NSMA_RAT
ID NSMA_RAT Reviewed; 422 AA.
AC Q9ET64; Q5BKB2;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Sphingomyelin phosphodiesterase 2;
DE EC=3.1.4.12;
DE AltName: Full=Lyso-platelet-activating factor-phospholipase C;
DE Short=Lyso-PAF-PLC;
DE AltName: Full=Neutral sphingomyelinase;
DE Short=N-SMase;
DE Short=nSMase;
GN Name=Smpd2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND MUTAGENESIS.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=10832103; DOI=10.1016/s1388-1981(00)00059-7;
RA Mizutani Y., Tamiya-Koizumi K., Irie F., Hirabayashi Y., Miwa M.,
RA Yoshida S.;
RT "Cloning and expression of rat neutral sphingomyelinase: enzymological
RT characterization and identification of essential histidine residues.";
RL Biochim. Biophys. Acta 1485:236-246(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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).
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. Hydrolyze 1-acyl-2-lyso-sn-glycero-3-
CC phosphocholine (lyso-PC) and 1-O-alkyl-2-lyso-sn-glycero-3-
CC phosphocholine (lyso-platelet-activating factor).
CC {ECO:0000250|UniProtKB:O60906}.
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:O60906};
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:O60906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39924;
CC Evidence={ECO:0000250|UniProtKB:O60906};
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:O60906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45301;
CC Evidence={ECO:0000250|UniProtKB:O60906};
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:O60906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000250|UniProtKB:O60906};
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:O60906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45297;
CC Evidence={ECO:0000250|UniProtKB:O60906};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC hexadecyl-sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:36087,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:34115,
CC ChEBI:CHEBI:64496, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:O60906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36088;
CC Evidence={ECO:0000250|UniProtKB:O60906};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000250|UniProtKB:O60906}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
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DR EMBL; AB047002; BAB08219.1; -; mRNA.
DR EMBL; BC091139; AAH91139.1; -; mRNA.
DR RefSeq; NP_112650.1; NM_031360.2.
DR AlphaFoldDB; Q9ET64; -.
DR SMR; Q9ET64; -.
DR STRING; 10116.ENSRNOP00000000336; -.
DR BindingDB; Q9ET64; -.
DR ChEMBL; CHEMBL3528; -.
DR PaxDb; Q9ET64; -.
DR PRIDE; Q9ET64; -.
DR Ensembl; ENSRNOT00000000336; ENSRNOP00000000336; ENSRNOG00000000306.
DR GeneID; 83537; -.
DR KEGG; rno:83537; -.
DR CTD; 6610; -.
DR RGD; 619753; Smpd2.
DR eggNOG; KOG3873; Eukaryota.
DR GeneTree; ENSGT00390000009166; -.
DR HOGENOM; CLU_034001_4_0_1; -.
DR InParanoid; Q9ET64; -.
DR OMA; IEVNCQV; -.
DR OrthoDB; 589366at2759; -.
DR PhylomeDB; Q9ET64; -.
DR TreeFam; TF313899; -.
DR BRENDA; 3.1.4.12; 5301.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR Reactome; R-RNO-5626978; TNFR1-mediated ceramide production.
DR SABIO-RK; Q9ET64; -.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q9ET64; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000306; Expressed in jejunum and 20 other tissues.
DR Genevisible; Q9ET64; RN.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0071944; C:cell periphery; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISO:RGD.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:RGD.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IMP:RGD.
DR GO; GO:0030149; P:sphingolipid catabolic process; IBA:GO_Central.
DR GO; GO:0006685; P:sphingomyelin catabolic process; ISO:RGD.
DR GO; GO:0006684; P:sphingomyelin metabolic process; IBA:GO_Central.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR038772; SMPD2-like.
DR PANTHER; PTHR12393; PTHR12393; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Lipid metabolism; Magnesium; Membrane; Metal-binding;
KW Reference proteome; Sphingolipid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..422
FT /note="Sphingomyelin phosphodiesterase 2"
FT /id="PRO_0000075688"
FT TRANSMEM 325..345
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 397..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 272
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 180
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
FT MUTAGEN 136
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:10832103"
FT MUTAGEN 151
FT /note="H->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:10832103"
FT MUTAGEN 151
FT /note="H->Y: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:10832103"
FT MUTAGEN 272
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:10832103"
SQ SEQUENCE 422 AA; 47645 MW; 109A5133A056AAF1 CRC64;
MKHNFSLRLR VFNLNCWDIP YLSKHRADRM KRLGDFLNLE SFDLALLEEV WSEQDFQYLK
QKLSLTYPDA HYFRSGIIGS GLCVFSRHPI QEIVQHVYTL NGYPYKFYHG DWFCGKAVGL
LVLHLSGLVL NAYVTHLHAE YSRQKDIYFA HRVAQAWELA QFIHHTSKKA NVVLLCGDLN
MHPKDLGCCL LKEWTGLRDA FVETEDFKGS EDGCTMVPKN CYVSQQDLGP FPFGVRIDYV
LYKAVSGFHI CCKTLKTTTG CDPHNGTPFS DHEALMATLC VKHSPPQEDP CSAHGSAERS
ALISALREAR TELGRGIAQA RWWAALFGYV MILGLSLLVL LCVLAAGEEA REVAIMLWTP
SVGLVLGAGA VYLFHKQEAK SLCRAQAEIQ HVLTRTTETQ DLGSEPHPTH CRQQEADRAE
EK
