CDA2_CRYNH
ID CDA2_CRYNH Reviewed; 455 AA.
AC J9VND2;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Chitin deacetylase 2 {ECO:0000303|PubMed:17400891};
DE EC=3.5.1.41 {ECO:0000305|PubMed:17400891, ECO:0000305|PubMed:22354955};
DE Flags: Precursor;
GN Name=CDA2 {ECO:0000303|PubMed:17400891};
GN Synonyms=MP98 {ECO:0000303|PubMed:17400891};
GN ORFNames=CNAG_01230 {ECO:0000312|EMBL:AFR94916.1};
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 FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP 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 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] {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:22354955). Chitosan is required to anchor melanin to the cell
CC wall, for maintenance of cell wall integrity, and for proper
CC cytokinesis (PubMed:17400891). Chitosan offers an advantage during
CC infection as it is less readily detected than chitin by host
CC immunosurveillance mechanisms (PubMed:21784998, PubMed:32071275,
CC PubMed:27165801). {ECO:0000269|PubMed:17400891,
CC ECO:0000269|PubMed:21784998, ECO:0000269|PubMed:22354955,
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, ECO:0000305|PubMed:22354955};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10465;
CC Evidence={ECO:0000305|PubMed:17400891, ECO:0000305|PubMed:22354955};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:Q6DWK3};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22354955}. Secreted,
CC cell wall {ECO:0000269|PubMed:22354955}. Cell membrane
CC {ECO:0000269|PubMed:22354955}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:22354955}. Note=GPI-anchored cell membrane protein
CC (GPI-PMP) (PubMed:22354955). Non-covalently associated to the cell wall
CC independently of both its GPI-anchor and beta-1,6-glucan
CC (PubMed:22354955). Cell membrane localization is critical for effective
CC deacetylase activity (PubMed:22354955). {ECO:0000269|PubMed:22354955}.
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 -!- PTM: The GPI anchor is required for the attachment to the cell membrane
CC but not for cell surface targeting. {ECO:0000269|PubMed:22354955}.
CC -!- DISRUPTION PHENOTYPE: Triple knockout of CDA1, CDA2 and CDA3 results in
CC an 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. {ECO:0000269|PubMed:17400891,
CC ECO:0000269|PubMed:21784998, ECO:0000269|PubMed:27165801,
CC ECO:0000269|PubMed:32071275}.
CC -!- BIOTECHNOLOGY: Recombinant CDA2 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; CP003824; AFR94916.1; -; Genomic_DNA.
DR RefSeq; XP_012049402.1; XM_012194012.1.
DR AlphaFoldDB; J9VND2; -.
DR SMR; J9VND2; -.
DR EnsemblFungi; AFR94916; AFR94916; CNAG_01230.
DR GeneID; 23884964; -.
DR VEuPathDB; FungiDB:CNAG_01230; -.
DR HOGENOM; CLU_035539_0_0_1; -.
DR PHI-base; PHI:8599; -.
DR Proteomes; UP000010091; Chromosome 5.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008061; F:chitin binding; IEA:UniProtKB-KW.
DR GO; GO:0004099; F:chitin deacetylase activity; IMP: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;
KW Cell wall biogenesis/degradation; Chitin degradation; Chitin-binding;
KW Cobalt; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane;
KW Metal-binding; Polysaccharide degradation; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..429
FT /note="Chitin deacetylase 2"
FT /evidence="ECO:0000255"
FT /id="PRO_5003827992"
FT PROPEP 430..455
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000451810"
FT DOMAIN 157..347
FT /note="NodB homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT REGION 381..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 164
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT ACT_SITE 321
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 164
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT BINDING 165
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 214
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 218
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 255
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000250|UniProtKB:Q6DWK3"
FT LIPID 429
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 455 AA; 48289 MW; 1E07A1296FFEF9D4 CRC64;
MIPSTAAALL TLTAGAAFAH TGCGGHEIGR RNVGGPMLYR RAVTDEASAA VSTDINTECT
AYSYAPVTEL ISSFPTIWQT ASIPSNDTEA QQLFGKINST LNTKIPNDVP HGTPTGDWTG
VNYSNSDPDC WWTHNKCTTP SNDTGLQADI SIAPEPMTWG LGFDDGPNCS HNALYDLLLE
NNQKATMFFI GSNVLDWPLQ AMRAHDEGHE ICVHTWSHQY MTALSNEVVF AELYYTQKAI
KAVLGVTPQC WRPPYGDVDN RVRMIAEGLN LTTIIWSDDT DDWAAGTNGV TEQDVTNNYQ
SVIDKAGNGT YTTHGPVVLN HELTNYTMSV FMTMFPKIKS AFNYIVPICT AYNITQPYAE
SNITCPNFET YISGVTNISS STTQKDGSSS TNTASGSGAA GSASATSSSD DSSSSGGSSG
SSGSNNASSG ALGMFDSLSG VGLILGGVVA GVMLL
