed:16839200,
CC ECO:0000269|PubMed:17030992, ECO:0000269|PubMed:17277173,
CC ECO:0000269|PubMed:19197361, ECO:0000269|PubMed:19959578,
CC ECO:0000269|PubMed:20223293, ECO:0000269|PubMed:20415594,
CC ECO:0000269|PubMed:20705667, ECO:0000269|PubMed:21283544,
CC ECO:0000269|PubMed:21407800, ECO:0000269|PubMed:21829325,
CC ECO:0000269|PubMed:22145027, ECO:0000269|PubMed:22265407,
CC ECO:0000269|PubMed:22359502, ECO:0000269|PubMed:22544909,
CC ECO:0000269|PubMed:22589718, ECO:0000269|PubMed:22882910}.
CC -!- SUBUNIT: Interacts with CBK1. {ECO:0000269|PubMed:22589718}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- INDUCTION: Expression is under the positive control of the hyphal
CC regulator TEC1 and repressed by TUP1 (PubMed:15814840,
CC PubMed:15964282). Also induced by acetic acid-stress in a MNL1-
CC dependent manner (PubMed:18653474). {ECO:0000269|PubMed:15814840,
CC ECO:0000269|PubMed:15964282, ECO:0000269|PubMed:18653474}.
CC -!- PTM: Phosphorylated at Thr-191 and Ser-556 by CBK1. Phosphorylation by
CC CBK1 is required for ALS1 and ALS3 expression, adherence, and biofilm
CC formation. {ECO:0000269|PubMed:22589718}.
CC -!- DISRUPTION PHENOTYPE: Produces poor biofilms and decreases infection on
CC rat denture models (PubMed:20605982, PubMed:20705667). Increases
CC phagocytosis of the fungus by host cells in presence of estrogen
CC (PubMed:34986357). Decreases expression of GPD2 (PubMed:34986357).
CC {ECO:0000269|PubMed:20605982, ECO:0000269|PubMed:20705667,
CC ECO:0000269|PubMed:34986357}.
CC -!- MISCELLANEOUS: Implanted medical devices, such as venous catheters, are
CC a serious risk factor for C.albicans infection since they are
CC substrates for the formation of biofilms, which in turn serve as
CC reservoirs of cells to continually seed an infection.
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DR EMBL; CP017630; AOW31343.1; -; Genomic_DNA.
DR RefSeq; XP_713082.2; XM_707989.2.
DR AlphaFoldDB; Q59U10; -.
DR SMR; Q59U10; -.
DR BioGRID; 1228337; 2.
DR ELM; Q59U10; -.
DR STRING; 237561.Q59U10; -.
DR iPTMnet; Q59U10; -.
DR PRIDE; Q59U10; -.
DR GeneID; 3645280; -.
DR KEGG; cal:CAALFM_CR06440CA; -.
DR CGD; CAL0000177853; BCR1.
DR VEuPathDB; FungiDB:CR_06440C_A; -.
DR eggNOG; KOG1721; Eukaryota.
DR HOGENOM; CLU_377214_0_0_1; -.
DR InParanoid; Q59U10; -.
DR OrthoDB; 1404639at2759; -.
DR PHI-base; PHI:3798; -.
DR PHI-base; PHI:6672; -.
DR PRO; PR:Q59U10; -.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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: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; 2.
DR SMART; SM00355; ZnF_C2H2; 2.
DR SUPFAM; SSF57667; SSF57667; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE 1: Evidence at protein level;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..740
FT /note="Biofilm and cell wall regulator 1"
FT /id="PRO_0000420232"
FT ZN_FING 165..190
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 196..219
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 513..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 698..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..57
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..105
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 126..155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..299
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..315
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..365
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 580..606
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 613..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 191
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22589718"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22589718"
FT MUTAGEN 191
FT /note="T->A: Impairs BCR1 function during biofilm formation
FT and virulence in a mouse model of disseminated
FT candidiasis."
FT /evidence="ECO:0000269|PubMed:22589718"
FT MUTAGEN 556
FT /note="S->A: Impairs BCR1 function during biofilm formation
FT and virulence in a mouse model of disseminated
FT candidiasis."
FT /evidence="ECO:0000269|PubMed:22589718"
SQ SEQUENCE 740 AA; 80967 MW; 5680E0352D9011C0 CRC64;
MSGTSQVLQN DSHQSQHASM AYNQRQPMMY PPPPQQQPLH SQNSLPPLPP IPAPSLPPIS
NNISNGNTNE LNNNNQQQQQ HGQPPLPPPP INANQQYYAV PPLRAPPPLN TLSSVVNSLP
TLTPTLTNAT HSTMSSNSSA ESSASSSSNS ITKPKSKRSS KGRVFQCTGY PGCNMSFTRS
EHLARHKRKH TGERPFTCPY CSKNFSRLDN LRQHKQTVHA YETYLTKDNR DSKLLIERSK
SKKKLKQQEK KAQQQAQLQA QAQAQAQAQV HMQQHQQNGY NFQPPYPQFH NQYYANNQYQ
GPQPPPPPAP QQQVPGQQQP QPQQGMPAGY LDPYRQYPPN TTFDPMALPP PPKINAHPQK
PLPPLPHQMG GGQEQPSDNV SQQGLKIPDH AFTPKRRPEP LALQHSTHSN ENISNEGNIN
ANTNTNMNTV TSSITSDAVY PPPPRSATSA ASLTPNLASP LSPLFHQSFS QTTLKSTPDP
RGSTITNSSI SIKSPMSQHF SILSGNSNYS NNTTNSLPSV SNLPHPNWGS TNGTTGSNGT
SGGSYQQNSF HQRQSSVVSD FSIFSNSDNR KDIKSNWLKG VLNDDNNNNN NNNNEQQQQQ
LQDPKLASPA PTLPPVSSIT GGGTSNGNDS MMVDNMENKN DVSQSNVIID SNNNNGDKMV
NKLNFQSIEL HDNNNNNTPS IKSTHSTETI QTTMVVVNKS DPPPLSTPTT NTNTNTNSTA
TTNATGYVSK KPTINNLISQ
