ID   NSMA3_XENLA             Reviewed;         824 AA.
AC   Q5XHG1; Q4V7Y8;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   03-AUG-2022, entry version 64.
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;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Kidney, and Ovary;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (OCT-2004) 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}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5XHG1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5XHG1-2; Sequence=VSP_022488;
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH84096.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; BC084096; AAH84096.1; ALT_INIT; mRNA.
DR   EMBL; BC097653; AAH97653.1; -; mRNA.
DR   RefSeq; NP_001088184.1; NM_001094715.1. [Q5XHG1-2]
DR   AlphaFoldDB; Q5XHG1; -.
DR   PRIDE; Q5XHG1; -.
DR   DNASU; 495009; -.
DR   GeneID; 495009; -.
DR   KEGG; xla:495009; -.
DR   CTD; 495009; -.
DR   Xenbase; XB-GENE-962471; smpd4.L.
DR   OMA; AYAWRSE; -.
DR   Proteomes; UP000186698; Chromosome 1L.
DR   Bgee; 495009; Expressed in egg cell and 19 other tissues.
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; IEA:InterPro.
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:0006685; P:sphingomyelin catabolic process; ISS:UniProtKB.
DR   InterPro; IPR024129; Sphingomy_SMPD4.
DR   PANTHER; PTHR12988; PTHR12988; 1.
DR   Pfam; PF14724; mit_SMPDase; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Endoplasmic reticulum;
KW   Golgi apparatus; Hydrolase; Lipid metabolism; Magnesium; Membrane;
KW   Metal-binding; Nucleus; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..824
FT                   /note="Sphingomyelin phosphodiesterase 4"
FT                   /id="PRO_0000273166"
FT   TRANSMEM        777..797
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         289..316
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_022488"
SQ   SEQUENCE   824 AA;  93796 MW;  3090723AA5A777FC CRC64;
     MLLAGGSPQP SFLLGSLKAD CVTKPFLQRC QDLVRVIEDF PAKELHAIFP WLIETVFGSL
     DGSILGWNLR GLHERINPLE FHTALEFLDP SGAMMKLVYK LQAEEYKYDF PVSFLPGPVR
     ASIQERVLPE CPLYHNKIQF PASGGVSFNL ALNSFEYFMF HFAFCLLKQR NYPQGLHFST
     ADSAYYILVD KYLKWFLPVE GNVPPPHSPN TGGTVPSPAP RSPSLSFTSY GSHTSLLKRH
     ISHQHLVNAD PAAQEIWRTE TLLQVFVEIW LHHYSLEMYQ KMQSPNAKLE ALHNRLSVSS
     APPIYPALPG SLHSYQELFQ PTEEHVLVVR LLVKHLHTFS NSIRPEQVSP STHSHTASPL
     EELKRVVVPR FIQQKLYIFL QHCFGHWPLD ASFRAVLEMW LSYVQPWRYV LERSSPVSGE
     MQNRNVPEKW STFVQENLLF YTKLFLRFLS RALRTDLVNP KNALMVFRAA KVFSQLNLPE
     MILNGEQLFL KPEHVIPHRQ HRLLLTPNLG GSFLSSWQPP ITDTSLKVKS HVFSLEGQDC
     QYMQMFGPEA RNLVLRLAQM ISQAKQTAKS ISNHSPDSSA NQSFLSWFGL GSPDFNGSYN
     GSDLDEAGYD TIRKTDEHLE KALDYFCQIF RLNPTQLGQL TANVDSSQDD DGKNKLPDCI
     QSEDGVVLTS LGRYQIINGL RKFDIEYQGD PELQPIRSYE NAMLVRYLYR LSSVINKRFA
     NSMGALCARK DFLGKLCRHH LTSSSRKCKK SPITSVSPSE PAAPHIRLRF LASYRTLAFL
     FIFYILGSLL SLGPLICTFL LLIGCMFYAI VQTLLSEEQK PHNN