ID   SMD_AJECG               Reviewed;         319 AA.
AC   C0NUU1;
DT   04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 1.
DT   03-AUG-2022, entry version 38.
DE   RecName: Full=Sphingomyelinase D {ECO:0000303|PubMed:24223912};
DE            Short=SMase D {ECO:0000303|PubMed:24223912};
DE            EC=3.1.4.41 {ECO:0000250|UniProtKB:B8NQ51};
DE   Flags: Precursor;
GN   ORFNames=HCBG_06705 {ECO:0000312|EMBL:EEH04754.1};
OS   Ajellomyces capsulatus (strain G186AR / H82 / ATCC MYA-2454 / RMSCC 2432)
OS   (Darling's disease fungus) (Histoplasma capsulatum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Ajellomycetaceae; Histoplasma.
OX   NCBI_TaxID=447093;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=G186AR / H82 / ATCC MYA-2454 / RMSCC 2432
RC   {ECO:0000312|Proteomes:UP000001631};
RA   Champion M., Cuomo C.A., Ma L.-J., Henn M.R., Sil A., Goldman B.,
RA   Young S.K., Kodira C.D., Zeng Q., Koehrsen M., Alvarado L., Berlin A.,
RA   Borenstein D., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J.,
RA   Griggs A., Gujja S., Heiman D., Hepburn T., Howarth C., Jen D., Larson L.,
RA   Lewis B., Mehta T., Park D., Pearson M., Roberts A., Saif S., Shea T.,
RA   Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J., Yandava C.,
RA   Klein B., McEwen J.G., Puccia R., Goldman G.H., Felipe M.S., Nino-Vega G.,
RA   San-Blas G., Taylor J., Mendoza L., Galagan J.E., Nusbaum C., Birren B.W.;
RT   "The genome sequence of Ajellomyces capsulatus strain G186AR.";
RL   Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   IDENTIFICATION.
RX   PubMed=24223912; DOI=10.1371/journal.pone.0079240;
RA   Dias-Lopes C., Neshich I.A., Neshich G., Ortega J.M., Granier C.,
RA   Chavez-Olortegui C., Molina F., Felicori L.;
RT   "Identification of new sphingomyelinases D in pathogenic fungi and other
RT   pathogenic organisms.";
RL   PLoS ONE 8:E79240-E79240(2013).
CC   -!- FUNCTION: Catalyzes the hydrolysis of sphingomyelin. Sphingomyelinases
CC       D are produced by some spider in their venoms, but also by arthropods
CC       such as ticks, or pathogenic bacteria and fungi. They might play a role
CC       in pathogenicity through different mechanisms, such as membrane
CC       destabilization and host cell penetration, but also pulmonary
CC       inflammation and cutaneous lesions. {ECO:0000250|UniProtKB:B8NQ51}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine 1-phosphate +
CC         choline + H(+); Xref=Rhea:RHEA:20984, ChEBI:CHEBI:15354,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17636,
CC         ChEBI:CHEBI:57674; EC=3.1.4.41;
CC         Evidence={ECO:0000250|UniProtKB:B8NQ51};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q8I914};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8I914};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- DOMAIN: The SMD-tail motif is highly conserved and may be responsible
CC       for structural stabilization. {ECO:0000303|PubMed:24223912}.
CC   -!- SIMILARITY: Belongs to the sphingomyelinase D/phospholipase D family.
CC       {ECO:0000305}.
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DR   EMBL; GG663372; EEH04754.1; -; Genomic_DNA.
DR   AlphaFoldDB; C0NUU1; -.
DR   SMR; C0NUU1; -.
DR   STRING; 447093.C0NUU1; -.
DR   EnsemblFungi; EEH04754; EEH04754; HCBG_06705.
DR   VEuPathDB; FungiDB:HCBG_06705; -.
DR   HOGENOM; CLU_059400_0_0_1; -.
DR   InParanoid; C0NUU1; -.
DR   OrthoDB; 1048800at2759; -.
DR   Proteomes; UP000001631; Unassembled WGS sequence.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0050290; F:sphingomyelin phosphodiesterase D activity; IEA:UniProtKB-EC.
DR   GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.20.20.190; -; 1.
DR   InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
PE   3: Inferred from homology;
KW   Hydrolase; Lipid degradation; Lipid metabolism; Magnesium; Metal-binding;
KW   Reference proteome; Secreted; Signal; Virulence.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..319
FT                   /note="Sphingomyelinase D"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000431986"
FT   MOTIF           312..319
FT                   /note="SMD-tail"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        44
FT                   /evidence="ECO:0000250|UniProtKB:Q8I914"
FT   BINDING         64
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I914"
FT   BINDING         66
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I914"
FT   BINDING         109
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I914"
SQ   SEQUENCE   319 AA;  35095 MW;  F482FD77D1728755 CRC64;
     MTPLLRTICA ILCILIAVPL TFACPTKAGV SKQANKRPTY AIAHMVLDRK GLKDAIKNGA
     NSVEIDIAAY KEGWWADHDI RGRSWGDSLE DMFKAVAKES KNIAFVWLDL KTPDMCSGAT
     CNKDVLDPSK CKPKDKCSMN SLQELAQKIL NPAGVRILYG FFGAGATDSA GFNYIQGNLK
     AGEAVCLSGE VENVLNVYKK KGRGVKPQQR VMDYGYTQLE TGFGNCKEKG YNTCAGLRNG
     AKARDKGDVK RVFGWTSRVG DGERVGQLLD KAHVDGIIYG FAITRYYDHE DSRAAARDIT
     QRVQKSDDRY MATGADKPW