NSMA5_MOUSE
ID NSMA5_MOUSE Reviewed; 483 AA.
AC D6MZJ6;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Sphingomyelin phosphodiesterase 5;
DE EC=3.1.4.12 {ECO:0000269|PubMed:20378533};
DE AltName: Full=Mitochondrial neutral sphingomyelinase;
DE Short=mtnSMase;
GN Name=Smpd5 {ECO:0000312|MGI:MGI:3709877};
GN Synonyms=Gm10345 {ECO:0000312|MGI:MGI:3709877};
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 {ECO:0000312|EMBL:ADG03437.1};
RN [1] {ECO:0000312|EMBL:ADG03437.1}
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, COFACTOR, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:ADG03437.1};
RX PubMed=20378533; DOI=10.1074/jbc.m110.102988;
RA Wu B.X., Rajagopalan V., Roddy P.L., Clarke C.J., Hannun Y.A.;
RT "Identification and characterization of murine mitochondria-associated
RT neutral sphingomyelinase (MA-nSMase), the mammalian sphingomyelin
RT phosphodiesterase 5.";
RL J. Biol. Chem. 285:17993-18002(2010).
RN [2] {ECO:0000312|Ensembl:ENSMUSP00000134687, ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000134687,
RC ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Catalyzes the hydrolysis of membrane sphingomyelin to form
CC phosphorylcholine and ceramide. {ECO:0000250|UniProtKB:F1QG30}.
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:20378533};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000305|PubMed:20378533};
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:20378533};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45645;
CC Evidence={ECO:0000305|PubMed:20378533};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20378533};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:20378533};
CC -!- ACTIVITY REGULATION: Activated by anionic phospholipids, specially
CC cardiolipin and phosphatidylserine. {ECO:0000269|PubMed:20378533}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:20378533};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:20378533}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20378533}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:F1QG30}; Intermembrane side
CC {ECO:0000250|UniProtKB:F1QG30}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20378533}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, pancreas, epididymis,
CC and brain. {ECO:0000269|PubMed:20378533}.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
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DR EMBL; GU144514; ADG03437.1; -; mRNA.
DR EMBL; AC155074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS56988.1; -.
DR RefSeq; NP_001182466.1; NM_001195537.1.
DR AlphaFoldDB; D6MZJ6; -.
DR SMR; D6MZJ6; -.
DR STRING; 10090.ENSMUSP00000134687; -.
DR SwissLipids; SLP:000001137; -.
DR PaxDb; D6MZJ6; -.
DR PRIDE; D6MZJ6; -.
DR ProteomicsDB; 337062; -.
DR Ensembl; ENSMUST00000163991; ENSMUSP00000134687; ENSMUSG00000071724.
DR GeneID; 100503915; -.
DR KEGG; mmu:100503915; -.
DR UCSC; uc011zut.1; mouse.
DR CTD; 392275; -.
DR MGI; MGI:3709877; Smpd5.
DR VEuPathDB; HostDB:ENSMUSG00000071724; -.
DR eggNOG; ENOG502QVRH; Eukaryota.
DR GeneTree; ENSGT00400000022168; -.
DR HOGENOM; CLU_028243_0_0_1; -.
DR InParanoid; D6MZJ6; -.
DR OMA; LGCWAPA; -.
DR OrthoDB; 455705at2759; -.
DR PhylomeDB; D6MZJ6; -.
DR TreeFam; TF328678; -.
DR BRENDA; 3.1.4.12; 3474.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 100503915; 1 hit in 72 CRISPR screens.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; D6MZJ6; protein.
DR Bgee; ENSMUSG00000071724; Expressed in spermatocyte and 62 other tissues.
DR ExpressionAtlas; D6MZJ6; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:MGI.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IDA:UniProtKB.
DR GO; GO:0006684; P:sphingomyelin metabolic process; IBA:GO_Central.
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 Endoplasmic reticulum; Hydrolase; Lipid metabolism; Magnesium; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Signal-anchor; Sphingolipid metabolism;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT CHAIN 1..483
FT /note="Sphingomyelin phosphodiesterase 5"
FT /id="PRO_0000451401"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 471
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:F1QG30"
FT BINDING 209
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 351
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
SQ SEQUENCE 483 AA; 53869 MW; E7C3281315FC8E07 CRC64;
MSLPDISRRR SPVPQEDWPL TPNALRPSPF PNPVLQALYS LSRVLLFPTY WSLDQLLGCW
APSVRSKSLG WFKVLAGSGV LLPLVVVGLP LALVGLALWL PLQVWRRPFC YQPPPACWVW
PQPWHPPAER RRCFVFLTAN LCLLPHGLAH FNNLSHSLQR AEAVGAALLD SLQSSQYRVS
ECSQPPPRVP GGELKATLPM GLDFVCLQEV FDLRAARRLV RVLVPNLGPV IYDVGTFGLM
AGPYIKVLGS GLLLASRYPL LRATFRCFPN ARREDAMASK GLLSVQAQLG IVDGHPIVGY
LHCTHLHAPV EDGHIRCKQL TLLLEWVEEF EAENRQSDEA VAFSVLLGDL NFDNCSQDHA
KEQGHKLFSC FQDPCRLGVC QEQPWALGTI LNSSMLRHSI ACSPEMLRRA LRQEKGRRLY
LSGPLHGSYP AQSWKGRRLD YITYRRVPGS RLSPEAEQVT FSTAFAGLTD HLAMGLKLQV
VCS
