NADA_ASPFU
ID NADA_ASPFU Reviewed; 234 AA.
AC Q4WL81;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Conidial surface nicotinamide adenine dinucleotide glycohydrolase nadA {ECO:0000303|PubMed:33712585};
DE Short=NADase {ECO:0000303|PubMed:33712585};
DE AltName: Full=NAD(+) hydrolase nadA {ECO:0000303|PubMed:33712585};
DE EC=3.2.2.5 {ECO:0000269|PubMed:33712585};
DE AltName: Full=NADP(+) hydrolase nadA {ECO:0000303|PubMed:33712585};
DE EC=3.2.2.- {ECO:0000269|PubMed:33712585};
DE Flags: Precursor;
GN Name=nadA {ECO:0000303|PubMed:33712585}; ORFNames=AFUA_6G14470;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP INDUCTION.
RX PubMed=29113011; DOI=10.1111/cmi.12802;
RA Takahashi-Nakaguchi A., Sakai K., Takahashi H., Hagiwara D., Toyotome T.,
RA Chibana H., Watanabe A., Yaguchi T., Yamaguchi M., Kamei K., Gonoi T.;
RT "Aspergillus fumigatus adhesion factors in dormant conidia revealed through
RT comparative phenotypic and transcriptomic analyses.";
RL Cell. Microbiol. 20:0-0(2018).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NAD, IDENTIFICATION
RP BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, SUBUNIT,
RP DISULFIDE BOND, GLYCOSYLATION AT ASN-45; ASN-95 AND ASN-118, FUNCTION,
RP DOMAIN, ACTIVE SITE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF ARG-129; PHE-130; PHE-137; GLN-194
RP AND 219-ASP-GLU-220.
RX PubMed=33712585; DOI=10.1038/s41467-021-21307-z;
RA Stroemland O., Kallio J.P., Pschibul A., Skoge R.H., Hardardottir H.M.,
RA Sverkeli L.J., Heinekamp T., Kniemeyer O., Migaud M., Makarov M.V.,
RA Gossmann T.I., Brakhage A.A., Ziegler M.;
RT "Discovery of fungal surface NADases predominantly present in pathogenic
RT species.";
RL Nat. Commun. 12:1631-1631(2021).
RN [4]
RP ERRATUM OF PUBMED:33712585.
RX PubMed=33767192; DOI=10.1038/s41467-021-22476-7;
RA Stroemland O., Kallio J.P., Pschibul A., Skoge R.H., Hardardottir H.M.,
RA Sverkeli L.J., Heinekamp T., Kniemeyer O., Migaud M., Makarov M.V.,
RA Gossmann T.I., Brakhage A.A., Ziegler M.;
RT "Author Correction: Discovery of fungal surface NADases predominantly
RT present in pathogenic species.";
RL Nat. Commun. 12:2004-2004(2021).
CC -!- FUNCTION: Conidial surface nicotinamide adenine dinucleotide
CC glycohydrolase that cleave NAD(+) and NADP(+) but not their reduced
CC counterparts, NADH and NADPH (PubMed:33712585). Lacks both ADP-ribosyl
CC cyclase and base exchange activity and does not mediate synthesis of
CC calcium messengers cADPR or NAADP (PubMed:33712585). Plays a role in
CC pathogenicity by depleting the host's NAD(+) pool (PubMed:33712585).
CC {ECO:0000269|PubMed:33712585}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.5;
CC Evidence={ECO:0000269|PubMed:33712585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000269|PubMed:33712585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NADP(+) = ADP-D-ribose 2'-phosphate + H(+) +
CC nicotinamide; Xref=Rhea:RHEA:19849, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58673; Evidence={ECO:0000269|PubMed:33712585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19850;
CC Evidence={ECO:0000269|PubMed:33712585};
CC -!- ACTIVITY REGULATION: The catalytic activity is positively regulated by
CC calcium via its binding to the calcium-binding site.
CC {ECO:0000269|PubMed:33712585}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=119 uM for NAD(+) {ECO:0000269|PubMed:33712585};
CC KM=106 uM for NADP(+) {ECO:0000269|PubMed:33712585};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:33712585}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33712585}.
CC Note=Localizes on the surface of conidia.
CC {ECO:0000269|PubMed:33712585}.
CC -!- INDUCTION: Expression is up-regulated during conidiation of A.fumigatus
CC strains displaying high adherence to pulmonary epithelial cells.
CC {ECO:0000269|PubMed:29113011}.
CC -!- DOMAIN: The C-terminus contains also a calcium binding site (residues
CC 215-224) that might be involved in NADase activity regulation
CC (PubMed:33712585). The calcium-binding site is not alweays present
CC since it emerged in the order Eurotiales, which includes Aspergillus
CC species (PubMed:33712585). {ECO:0000269|PubMed:33712585}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:33767192}.
CC -!- DISRUPTION PHENOTYPE: Impairs NADase cleavage in conidia.
CC {ECO:0000269|PubMed:33712585}.
CC -!- SIMILARITY: Belongs to the fungal surface NADase family. {ECO:0000305}.
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DR EMBL; AAHF01000006; EAL89283.1; -; Genomic_DNA.
DR RefSeq; XP_751321.1; XM_746228.1.
DR PDB; 6YGE; X-ray; 1.60 A; A/B=26-234.
DR PDB; 6YGF; X-ray; 1.70 A; A/B=25-234.
DR PDB; 6YGG; X-ray; 1.85 A; A/B=26-234.
DR PDBsum; 6YGE; -.
DR PDBsum; 6YGF; -.
DR PDBsum; 6YGG; -.
DR SMR; Q4WL81; -.
DR EnsemblFungi; EAL89283; EAL89283; AFUA_6G14470.
DR GeneID; 3508638; -.
DR KEGG; afm:AFUA_6G14470; -.
DR VEuPathDB; FungiDB:Afu6g14470; -.
DR eggNOG; ENOG502S1C9; Eukaryota.
DR HOGENOM; CLU_083054_0_0_1; -.
DR InParanoid; Q4WL81; -.
DR OMA; RCYPDPC; -.
DR OrthoDB; 1214206at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061810; F:NAD glycohydrolase activity; IEA:InterPro.
DR InterPro; IPR025331; TNT.
DR Pfam; PF14021; TNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Disulfide bond; Glycoprotein; Hydrolase;
KW Metal-binding; NAD; Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:33712585"
FT CHAIN 21..234
FT /note="Conidial surface nicotinamide adenine dinucleotide
FT glycohydrolase nadA"
FT /id="PRO_5004246304"
FT DOMAIN 120..212
FT /note="TNT"
FT /evidence="ECO:0000255"
FT REGION 21..117
FT /note="Thump"
FT /evidence="ECO:0000269|PubMed:33712585"
FT ACT_SITE 129
FT /evidence="ECO:0000269|PubMed:33712585"
FT ACT_SITE 194
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 130
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 136
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 148
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 216
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:33712585"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:33712585"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:33712585"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:33712585"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:33712585"
FT DISULFID 33..80
FT /evidence="ECO:0000269|PubMed:33712585"
FT DISULFID 38..50
FT /evidence="ECO:0000269|PubMed:33712585"
FT MUTAGEN 129
FT /note="R->A: Abolishes the NADase activity."
FT /evidence="ECO:0000269|PubMed:33712585"
FT MUTAGEN 130
FT /note="F->A: Reduces the NADase activity."
FT /evidence="ECO:0000269|PubMed:33712585"
FT MUTAGEN 137
FT /note="F->A: Abolishes the NADase activity."
FT /evidence="ECO:0000269|PubMed:33712585"
FT MUTAGEN 194
FT /note="Q->A,K: Abolishes the NADase activity."
FT /evidence="ECO:0000269|PubMed:33712585"
FT MUTAGEN 219..220
FT /note="DE->AA: Leads to a sevenfold reduction of the NADase
FT activity."
FT /evidence="ECO:0000269|PubMed:33712585"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:6YGE"
FT TURN 37..40
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:6YGE"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 166..173
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 175..182
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 201..206
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:6YGE"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:6YGE"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6YGE"
SQ SEQUENCE 234 AA; 26022 MW; 6363C1F09E3008AD CRC64;
MIFTNAILVI SALLPATVLS LQHTEDSLFP ARCWPDPCAG ITFQNDTYVC GDPRLGPVVL
PQKFPLNNEL RTYARFGALC PAEFLDKWAT DVAPNGTYIY PPANGFALDT EEQPILGNAT
LPVGMKLDRF GSEYGTFLAP LGAPYIERSL PPSNLNTFDG MYPYNYHVYQ VTKEFVVGLG
PIAPWFEQPG MGTQFVTYTN VLGLIDDGYL RRLDESEYDE KVEYSNPYTP GPNQ
