CDA1_CRYNH
ID CDA1_CRYNH Reviewed; 470 AA.
AC J9VPD7;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Chitin deacetylase 1 {ECO:0000303|PubMed:17400891};
DE EC=3.5.1.41 {ECO:0000305|PubMed:17400891, ECO:0000305|PubMed:30459196};
DE Flags: Precursor;
GN Name=CDA1 {ECO:0000303|PubMed:17400891};
GN ORFNames=CNAG_05799 {ECO:0000312|EMBL:AFR96118.1};
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 FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=KN99;
RX PubMed=17400891; DOI=10.1128/ec.00399-06;
RA Baker L.G., Specht C.A., Donlin M.J., Lodge J.K.;
RT "Chitosan, the deacetylated form of chitin, is necessary for cell wall
RT integrity in Cryptococcus neoformans.";
RL Eukaryot. Cell 6:855-867(2007).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=KN99;
RX PubMed=21784998; DOI=10.1128/ec.05138-11;
RA Baker L.G., Specht C.A., Lodge J.K.;
RT "Cell wall chitosan is necessary for virulence in the opportunistic
RT pathogen Cryptococcus neoformans.";
RL Eukaryot. Cell 10:1264-1268(2011).
RN [4] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487, and KN99;
RX PubMed=22354955; DOI=10.1128/mbio.00007-12;
RA Gilbert N.M., Baker L.G., Specht C.A., Lodge J.K.;
RT "A glycosylphosphatidylinositol anchor is required for membrane
RT localization but dispensable for cell wall association of chitin
RT deacetylase 2 in Cryptococcus neoformans.";
RL MBio 3:0-0(2012).
RN [5] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RC STRAIN=KN99;
RX PubMed=27165801; DOI=10.1128/mbio.00547-16;
RA Upadhya R., Lam W.C., Maybruck B., Specht C.A., Levitz S.M., Lodge J.K.;
RT "Induction of Protective Immunity to Cryptococcal Infection in Mice by a
RT Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans.";
RL MBio 7:0-0(2016).
RN [6] {ECO:0000305}
RP BIOTECHNOLOGY.
RX PubMed=29184017; DOI=10.1128/mbio.01872-17;
RA Specht C.A., Lee C.K., Huang H., Hester M.M., Liu J., Luckie B.A.,
RA Torres Santana M.A., Mirza Z., Khoshkenar P., Abraham A., Shen Z.T.,
RA Lodge J.K., Akalin A., Homan J., Ostroff G.R., Levitz S.M.;
RT "Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles
RT Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse
RT Strain and Cryptococcal Species.";
RL MBio 8:0-0(2017).
RN [7] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ASP-166; ASP-167; HIS-216; HIS-220; ARG-254
RP AND ASP-294.
RC STRAIN=KN99;
RX PubMed=30459196; DOI=10.1128/mbio.02087-18;
RA Upadhya R., Baker L.G., Lam W.C., Specht C.A., Donlin M.J., Lodge J.K.;
RT "Cryptococcus neoformans Cda1 and Its Chitin Deacetylase Activity Are
RT Required for Fungal Pathogenesis.";
RL MBio 9:0-0(2018).
RN [8] {ECO:0000305}
RP INDUCTION.
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).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32071275; DOI=10.1128/mbio.03373-19;
RA Hole C.R., Lam W.C., Upadhya R., Lodge J.K.;
RT "Cryptococcus neoformans Chitin Synthase 3 Plays a Critical Role in
RT Dampening Host Inflammatory Responses.";
RL MBio 11:0-0(2020).
CC -!- FUNCTION: Hydrolyzes the N-acetamido groups of N-acetyl-D-glucosamine
CC residues in chitin to form chitosan and acetate (PubMed:17400891,
CC PubMed:30459196). Chitosan is required to anchor melanin to the cell
CC wall, for maintenance of cell wall integrity, and for proper
CC cytokinesis (PubMed:17400891). Plays a major role in synthesizing cell
CC wall chitosan during host infection; chitosan offers an advantage
CC during infection as it is less readily detected than chitin by host
CC immunosurveillance mechanisms (PubMed:21784998, PubMed:30459196,
CC PubMed:32071275, PubMed:27165801). {ECO:0000269|PubMed:17400891,
CC ECO:0000269|PubMed:21784998, ECO:0000269|PubMed:27165801,
CC ECO:0000269|PubMed:30459196, ECO:0000269|PubMed:32071275}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1->4)-N-acetyl-beta-D-glucosaminyl](n) + n H2O = n acetate +
CC chitosan; Xref=Rhea:RHEA:10464, Rhea:RHEA-COMP:9593, Rhea:RHEA-
CC COMP:9597, ChEBI:CHEBI:15377, ChEBI:CHEBI:17029, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:57704; EC=3.5.1.41;
CC Evidence={ECO:0000305|PubMed:17400891, ECO:0000305|PubMed:30459196};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10465;
CC Evidence={ECO:0000305|PubMed:17400891, ECO:0000305|PubMed:30459196};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:Q6DWK3};
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:30459196}. Cell membrane
CC {ECO:0000269|PubMed:30459196}; Lipid-anchor, GPI-anchor {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed during vegetative unicellular growth.
CC {ECO:0000269|PubMed:17400891}.
CC -!- INDUCTION: Induced during host infection (PubMed:30459196). Induced by
CC the antifungal agent caspofungin (PubMed:31266771).
CC {ECO:0000269|PubMed:30459196, ECO:0000269|PubMed:31266771}.
CC -!- DISRUPTION PHENOTYPE: Decreases chitosan levels during growth in host
CC tissue (PubMed:30459196). Attenuates virulence in a mouse intranasal
CC infection model; decreases fungal burden in mouse lung
CC (PubMed:30459196). Triple knockout of CDA1, CDA2 and CDA3 results in an
CC absence of cell wall chitosan, melanization of surrounding media, an
CC increase in capsule size, sensitivity to cell wall (sodium dodecyl
CC sulfate), osmotic (NaCl) and heat stress, and avirulence in a mouse
CC intranasal infection model (PubMed:17400891, PubMed:21784998,
CC PubMed:32071275, PubMed:27165801, PubMed:22354955).
CC {ECO:0000269|PubMed:17400891, ECO:0000269|PubMed:21784998,
CC ECO:0000269|PubMed:22354955, ECO:0000269|PubMed:27165801,
CC ECO:0000269|PubMed:30459196, ECO:0000269|PubMed:32071275}.
CC -!- BIOTECHNOLOGY: Recombinant CDA1 is a potential vaccine candidiate;
CC induces protective immunity in mice against infection
CC (PubMed:29184017). A strain lacking CDA1, CDA2, and CDA3 is a potential
CC vaccine candidate; inoculation with heat-killed CDA1-CDA2-CDA3 knockout
CC cells in mouse induces protective immunity to subsequent virulent
CC fungal infection (PubMed:27165801). {ECO:0000269|PubMed:27165801,
CC ECO:0000269|PubMed:29184017}.
CC -!- SIMILARITY: Belongs to the polysaccharide deacetylase family.
CC {ECO:0000305}.
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DR EMBL; CP003826; AFR96118.1; -; Genomic_DNA.
DR RefSeq; XP_012050538.1; XM_012195148.1.
DR AlphaFoldDB; J9VPD7; -.
DR SMR; J9VPD7; -.
DR EnsemblFungi; AFR96118; AFR96118; CNAG_05799.
DR GeneID; 23889088; -.
DR VEuPathDB; FungiDB:CNAG_05799; -.
DR HOGENOM; CLU_030200_2_0_1; -.
DR PHI-base; PHI:8598; -.
DR Proteomes; UP000010091; Chromosome 7.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0009277; C:fungal-type cell wall; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008061; F:chitin binding; IEA:UniProtKB-KW.
DR GO; GO:0004099; F:chitin deacetylase activity; IGI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006039; P:cell wall chitin catabolic process; IGI:UniProtKB.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0042783; P:evasion of host immune response; IMP:UniProtKB.
DR GO; GO:0009272; P:fungal-type cell wall biogenesis; IGI:UniProtKB.
DR GO; GO:0000272; P:polysaccharide catabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR011330; Glyco_hydro/deAcase_b/a-brl.
DR InterPro; IPR002509; NODB_dom.
DR Pfam; PF01522; Polysacc_deac_1; 1.
DR SUPFAM; SSF88713; SSF88713; 1.
DR PROSITE; PS51677; NODB; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Cell membrane; Cell wall;
KW Cell wall biogenesis/degradation; Chitin degradation; Chitin-binding;
KW Cobalt; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein;
KW Membrane; Metal-binding; Polysaccharide degradation; Secreted; Signal;
KW Virulence.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..444
FT /note="Chitin deacetylase 1"
FT /evidence="ECO:0000255"
FT /id="PRO_5003828006"
FT PROPEP 445..470
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451809"
FT DOMAIN 159..358
FT /note="NodB homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT REGION 406..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT ACT_SITE 331
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 166
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 167
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 216
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 220
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 257
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT LIPID 444
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 155..363
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT MUTAGEN 166
FT /note="D->N: Abolishes CDA1 activity and results in
FT avirulence in a mouse intranasal infection model, CDA1
FT localization is unaffected; when associated with A-254 and
FT N-294."
FT /evidence="ECO:0000269|PubMed:30459196"
FT MUTAGEN 167
FT /note="D->N: Abolishes CDA1 protein expression; when
FT associated with A-216 and A-220."
FT /evidence="ECO:0000269|PubMed:30459196"
FT MUTAGEN 216
FT /note="H->A: Abolishes CDA1 protein expression; when
FT associated with N-167 and A-220."
FT /evidence="ECO:0000269|PubMed:30459196"
FT MUTAGEN 220
FT /note="H->A: Abolishes CDA1 protein expression; when
FT associated with N-167 and A-216."
FT /evidence="ECO:0000269|PubMed:30459196"
FT MUTAGEN 254
FT /note="R->A: Abolishes CDA1 activity and results in
FT avirulence in a mouse intranasal infection model, CDA1
FT localization is unaffected; when associated with N-166 and
FT N-294."
FT /evidence="ECO:0000269|PubMed:30459196"
FT MUTAGEN 294
FT /note="D->N: Abolishes CDA1 activity and results in
FT avirulence in a mouse intranasal infection model, CDA1
FT localization is unaffected; when associated with N-166 and
FT A-254."
FT /evidence="ECO:0000269|PubMed:30459196"
SQ SEQUENCE 470 AA; 48854 MW; 25C28A45B73A74C7 CRC64;
MFTFAAFSAL LISLAGVVAQ TTGTSVDSSI LTKTADSTGP SGFSIPALSE LTSGAPTDST
VALYSTFAAG ATPTVSGAPV LPTSALTIAD YPALDVTPPT NSSLVKDWMA KIDLSKVPSY
NVTTGDCSTD AAAISDGRCW WTCGGCTRET DIVECPDKNV WGLSYDDGPS PFTPLLIDYL
QEKNIKTTFF VVGSRVLSRP EMLQTEYMSG HQISIHTWSH PALTTLTNEE IVAELGWTMK
VIKDTLGVTP NTFRPPYGDI DDRVRAIAAQ MGLTPVIWTS YTDGSTTVNF DTNDWHISGG
TATGASSYET FEKILTEYAP KLDTGFITLE HDIYQQSVDL AVGYILPQVL ANGTYQLKSI
INCLGKDTSE AYIETSSNQT TTQITAATGS QSTFFQPIVG TATGAEVSAP SEATGSTAAG
SAASTTSGSG ASASTGAASN TSSSGSGRSA TMGGALIALA AVAVGMVYVA
