ID   ASM_BOVIN               Reviewed;         625 AA.
AC   Q0VD19;
DT   29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 1.
DT   24-JAN-2024, entry version 101.
DE   RecName: Full=Sphingomyelin phosphodiesterase;
DE            EC=3.1.4.12 {ECO:0000250|UniProtKB:P17405};
DE            EC=3.1.4.3 {ECO:0000250|UniProtKB:P17405};
DE   AltName: Full=Acid sphingomyelinase;
DE            Short=aSMase;
DE   Contains:
DE     RecName: Full=Sphingomyelin phosphodiesterase, processed form {ECO:0000305};
DE   Flags: Precursor;
GN   Name=SMPD1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Converts sphingomyelin to ceramide. Exists as two enzymatic
CC       forms that arise from alternative trafficking of a single protein
CC       precursor, one that is targeted to the endolysosomal compartment,
CC       whereas the other is released extracellularly. However, in response to
CC       various forms of stress, lysosomal exocytosis may represent a major
CC       source of the secretory form. {ECO:0000250|UniProtKB:P17405}.
CC   -!- FUNCTION: In the lysosomes, converts sphingomyelin to ceramide. Plays
CC       an important role in the export of cholesterol from the
CC       intraendolysosomal membranes. Also has phospholipase C activities
CC       toward 1,2-diacylglycerolphosphocholine and 1,2-
CC       diacylglycerolphosphoglycerol. Modulates stress-induced apoptosis
CC       through the production of ceramide. {ECO:0000250|UniProtKB:P17405}.
CC   -!- FUNCTION: When secreted, modulates cell signaling with its ability to
CC       reorganize the plasma membrane by converting sphingomyelin to ceramide.
CC       Secreted form is increased in response to stress and inflammatory
CC       mediators such as IL1B, IFNG or TNF as well as upon infection with
CC       bacteria and viruses. Produces the release of ceramide in the outer
CC       leaflet of the plasma membrane playing a central role in host defense.
CC       Ceramide reorganizes these rafts into larger signaling platforms that
CC       are required to internalize bacteria, induce apoptosis and regulate the
CC       cytokine response in infected cells. In wounded cells, the lysosomal
CC       form is released extracellularly in the presence of Ca(2+) and promotes
CC       endocytosis and plasma membrane repair. {ECO:0000250|UniProtKB:P17405}.
CC   -!- FUNCTION: [Sphingomyelin phosphodiesterase, processed form]: This form
CC       is generated following cleavage by CASP7 in the extracellular milieu in
CC       response to bacterial infection (By similarity). It shows increased
CC       ability to convert sphingomyelin to ceramide and promotes plasma
CC       membrane repair. Plasma membrane repair by ceramide counteracts the
CC       action of gasdermin-D (GSDMD) perforin (PRF1) pores that are formed in
CC       response to bacterial infection (By similarity).
CC       {ECO:0000250|UniProtKB:Q04519}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC         phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC         ChEBI:CHEBI:295975; EC=3.1.4.12;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-(octadecanoyl)-sphing-4-enine-1-phosphocholine = H(+)
CC         + N-octadecanoylsphing-4-enine + phosphocholine;
CC         Xref=Rhea:RHEA:54284, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:72961, ChEBI:CHEBI:83358, ChEBI:CHEBI:295975;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54285;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC         sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:10604,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815,
CC         ChEBI:CHEBI:57643, ChEBI:CHEBI:295975; EC=3.1.4.3;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10605;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC         dihexadecanoyl-sn-glycerol + H(+) + phosphocholine;
CC         Xref=Rhea:RHEA:45304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:72999, ChEBI:CHEBI:82929, ChEBI:CHEBI:295975;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45305;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC   -!- CATALYTIC ACTIVITY: [Sphingomyelin phosphodiesterase, processed form]:
CC       Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC         phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC         ChEBI:CHEBI:295975; EC=3.1.4.12;
CC         Evidence={ECO:0000250|UniProtKB:Q04519};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC         Evidence={ECO:0000250|UniProtKB:Q04519};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P17405};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P17405};
CC   -!- ACTIVITY REGULATION: Hydrolysis of liposomal sphingomyelin is
CC       stimulated by incorporation of diacylglycerol (DAG), ceramide and free
CC       fatty acids into the liposomal membranes. Phosphatidylcholine
CC       hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG,
CC       monoacylglycerol and fatty acids. {ECO:0000250|UniProtKB:P17405}.
CC   -!- SUBUNIT: Monomer. Interacts with SORT1; the interaction is required for
CC       SMPD1 targeting to lysosomes. {ECO:0000250|UniProtKB:P17405}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P17405}. Lipid
CC       droplet {ECO:0000250|UniProtKB:P17405}. Secreted
CC       {ECO:0000250|UniProtKB:P17405}. Note=The secreted form is induced in a
CC       time- and dose-dependent by IL1B and TNF as well as stress and viral
CC       infection. This increase of the secreted form seems to be due to
CC       exocytosis of the lysosomal form and is Ca(2+)-dependent. Secretion is
CC       dependent of phosphorylation at Ser-504. Secretion is induced by
CC       inflammatory mediators such as IL1B, IFNG or TNF as well as infection
CC       with bacteria and viruses. {ECO:0000250|UniProtKB:P17405}.
CC   -!- SUBCELLULAR LOCATION: [Sphingomyelin phosphodiesterase, processed
CC       form]: Secreted, extracellular space {ECO:0000250|UniProtKB:Q04519}.
CC       Note=This form is generated following cleavage by CASP7.
CC       {ECO:0000250|UniProtKB:Q04519}.
CC   -!- PTM: Proteolytically processed. Mature lysosomal form arises from C-
CC       terminal proteolytic processing of pro-sphingomyelin phosphodiesterase.
CC       {ECO:0000250|UniProtKB:P17405}.
CC   -!- PTM: Both lysosomal and secreted forms are glycosylated but they show a
CC       differential pattern of glycosylation. {ECO:0000250|UniProtKB:P17405}.
CC   -!- PTM: Phosphorylated at Ser-504 by PRKCD upon stress stimuli.
CC       Phosphorylation is required for secretion.
CC       {ECO:0000250|UniProtKB:P17405}.
CC   -!- PTM: [Sphingomyelin phosphodiesterase, processed form]: This form is
CC       generated following cleavage by CASP7 in the extracellular milieu (By
CC       similarity). It shows increased activity (By similarity).
CC       {ECO:0000250|UniProtKB:Q04519}.
CC   -!- MISCELLANEOUS: There are two types of sphingomyelinases: ASM (acid),
CC       and NSM (neutral).
CC   -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR   EMBL; BC119881; AAI19882.1; -; mRNA.
DR   RefSeq; NP_001068655.1; NM_001075187.1.
DR   AlphaFoldDB; Q0VD19; -.
DR   SMR; Q0VD19; -.
DR   STRING; 9913.ENSBTAP00000020758; -.
DR   BindingDB; Q0VD19; -.
DR   ChEMBL; CHEMBL4295808; -.
DR   GlyCosmos; Q0VD19; 6 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000020758; -.
DR   Ensembl; ENSBTAT00000020758.4; ENSBTAP00000020758.3; ENSBTAG00000015628.4.
DR   GeneID; 505097; -.
DR   KEGG; bta:505097; -.
DR   CTD; 6609; -.
DR   VEuPathDB; HostDB:ENSBTAG00000015628; -.
DR   VGNC; VGNC:35029; SMPD1.
DR   eggNOG; KOG3770; Eukaryota.
DR   GeneTree; ENSGT00950000183182; -.
DR   HOGENOM; CLU_014743_3_1_1; -.
DR   InParanoid; Q0VD19; -.
DR   OMA; VWSQTRK; -.
DR   OrthoDB; 205363at2759; -.
DR   TreeFam; TF313674; -.
DR   Reactome; R-BTA-9840310; Glycosphingolipid catabolism.
DR   Proteomes; UP000009136; Chromosome 15.
DR   Bgee; ENSBTAG00000015628; Expressed in pons and 103 other cell types or tissues.
DR   GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IDA:AgBase.
DR   GO; GO:0005764; C:lysosome; IDA:AgBase.
DR   GO; GO:0045121; C:membrane raft; IDA:AgBase.
DR   GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR   GO; GO:0061750; F:acid sphingomyelin phosphodiesterase activity; ISS:UniProtKB.
DR   GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR   GO; GO:0034480; F:phosphatidylcholine phospholipase C activity; IEA:RHEA.
DR   GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR   GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR   GO; GO:0046513; P:ceramide biosynthetic process; IDA:AgBase.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR   GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR   GO; GO:0035307; P:positive regulation of protein dephosphorylation; IEA:Ensembl.
DR   GO; GO:0046598; P:positive regulation of viral entry into host cell; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; ISS:UniProtKB.
DR   GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR   GO; GO:0034612; P:response to tumor necrosis factor; ISS:UniProtKB.
DR   GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR   GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR   GO; GO:0006685; P:sphingomyelin catabolic process; ISS:UniProtKB.
DR   GO; GO:0023021; P:termination of signal transduction; IEA:Ensembl.
DR   GO; GO:0046718; P:viral entry into host cell; ISS:UniProtKB.
DR   GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR   CDD; cd00842; MPP_ASMase; 1.
DR   Gene3D; 3.60.21.10; -; 1.
DR   InterPro; IPR045473; ASM_C.
DR   InterPro; IPR041805; ASMase/PPN1_MPP.
DR   InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR   InterPro; IPR029052; Metallo-depent_PP-like.
DR   InterPro; IPR011001; Saposin-like.
DR   InterPro; IPR008139; SaposinB_dom.
DR   InterPro; IPR011160; Sphingomy_PDE.
DR   PANTHER; PTHR10340; SPHINGOMYELIN PHOSPHODIESTERASE; 1.
DR   PANTHER; PTHR10340:SF34; SPHINGOMYELIN PHOSPHODIESTERASE; 1.
DR   Pfam; PF19272; ASMase_C; 1.
DR   Pfam; PF00149; Metallophos; 1.
DR   PIRSF; PIRSF000948; Sphingomy_PDE; 1.
DR   SMART; SM00741; SapB; 1.
DR   SUPFAM; SSF56300; Metallo-dependent phosphatases; 1.
DR   SUPFAM; SSF47862; Saposin; 1.
DR   PROSITE; PS50015; SAP_B; 1.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lipid droplet;
KW   Lipid metabolism; Lysosome; Metal-binding; Phosphoprotein;
KW   Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..40
FT                   /evidence="ECO:0000255"
FT   CHAIN           41..625
FT                   /note="Sphingomyelin phosphodiesterase"
FT                   /id="PRO_0000288775"
FT   CHAIN           248..625
FT                   /note="Sphingomyelin phosphodiesterase, processed form"
FT                   /evidence="ECO:0000250|UniProtKB:Q04519"
FT                   /id="PRO_0000456683"
FT   DOMAIN          81..165
FT                   /note="Saposin B-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         202
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         204
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         274
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         274
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         314
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         421
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         453
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   BINDING         455
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   SITE            247..248
FT                   /note="Cleavage; by CASP7"
FT                   /evidence="ECO:0000250|UniProtKB:Q04519"
FT   MOD_RES         504
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   CARBOHYD        171
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   CARBOHYD        391
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   CARBOHYD        499
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   CARBOHYD        516
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        85..161
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        88..153
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        116..127
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        217..222
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        223..246
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        381..427
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        580..584
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        590..603
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
SQ   SEQUENCE   625 AA;  69392 MW;  1A87AAFEDDC0C959 CRC64;
     MPRHGVSPGQ GLPRSGREQA SDRSLGAPCL RLLWLGLALA LALPNSPVLW SPAEARPLPT
     QGHPAKFIRI APQLQEAFGW WNLTCPTCKG LFTAIDFGLR NQASVAWVGS VAIKLCVLLK
     IAPPAVCQSA VQLFEDDMVE VWTRSVLSPS EACGLLLGSS CGHWDIFSSW NISLPAVPKP
     PPQPPKPPAP GSPVSRVLFL TDLHWDHDYL EGTDPNCENP LCCRRDSGPP PASQPGAGYW
     GEYSKCDLPL RTLESLLSGL GPAGPFDMVY WTGDIPAHNI WQQSRQDQLR ALTTITALVK
     KFLGPVPVYP AVGNHESTPV NGFPPPFIKG NQSSHWLYEA MAEAWEPWLP AEALRTLRIG
     GFYALSPRPG LRLISLNMNF CSRENFWLLI NSTDPAGQLQ WLVGELQAAE DRGDKVHIIG
     HIPPGHCLKS WSWNYYRIVE RYENTLAGQF FGHTHVDEFE VFYDEETLSR PLSVAFLAPS
     ATTYIGLNPG YRVYQIDGNY SGSSHVVLDH ETYIMNLTEA NEPGATPHWY LLYRARETYG
     LPNALPTAWH DLVYRMRKDT QLFQTFWFLY HKGHPPSEPC GTPCRLATLC AQLSARSDSP
     ALCRHLVPDA SLPDVQSLWS MPLLC
//