NSMA2_MOUSE
ID NSMA2_MOUSE Reviewed; 655 AA.
AC Q9JJY3; Q3UTQ5;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Sphingomyelin phosphodiesterase 3 {ECO:0000305};
DE EC=3.1.4.12 {ECO:0000269|PubMed:12566438, ECO:0000269|PubMed:15051724};
DE AltName: Full=Neutral sphingomyelinase 2;
DE Short=nSMase-2;
DE Short=nSMase2 {ECO:0000303|PubMed:21550973};
DE AltName: Full=Neutral sphingomyelinase II;
GN Name=Smpd3 {ECO:0000312|MGI:MGI:1927578};
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], 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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Skin;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Colon;
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 CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=12566438; DOI=10.1074/jbc.m212262200;
RA Marchesini N., Luberto C., Hannun Y.A.;
RT "Biochemical properties of mammalian neutral sphingomyelinase 2 and its
RT role in sphingolipid metabolism.";
RL J. Biol. Chem. 278:13775-13783(2003).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 FUNCTION.
RX PubMed=15929065; DOI=10.1002/jnr.20549;
RA Goswami R., Ahmed M., Kilkus J., Han T., Dawson S.A., Dawson G.;
RT "Differential regulation of ceramide in lipid-rich microdomains (rafts):
RT antagonistic role of palmitoyl:protein thioesterase and neutral
RT sphingomyelinase 2.";
RL J. Neurosci. Res. 81:208-217(2005).
RN [7]
RP FUNCTION.
RX PubMed=16025116; DOI=10.1038/ng1603;
RA Aubin I., Adams C.P., Opsahl S., Septier D., Bishop C.E., Auge N.,
RA Salvayre R., Negre-Salvayre A., Goldberg M., Guenet J.-L., Poirier C.;
RT "A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3)
RT results in osteogenesis and dentinogenesis imperfecta in the mouse.";
RL Nat. Genet. 37:803-805(2005).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=15764706; DOI=10.1073/pnas.0406380102;
RA Stoffel W., Jenke B., Bloeck B., Zumbansen M., Koebke J.;
RT "Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and
RT development.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4554-4559(2005).
RN [9]
RP SUBCELLULAR LOCATION, AND PALMITOYLATION AT CYS-53; CYS-54; CYS-59; CYS-395
RP AND CYS-396.
RX PubMed=17272284; DOI=10.1074/jbc.m611249200;
RA Tani M., Hannun Y.A.;
RT "Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues.
RT Role of palmitoylation in subcellular localization.";
RL J. Biol. Chem. 282:10047-10056(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178 AND SER-289, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF ARG-33;
RP 45-LYS--ARG-48; 92-ARG-ARG-93; ARG-92; ARG-93 AND ARG-99, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21550973; DOI=10.1074/jbc.m110.156471;
RA Wu B.X., Clarke C.J., Matmati N., Montefusco D., Bartke N., Hannun Y.A.;
RT "Identification of novel anionic phospholipid binding domains in neutral
RT sphingomyelinase 2 with selective binding preference.";
RL J. Biol. Chem. 286:22362-22371(2011).
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:15051724, PubMed:15764706, PubMed:15929065,
CC PubMed:16025116). Binds to anionic phospholipids (APLs) such as
CC phosphatidylserine (PS) and phosphatidic acid (PA) that modulate
CC enzymatic activity and subcellular location (PubMed:21550973). May be
CC involved in IL-1-beta-induced JNK activation in hepatocytes (By
CC similarity). May act as a mediator in transcriptional regulation of
CC NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions
CC (By similarity). {ECO:0000250|UniProtKB:O35049,
CC ECO:0000269|PubMed:15051724, ECO:0000269|PubMed:15764706,
CC ECO:0000269|PubMed:15929065, ECO:0000269|PubMed:16025116,
CC ECO:0000269|PubMed:21550973}.
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:12566438, 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=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:0000269|PubMed:21550973};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45645;
CC Evidence={ECO:0000305|PubMed:21550973};
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:0000250|UniProtKB:Q9NY59};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45301;
CC Evidence={ECO:0000250|UniProtKB:Q9NY59};
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:0000250|UniProtKB:Q9NY59};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000250|UniProtKB:Q9NY59};
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:0000250|UniProtKB:Q9NY59};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39924;
CC Evidence={ECO:0000250|UniProtKB:Q9NY59};
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:0000250|UniProtKB:Q9NY59};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45297;
CC Evidence={ECO:0000250|UniProtKB:Q9NY59};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12566438};
CC -!- ACTIVITY REGULATION: Inhibited by nSMase inhibitor GW4869. Binding of
CC anionic phospholipids (APLs) such as phosphatidylserine (PS) and
CC phosphatidic acid (PA) increases enzymatic activity (PubMed:21550973).
CC {ECO:0000269|PubMed:12566438, ECO:0000269|PubMed:21550973}.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:15051724}.
CC -!- INTERACTION:
CC Q9JJY3; O75530: EED; Xeno; NbExp=5; IntAct=EBI-9817007, EBI-923794;
CC Q9JJY3; P10809: HSPD1; Xeno; NbExp=3; IntAct=EBI-9817007, EBI-352528;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:15764706}; Lipid-anchor
CC {ECO:0000269|PubMed:15764706}. Cell membrane
CC {ECO:0000269|PubMed:17272284, ECO:0000269|PubMed:21550973}; Lipid-
CC anchor {ECO:0000269|PubMed:17272284}. Note=May localize to detergent-
CC resistant subdomains of Golgi membranes of hypothalamic neurosecretory
CC neurons (PubMed:15764706).
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain (at protein
CC level). {ECO:0000269|PubMed:10823942}.
CC -!- PTM: Palmitoylated, palmitoylation-deficient proteins are targeted for
CC lysosomal degradation. {ECO:0000269|PubMed:17272284}.
CC -!- DISRUPTION PHENOTYPE: Defects in smpd3 are the cause of fragilitas
CC ossium (fro) mutation characterized by severe osteogenesis and
CC dentinogenesis imperfecta with no detectable collagen defect. Mice
CC lacking Smpd2 and Smpd3 are completely devoid of neutral SMase activity
CC but do not developed sphingomyelin storage abnormalities. Mice lacking
CC Smpd3 develop a form of dwarfism and delayed puberty as part of a
CC hypothalamus-induced combined pituitary hormone deficiency (CPHD).
CC Growth retardation is probably due to delayed ossification of long
CC bones. {ECO:0000269|PubMed:15764706}.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
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DR EMBL; AJ250461; CAB92970.1; -; mRNA.
DR EMBL; AK019476; BAB31745.1; -; mRNA.
DR EMBL; AK139226; BAE23925.1; -; mRNA.
DR EMBL; BC043077; AAH43077.1; -; mRNA.
DR EMBL; BC046980; AAH46980.1; -; mRNA.
DR CCDS; CCDS22634.1; -.
DR RefSeq; NP_067466.1; NM_021491.3.
DR RefSeq; XP_006531304.1; XM_006531241.3.
DR RefSeq; XP_011246764.1; XM_011248462.1.
DR RefSeq; XP_011246765.1; XM_011248463.2.
DR AlphaFoldDB; Q9JJY3; -.
DR SMR; Q9JJY3; -.
DR BioGRID; 208469; 3.
DR DIP; DIP-60430N; -.
DR IntAct; Q9JJY3; 2.
DR STRING; 10090.ENSMUSP00000069255; -.
DR SwissLipids; SLP:000000215; -.
DR iPTMnet; Q9JJY3; -.
DR PhosphoSitePlus; Q9JJY3; -.
DR SwissPalm; Q9JJY3; -.
DR MaxQB; Q9JJY3; -.
DR PaxDb; Q9JJY3; -.
DR PeptideAtlas; Q9JJY3; -.
DR PRIDE; Q9JJY3; -.
DR ProteomicsDB; 287826; -.
DR Antibodypedia; 29783; 171 antibodies from 21 providers.
DR DNASU; 58994; -.
DR Ensembl; ENSMUST00000067512; ENSMUSP00000069255; ENSMUSG00000031906.
DR Ensembl; ENSMUST00000212896; ENSMUSP00000148282; ENSMUSG00000031906.
DR GeneID; 58994; -.
DR KEGG; mmu:58994; -.
DR UCSC; uc009nfx.1; mouse.
DR CTD; 55512; -.
DR MGI; MGI:1927578; Smpd3.
DR VEuPathDB; HostDB:ENSMUSG00000031906; -.
DR eggNOG; ENOG502QVS2; Eukaryota.
DR GeneTree; ENSGT00400000022168; -.
DR HOGENOM; CLU_028243_0_0_1; -.
DR InParanoid; Q9JJY3; -.
DR OMA; TGKSFCF; -.
DR OrthoDB; 455705at2759; -.
DR PhylomeDB; Q9JJY3; -.
DR TreeFam; TF328678; -.
DR BRENDA; 3.1.4.12; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-5626978; TNFR1-mediated ceramide production.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 58994; 7 hits in 74 CRISPR screens.
DR ChiTaRS; Smpd3; mouse.
DR PRO; PR:Q9JJY3; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9JJY3; protein.
DR Bgee; ENSMUSG00000031906; Expressed in intramembranous bone and 165 other tissues.
DR Genevisible; Q9JJY3; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:InterPro.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000137; C:Golgi cis cisterna; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061751; F:neutral sphingomyelin phosphodiesterase activity; IDA:MGI.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISO:MGI.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0014824; P:artery smooth muscle contraction; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0098868; P:bone growth; IMP:MGI.
DR GO; GO:0030282; P:bone mineralization; IDA:MGI.
DR GO; GO:0051216; P:cartilage development; IDA:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI.
DR GO; GO:0071286; P:cellular response to magnesium ion; IDA:MGI.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IMP:MGI.
DR GO; GO:1901653; P:cellular response to peptide; IMP:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:MGI.
DR GO; GO:0071461; P:cellular response to redox state; IMP:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:MGI.
DR GO; GO:0006672; P:ceramide metabolic process; IMP:MGI.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0003433; P:chondrocyte development involved in endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0032963; P:collagen metabolic process; IMP:MGI.
DR GO; GO:0097187; P:dentinogenesis; IMP:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; IMP:MGI.
DR GO; GO:0090494; P:dopamine uptake; ISO:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0085029; P:extracellular matrix assembly; IMP:MGI.
DR GO; GO:0070314; P:G1 to G0 transition; IMP:MGI.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0140014; P:mitotic nuclear division; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IDA:MGI.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; IMP:MGI.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0030072; P:peptide hormone secretion; IMP:MGI.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0015774; P:polysaccharide transport; IMP:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISO:MGI.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IGI:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0061035; P:regulation of cartilage development; IMP:MGI.
DR GO; GO:1900125; P:regulation of hyaluronan biosynthetic process; IMP:MGI.
DR GO; GO:0002685; P:regulation of leukocyte migration; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0060541; P:respiratory system development; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR GO; GO:0001501; P:skeletal system development; IDA:MGI.
DR GO; GO:0090520; P:sphingolipid mediated signaling pathway; IDA:MGI.
DR GO; GO:0006665; P:sphingolipid metabolic process; IMP:MGI.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IMP:MGI.
DR GO; GO:0006684; P:sphingomyelin metabolic process; IDA:UniProtKB.
DR CDD; cd09078; nSMase; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR017766; Sphingomyelinase/PLipase_C.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell membrane; Developmental protein; Golgi apparatus;
KW Hydrolase; Lipid metabolism; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Reference proteome;
KW Sphingolipid metabolism.
FT CHAIN 1..655
FT /note="Sphingomyelin phosphodiesterase 3"
FT /id="PRO_0000075693"
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 209..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..296
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 362
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 510
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 53
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:17272284"
FT LIPID 54
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:17272284"
FT LIPID 59
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:17272284"
FT LIPID 395
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:17272284"
FT LIPID 396
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:17272284"
FT MUTAGEN 33
FT /note="R->A: Strongly decreases binding with phosphatidic
FT acid and phosphatidylserine. Abolishes binding with
FT phosphatidic acid and phosphatidylserine; when associated
FT with 45-DEL-48. Strongly decreases sphingomyelin
FT phosphodiesterase activity; when associated with 45-DEL-48.
FT Abolishes sphingomyelin phosphodiesterase activity and
FT locates at endoplasmic reticulum; when associated with 45-
FT DEL-48 and 92-A-A-93."
FT /evidence="ECO:0000269|PubMed:21550973"
FT MUTAGEN 45..48
FT /note="Missing: Strongly decreases binding with
FT phosphatidic acid and phosphatidylserine. Abolishes binding
FT with phosphatidic acid and phosphatidylserine; when
FT associated with A-33. Strongly decreases sphingomyelin
FT phosphodiesterase activity; when associated with A-33.
FT Abolishes sphingomyelin phosphodiesterase activity and
FT locates at endoplasmic reticulum; when associated with A-33
FT and 92-A-A-93."
FT /evidence="ECO:0000269|PubMed:21550973"
FT MUTAGEN 92..93
FT /note="RR->AA: Abolishes binding with phosphatidic acid. No
FT effect on cell membrane location. Strongly decreases
FT sphingomyelin phosphodiesterase activity. Abolishes
FT sphingomyelin phosphodiesterase activity and locates at
FT endoplasmic reticulum; when associated with A-33 and 45-
FT DEL-48."
FT /evidence="ECO:0000269|PubMed:21550973"
FT MUTAGEN 92
FT /note="R->A: Strongly decreases binding with phosphatidic
FT acid."
FT /evidence="ECO:0000269|PubMed:21550973"
FT MUTAGEN 93
FT /note="R->A: Strongly decreases binding with phosphatidic
FT acid."
FT /evidence="ECO:0000269|PubMed:21550973"
FT MUTAGEN 99
FT /note="R->A: No effect on binding with phosphatidic acid."
FT /evidence="ECO:0000269|PubMed:21550973"
SQ SEQUENCE 655 AA; 71197 MW; 6764769EEAB5A168 CRC64;
MVLYTTPFPN SCLSALHAVS WALIFPCYWL VDRLLASFIP TTYEKRQRAD DPCCLQLFCT
VLFTPVYLAL LVAALPFAFL GFIFWSPLQS ARRPYSYSRL EDKNPAGGAA LLSEWKGTGA
GKSFCFATAN VCLLPDSLAR LNNVFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS
AASFSSLVSP QGGDGSRAVP GSIKRTASVE YKGDGGRHPS DEAANGPASG EQADGSLEDS
CIVRIGGEEG GRPQEADDPA AGSQARNGAG GTPKGQTPNH NQRDGDSGSL GSPSASRESL
VKARAGQDSG GSGEPGANSK LLYKTSVVKK AAARRRRHPD EAFDHEVSAF FPANLDFLCL
QEVFDKRAAA KLKEQLHGYF EYILYDVGVY GCHGCCNFKC LNSGLFFASR YPVMDVAYHC
YPNGCSFDAL ASKGALFLKV QVGSTPQDQR IVGYIACTHL HAPPEDSAVR CEQLDLLQDW
LADFRKSTSS TSTANPEELV VFDVICGDLN FDNCSSDDKL EQQHSLFTRY KDPCRLGPGE
EKPWAIGTLL DTNGLYDEDV CTPDNLQKVL ESEEGRREYL AFPTSKSPGA GQKGRKDLLK
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSA GEEEA
