CRZ1_CRYNH
ID CRZ1_CRYNH Reviewed; 1094 AA.
AC J9VE33;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 25-MAY-2022, entry version 48.
DE RecName: Full=Transcriptional regulator CRZ1 {ECO:0000303|PubMed:23251520};
GN Name=CRZ1 {ECO:0000303|PubMed:23251520};
GN Synonyms=SP1 {ECO:0000303|PubMed:21487010};
GN ORFNames=CNAG_00156 {ECO:0000312|EMBL:AFR92293.1};
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 {ECO:0000312|Proteomes:UP000010091};
RN [1] {ECO:0000312|Proteomes:UP000010091}
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] {ECO:0000305}
RP SUBCELLULAR LOCATION, INDUCTION BY GLUCOSE STARVATION, PHOSPHORYLATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=21487010; DOI=10.1074/jbc.m111.230268;
RA Adler A., Park Y.D., Larsen P., Nagarajan V., Wollenberg K., Qiu J.,
RA Myers T.G., Williamson P.R.;
RT "A novel specificity protein 1 (SP1)-like gene regulating protein kinase C-
RT 1 (Pkc1)-dependent cell wall integrity and virulence factors in
RT Cryptococcus neoformans.";
RL J. Biol. Chem. 286:20977-20990(2011).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23251520; DOI=10.1371/journal.pone.0051403;
RA Lev S., Desmarini D., Chayakulkeeree M., Sorrell T.C., Djordjevic J.T.;
RT "The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated
RT by calcineurin and regulates cell wall integrity.";
RL PLoS ONE 7:e51403-e51403(2012).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=24520056; DOI=10.1128/mbio.00765-13;
RA Butts A., Koselny K., Chabrier-Rosello Y., Semighini C.P., Brown J.C.,
RA Wang X., Annadurai S., DiDone L., Tabroff J., Childers W.E. Jr.,
RA Abou-Gharbia M., Wellington M., Cardenas M.E., Madhani H.D., Heitman J.,
RA Krysan D.J.;
RT "Estrogen receptor antagonists are anti-cryptococcal agents that directly
RT bind EF hand proteins and synergize with fluconazole in vivo.";
RL MBio 5:e00765-e00765(2014).
RN [5] {ECO:0000305}
RP SUBCELLULAR LOCATION, DEPHOSPHORYLATION BY CNA1, IDENTIFICATION BY MASS
RP SPECTROMETRY, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-103; SER-288;
RP SER-329; SER-508; SER-569; SER-765 AND SER-810, AND MUTAGENESIS OF SER-288
RP AND SER-508.
RX PubMed=27611567; DOI=10.1371/journal.ppat.1005873;
RA Park H.S., Chow E.W., Fu C., Soderblom E.J., Moseley M.A., Heitman J.,
RA Cardenas M.E.;
RT "Calcineurin Targets Involved in Stress Survival and Fungal Virulence.";
RL PLoS Pathog. 12:e1005873-e1005873(2016).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 451-PRO--GLN-456.
RX PubMed=28376087; DOI=10.1371/journal.pgen.1006667;
RA Chow E.W., Clancey S.A., Billmyre R.B., Averette A.F., Granek J.A.,
RA Mieczkowski P., Cardenas M.E., Heitman J.;
RT "Elucidation of the calcineurin-Crz1 stress response transcriptional
RT network in the human fungal pathogen Cryptococcus neoformans.";
RL PLoS Genet. 13:e1006667-e1006667(2017).
RN [7] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=28898238; DOI=10.1371/journal.pgen.1006982;
RA Xu X., Lin J., Zhao Y., Kirkman E., So Y.S., Bahn Y.S., Lin X.;
RT "Glucosamine stimulates pheromone-independent dimorphic transition in
RT Cryptococcus neoformans by promoting Crz1 nuclear translocation.";
RL PLoS Genet. 13:e1006982-e1006982(2017).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29113016; DOI=10.1111/cmi.12803;
RA Squizani E.D., Oliveira N.K., Reuwsaat J.C.V., Marques B.M., Lopes W.,
RA Gerber A.L., de Vasconcelos A.T.R., Lev S., Djordjevic J.T., Schrank A.,
RA Vainstein M.H., Staats C.C., Kmetzsch L.;
RT "Cryptococcal dissemination to the central nervous system requires the
RT vacuolar calcium transporter Pmc1.";
RL Cell. Microbiol. 20:0-0(2018).
RN [9] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=29233914; DOI=10.1534/g3.117.300444;
RA Jung W.H., Son Y.E., Oh S.H., Fu C., Kim H.S., Kwak J.H., Cardenas M.E.,
RA Heitman J., Park H.S.;
RT "Had1 Is Required for Cell Wall Integrity and Fungal Virulence in
RT Cryptococcus neoformans.";
RL G3 (Bethesda) 8:643-652(2018).
RN [10]
RP SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=31266771; DOI=10.1534/genetics.119.302290;
RA Pianalto K.M., Billmyre R.B., Telzrow C.L., Alspaugh J.A.;
RT "Roles for Stress Response and Cell Wall Biosynthesis Pathways in
RT Caspofungin Tolerance in Cryptococcus neoformans.";
RL Genetics 213:213-227(2019).
CC -!- FUNCTION: DNA-binding transcriptional activator that interacts with
CC calcineurin-dependent response element (CDRE) promoters
CC (PubMed:28376087). Activates expression of genes required to maintain
CC cell wall integrity during stress (PubMed:23251520, PubMed:28376087).
CC Activates expression of genes required for transepithelial migration
CC through the host blood-brain barrier (PubMed:29113016). Required for
CC adaptation to host temperature during infection (PubMed:28376087).
CC {ECO:0000269|PubMed:23251520, ECO:0000269|PubMed:28376087,
CC ECO:0000303|PubMed:28376087, ECO:0000303|PubMed:29113016}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23251520,
CC ECO:0000269|PubMed:27611567, ECO:0000269|PubMed:28376087,
CC ECO:0000269|PubMed:28898238, ECO:0000269|PubMed:31266771}. Nucleus
CC {ECO:0000269|PubMed:21487010, ECO:0000269|PubMed:23251520,
CC ECO:0000269|PubMed:24520056, ECO:0000269|PubMed:27611567,
CC ECO:0000269|PubMed:28376087, ECO:0000269|PubMed:28898238,
CC ECO:0000269|PubMed:31266771}. Note=Localizes to the nucleus during
CC calcium signaling, cell wall and heat stress (PubMed:21487010,
CC PubMed:23251520, PubMed:24520056, PubMed:27611567, PubMed:28376087,
CC PubMed:28898238, PubMed:31266771). Localizes to the nucleus following
CC dephosphorylation by CNA1 (calcineurin) (PubMed:27611567). Localizes to
CC the nucleus during growth on glucosamine carbon source
CC (PubMed:28898238). Localizes to the cytosol during vegetative growth
CC and osmotic stress (PubMed:23251520, PubMed:28376087, PubMed:28898238).
CC {ECO:0000269|PubMed:21487010, ECO:0000269|PubMed:23251520,
CC ECO:0000269|PubMed:24520056, ECO:0000269|PubMed:27611567,
CC ECO:0000269|PubMed:28376087, ECO:0000269|PubMed:28898238,
CC ECO:0000269|PubMed:31266771}.
CC -!- INDUCTION: Induced during glucose starvation.
CC {ECO:0000269|PubMed:21487010}.
CC -!- PTM: Phosphorylated (PubMed:21487010, PubMed:27611567).
CC Dephosphorylated by calcineurin (CNA1) which promotes nuclear
CC localization (PubMed:27611567). {ECO:0000269|PubMed:21487010,
CC ECO:0000269|PubMed:27611567}.
CC -!- DISRUPTION PHENOTYPE: Decreases virulence in a mouse intranasal
CC inhalation model and intravenous model for infection (PubMed:21487010,
CC PubMed:27611567, PubMed:28376087, PubMed:29233914). Decreases virulence
CC in a moth model (PubMed:28376087). Decreases urease activity
CC (PubMed:29113016). Decreases levels of: laccase and melanin
CC (PubMed:21487010). Hypercapsular with mucoid colony morphology
CC (PubMed:21487010). Sensitive to: calcium; lithium; sodium nitrite; high
CC temperature; sodium dodecyl sulfate (cell wall stress inducer);
CC Calcofluor White (cell wall stress inducer); Congo Red (cell wall
CC stress inducer); caspofungin (cell wall stress inducer)
CC (PubMed:21487010, PubMed:27611567, PubMed:28376087, PubMed:29233914,
CC PubMed:31266771). Abolishes filamentation during growth on glucosamine
CC carbon source (PubMed:28898238). Decreases RNA level of genes involved
CC in membrane transport, carbohydrate metabolism, signaling, DNA
CC replication, and sterol biosynthesis during heat stress
CC (PubMed:28376087). Decreases CHS5 and CHS6 RNA level during heat stress
CC (PubMed:27611567, PubMed:28376087). Decreases RNA level of ZNF2 during
CC growth on glucosamine carbon source (PubMed:28898238). Increases
CC MFalpha1 expression during mating (PubMed:27611567). Normal hyphal
CC morphology during mating (PubMed:23251520, PubMed:28376087).
CC Simultaneous disruption of HAD1, PUF4 or LHP1 results in phenotypic
CC enhancement (PubMed:27611567, PubMed:29233914).
CC {ECO:0000269|PubMed:21487010, ECO:0000269|PubMed:23251520,
CC ECO:0000269|PubMed:27611567, ECO:0000269|PubMed:28376087,
CC ECO:0000269|PubMed:28898238, ECO:0000269|PubMed:29113016,
CC ECO:0000269|PubMed:29233914, ECO:0000269|PubMed:31266771}.
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DR EMBL; CP003820; AFR92293.1; -; Genomic_DNA.
DR EMBL; CP003820; AGV15273.1; -; Genomic_DNA.
DR RefSeq; XP_012046570.1; XM_012191180.1.
DR RefSeq; XP_012046571.1; XM_012191181.1.
DR AlphaFoldDB; J9VE33; -.
DR EnsemblFungi; AFR92293; AFR92293; CNAG_00156.
DR EnsemblFungi; AGV15273; AGV15273; CNAG_00156.
DR GeneID; 23884019; -.
DR VEuPathDB; FungiDB:CNAG_00156; -.
DR HOGENOM; CLU_284407_0_0_1; -.
DR PHI-base; PHI:2424; -.
DR PHI-base; PHI:7868; -.
DR Proteomes; UP000010091; Chromosome 1.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0140471; P:positive regulation of transepithelial migration of symbiont in host; IMP:UniProtKB.
DR GO; GO:0060237; P:regulation of fungal-type cell wall organization; IMP:UniProtKB.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Repeat; Transcription; Transcription regulation; Virulence; Zinc;
KW Zinc-finger.
FT CHAIN 1..1094
FT /note="Transcriptional regulator CRZ1"
FT /id="PRO_0000451159"
FT ZN_FING 944..968
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 1007..1029
FT /note="C2H2-type 2; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 477..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 835..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1037..1094
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 851..884
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1043..1081
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 569
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 765
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27611567"
FT MUTAGEN 288
FT /note="S->A: Increases CRZ1 localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:27611567"
FT MUTAGEN 451..456
FT /note="Missing: Abolishes nuclear localization during heat
FT stress and confers sensitivity to high temperature, Congo
FT Red and sodium dodecyl sulfate."
FT /evidence="ECO:0000269|PubMed:28376087"
FT MUTAGEN 508
FT /note="S->A: Increases CRZ1 localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:27611567"
SQ SEQUENCE 1094 AA; 117964 MW; A8104E5A22F9D8F4 CRC64;
MADPASPPSF DAIFAQQPVR RSSSTSTSSF ANYTYSALQQ HQQFNSDAPL VDEPQSLSEQ
ARKQQRDPSK DGNNKRYLDM MSGLADGYGV INGRRQESLR KESLPFNPQE DSTLIATAPK
RGERNGLGRN GYSSPIGDIM FGPEQTIPNQ PQQPSQQPPW GEGRMSEQSV HYASVQQPQY
SSFQSSGPGA GSAGIDYLPR GTTSSMNDSM LSSQISPYLN HDVASEGQPP QQQQQQQQQQ
QGEWGQEFIG VEQQQQYAQG EGQSNGMEDM LTMGDESPFE SELQRVISNT SHPSQYPSRT
SSPFPQQSQS NMVPASTVNQ TRTESFPASR SPSPFAPQQA SQTEASNHVV STPSMGQPTY
PRASSSPRTN PNSPFFNKPQ SPPALIIPNS PVLPNIVTQS TSNNHSKGLN QPHTRHASNG
AGGLFPPSNP ALEHLTGMAG ISPIAPNADG PMICIQPSTP ISGLKEGRGL FDAALRRAGA
ARGAQRQGPQ GQGESQEDRR QDGFNVPSPQ SHPLPRTLSS DQVNQGVEMQ GMDFAAQMQS
YEQQGWANDT LRIAGPSRPR AKSDSIIPSP TADSFDRQAF LAFIGAGNAQ PPPPNVEMQP
GYVDVSEQWR NTVSAWKAGL GEGELNSQPT LDPRLLPGRE SNEAVYQQLL MQQQTGQMPR
LDPDQLHQLT QLEGQRARFS LNTNIAPPKY EPGEISPTSM VFYQSMGLYP HAAPELSGTV
SAPWSQTAFG QVPGPGPVGH PATAGPAQQH FLTPTLSHAT VRRRSFGGGE HPAMGAGTPG
YGMEFSSPFA GKSVGQIRGV NMGHRRAARS EDFGRGGTGW GVGAGGSTAE FLQSITGDDG
SLLPPSNRGH AMSHSRHSST SSIRSASPAL SISSQGSSFS HHSPRMDMPD SIYPGHPIIA
PATPLQVSGL YEEQQTPARV AKMKVTSVAT EVASTSRRTN SGIFKCPVPG CGSTFTRHFN
LKGHLRSHND ERPFKCLYEG CPKAIVGFAR QHDCKRHMLL HEGLRLFECE GCGKKFARLD
ALTRHHKSEQ GQECAITHPL PTNFDGSPMS ESQYKTYKGI KSTPEGSGRR LSSTASGSGS
GKRRSKKSET SEED
