ID   NSMA3_DANRE             Reviewed;         791 AA.
AC   Q6PFJ7;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=Sphingomyelin phosphodiesterase 4;
DE            EC=3.1.4.12;
DE   AltName: Full=Neutral sphingomyelinase 3;
DE            Short=nSMase-3;
DE            Short=nSMase3;
DE   AltName: Full=Neutral sphingomyelinase III;
GN   Name=smpd4; ORFNames=zgc:66367;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=SJD;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the hydrolysis of membrane sphingomyelin to form
CC       phosphorylcholine and ceramide. It has a relevant role in the
CC       homeostasis of membrane sphingolipids, thereby influencing membrane
CC       integrity, and endoplasmic reticulum organization and function. May
CC       sensitize cells to DNA damage-induced apoptosis.
CC       {ECO:0000250|UniProtKB:Q9NXE4}.
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:Q9NXE4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC         Evidence={ECO:0000250|UniProtKB:Q9NXE4};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q9NXE4};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q9NXE4}; Single-pass membrane protein
CC       {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9NXE4};
CC       Single-pass membrane protein {ECO:0000255}. Nucleus envelope
CC       {ECO:0000250|UniProtKB:Q9NXE4}. Cell membrane, sarcolemma
CC       {ECO:0000250|UniProtKB:Q6ZPR5}.
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DR   EMBL; BC057525; AAH57525.1; -; mRNA.
DR   RefSeq; NP_998520.1; NM_213355.1.
DR   AlphaFoldDB; Q6PFJ7; -.
DR   STRING; 7955.ENSDARP00000107263; -.
DR   PaxDb; Q6PFJ7; -.
DR   PRIDE; Q6PFJ7; -.
DR   GeneID; 793294; -.
DR   KEGG; dre:793294; -.
DR   CTD; 55627; -.
DR   ZFIN; ZDB-GENE-040426-2672; smpd4.
DR   eggNOG; KOG4396; Eukaryota.
DR   InParanoid; Q6PFJ7; -.
DR   OrthoDB; 470341at2759; -.
DR   PhylomeDB; Q6PFJ7; -.
DR   Reactome; R-DRE-1660662; Glycosphingolipid metabolism.
DR   PRO; PR:Q6PFJ7; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR   GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; ISS:UniProtKB.
DR   GO; GO:0050290; F:sphingomyelin phosphodiesterase D activity; IBA:GO_Central.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR   GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central.
DR   GO; GO:0006685; P:sphingomyelin catabolic process; ISS:UniProtKB.
DR   InterPro; IPR024129; Sphingomy_SMPD4.
DR   PANTHER; PTHR12988; PTHR12988; 1.
DR   Pfam; PF14724; mit_SMPDase; 2.
PE   2: Evidence at transcript level;
KW   Cell membrane; Endoplasmic reticulum; Golgi apparatus; Hydrolase;
KW   Lipid metabolism; Magnesium; Membrane; Metal-binding; Nucleus;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..791
FT                   /note="Sphingomyelin phosphodiesterase 4"
FT                   /id="PRO_0000273165"
FT   TRANSMEM        755..775
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   791 AA;  89990 MW;  6EFCAD6148CF7D78 CRC64;
     MAASALQQPS YLLANLKADW TNKPLHQRCH ELCKIIDDYP AKELHAIFPW LVECVFGSLD
     GILTGWNLRF LQARSAEYSI AMEFLDPSGP MMKLVYKLQA EEYKYEFPIS YLPGPIKSSI
     HAGVLPDCPL FHNKIQFPMS GLLFLNPFEY YMFNFASSLI APKNYPQGQH GSSSDSAYFV
     LVDTYLKYFL PTEGNVPPSP FSDTRGTVAS PAPRSTNVPY VGYGGHSTSL LKRHITHQSS
     VNADPAAQEI WRSETLLQVF VEMWLHHYSL EMYQKLQSPQ VKEPFMPSEE HVLVVRLLVK
     HLHTFSSSLK PESISSSPSA HSHSSPLEEL KRVVVQRFVQ QKLYVFLQHC FGHWPLDASF
     RAVLETWLSY IQPWRYTGDK NNTQTDGPNR TVPDKWASFV QENLLLYTKL FQGFLNRAMR
     TDLVNAKNAL MVFRVAKVFA QPSLSEMIQK GEQLFLEPEH AILQRHNRVF LTPSHGGSFL
     SARQPMGTDN VFKVKSHVYS LEGQDCQYNL MFGPDQRKNV LKLIQIIAQA RQTAKRISDH
     STEMAANNSF LSWFGVGSPD HNSTFTGGEM DEMGGEGVKK THEFLDKALD YLCQIFRLNA
     GQLSQLISNV ASVDNNGASK QLPDCIPSEN GLVLTDLGRL QIINGLRRFE IEYQGDPELQ
     PIRSYENAFL VRLLFQISSF INERLGEHME VLCSRQDFLG SVGRHYLSSS SAVVEQRRKS
     PVTRQMRDRP QRARLSLRAL ASYRTLLTLL LLYMLFALLS FGLFSSTGLI LIISFLYELL
     SNFFHEKLKT H