ID   ASM_MOUSE               Reviewed;         627 AA.
AC   Q04519; Q3UL52;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   24-JAN-2024, entry version 175.
DE   RecName: Full=Sphingomyelin phosphodiesterase;
DE            EC=3.1.4.12 {ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8702487};
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 {ECO:0000303|PubMed:27435900};
GN   Synonyms=Asm {ECO:0000303|PubMed:27435900};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=1292508; DOI=10.1515/bchm3.1992.373.2.1233;
RA   Newrzella D., Stoffel W.;
RT   "Molecular cloning of the acid sphingomyelinase of the mouse and the
RT   organization and complete nucleotide sequence of the gene.";
RL   Biol. Chem. Hoppe-Seyler 373:1233-1238(1992).
RN   [2]
RP   SEQUENCE REVISION TO 224-225 AND 384.
RA   Hofmann K.;
RL   Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Hippocampus, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=8706124; DOI=10.1016/s0092-8674(00)80091-4;
RA   Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D.,
RA   McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.;
RT   "Acid sphingomyelinase-deficient human lymphoblasts and mice are defective
RT   in radiation-induced apoptosis.";
RL   Cell 86:189-199(1996).
RN   [6]
RP   CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX   PubMed=8702487; DOI=10.1074/jbc.271.31.18431;
RA   Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.;
RT   "Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a
RT   product of the acid sphingomyelinase gene.";
RL   J. Biol. Chem. 271:18431-18436(1996).
RN   [7]
RP   FUNCTION, AND COFACTOR.
RX   PubMed=9660788; DOI=10.1074/jbc.273.29.18250;
RA   Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.;
RT   "The cellular trafficking and zinc dependence of secretory and lysosomal
RT   sphingomyelinase, two products of the acid sphingomyelinase gene.";
RL   J. Biol. Chem. 273:18250-18259(1998).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=12563314; DOI=10.1038/nm823;
RA   Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J.,
RA   Schwarz H., Weller M., Kolesnick R., Gulbins E.;
RT   "Host defense against Pseudomonas aeruginosa requires ceramide-rich
RT   membrane rafts.";
RL   Nat. Med. 9:322-330(2003).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP   AND MUTAGENESIS OF ASP-249.
RX   PubMed=35705808; DOI=10.1038/s41586-022-04825-8;
RA   Nozaki K., Maltez V.I., Rayamajhi M., Tubbs A.L., Mitchell J.E.,
RA   Lacey C.A., Harvest C.K., Li L., Nash W.T., Larson H.N., McGlaughon B.D.,
RA   Moorman N.J., Brown M.G., Whitmire J.K., Miao E.A.;
RT   "Caspase-7 activates ASM to repair gasdermin and perforin pores.";
RL   Nature 0:0-0(2022).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 84-611 IN COMPLEXES WITH ZINC AND
RP   INHIBITOR, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-84; ASN-173;
RP   ASN-333; ASN-393 AND ASN-518, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP   MUTAGENESIS OF VAL-128; VAL-143; HIS-280; TRP-283; HIS-317; PRO-321;
RP   PHE-388 AND LEU-391.
RX   PubMed=27435900; DOI=10.1038/ncomms12196;
RA   Gorelik A., Illes K., Heinz L.X., Superti-Furga G., Nagar B.;
RT   "Crystal structure of mammalian acid sphingomyelinase.";
RL   Nat. Commun. 7:12196-12196(2016).
CC   -!- FUNCTION: Converts sphingomyelin to ceramide (PubMed:9660788,
CC       PubMed:8706124). Exists as two enzymatic forms that arise from
CC       alternative trafficking of a single protein precursor, one that is
CC       targeted to the endolysosomal compartment, whereas the other is
CC       released extracellularly. However, in response to various forms of
CC       stress, lysosomal exocytosis may represent a major source of the
CC       secretory form (By similarity). {ECO:0000250|UniProtKB:P17405,
CC       ECO:0000269|PubMed:8706124, ECO:0000269|PubMed:9660788}.
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 (PubMed:27435900). Modulates stress-
CC       induced apoptosis through the production of ceramide (PubMed:8706124).
CC       {ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8706124}.
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 P. aeruginosa, induce apoptosis and
CC       regulate the cytokine response in infected cells. In wounded cells, the
CC       lysosomal form is released extracellularly in the presence of Ca(2+)
CC       and promotes endocytosis and plasma membrane repair.
CC       {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 (PubMed:35705808). 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 (PubMed:35705808).
CC       {ECO:0000269|PubMed:35705808}.
CC   -!- FUNCTION: (Microbial infection) Secretion is activated by bacteria such
CC       as P. aeruginos, this activation results in the release of ceramide in
CC       the outer leaflet of the plasma membrane which facilitates the
CC       infection. {ECO:0000269|PubMed:12563314}.
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:0000269|PubMed:27435900, ECO:0000269|PubMed:8702487,
CC         ECO:0000269|PubMed:8706124, ECO:0000269|PubMed:9660788};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC         Evidence={ECO:0000269|PubMed:8706124, ECO:0000305|PubMed:27435900};
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:0000269|PubMed:35705808};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC         Evidence={ECO:0000305|PubMed:35705808};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:8702487, ECO:0000269|PubMed:9660788};
CC       Note=Binds 2 Zn(2+) ions per subunit (PubMed:27435900).;
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 (PubMed:27435900). Interacts with SORT1; the
CC       interaction is required for SMPD1 targeting to lysosomes (By
CC       similarity). {ECO:0000250|UniProtKB:P17405,
CC       ECO:0000269|PubMed:27435900}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P17405}. Lipid
CC       droplet {ECO:0000250|UniProtKB:P17405}. Secreted
CC       {ECO:0000269|PubMed:8702487}. 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-506. 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:0000269|PubMed:35705808}.
CC       Note=This form is generated following cleavage by CASP7.
CC       {ECO:0000269|PubMed:35705808}.
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-506 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
CC       (PubMed:35705808). It shows increased activity (PubMed:35705808).
CC       {ECO:0000269|PubMed:35705808}.
CC   -!- DISRUPTION PHENOTYPE: Mutants infected with Pseudomonas aeruginosa die
CC       within 7 days whereas all wild-type mice survive the infection
CC       (PubMed:12563314). Mutants are defective in radiation-induced apoptosis
CC       (PubMed:8706124). {ECO:0000269|PubMed:12563314,
CC       ECO:0000269|PubMed:8706124}.
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; Z14252; CAA78619.1; -; mRNA.
DR   EMBL; Z14132; CAA78506.1; -; Genomic_DNA.
DR   EMBL; AK088147; BAC40171.1; -; mRNA.
DR   EMBL; AK145534; BAE26489.1; -; mRNA.
DR   EMBL; AK145702; BAE26598.1; -; mRNA.
DR   EMBL; AK164167; BAE37659.1; -; mRNA.
DR   EMBL; BC011304; AAH11304.1; -; mRNA.
DR   CCDS; CCDS21653.1; -.
DR   PIR; A58720; S27393.
DR   RefSeq; NP_035551.1; NM_011421.2.
DR   PDB; 5FI9; X-ray; 2.54 A; A/B=84-611.
DR   PDB; 5FIB; X-ray; 2.80 A; A/B=84-611.
DR   PDB; 5FIC; X-ray; 2.80 A; A/B/C/D=84-611.
DR   PDB; 5HQN; X-ray; 2.60 A; A/B=165-627.
DR   PDBsum; 5FI9; -.
DR   PDBsum; 5FIB; -.
DR   PDBsum; 5FIC; -.
DR   PDBsum; 5HQN; -.
DR   AlphaFoldDB; Q04519; -.
DR   SMR; Q04519; -.
DR   BioGRID; 203345; 3.
DR   STRING; 10090.ENSMUSP00000042187; -.
DR   ChEMBL; CHEMBL4295802; -.
DR   GlyCosmos; Q04519; 6 sites, No reported glycans.
DR   GlyGen; Q04519; 6 sites.
DR   iPTMnet; Q04519; -.
DR   PhosphoSitePlus; Q04519; -.
DR   SwissPalm; Q04519; -.
DR   EPD; Q04519; -.
DR   MaxQB; Q04519; -.
DR   PaxDb; 10090-ENSMUSP00000042187; -.
DR   PeptideAtlas; Q04519; -.
DR   ProteomicsDB; 281814; -.
DR   Antibodypedia; 1065; 356 antibodies from 31 providers.
DR   DNASU; 20597; -.
DR   Ensembl; ENSMUST00000046983.10; ENSMUSP00000042187.9; ENSMUSG00000037049.10.
DR   GeneID; 20597; -.
DR   KEGG; mmu:20597; -.
DR   UCSC; uc009iyf.2; mouse.
DR   AGR; MGI:98325; -.
DR   CTD; 6609; -.
DR   MGI; MGI:98325; Smpd1.
DR   VEuPathDB; HostDB:ENSMUSG00000037049; -.
DR   eggNOG; KOG3770; Eukaryota.
DR   GeneTree; ENSGT00950000183182; -.
DR   HOGENOM; CLU_014743_3_1_1; -.
DR   InParanoid; Q04519; -.
DR   OMA; VWSQTRK; -.
DR   OrthoDB; 205363at2759; -.
DR   PhylomeDB; Q04519; -.
DR   TreeFam; TF313674; -.
DR   BRENDA; 3.1.4.12; 3474.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
DR   BioGRID-ORCS; 20597; 10 hits in 80 CRISPR screens.
DR   ChiTaRS; Smpd1; mouse.
DR   PRO; PR:Q04519; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q04519; Protein.
DR   Bgee; ENSMUSG00000037049; Expressed in choroid plexus of fourth ventricle and 266 other cell types or tissues.
DR   GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR   GO; GO:0005768; C:endosome; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0042599; C:lamellar body; ISO:MGI.
DR   GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0061750; F:acid sphingomyelin phosphodiesterase activity; IDA: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; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IDA: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:UniProt.
DR   GO; GO:0006672; P:ceramide metabolic process; IMP:MGI.
DR   GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR   GO; GO:0001778; P:plasma membrane repair; IDA:UniProt.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR   GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR   GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:MGI.
DR   GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:MGI.
DR   GO; GO:0042220; P:response to cocaine; ISO:MGI.
DR   GO; GO:0070555; P:response to interleukin-1; ISS:UniProtKB.
DR   GO; GO:0010212; P:response to ionizing radiation; IMP: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:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0006685; P:sphingomyelin catabolic process; IMP:MGI.
DR   GO; GO:0023021; P:termination of signal transduction; ISO:MGI.
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   Gene3D; 1.10.225.10; Saposin-like; 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.
DR   Genevisible; Q04519; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW   Lipid droplet; Lipid metabolism; Lysosome; Metal-binding; Phosphoprotein;
KW   Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..44
FT                   /evidence="ECO:0000255"
FT   CHAIN           45..627
FT                   /note="Sphingomyelin phosphodiesterase"
FT                   /id="PRO_0000002324"
FT   CHAIN           250..627
FT                   /note="Sphingomyelin phosphodiesterase, processed form"
FT                   /evidence="ECO:0000305|PubMed:35705808"
FT                   /id="PRO_0000456685"
FT   DOMAIN          83..167
FT                   /note="Saposin B-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   BINDING         204
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         206
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         276
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         276
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         316
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         423
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         455
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:27435900,
FT                   ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   BINDING         457
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5FI9, ECO:0007744|PDB:5FIB,
FT                   ECO:0007744|PDB:5FIC, ECO:0007744|PDB:5HQN"
FT   SITE            249..250
FT                   /note="Cleavage; by CASP7"
FT                   /evidence="ECO:0000305|PubMed:35705808"
FT   MOD_RES         506
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P17405"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB"
FT   CARBOHYD        173
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5HQN"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5HQN"
FT   CARBOHYD        393
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   CARBOHYD        518
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT   DISULFID        87..163
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        90..155
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        118..129
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        219..224
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        225..248
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        383..429
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        582..586
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   DISULFID        592..605
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT                   ECO:0000269|PubMed:27435900, ECO:0007744|PDB:5FI9,
FT                   ECO:0007744|PDB:5FIB, ECO:0007744|PDB:5FIC,
FT                   ECO:0007744|PDB:5HQN"
FT   MUTAGEN         128
FT                   /note="V->E: Retains 20% of wild-type activity with
FT                   sphingomyelin as substrate; retains 70% of wild-type
FT                   activity with bis(p-nitrophenyl) phosphate as substrate."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         143
FT                   /note="V->R: Retains 10% of wild-type activity with
FT                   sphingomyelin as substrate; retains 70% of wild-type
FT                   activity with bis(p-nitrophenyl) phosphate as substrate."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         249
FT                   /note="D->A: Knockin mice are fertile and healthy but show
FT                   increased burdens in response to bacterial infection.
FT                   Cleavage by Casp7 is abolished, ceramide synthesis is
FT                   decreased, leading to increased burdens in response to
FT                   bacterial infection."
FT                   /evidence="ECO:0000269|PubMed:35705808"
FT   MUTAGEN         280
FT                   /note="H->A: Complete loss of activity."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         283
FT                   /note="W->N: Retains 10% of wild-type activity."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         317
FT                   /note="H->A: No activity with sphingomyelin as substrate;
FT                   retains 70% of wild-type activity with bis(p-nitrophenyl)
FT                   phosphate as substrate."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         321
FT                   /note="P->E: Retains 10% of wild-type activity."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         388
FT                   /note="F->R: Retains 10% of wild-type activity."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   MUTAGEN         391
FT                   /note="L->R: Retains 20% of wild-type activity with
FT                   sphingomyelin as substrate; retains 50% of wild-type
FT                   activity with bis(p-nitrophenyl) phosphate as substrate."
FT                   /evidence="ECO:0000269|PubMed:27435900"
FT   CONFLICT        48
FT                   /note="S -> T (in Ref. 4; AAH11304)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        450
FT                   /note="G -> S (in Ref. 4; AAH11304)"
FT                   /evidence="ECO:0000305"
FT   HELIX           87..101
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           107..121
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           126..136
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           140..145
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            147..149
FT                   /evidence="ECO:0007829|PDB:5FIC"
FT   HELIX           151..159
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            161..163
FT                   /evidence="ECO:0007829|PDB:5FIB"
FT   TURN            166..168
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          196..202
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          220..223
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          225..227
FT                   /evidence="ECO:0007829|PDB:5HQN"
FT   HELIX           235..237
FT                   /evidence="ECO:0007829|PDB:5HQN"
FT   STRAND          245..247
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           252..260
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           261..265
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          269..273
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           282..284
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           287..305
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          310..312
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          316..321
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           337..346
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            347..350
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           353..362
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          365..370
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          373..377
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           380..383
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           388..391
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           397..399
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           400..414
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          417..421
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           426..428
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           431..443
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            444..447
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          448..453
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          460..465
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            467..469
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          472..479
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            486..488
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          492..499
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          509..517
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           519..522
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          531..536
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           537..541
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           548..560
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           562..572
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            573..575
FT                   /evidence="ECO:0007829|PDB:5HQN"
FT   HELIX           584..594
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   STRAND          598..600
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   HELIX           602..605
FT                   /evidence="ECO:0007829|PDB:5FI9"
FT   TURN            606..608
FT                   /evidence="ECO:0007829|PDB:5FIB"
SQ   SEQUENCE   627 AA;  69927 MW;  0FFC7EA74EE71E91 CRC64;
     MPHHRASSGQ DHLRAGWEQR LERSLPAPRV GLLWMGLGLA LVLALFDSTV LWVPARAYPL
     PSEGHSVKFS AIAPPLQSAF GWQNLTCPAC KVLFTALNHG LKKEPNVARV GSVAIKICKM
     LNIAPLDVCQ SAVHLFEDDV VEVWTRSVLS PSEACGLLLG SSCGHWDIFS TWNISLPSVP
     KPPPKPPSPP APGAPVSRVL FLTDLHWDHE YLEGTDPYCA DPLCCRRGSG WPPNSQKGAG
     FWGEYSKCDL PLRTLESLLK GLGPAGPFEM VYWTGDIPAH DVWQQSRQDQ LRALTTITDL
     VRKFLGPVPV YPAVGNHEST PVNGFPPPFI KGNQSSQWLY EAMAKAWEPW LPADALHTLR
     IGGFYALTPR PGLRLISLNM NFCSRENFWL LINSTDPAGQ LQWLVEELQA AENRGDKVHI
     IGHIPPGHCL KSWSWNYYKI IARYENTLAG QFFGHTHVDE FEIFYDEETL SRPLAVAFLA
     PSATTFINLN PGYRVYQIDG NYPGSSHVVL DHETYILNLT QANAAGGTPS WKRLYRARET
     YGLPDAMPAS WHNLVYRMRD DEQLFQTFWF LYHKGHPPSE PCGTPCRLAT LCAQLSARAD
     SPALCRHLMP NGSLPDANRL WSRPLLC
//