CDA3_CRYNH
ID CDA3_CRYNH Reviewed; 412 AA.
AC P82476; J9VKC9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 3.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Chitin deacetylase 3 {ECO:0000303|PubMed:17400891};
DE EC=3.5.1.41 {ECO:0000269|PubMed:17400891};
DE Flags: Precursor;
GN Name=CDA3 {ECO:0000303|PubMed:17400891}; ORFNames=CNAG_01239;
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 PROTEIN SEQUENCE OF 40-58; 73-91; 305-310 AND 315-330.
RC STRAIN=BL-1;
RX PubMed=10749672; DOI=10.1042/0264-6021:3470431;
RA Chen S.C.A., Wright L.C., Golding J.C., Sorrell T.C.;
RT "Purification and characterization of secretory phospholipase B,
RT lysophospholipase and lysophospholipase/transacylase from a virulent strain
RT of the pathogenic fungus Cryptococcus neoformans.";
RL Biochem. J. 347:431-439(2000).
RN [3]
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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
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 Chitosan is required to anchor melanin to the cell wall, for
CC maintenance of cell wall integrity, and for proper cytokinesis
CC (PubMed:17400891). Chitosan offers an advantage during infection as it
CC is less readily detected than chitin by host immunosurveillance
CC mechanisms (PubMed:21784998, PubMed:32071275, PubMed:27165801).
CC {ECO:0000269|PubMed:17400891, ECO:0000269|PubMed:21784998,
CC ECO:0000269|PubMed:27165801, 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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10465;
CC Evidence={ECO:0000305|PubMed:17400891};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:Q6DWK3};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Lipid-anchor, GPI-
CC anchor {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed during unicellular vegetative growth.
CC {ECO:0000269|PubMed:17400891}.
CC -!- INDUCTION: Repressed by the antifungal agent caspofungin.
CC {ECO:0000269|PubMed:31266771}.
CC -!- DISRUPTION PHENOTYPE: Inoculation of live or dead cells in mouse leads
CC to an aberrant host hyperinflammatory immune response and host death
CC (PubMed:32071275). 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:32071275}.
CC -!- BIOTECHNOLOGY: 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. {ECO:0000269|PubMed:27165801}.
CC -!- SIMILARITY: Belongs to the polysaccharide deacetylase family.
CC {ECO:0000305}.
CC -!- CAUTION: The protein characterized in PubMed:10749672 is not a chitin
CC deacetylase, the peptides sequenced being copurified contaminants of
CC the protein under study. {ECO:0000305}.
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DR EMBL; CP003824; AFR94907.1; -; Genomic_DNA.
DR RefSeq; XP_012049409.1; XM_012194019.1.
DR AlphaFoldDB; P82476; -.
DR SMR; P82476; -.
DR EnsemblFungi; AFR94907; AFR94907; CNAG_01239.
DR GeneID; 23884973; -.
DR VEuPathDB; FungiDB:CNAG_01239; -.
DR HOGENOM; CLU_042090_2_0_1; -.
DR PHI-base; PHI:8600; -.
DR Proteomes; UP000010091; Chromosome 5.
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: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 biogenesis/degradation;
KW Chitin degradation; Chitin-binding; Cleavage on pair of basic residues;
KW Cobalt; Direct protein sequencing; Glycoprotein; GPI-anchor; Hydrolase;
KW Lipoprotein; Membrane; Metal-binding; Polysaccharide degradation; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..39
FT /evidence="ECO:0000269|PubMed:10749672"
FT /id="PRO_0000024830"
FT CHAIN 40..387
FT /note="Chitin deacetylase 3"
FT /id="PRO_0000024831"
FT PROPEP 388..412
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451831"
FT DOMAIN 124..314
FT /note="NodB homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT REGION 82..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 131
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT ACT_SITE 289
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 131
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 132
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 183
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 187
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 225
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT LIPID 387
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 54..57
FT /note="PGPG -> SSPP (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="P -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="G -> K (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 44158 MW; C04C77223646E647 CRC64;
MYGHLSLSAL SLFAVVAAAP FRESWLQPRD SPVSQLFRRT APDPNSNDYM SYYPGPGSTP
NVSTIPQAWL DKLATVNLPN VPVATPDGGR PTYPNNEDDG DSTICSFTDQ CRVEDDLYSP
PGEKIWALSF DDGPTDVSPA LYDYLAQNNI SSSATHFMIG GNVITSPQSV LVAVKAGGHL
AVHTWSHPYM TTLTNEQVVG ELGWTMQALS DLNGGRIPMY WRPPYGDVDN RVRAIAKEVF
GLVTVLWDSD TNDWAITDEP GQYSVASVEA YFDTLVTGNR TQGLLLLEHE LDNNTVEVFE
TEYPKAVGNG WTVKNVADAF NMEWYLNSGK GNNDVVTTMS VAGTLTTATP TNTSTYVASS
TAASSASVTD SAGVSIASAA SSEASSSWAI ANRPSHFVIA IACGLALAAI MV
