CUF1_CRYNH
ID CUF1_CRYNH Reviewed; 1048 AA.
AC J9VT33;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Copper-dependent transcription factor 1 {ECO:0000303|PubMed:17290306};
GN Name=CUF1 {ECO:0000303|PubMed:17290306}; ORFNames=CNAG_07724;
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2]
RP FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=17290306; DOI=10.1172/jci30006;
RA Waterman S.R., Hacham M., Hu G., Zhu X., Park Y.D., Shin S., Panepinto J.,
RA Valyi-Nagy T., Beam C., Husain S., Singh N., Williamson P.R.;
RT "Role of a CUF1/CTR4 copper regulatory axis in the virulence of
RT Cryptococcus neoformans.";
RL J. Clin. Invest. 117:794-802(2007).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19459959; DOI=10.1111/j.1574-6968.2009.01619.x;
RA Jiang N., Sun N., Xiao D., Pan J., Wang Y., Zhu X.;
RT "A copper-responsive factor gene CUF1 is required for copper induction of
RT laccase in Cryptococcus neoformans.";
RL FEMS Microbiol. Lett. 296:84-90(2009).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20112673;
RA Jiang N., Liu X., Pan J., Wang Y., Zhu X.;
RT "Effect of the copper-responsive factor Cuf1 on the capsule biosynthesis in
RT Cryptococcus neoformans.";
RL Wei Sheng Wu Xue Bao 49:1459-1464(2009).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=21489137; DOI=10.1111/j.1567-1364.2011.00733.x;
RA Jiang N., Liu X., Yang J., Li Z., Pan J., Zhu X.;
RT "Regulation of copper homeostasis by Cuf1 associates with its subcellular
RT localization in the pathogenic yeast Cryptococcus neoformans H99.";
RL FEMS Yeast Res. 11:440-448(2011).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21819456; DOI=10.1111/j.1365-2958.2011.07794.x;
RA Ding C., Yin J., Tovar E.M., Fitzpatrick D.A., Higgins D.G., Thiele D.J.;
RT "The copper regulon of the human fungal pathogen Cryptococcus neoformans
RT H99.";
RL Mol. Microbiol. 81:1560-1576(2011).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23511945; DOI=10.1039/c3mt20220h;
RA Raja M.R., Waterman S.R., Qiu J., Bleher R., Williamson P.R.,
RA O'Halloran T.V.;
RT "A copper hyperaccumulation phenotype correlates with pathogenesis in
RT Cryptococcus neoformans.";
RL Metallomics 5:363-371(2013).
RN [8]
RP FUNCTION.
RX PubMed=29089435; DOI=10.1128/mbio.01742-17;
RA Garcia-Santamarina S., Uzarska M.A., Festa R.A., Lill R., Thiele D.J.;
RT "Cryptococcus neoformans iron-sulfur protein biogenesis machinery is a
RT novel layer of protection against Cu stress.";
RL MBio 8:0-0(2017).
RN [9]
RP FUNCTION, DNA-BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=29608794; DOI=10.1111/mmi.13960;
RA Garcia-Santamarina S., Festa R.A., Smith A.D., Yu C.H., Probst C., Ding C.,
RA Homer C.M., Yin J., Noonan J.P., Madhani H., Perfect J.R., Thiele D.J.;
RT "Genome-wide analysis of the regulation of Cu metabolism in Cryptococcus
RT neoformans.";
RL Mol. Microbiol. 108:473-494(2018).
RN [10]
RP FUNCTION, DNA-BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=31932719; DOI=10.1038/s41589-019-0437-9;
RA Garcia-Santamarina S., Probst C., Festa R.A., Ding C., Smith A.D.,
RA Conklin S.E., Brander S., Kinch L.N., Grishin N.V., Franz K.J.,
RA Riggs-Gelasco P., Lo Leggio L., Johansen K.S., Thiele D.J.;
RT "A lytic polysaccharide monooxygenase-like protein functions in fungal
RT copper import and meningitis.";
RL Nat. Chem. Biol. 16:337-344(2020).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=33567338; DOI=10.1016/j.jbc.2021.100391;
RA Smith A.D., Garcia-Santamarina S., Ralle M., Loiselle D.R., Haystead T.A.,
RA Thiele D.J.;
RT "Transcription factor-driven alternative localization of Cryptococcus
RT neoformans superoxide dismutase.";
RL J. Biol. Chem. 296:100391-100391(2021).
CC -!- FUNCTION: Transcription factor that regulates copper acquisition and
CC homeostasis, and which plays a central role in fungal pathogenesis
CC during neurologic infection (PubMed:21489137, PubMed:23511945,
CC PubMed:29608794). The transcriptional regulation exerted by CUF1 is
CC intrinsically complex since it acts as a dual sensor of copper levels,
CC responsible for expression of a set of copper-specific copper
CC transporters, CTR1 and CTR4, at low copper concentrations, and 2
CC metallothioneins, CMT1 and CMT2, at high copper concentrations
CC (PubMed:17290306, PubMed:21489137, PubMed:21819456, PubMed:29608794).
CC Positively regulates the expression of the copper acquisition factor
CC BIM1 under copper-limiting conditions (PubMed:31932719). Also
CC positively regulates the expression of super oxide dismutase SOD2
CC isoform 2 during oxidative stress and copper-limiting conditions
CC (PubMed:33567338). Negatively regulates the expression of super oxide
CC dismutase SOD1 during copper-limiting conditions (PubMed:33567338).
CC Regulates also ATM1, an ABC transporter with functions in the iron-
CC sulfur clusters (ISC) export machinery, during copper stress
CC (PubMed:29089435). Another target of CUF1 is the gene encoding the
CC laccase LAC1 (PubMed:19459959). Binds promoters of target genes at Cu-
CC responsive elements (CuREs) that contain a variable A/T rich 5' region
CC followed by the core consensus sequence 5'-G(G/C)CTC(A/G)-3'
CC (PubMed:29608794, PubMed:31932719, PubMed:33567338). Negatively
CC regulates capsule biosynthesis, probably via modulating iron
CC acquisition through the high-affinity iron uptake pathway
CC (PubMed:20112673). {ECO:0000269|PubMed:17290306,
CC ECO:0000269|PubMed:19459959, ECO:0000269|PubMed:20112673,
CC ECO:0000269|PubMed:21489137, ECO:0000269|PubMed:21819456,
CC ECO:0000269|PubMed:23511945, ECO:0000269|PubMed:29089435,
CC ECO:0000269|PubMed:29608794, ECO:0000269|PubMed:31932719,
CC ECO:0000269|PubMed:33567338}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21489137,
CC ECO:0000269|PubMed:33567338}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:21489137}. Note=Upon copper depletion, localizes
CC exclusively to the nucleus as an activator for CTR4 transcription,
CC while it is located to the cell periphery in the presence of exogenous
CC copper. {ECO:0000269|PubMed:21489137}.
CC -!- DOMAIN: The CRM-I motif (C-X-C-X3-C-X-C-X2-C-X2-H) and CRM-II motif (C-
CC C-X3-C-X-C-X4-C-X-C-X3-C-C-X-C-C-X2-C-X-C) correspond to cystein-rich
CC copper-binding domains. {ECO:0000305|PubMed:17290306,
CC ECO:0000305|PubMed:21489137, ECO:0000305|PubMed:29608794}.
CC -!- DISRUPTION PHENOTYPE: Leads to a clear defect in the ability to grow in
CC both copper excess or copper deficiency conditions (PubMed:29608794).
CC Impairs the activation of laccase LAC1 transcription by copper
CC (PubMed:17290306, PubMed:19459959). Reduces also the expression of the
CC genes coding for the copper transporters CTR1 and CTR4, and the
CC metallothioneins CMT1 and CMT2 (PubMed:21819456). Impairs the induction
CC of the copper acquisition factor BIM1 under copper-limiting conditions
CC (PubMed:31932719). Impairs induction of super oxide dismutase SOD2
CC under copper-limiting conditions (PubMed:33567338). Impairs repression
CC of super oxide dismutase SOD1 under copper-limiting conditions
CC (PubMed:33567338). Leads to increased cell size and number of
CC mitochondria within the cells, and a higher production of capsules
CC (PubMed:20112673, PubMed:23511945). In copper-limited growth, exhibits
CC copper deficiency, growth defect on glycerol and sensitivity to
CC hydrogen peroxide and methionine (PubMed:17290306, PubMed:21489137).
CC Shows severe hypersensitivity to exogenous copper, while a high level
CC of copper accumulates when copper is in excess (PubMed:21489137).
CC Results in attenuated virulence in an in vivo mouse model of
CC cryptococcosis (PubMed:17290306). In mouse models, exhibits reduced
CC dissemination to the brain, but no change in lung growth
CC (PubMed:17290306). {ECO:0000269|PubMed:17290306,
CC ECO:0000269|PubMed:19459959, ECO:0000269|PubMed:20112673,
CC ECO:0000269|PubMed:21489137, ECO:0000269|PubMed:21819456,
CC ECO:0000269|PubMed:23511945, ECO:0000269|PubMed:29608794,
CC ECO:0000269|PubMed:31932719}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Either you, or me - Issue
CC 228 of September 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/228/";
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DR EMBL; CP003827; AFR96571.1; -; Genomic_DNA.
DR RefSeq; XP_012051375.1; XM_012195985.1.
DR AlphaFoldDB; J9VT33; -.
DR SMR; J9VT33; -.
DR EnsemblFungi; AFR96571; AFR96571; CNAG_07724.
DR GeneID; 23890545; -.
DR VEuPathDB; FungiDB:CNAG_07724; -.
DR HOGENOM; CLU_291511_0_0_1; -.
DR Proteomes; UP000010091; Chromosome 8.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IC:UniProtKB.
DR GO; GO:1901670; P:negative regulation of superoxide dismutase activity; IDA:UniProtKB.
DR Gene3D; 3.90.430.10; -; 1.
DR InterPro; IPR001083; Cu_fist_DNA-bd_dom.
DR InterPro; IPR036395; Cu_fist_DNA-bd_dom_sf.
DR Pfam; PF00649; Copper-fist; 1.
DR PRINTS; PR00617; COPPERFIST.
DR SMART; SM01090; Copper-fist; 1.
DR SMART; SM00412; Cu_FIST; 1.
DR SUPFAM; SSF57879; SSF57879; 1.
DR PROSITE; PS50073; COPPER_FIST_2; 1.
PE 1: Evidence at protein level;
KW Copper; Cytoplasm; Metal-binding; Nucleus; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..1048
FT /note="Copper-dependent transcription factor 1"
FT /id="PRO_0000449498"
FT DNA_BIND 1..40
FT /note="Copper-fist"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00055"
FT REGION 85..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 835..876
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 348..362
FT /note="CRM-I"
FT /evidence="ECO:0000305|PubMed:17290306,
FT ECO:0000305|PubMed:21489137, ECO:0000305|PubMed:29608794"
FT MOTIF 455..482
FT /note="CRM-II"
FT /evidence="ECO:0000305|PubMed:21489137,
FT ECO:0000305|PubMed:29608794"
FT COMPBIAS 89..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..538
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 623..653
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 835..863
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 11
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00055"
FT BINDING 14
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00055"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00055"
FT BINDING 25
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00055"
SQ SEQUENCE 1048 AA; 110781 MW; 66941210664729AD CRC64;
MVLINDKKFA CEKCIKGHRV SACTHTDRPL FEVKKKGRPS TQCRHCKEKR KSAGSSVHTK
CQCGATDPKT LKDILASVNA AHAAANESGG ASATANTSAE PEIETRKGQP GSKPTFPRGL
KDVHEIAAAA NALQGWGEDD QVVKAAERTV QALLNPCKCE LGGPCTCCQI KTKPRRKHSG
HEFENPASAG ATPPGGGCCG SSVHSRDDVA TRNSPTSINS SEAIHHPPQT APMLHKTRLF
SPYSTDLRRR DSSSSTGSKT PGWASPRAMR PPVSRIKPLT DMRRLMNAAV NQDGTLASEI
PRSVVGLPTL PGIESFNTSA NLENGEKSKD VDMPLAFPTS EDVVIGACMC GDDCSCPGCA
THDHHNISPS NRTHDGSCGE SCKGHNDCAH SIPIPSGVQS IAQLICIAAS QVPPPPPNRT
DSLNPHDTRI LPPSVSLSED VARTMGIVPL KPLECCGGKC GCPPGECACT KQCCGCCGEC
TCEKDEDTRM EEEGEYTESA RDVTTSSCGG CKGKEKQSGF SDMMSPQIPQ SVSPTSYHVP
PLQPKPLNLP VSTIHHSTLS PSFNTPQPSP PAVSSPADSL SMAVHPSNGP NVRPVPMIQP
RPILPKRASD TGLVMPQGSR PPSALGRSGS MTATKRSGTS TGVRRSNSDV RKVVGPSQPH
HRPSIQSSSD RSFYIGSPSN QIAPGGVPMA SAPSQMTAPL NSADSNSDLL AFIQQQWSAD
KTSNSNSDMN PSHPTMPVSL TAEPWAFPPQ NETTDDSAPV PFDLDAFLMS IGVQPDGELR
NDRPLSSQPP QSLMPNIPPT QPIAPLPPIP PSMSDVRPGY DMTFANFFLN STPSGPSGPS
AIPATNIPSR HTTPQASRPL TPPESSFTEP PRWKFPGDLG GEIPIWNGPE ALEGFGVLGS
PVSEKEEVTE ESQNEKDIID LSKPLDSAAL TKIMKALEKQ GGGQSSSQGA PSVANTDQQL
QSLPALQTVP PVHPASVISP TRADPAHELD DMFSQFVTLD GTPIGSNNDG LGLNGGPGMM
ALPTNLSLGD ELGFGGEMRW DQARMWSN
