ASM_BOVIN
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 03-AUG-2022, entry version 93.
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 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 -!- 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 -!- 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 -!- 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 -!- 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 PaxDb; Q0VD19; -.
DR PRIDE; Q0VD19; -.
DR Ensembl; ENSBTAT00000020758; ENSBTAP00000020758; ENSBTAG00000015628.
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; WPTEACA; -.
DR OrthoDB; 1142100at2759; -.
DR TreeFam; TF313674; -.
DR Reactome; R-BTA-1660662; Glycosphingolipid metabolism.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000015628; Expressed in pons and 103 other 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:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central.
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:0043407; P:negative regulation of MAP kinase activity; 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: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 Pfam; PF19272; ASMase_C; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF000948; Sphingomy_PDE; 1.
DR SMART; SM00741; SapB; 1.
DR SUPFAM; SSF47862; SSF47862; 1.
DR SUPFAM; SSF56300; SSF56300; 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 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 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
