NSMA5_DANRE
ID NSMA5_DANRE Reviewed; 545 AA.
AC F1QG30; A0AUR7; A9JRN5; B1B5D8;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Sphingomyelin phosphodiesterase 5 {ECO:0000305};
DE EC=3.1.4.12 {ECO:0000269|PubMed:19429680};
DE AltName: Full=Mitochondrial neutral sphingomyelinase {ECO:0000303|PubMed:19429680};
DE Short=mtnSMase {ECO:0000303|PubMed:19429680};
DE Flags: Precursor;
GN Name=smpd5 {ECO:0000312|ZFIN:ZDB-GENE-061110-22};
GN Synonyms=smpdm {ECO:0000312|ZFIN:ZDB-GENE-061110-22};
GN ORFNames=zgc:153995 {ECO:0000312|EMBL:AAI24789.1};
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 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|EMBL:BAG12869.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP TOPOLOGY, MUTAGENESIS OF HIS-529, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19429680; DOI=10.1074/jbc.m109.004580;
RA Yabu T., Shimuzu A., Yamashita M.;
RT "A novel mitochondrial sphingomyelinase in zebrafish cells.";
RL J. Biol. Chem. 284:20349-20363(2009).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000312|EMBL:AAI55731.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary {ECO:0000312|EMBL:AAI55731.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the hydrolysis of membrane sphingomyelin to form
CC phosphorylcholine and ceramide. {ECO:0000269|PubMed:19429680}.
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:19429680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000305|PubMed:19429680};
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:0000250|UniProtKB:D6MZJ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45645;
CC Evidence={ECO:0000250|UniProtKB:D6MZJ6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19429680};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:D6MZJ6};
CC -!- ACTIVITY REGULATION: Activated by the phospholipids cardiolipin,
CC phosphatidylserine, and phosphatidylethanolamine. Strongest activation
CC with cardiolipin. {ECO:0000269|PubMed:19429680}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:19429680};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:19429680}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:19429680}; Single-pass type II membrane protein
CC {ECO:0000305|PubMed:19429680}; Intermembrane side
CC {ECO:0000269|PubMed:19429680}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:D6MZJ6}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
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DR EMBL; AB361066; BAG12869.1; -; mRNA.
DR EMBL; CR759845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC124788; AAI24789.1; -; mRNA.
DR EMBL; BC155730; AAI55731.1; -; mRNA.
DR EMBL; BC165400; AAI65400.1; -; mRNA.
DR RefSeq; NP_001071083.1; NM_001077615.1.
DR RefSeq; XP_005158509.1; XM_005158452.3.
DR RefSeq; XP_005158510.1; XM_005158453.3.
DR AlphaFoldDB; F1QG30; -.
DR SMR; F1QG30; -.
DR STRING; 7955.ENSDARP00000104571; -.
DR PaxDb; F1QG30; -.
DR Ensembl; ENSDART00000083558; ENSDARP00000077993; ENSDARG00000059811.
DR Ensembl; ENSDART00000124691; ENSDARP00000104571; ENSDARG00000059811.
DR GeneID; 567592; -.
DR KEGG; dre:567592; -.
DR CTD; 392275; -.
DR ZFIN; ZDB-GENE-061110-22; smpd5.
DR eggNOG; ENOG502QVS2; Eukaryota.
DR GeneTree; ENSGT00400000022168; -.
DR HOGENOM; CLU_028243_0_0_1; -.
DR InParanoid; F1QG30; -.
DR OMA; WFPNSRG; -.
DR OrthoDB; 455705at2759; -.
DR PhylomeDB; F1QG30; -.
DR TreeFam; TF328678; -.
DR UniPathway; UPA00222; -.
DR PRO; PR:F1QG30; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 16.
DR Bgee; ENSDARG00000059811; Expressed in pharyngeal gill and 21 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS: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:0005758; C:mitochondrial intermembrane space; IDA:ZFIN.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
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:ZFIN.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; IDA:ZFIN.
DR GO; GO:0006685; P:sphingomyelin catabolic process; ISS: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; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR017766; Sphingomyelinase/PLipase_C.
DR Pfam; PF03372; Exo_endo_phos; 1.
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 TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:19429680"
FT CHAIN 36..545
FT /note="Sphingomyelin phosphodiesterase 5"
FT /id="PRO_0000436567"
FT TOPO_DOM 36..64
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 65..85
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..545
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:19429680"
FT ACT_SITE 529
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:19429680"
FT BINDING 258
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 404
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
FT MUTAGEN 529
FT /note="H->A: Severely impairs sphingomyelinase activity. No
FT effect on mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:19429680"
FT CONFLICT 77
FT /note="F -> S (in Ref. 3; AAI55731)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="I -> T (in Ref. 1; BAG12869)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="V -> L (in Ref. 3; AAI24789/AAI65400)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="I -> V (in Ref. 3; AAI24789/AAI55731/AAI65400)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="H -> R (in Ref. 1; BAG12869)"
FT /evidence="ECO:0000305"
FT CONFLICT 206..207
FT /note="EV -> DA (in Ref. 3; AAI55731)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="R -> K (in Ref. 3; AAI24789/AAI65400)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 545 AA; 61344 MW; DB7B8D36709E13A9 CRC64;
MSLRESPFPN GFLEGLHAVG WGLIFPCFWF LDRLIAVCIS TTLERMWRLE QECYLHPLKV
VFGSILFFIL FVISTPFALL GFILWAPLQA IRRPFSYHKQ EQSIPMENRN ARWEEMGKIS
FGFLTANVCL LPDGIARFNN LGHTQKRALI IGKSIVQGVT RPHIRIFVDS PSSCGTVTPS
SSLIPQPNAS SYGSVDASGE LPDAIEVNEI TPKPNCNQNS NHQKHPPRSL RTLLRDADIP
MEVSALFPPS VDIVCLQEVF DKRAARKLTQ ALGPLYGHVL YDVGVYACHP AGSCSSFKFF
NSGLFLASRF PIMEAEYRCF PNGRGEDALA AKGLLTVKVD IGLQKGEKRM VGFINCTHLH
APEGDGAIRF EQLNMLSKWT SEFQTLNRRD DELPLFDVLC GDFNFDNCSP DDRLEQSHSV
FDEYTDPCRA AAGKEKPWVI GTLLEQPTLY DENMRTPDNL QRTLESEDLR KDFISPPVAL
DGVPLVYPEA DQPWIGRRID YLLYREKSGH RTEVEELTYV TQLAGLTDHI PVGFRLSVSL
DSEQN
