CHS3_CRYNH
ID CHS3_CRYNH Reviewed; 1421 AA.
AC J9VXM5;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 25-MAY-2022, entry version 46.
DE RecName: Full=Chitin synthase 3 {ECO:0000250|UniProtKB:P29465};
DE EC=2.4.1.16 {ECO:0000250|UniProtKB:P29465};
DE AltName: Full=Chitin-UDP acetyl-glucosaminyl transferase 3;
DE AltName: Full=Class-IV chitin synthase 3;
GN Name=CHS3 {ECO:0000303|PubMed:25970403}; ORFNames=CNAG_05581;
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, AND DISRUPTION PHENOTYPE.
RX PubMed=16278457; DOI=10.1128/ec.4.11.1902-1912.2005;
RA Banks I.R., Specht C.A., Donlin M.J., Gerik K.J., Levitz S.M., Lodge J.K.;
RT "A chitin synthase and its regulator protein are critical for chitosan
RT production and growth of the fungal pathogen Cryptococcus neoformans.";
RL Eukaryot. Cell 4:1902-1912(2005).
RN [3]
RP FUNCTION.
RX PubMed=16102007; DOI=10.1111/j.1365-2958.2005.04779.x;
RA Walton F.J., Idnurm A., Heitman J.;
RT "Novel gene functions required for melanization of the human pathogen
RT Cryptococcus neoformans.";
RL Mol. Microbiol. 57:1381-1396(2005).
RN [4]
RP FUNCTION, AND DISRUPTION 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 [5]
RP SUBCELLULAR LOCATION, AND PALMITOYLATION.
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=25970403; DOI=10.1371/journal.ppat.1004908;
RA Santiago-Tirado F.H., Peng T., Yang M., Hang H.C., Doering T.L.;
RT "A single protein S-acyl transferase acts through diverse substrates to
RT determine cryptococcal morphology, stress tolerance, and pathogenic
RT outcome.";
RL PLoS Pathog. 11:E1004908-E1004908(2015).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32743128; DOI=10.1016/j.tcsw.2018.05.002;
RA Rodrigues J., Ramos C.L., Frases S., Godinho R.M.D.C., Fonseca F.L.,
RA Rodrigues M.L.;
RT "Lack of chitin synthase genes impacts capsular architecture and cellular
RT physiology in Cryptococcus neoformans.";
RL Cell Surf. 2:14-23(2018).
RN [7]
RP 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).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=KN99;
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: Polymerizes chitin, a structural polymer of the cell wall and
CC septum, by transferring the sugar moiety of UDP-GlcNAc to the non-
CC reducing end of the growing chitin polymer (PubMed:16278457). Activated
CC by CSR2, it produces chitin that is deacetyled to chitosan, which is
CC required to maintain cell wall integrity (PubMed:16278457,
CC PubMed:16102007, PubMed:17400891, PubMed:32743128). Conversion of
CC chitin to chitosan offers an advantage during infection, as chitosan is
CC less readily detected by host immunosurveillance mechanisms
CC (PubMed:32071275). {ECO:0000269|PubMed:16102007,
CC ECO:0000269|PubMed:16278457, ECO:0000269|PubMed:17400891,
CC ECO:0000269|PubMed:32071275, ECO:0000269|PubMed:32743128}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1->4)-N-acetyl-beta-D-glucosaminyl](n) + UDP-N-acetyl-alpha-
CC D-glucosamine = [(1->4)-N-acetyl-beta-D-glucosaminyl](n+1) + H(+) +
CC UDP; Xref=Rhea:RHEA:16637, Rhea:RHEA-COMP:9593, Rhea:RHEA-COMP:9595,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17029, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223; EC=2.4.1.16;
CC Evidence={ECO:0000250|UniProtKB:P29465};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25970403};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- PTM: Palmitoylated by PFA4; required for proper subcellular
CC localization. {ECO:0000269|PubMed:25970403}.
CC -!- DISRUPTION PHENOTYPE: Increases cellular chitin level and decreases
CC cellular chitosan level (PubMed:16278457, PubMed:17400891,
CC PubMed:32071275). Swollen cell with abnormal cytokinesis
CC (PubMed:16278457, PubMed:17400891, PubMed:32743128, PubMed:32071275).
CC Abnormal capsular morphology: lower fiber density, short fibers,
CC decreases capsular diameter (PubMed:32743128). Decreases extracellular
CC vesicle secretion (PubMed:32743128). Melanization of surrounding media
CC (PubMed:16278457, PubMed:17400891). Increases CHS5 and CHS7 RNA level
CC (PubMed:16278457). Sensitive to: caspofungin (cell wall stress
CC inducer), sodium dodecyl sulfate (cell wall stress inducer), Congo Red
CC (cell wall stress inducer), Calcofluor White (cell wall stressor),
CC caffeine, NaCl (osmotic stressor), high temperature (PubMed:16278457,
CC PubMed:17400891, PubMed:31266771, PubMed:32071275). Intranasal
CC inoculation with high inoculum causes rapid mortality in mouse;
CC mortality is not due to fungal burden but to a strong hyperinflammatory
CC response in the host driven by host neutrophils (PubMed:32071275).
CC {ECO:0000269|PubMed:16278457, ECO:0000269|PubMed:17400891,
CC ECO:0000269|PubMed:31266771, ECO:0000269|PubMed:32071275,
CC ECO:0000269|PubMed:32743128}.
CC -!- SIMILARITY: Belongs to the chitin synthase family. Class IV subfamily.
CC {ECO:0000305}.
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DR EMBL; CP003833; AFR99008.1; -; Genomic_DNA.
DR RefSeq; XP_012053858.1; XM_012198468.1.
DR AlphaFoldDB; J9VXM5; -.
DR SwissPalm; J9VXM5; -.
DR PRIDE; J9VXM5; -.
DR EnsemblFungi; AFR99008; AFR99008; CNAG_05581.
DR GeneID; 23888883; -.
DR VEuPathDB; FungiDB:CNAG_05581; -.
DR HOGENOM; CLU_002572_1_0_1; -.
DR Proteomes; UP000010091; Chromosome 14.
DR GO; GO:0005935; C:cellular bud neck; IEA:EnsemblFungi.
DR GO; GO:0045009; C:chitosome; IEA:EnsemblFungi.
DR GO; GO:0000131; C:incipient cellular bud site; IEA:EnsemblFungi.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004100; F:chitin synthase activity; IMP:UniProtKB.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0034221; P:fungal-type cell wall chitin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0097271; P:protein localization to bud neck; IEA:EnsemblFungi.
DR InterPro; IPR004835; Chitin_synth.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR22914; PTHR22914; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell wall biogenesis/degradation; Glycoprotein;
KW Glycosyltransferase; Membrane; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1421
FT /note="Chitin synthase 3"
FT /id="PRO_0000435135"
FT TOPO_DOM 1..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..247
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..1067
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1068..1088
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1089..1097
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1098..1118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1119..1122
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1123..1143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1144..1421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 170..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1256..1319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1338..1421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..32
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 592..617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1256..1271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1287..1319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1338..1367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1393..1408
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 906
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1035
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1421 AA; 158184 MW; 5B2C3D71C7D80E46 CRC64;
MSRPHLQQNV SFQDTKPPSR RAGRDDIPPR PPTKSDPSKA SLTTTTTVQS VGGYNNHQLD
FDDNAYVDAG SSNPQGFSDY NGVRRKKSMV RPERERIDPN HRLWHYREHA AEDQVDIQPS
STGNQPYNQY NNQRPGANLR RGKSLLARET DDVDDSSGLN IFKRGATIRR KASRATPRQA
PTGAQSNRVS AGQKEDEECC CLGNFAPGPK NCWMIYCYLL TICIPGFVIA KVFGKKTPDA
QRAWREKIGI VSIVLYLMGA VGFITFGFTQ TVCGDTQLRL PGGSANTGSL VINGYDYDFS
TWRHPVAGDT FNGTTSPLYM DQYMAGGMDA SFLFQNVNQN CLGLITPASG TGIDHDGDQM
GWYFPCNLHD QNGTSAANLT GITDRTNCHV SSYARSNFSA VVPTAEIYYT WDRVKDESRN
LAVYKSAVID MNLLQWLDDT QVSYPEFFNT IKNRNDSYAG KDITALIERA GLSQYARCLT
DVIQIGFVDT ITIGCIMSEL VLYVSLVFIL GAVFIKFGMA VVFGWFLSWR MGNFKGESYQ
ERMKRAAEIE NWTDDIYRPA PGYLRPNATG TARTGVKKNF LPTTSRFSRA EPMLVSSSRP
STSYGMVGET RRQGSSIYGN KLGPPAHTTP PGSPLLRNSR SSTSLPFRDD SRHSISDRSV
NNNVPCPFPL GNVVPQPAPD FEPFGYPLIH SICLVTAYSE SIEGLRTTLD SLATTDYPNS
HKLILVICDG MVRGSGSKQY TPEIVLGMMK ELVTPAEEVE AHSYVAIADG HKRHNMAKVY
AGFYAYDSET VEASKQQRVP MVLVSKVGNP LEVNDAKPGN RGKRDSQIVL MSFLQKVMFD
ERMTTLEYEF FNAVWRCTGI PPDRYETVLC VDADTKVFPD SLTRMNACMV NDHEIMGLCG
ETKIANKSET WVTMIQVFEY YISHHNTKAF ESVFGGVTCL PGCFSMYRIK APKGERGFWV
PILANPDICE HYAENVVDTL HKKNLLLLGE DRYLSTLMLK TFPKRKMVFC PQAVCKTIVP
DTFRVLLSQR RRWINSTVHN LCELILVRDL CGTFCFSMQF VVFMDLVGTL VLPAAISFTL
YIIMISIIPQ SVTGMPRPYV SLVLLAFILG LPGVLIVITS RKIAYVGWML VYLISLPVWN
LILPAYSYWH MDDFTWGETR KIAGEVKEEA HGGKEGTFDS SHIVMKKWAE FERERRWRTG
TASRDSQYFD VVQRANSPRS GIPSNRYSIV STSETFNSGL GTAESNHLFR QSQSFASMSQ
VAPSPETNYG NVPQLALPPP RGASIGREHS PSSTESGTSN NYAYGSTEEP TASNVDPYYQ
PFTNEVYQDE AEQPILPSEY TTTSPEPVYQ TAPARVRQPS QRGVSLVDTG PVRSAQAAPH
DAVRRVSRHQ RRSSSKNQLV SPISSGGHTG SLPPGAAPPQ Y
