NSMA_DROME
ID NSMA_DROME Reviewed; 442 AA.
AC Q9VZS6; Q961B4;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Putative neutral sphingomyelinase;
DE EC=3.1.4.12;
GN Name=nSMase {ECO:0000312|FlyBase:FBgn0035421};
GN ORFNames=CG12034 {ECO:0000312|FlyBase:FBgn0035421};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
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 -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the neutral sphingomyelinase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE014296; AAF47741.2; -; Genomic_DNA.
DR EMBL; AY051714; AAK93138.1; -; mRNA.
DR RefSeq; NP_647790.1; NM_139533.4.
DR AlphaFoldDB; Q9VZS6; -.
DR SMR; Q9VZS6; -.
DR BioGRID; 63892; 4.
DR DIP; DIP-18690N; -.
DR IntAct; Q9VZS6; 2.
DR STRING; 7227.FBpp0072907; -.
DR PaxDb; Q9VZS6; -.
DR PRIDE; Q9VZS6; -.
DR DNASU; 38396; -.
DR EnsemblMetazoa; FBtr0073043; FBpp0072907; FBgn0035421.
DR GeneID; 38396; -.
DR KEGG; dme:Dmel_CG12034; -.
DR UCSC; CG12034-RA; d. melanogaster.
DR CTD; 38396; -.
DR FlyBase; FBgn0035421; nSMase.
DR VEuPathDB; VectorBase:FBgn0035421; -.
DR eggNOG; KOG3873; Eukaryota.
DR GeneTree; ENSGT00390000009166; -.
DR HOGENOM; CLU_034001_1_0_1; -.
DR InParanoid; Q9VZS6; -.
DR OMA; IEVNCQV; -.
DR OrthoDB; 589366at2759; -.
DR PhylomeDB; Q9VZS6; -.
DR Reactome; R-DME-1660662; Glycosphingolipid metabolism.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 38396; 0 hits in 3 CRISPR screens.
DR ChiTaRS; CG12034; fly.
DR GenomeRNAi; 38396; -.
DR PRO; PR:Q9VZS6; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035421; Expressed in eye disc (Drosophila) and 34 other tissues.
DR Genevisible; Q9VZS6; DM.
DR GO; GO:0005901; C:caveola; IBA:GO_Central.
DR GO; GO:0071944; C:cell periphery; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0030149; P:sphingolipid catabolic process; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Hydrolase; Lipid metabolism; Magnesium; Membrane; Metal-binding;
KW Reference proteome; Sphingolipid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..442
FT /note="Putative neutral sphingomyelinase"
FT /id="PRO_0000075690"
FT TRANSMEM 362..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..413
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 309..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 264
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 46
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 177
FT /note="Important for substrate recognition"
FT /evidence="ECO:0000250"
SQ SEQUENCE 442 AA; 49643 MW; 7167808A4D9ABBE0 CRC64;
MLLLELNILT LNIWGIPYVS SDRRPRIDAI CKELASGKYD IVSLQEVWAQ EDSELLQKGT
EAVLPHSHYF HSGVMGAGLL VLSKYPILGT LFHAWSVNGY FHRIQHADWF GGKGVGLCRI
LVGGQMVHLY NAHLHAEYDN ANDEYKTHRV IQAFDTAQFI EATRGNSALQ ILAGDLNAQP
QDISYKVLLY TSKMLDSCDS DSFRTNECEH NSYTSKQARE RNPLGIRIDH IFVRGGDHVN
AEIAEYKLPF PERVPGEKFS FSDHEAVMAK LKLFKLEPRS EEPVATIEVN CLVEDGETCS
VREVGAGDAL TGEDDQSSQH QPEIQCNGSS TSIQSMPAAR TAALLEALAL CDASLLQLNT
DRILYYSAAT FLFVLLVLLV EFTAPVGMRT IFLLLKFIVF GVILFCVFMA SIWNYMERNG
VLQGKKSMEV MLHHAQKYEY FY
