NSMA2_HUMAN
ID NSMA2_HUMAN Reviewed; 655 AA.
AC Q9NY59; B7ZL82; Q2M1S8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Sphingomyelin phosphodiesterase 3 {ECO:0000305};
DE EC=3.1.4.12 {ECO:0000269|PubMed:15051724};
DE AltName: Full=Neutral sphingomyelinase 2;
DE Short=nSMase-2;
DE Short=nSMase2 {ECO:0000303|PubMed:15051724};
DE AltName: Full=Neutral sphingomyelinase II;
GN Name=SMPD3 {ECO:0000312|HGNC:HGNC:14240};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, COFACTOR, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10823942; DOI=10.1073/pnas.97.11.5895;
RA Hofmann K., Tomiuk S., Wolff G., Stoffel W.;
RT "Cloning and characterization of the mammalian brain-specific, Mg2+-
RT dependent neutral sphingomyelinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5895-5900(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=14741383; DOI=10.1016/s0014-5793(03)01523-0;
RA Miura Y., Gotoh E., Nara F., Nishijima M., Hanada K.;
RT "Hydrolysis of sphingosylphosphocholine by neutral sphingomyelinases.";
RL FEBS Lett. 557:288-292(2004).
RN [5]
RP FUNCTION, COFACTOR, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15051724; DOI=10.1074/jbc.m313662200;
RA Marchesini N., Osta W., Bielawski J., Luberto C., Obeid L.M., Hannun Y.A.;
RT "Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth
RT arrest of MCF7 cells.";
RL J. Biol. Chem. 279:25101-25111(2004).
RN [6]
RP TOPOLOGY.
RX PubMed=17349629; DOI=10.1016/j.febslet.2007.02.046;
RA Tani M., Hannun Y.A.;
RT "Analysis of membrane topology of neutral sphingomyelinase 2.";
RL FEBS Lett. 581:1323-1328(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-291, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Catalyzes the hydrolysis of sphingomyelin to form ceramide
CC and phosphocholine. Ceramide mediates numerous cellular functions, such
CC as apoptosis and growth arrest, and is capable of regulating these 2
CC cellular events independently. Also hydrolyzes
CC sphingosylphosphocholine. Regulates the cell cycle by acting as a
CC growth suppressor in confluent cells. Probably acts as a regulator of
CC postnatal development and participates in bone and dentin
CC mineralization (PubMed:10823942, PubMed:14741383, PubMed:15051724).
CC Binds to anionic phospholipids (APLs) such as phosphatidylserine (PS)
CC and phosphatidic acid (PA) that modulate enzymatic activity and
CC subcellular location. May be involved in IL-1-beta-induced JNK
CC activation in hepatocytes (By similarity). May act as a mediator in
CC transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation
CC under inflammatory conditions (By similarity).
CC {ECO:0000250|UniProtKB:O35049, ECO:0000250|UniProtKB:Q9JJY3,
CC ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383,
CC ECO:0000269|PubMed:15051724}.
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:15051724};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000305|PubMed:15051724};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(15Z-tetracosenoyl)sphing-4-enine-1-phosphocholine =
CC H(+) + N-(15Z-tetracosenoyl)-sphing-4-enine + phosphocholine;
CC Xref=Rhea:RHEA:45320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:74450, ChEBI:CHEBI:74535, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:15051724};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45321;
CC Evidence={ECO:0000305|PubMed:15051724};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(tetracosanoyl)-sphing-4-enine-1-phosphocholine = H(+)
CC + N-tetracosanoyl-sphing-4-enine + phosphocholine;
CC Xref=Rhea:RHEA:45324, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72965, ChEBI:CHEBI:83360, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:15051724};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45325;
CC Evidence={ECO:0000305|PubMed:15051724};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphocholine + H2O = an N-acyl-
CC sphingoid base + H(+) + phosphocholine; Xref=Rhea:RHEA:45300,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64583,
CC ChEBI:CHEBI:83273, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:14741383};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45301;
CC Evidence={ECO:0000305|PubMed:14741383};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:41119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:75542, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:14741383};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000305|PubMed:14741383};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-octadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC octadecyl-sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:39923,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74001,
CC ChEBI:CHEBI:75216, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:14741383};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39924;
CC Evidence={ECO:0000305|PubMed:14741383};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingosylphosphocholine + H2O = a sphingoid base + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:45296, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:84410, ChEBI:CHEBI:85171,
CC ChEBI:CHEBI:295975; Evidence={ECO:0000269|PubMed:14741383};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45297;
CC Evidence={ECO:0000305|PubMed:14741383};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine = H(+)
CC + N-hexadecanoylsphing-4-enine + phosphocholine;
CC Xref=Rhea:RHEA:45644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72959, ChEBI:CHEBI:78646, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q9JJY3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45645;
CC Evidence={ECO:0000250|UniProtKB:Q9JJY3};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:15051724};
CC -!- ACTIVITY REGULATION: Inhibited by nSMase inhibitor GW4869
CC (PubMed:10823942). Binding of anionic phospholipids (APLs) such as
CC phosphatidylserine (PS) and phosphatidic acid (PA) increases enzymatic
CC activity (By similarity). {ECO:0000250|UniProtKB:Q9JJY3,
CC ECO:0000269|PubMed:10823942}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=953 nmol/h/mg enzyme with sphingomyelin as substrate (at pH 7.5
CC and 37 degrees Celsius in presence of 0.1% Triton X-100)
CC {ECO:0000269|PubMed:14741383};
CC Vmax=152 nmol/h/mg enzyme with sphingosylphosphocholine as substrate
CC (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:14741383};
CC Vmax=8.6 nmol/h/mg enzyme with 1-O-octadecyl-sn-glycero-3-
CC phosphocholine as substrate (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:14741383};
CC Vmax=92.2 nmol/h/mg enzyme with 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine as substrate (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:14741383};
CC pH dependence:
CC Optimum pH is 7.5.;
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}.
CC -!- INTERACTION:
CC Q9NY59; O75530: EED; NbExp=2; IntAct=EBI-715400, EBI-923794;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:10823942}; Lipid-anchor
CC {ECO:0000269|PubMed:10823942}. Cell membrane
CC {ECO:0000269|PubMed:15051724}; Lipid-anchor
CC {ECO:0000269|PubMed:15051724}. Note=May localize to detergent-resistant
CC subdomains of Golgi membranes of hypothalamic neurosecretory neurons
CC (PubMed:10823942). Localizes to plasma membrane in confluent contact-
CC inhaibited cells (PubMed:15051724).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NY59-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NY59-2; Sequence=VSP_054334;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain.
CC {ECO:0000269|PubMed:10823942}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during G0/G1 phases.
CC -!- PTM: Palmitoylated, palmitoylation-deficient proteins are targeted for
CC lysosomal degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
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DR EMBL; AJ250460; CAB92964.1; -; mRNA.
DR EMBL; AC099521; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC112238; AAI12239.1; -; mRNA.
DR EMBL; BC143631; AAI43632.1; -; mRNA.
DR CCDS; CCDS10867.1; -. [Q9NY59-1]
DR RefSeq; NP_061137.1; NM_018667.3. [Q9NY59-1]
DR RefSeq; XP_005256088.1; XM_005256031.3. [Q9NY59-1]
DR RefSeq; XP_005256089.1; XM_005256032.3. [Q9NY59-1]
DR RefSeq; XP_011521509.1; XM_011523207.1. [Q9NY59-1]
DR RefSeq; XP_011521510.1; XM_011523208.2. [Q9NY59-1]
DR RefSeq; XP_011521511.1; XM_011523209.2. [Q9NY59-1]
DR RefSeq; XP_016878894.1; XM_017023405.1. [Q9NY59-1]
DR RefSeq; XP_016878895.1; XM_017023406.1. [Q9NY59-1]
DR RefSeq; XP_016878896.1; XM_017023407.1. [Q9NY59-1]
DR RefSeq; XP_016878897.1; XM_017023408.1. [Q9NY59-1]
DR PDB; 5UVG; X-ray; 1.85 A; A=117-651.
DR PDBsum; 5UVG; -.
DR AlphaFoldDB; Q9NY59; -.
DR SMR; Q9NY59; -.
DR BioGRID; 120692; 31.
DR DIP; DIP-60431N; -.
DR IntAct; Q9NY59; 22.
DR STRING; 9606.ENSP00000219334; -.
DR BindingDB; Q9NY59; -.
DR ChEMBL; CHEMBL4523470; -.
DR DrugBank; DB00144; Phosphatidyl serine.
DR SwissLipids; SLP:000001111; -.
DR iPTMnet; Q9NY59; -.
DR PhosphoSitePlus; Q9NY59; -.
DR SwissPalm; Q9NY59; -.
DR BioMuta; SMPD3; -.
DR DMDM; 73921262; -.
DR jPOST; Q9NY59; -.
DR MassIVE; Q9NY59; -.
DR PaxDb; Q9NY59; -.
DR PeptideAtlas; Q9NY59; -.
DR PRIDE; Q9NY59; -.
DR ProteomicsDB; 7214; -.
DR ProteomicsDB; 83180; -. [Q9NY59-1]
DR Antibodypedia; 29783; 171 antibodies from 21 providers.
DR DNASU; 55512; -.
DR Ensembl; ENST00000219334.10; ENSP00000219334.5; ENSG00000103056.12. [Q9NY59-1]
DR Ensembl; ENST00000563226.1; ENSP00000455955.1; ENSG00000103056.12. [Q9NY59-2]
DR GeneID; 55512; -.
DR KEGG; hsa:55512; -.
DR MANE-Select; ENST00000219334.10; ENSP00000219334.5; NM_018667.4; NP_061137.1.
DR UCSC; uc002ewa.4; human. [Q9NY59-1]
DR CTD; 55512; -.
DR DisGeNET; 55512; -.
DR GeneCards; SMPD3; -.
DR HGNC; HGNC:14240; SMPD3.
DR HPA; ENSG00000103056; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 605777; gene.
DR neXtProt; NX_Q9NY59; -.
DR OpenTargets; ENSG00000103056; -.
DR PharmGKB; PA37862; -.
DR VEuPathDB; HostDB:ENSG00000103056; -.
DR eggNOG; ENOG502QVS2; Eukaryota.
DR GeneTree; ENSGT00400000022168; -.
DR HOGENOM; CLU_028243_0_0_1; -.
DR InParanoid; Q9NY59; -.
DR OMA; TGKSFCF; -.
DR OrthoDB; 455705at2759; -.
DR PhylomeDB; Q9NY59; -.
DR TreeFam; TF328678; -.
DR BRENDA; 3.1.4.12; 2681.
DR PathwayCommons; Q9NY59; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-5626978; TNFR1-mediated ceramide production.
DR SignaLink; Q9NY59; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 55512; 44 hits in 1078 CRISPR screens.
DR ChiTaRS; SMPD3; human.
DR GeneWiki; SMPD3; -.
DR GenomeRNAi; 55512; -.
DR Pharos; Q9NY59; Tchem.
DR PRO; PR:Q9NY59; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NY59; protein.
DR Bgee; ENSG00000103056; Expressed in tibia and 134 other tissues.
DR ExpressionAtlas; Q9NY59; baseline and differential.
DR Genevisible; Q9NY59; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:InterPro.
DR GO; GO:0000137; C:Golgi cis cisterna; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061751; F:neutral sphingomyelin phosphodiesterase activity; IEA:Ensembl.
DR GO; GO:0070300; F:phosphatidic acid binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0098868; P:bone growth; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071286; P:cellular response to magnesium ion; IEA:Ensembl.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:0071461; P:cellular response to redox state; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0006672; P:ceramide metabolic process; IEA:Ensembl.
DR GO; GO:0003433; P:chondrocyte development involved in endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0032963; P:collagen metabolic process; IEA:Ensembl.
DR GO; GO:0097187; P:dentinogenesis; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0085029; P:extracellular matrix assembly; IEA:Ensembl.
DR GO; GO:0070314; P:G1 to G0 transition; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0140014; P:mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; IEA:Ensembl.
DR GO; GO:0030072; P:peptide hormone secretion; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0015774; P:polysaccharide transport; IEA:Ensembl.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISS:BHF-UCL.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0061035; P:regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0002685; P:regulation of leukocyte migration; IEA:Ensembl.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0090520; P:sphingolipid mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IDA:UniProtKB.
DR GO; GO:0006684; P:sphingomyelin metabolic process; ISS:UniProtKB.
DR CDD; cd09078; nSMase; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR017766; Sphingomyelinase/PLipase_C.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell membrane;
KW Developmental protein; Golgi apparatus; Hydrolase; Lipid metabolism;
KW Lipoprotein; Magnesium; Membrane; Metal-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Sphingolipid metabolism.
FT CHAIN 1..655
FT /note="Sphingomyelin phosphodiesterase 3"
FT /id="PRO_0000075692"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 210..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 639
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 364
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 512
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJY3"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT LIPID 53
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 54
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 59
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 397
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 398
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 541..548
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054334"
FT STRAND 122..133
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 147..163
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 343..352
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 359..365
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 368..378
FT /evidence="ECO:0007829|PDB:5UVG"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 389..392
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 408..413
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 415..422
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 436..446
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 452..461
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 469..489
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 500..510
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 518..520
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 521..524
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 565..572
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 575..581
FT /evidence="ECO:0007829|PDB:5UVG"
FT TURN 588..590
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:5UVG"
FT HELIX 596..598
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 607..616
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 620..630
FT /evidence="ECO:0007829|PDB:5UVG"
FT TURN 632..636
FT /evidence="ECO:0007829|PDB:5UVG"
FT STRAND 642..650
FT /evidence="ECO:0007829|PDB:5UVG"
SQ SEQUENCE 655 AA; 71081 MW; C06401571633C48E CRC64;
MVLYTTPFPN SCLSALHCVS WALIFPCYWL VDRLAASFIP TTYEKRQRAD DPCCLQLLCT
ALFTPIYLAL LVASLPFAFL GFLFWSPLQS ARRPYIYSRL EDKGLAGGAA LLSEWKGTGP
GKSFCFATAN VCLLPDSLAR VNNLFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS
AASFSSLVSP QGGDGVARAV PGSIKRTASV EYKGDGGRHP GDEAANGPAS GDPVDSSSPE
DACIVRIGGE EGGRPPEADD PVPGGQARNG AGGGPRGQTP NHNQQDGDSG SLGSPSASRE
SLVKGRAGPD TSASGEPGAN SKLLYKASVV KKAAARRRRH PDEAFDHEVS AFFPANLDFL
CLQEVFDKRA ATKLKEQLHG YFEYILYDVG VYGCQGCCSF KCLNSGLLFA SRYPIMDVAY
HCYPNKCNDD ALASKGALFL KVQVGSTPQD QRIVGYIACT HLHAPQEDSA IRCGQLDLLQ
DWLADFRKST SSSSAANPEE LVAFDVVCGD FNFDNCSSDD KLEQQHSLFT HYRDPCRLGP
GEEKPWAIGT LLDTNGLYDE DVCTPDNLQK VLESEEGRRE YLAFPTSKSS GQKGRKELLK
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSS GEEEA
