ID A0A0B4LGL2_DROME Unreviewed; 726 AA.
AC A0A0B4LGL2;
DT 01-APR-2015, integrated into UniProtKB/TrEMBL.
DT 01-APR-2015, sequence version 1.
DT 24-JAN-2024, entry version 59.
DE RecName: Full=Sphingomyelin phosphodiesterase {ECO:0000256|PIRNR:PIRNR000948};
DE EC=3.1.4.12 {ECO:0000256|PIRNR:PIRNR000948};
GN Name=aSMase {ECO:0000313|EMBL:AHN56628.1};
GN Synonyms=Dmel\CG3376 {ECO:0000313|EMBL:AHN56628.1};
GN ORFNames=CG3376 {ECO:0000313|EMBL:AHN56628.1,
GN ECO:0000313|FlyBase:FBgn0034997}, Dmel_CG3376
GN {ECO:0000313|EMBL:AHN56628.1};
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 {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803};
RN [1] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
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., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Gabor G.L., 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., 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., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J., 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., Scheeler F., Shen H.,
RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., Spier E.,
RA Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C.,
RA Turner R., Venter E., Wang A.H., Wang X., Wang Z.Y., Wassarman D.A.,
RA Weinstock G.M., Weissenbach J., Williams S.M., WoodageT, Worley K.C.,
RA Wu D., Yang S., Yao Q.A., Ye J., Yeh R.F., Zaveri J.S., Zhan M., Zhang G.,
RA Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.,
RA Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537568;
RA Celniker S.E., Wheeler D.A., Kronmiller B., Carlson J.W., Halpern A.,
RA Patel S., Adams M., Champe M., Dugan S.P., Frise E., Hodgson A.,
RA George R.A., Hoskins R.A., Laverty T., Muzny D.M., Nelson C.R.,
RA Pacleb J.M., Park S., Pfeiffer B.D., Richards S., Sodergren E.J.,
RA Svirskas R., Tabor P.E., Wan K., Stapleton M., Sutton G.G., Venter C.,
RA Weinstock G., Scherer S.E., Myers E.W., Gibbs R.A., Rubin G.M.;
RT "Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster
RT euchromatic genome sequence.";
RL Genome Biol. 3:RESEARCH0079-RESEARCH0079(2002).
RN [3] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
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 [4] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537573;
RA Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R.,
RA Patel S., Frise E., Wheeler D.A., Lewis S.E., Rubin G.M., Ashburner M.,
RA Celniker S.E.;
RT "The transposable elements of the Drosophila melanogaster euchromatin: a
RT genomics perspective.";
RL Genome Biol. 3:RESEARCH0084.1-RESEARCH0084.20(2002).
RN [5] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537574;
RA Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A.,
RA Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G.,
RA Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M.,
RA Karpen G.H.;
RT "Heterochromatic sequences in a Drosophila whole-genome shotgun assembly.";
RL Genome Biol. 3:RESEARCH0085-RESEARCH0085(2002).
RN [6] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=16110336; DOI=10.1371/journal.pcbi.0010022;
RA Quesneville H., Bergman C.M., Andrieu O., Autard D., Nouaud D.,
RA Ashburner M., Anxolabehere D.;
RT "Combined evidence annotation of transposable elements in genome
RT sequences.";
RL PLoS Comput. Biol. 1:166-175(2005).
RN [7] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569856; DOI=10.1126/science.1139815;
RA Smith C.D., Shu S., Mungall C.J., Karpen G.H.;
RT "The Release 5.1 annotation of Drosophila melanogaster heterochromatin.";
RL Science 316:1586-1591(2007).
RN [8] {ECO:0000313|EMBL:AHN56628.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569867; DOI=10.1126/science.1139816;
RA Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M.,
RA Frise E., Wan K.H., Park S., Mendez-Lago M., Rossi F., Villasante A.,
RA Dimitri P., Karpen G.H., Celniker S.E.;
RT "Sequence finishing and mapping of Drosophila melanogaster
RT heterochromatin.";
RL Science 316:1625-1628(2007).
CC -!- FUNCTION: Converts sphingomyelin to ceramide.
CC {ECO:0000256|PIRNR:PIRNR000948}.
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:0000256|ARBA:ARBA00023999};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000256|ARBA:ARBA00023999};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|PIRSR:PIRSR000948-1};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000256|PIRSR:PIRSR000948-
CC 1};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000256|ARBA:ARBA00004613}.
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family.
CC {ECO:0000256|ARBA:ARBA00008234, ECO:0000256|PIRNR:PIRNR000948}.
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DR EMBL; AE013599; AHN56628.1; -; Genomic_DNA.
DR RefSeq; NP_001286833.1; NM_001299904.1.
DR AlphaFoldDB; A0A0B4LGL2; -.
DR SMR; A0A0B4LGL2; -.
DR DNASU; 37884; -.
DR EnsemblMetazoa; FBtr0343442; FBpp0310086; FBgn0034997.
DR GeneID; 37884; -.
DR AGR; FB:FBgn0034997; -.
DR FlyBase; FBgn0034997; CG3376.
DR VEuPathDB; VectorBase:FBgn0034997; -.
DR GeneTree; ENSGT00950000183182; -.
DR OrthoDB; 205363at2759; -.
DR BioGRID-ORCS; 37884; 0 hits in 3 CRISPR screens.
DR ChiTaRS; CG3376; fly.
DR GenomeRNAi; 37884; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034997; Expressed in embryonic/larval hemocyte (Drosophila) and 45 other cell types or tissues.
DR ExpressionAtlas; A0A0B4LGL2; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046513; P:ceramide biosynthetic process; IEA:UniProt.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd00842; MPP_ASMase; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR Gene3D; 1.10.225.10; Saposin-like; 1.
DR InterPro; IPR045473; ASM_C.
DR InterPro; IPR041805; ASMase/PPN1_MPP.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR008139; SaposinB_dom.
DR InterPro; IPR011160; Sphingomy_PDE.
DR PANTHER; PTHR10340; SPHINGOMYELIN PHOSPHODIESTERASE; 1.
DR PANTHER; PTHR10340:SF34; SPHINGOMYELIN PHOSPHODIESTERASE; 1.
DR Pfam; PF19272; ASMase_C; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF000948; Sphingomy_PDE; 1.
DR SMART; SM00741; SapB; 1.
DR SUPFAM; SSF56300; Metallo-dependent phosphatases; 1.
DR SUPFAM; SSF47862; Saposin; 1.
DR PROSITE; PS50015; SAP_B; 1.
PE 1: Evidence at protein level;
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR000948-2};
KW Glycosidase {ECO:0000256|ARBA:ARBA00023295, ECO:0000256|PIRNR:PIRNR000948};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|PIRNR:PIRNR000948};
KW Membrane {ECO:0000256|SAM:Phobius};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR000948-1};
KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A0B4LGL2};
KW Reference proteome {ECO:0000313|Proteomes:UP000000803};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRSR:PIRSR000948-1}.
FT TRANSMEM 23..46
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 154..238
FT /note="Saposin B-type"
FT /evidence="ECO:0000259|PROSITE:PS50015"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 498
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 532
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT BINDING 534
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-1"
FT DISULFID 158..234
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 161..226
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 189..200
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 292..297
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 298..321
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 458..506
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 658..662
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
FT DISULFID 668..682
FT /evidence="ECO:0000256|PIRSR:PIRSR000948-2"
SQ SEQUENCE 726 AA; 83528 MW; 947DC6B8C0A03933 CRC64;
MTQQQPPWPS PISSSSSNPR GKCWLILVLM AVLPLVADVG ALPFLFTHIK PQINWTQPEM
ESWVIEEQPR SIEPHLEPVL HPNRTHRALS SDSTDAEFLQ RLVSIRHNQT ASSRMLWYDV
AGGDGLVYPP FVDKALKLLN LKQVAFEIEN SVMSKVTCTA CRAGAGMLQH QIQSGKTDAE
LIRMITDYCT NLNIQSARVC QGVAQLFGSE LIYVLKRVNL SPDELCSFVI GDGCADVYNP
YHEWEVIFPP VPKPPRLPDL PIPMEAAPFF KVLHISDTHY DPHYAEGSNA DCNEPLCCRL
SSGRPATPNA AAGKWGDYRK CDTPKRTVDH MLSHIAETHK DIDYILWTGD LPPHDVWNQT
KEENLAIIKD TVKQMVEMFP GVPIFPALGN HESAPVNSFP PPYVNQVDIS ISWLYDELDI
QWRRWLPQSV THTVRRGAFY SVLVRPGFRI ISLNMNYCNN KNWWLLLNST DPATELQWFI
YELQSAEFSN EKVHVIGHIP PGHSDCLKVW SRNFYKIISR YESTVTAQFY GHTHYDEFEM
FYDPHDLNHP NGIAYIGPSV SPYYDLNPGY RIYYVDGDHD ATTRLVIDHE SWIMNLKEAN
LYGYPIWYKL YTARAAYNMK ALRPSDWNNL LNELTNNQEL FELYYKYYWK NSPARPTCDA
ECKKRLICDC RSGRSHDRKH FCAEVESKID EESSKSWKSW FYKGLTNSYS LLSSITYLPK
YLLGYR
//