NCASE_DROME
ID NCASE_DROME Reviewed; 704 AA.
AC Q9VA70; Q7YTD8; Q86NP1;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Neutral ceramidase;
DE Short=N-CDase;
DE Short=NCDase;
DE EC=3.5.1.23;
DE AltName: Full=Neutral N-acylsphingosine amidohydrolase;
DE AltName: Full=Neutral acylsphingosine deacylase;
DE AltName: Full=Slug-a-bed protein;
DE Flags: Precursor;
GN Name=CDase; Synonyms=slab; ORFNames=CG1471;
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 [MRNA], ENZYME ACTIVITY, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RC TISSUE=Imaginal disk;
RX PubMed=12153720; DOI=10.1093/oxfordjournals.jbchem.a003215;
RA Yoshimura Y., Okino N., Tani M., Ito M.;
RT "Molecular cloning and characterization of a secretory neutral ceramidase
RT of Drosophila melanogaster.";
RL J. Biochem. 132:229-236(2002).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP OVEREXPRESSION.
RX PubMed=12637747; DOI=10.1126/science.1080549;
RA Acharya U., Patel S., Koundakjian E., Nagashima K., Han X., Acharya J.K.;
RT "Modulating sphingolipid biosynthetic pathway rescues photoreceptor
RT degeneration.";
RL Science 299:1740-1743(2003).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF VAL-264.
RX PubMed=15356190; DOI=10.1523/jneurosci.1146-04.2004;
RA Rohrbough J., Rushton E., Palanker L., Woodruff E. III, Matthies H.J.G.,
RA Acharya U., Acharya J.K., Broadie K.;
RT "Ceramidase regulates synaptic vesicle exocytosis and trafficking.";
RL J. Neurosci. 24:7789-7803(2004).
RN [7]
RP OVEREXPRESSION.
RX PubMed=14769922; DOI=10.1073/pnas.0308693100;
RA Acharya U., Mowen M.B., Nagashima K., Acharya J.K.;
RT "Ceramidase expression facilitates membrane turnover and endocytosis of
RT rhodopsin in photoreceptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:1922-1926(2004).
CC -!- FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and
CC free fatty acid at an optimal pH of 6.5-7.5. Acts as a key regulator of
CC sphingolipid signaling metabolites by generating sphingosine at the
CC cell surface. Regulates synaptic vesicle exocytosis and trafficking by
CC controlling presynaptic terminal sphingolipid composition.
CC {ECO:0000269|PubMed:15356190}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine;
CC Xref=Rhea:RHEA:20856, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57756; EC=3.5.1.23;
CC Evidence={ECO:0000269|PubMed:12153720};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12153720}.
CC -!- TISSUE SPECIFICITY: Widely expressed in different tissues but enriched
CC in neurons at all stages of development. {ECO:0000269|PubMed:15356190}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12153720}.
CC -!- MISCELLANEOUS: Overexpression rescues retinal degeneration in arrestin
CC and phospholipase C mutants, probably by facilitating membrane turnover
CC and endocytosis of rhodopsin in photoreceptors.
CC -!- SIMILARITY: Belongs to the neutral ceramidase family. {ECO:0000305}.
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DR EMBL; AB112076; BAC77635.1; -; mRNA.
DR EMBL; AE014297; AAN14231.1; -; Genomic_DNA.
DR EMBL; BT004471; AAO42635.1; -; mRNA.
DR RefSeq; NP_001263109.1; NM_001276180.1.
DR RefSeq; NP_651797.1; NM_143540.2.
DR RefSeq; NP_733367.1; NM_170488.2.
DR RefSeq; NP_733368.1; NM_170489.2.
DR RefSeq; NP_733369.1; NM_170490.2.
DR RefSeq; NP_733370.1; NM_170491.2.
DR AlphaFoldDB; Q9VA70; -.
DR SMR; Q9VA70; -.
DR BioGRID; 68472; 8.
DR IntAct; Q9VA70; 2.
DR STRING; 7227.FBpp0303775; -.
DR GlyGen; Q9VA70; 4 sites.
DR PaxDb; Q9VA70; -.
DR EnsemblMetazoa; FBtr0085645; FBpp0085007; FBgn0039774.
DR EnsemblMetazoa; FBtr0085646; FBpp0085008; FBgn0039774.
DR EnsemblMetazoa; FBtr0085647; FBpp0085009; FBgn0039774.
DR EnsemblMetazoa; FBtr0085648; FBpp0085010; FBgn0039774.
DR EnsemblMetazoa; FBtr0085649; FBpp0085011; FBgn0039774.
DR EnsemblMetazoa; FBtr0331357; FBpp0303775; FBgn0039774.
DR GeneID; 43618; -.
DR KEGG; dme:Dmel_CG1471; -.
DR UCSC; CG1471-RA; d. melanogaster.
DR CTD; 43618; -.
DR FlyBase; FBgn0039774; CDase.
DR VEuPathDB; VectorBase:FBgn0039774; -.
DR eggNOG; KOG2232; Eukaryota.
DR GeneTree; ENSGT00390000015792; -.
DR HOGENOM; CLU_011300_2_0_1; -.
DR InParanoid; Q9VA70; -.
DR OMA; VWHRTNT; -.
DR OrthoDB; 967085at2759; -.
DR PhylomeDB; Q9VA70; -.
DR BRENDA; 3.5.1.23; 1994.
DR Reactome; R-DME-1660662; Glycosphingolipid metabolism.
DR BioGRID-ORCS; 43618; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 43618; -.
DR PRO; PR:Q9VA70; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039774; Expressed in embryonic/larval hemocyte (Drosophila) and 24 other tissues.
DR ExpressionAtlas; Q9VA70; baseline and differential.
DR Genevisible; Q9VA70; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0046514; P:ceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:FlyBase.
DR GO; GO:0035187; P:hatching behavior; IMP:FlyBase.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:FlyBase.
DR GO; GO:0006665; P:sphingolipid metabolic process; IDA:UniProtKB.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IBA:GO_Central.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IMP:FlyBase.
DR GO; GO:0031629; P:synaptic vesicle fusion to presynaptic active zone membrane; IMP:UniProtKB.
DR Gene3D; 2.60.40.2300; -; 1.
DR InterPro; IPR006823; Ceramidase_alk.
DR InterPro; IPR038445; NCDase_C_sf.
DR InterPro; IPR031331; NEUT/ALK_ceramidase_C.
DR InterPro; IPR031329; NEUT/ALK_ceramidase_N.
DR PANTHER; PTHR12670; PTHR12670; 1.
DR Pfam; PF04734; Ceramidase_alk; 1.
DR Pfam; PF17048; Ceramidse_alk_C; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Hydrolase; Lipid metabolism; Reference proteome; Secreted;
KW Signal; Sphingolipid metabolism.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..704
FT /note="Neutral ceramidase"
FT /id="PRO_0000247106"
FT ACT_SITE 276
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 598
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 264
FT /note="V->M: In slab1; induces embryonic lethality."
FT /evidence="ECO:0000269|PubMed:15356190"
FT CONFLICT 21
FT /note="V -> A (in Ref. 1; BAC77635 and 4; AAO42635)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="R -> L (in Ref. 1; BAC77635)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="I -> V (in Ref. 1; BAC77635)"
FT /evidence="ECO:0000305"
FT CONFLICT 646
FT /note="V -> I (in Ref. 1; BAC77635 and 4; AAO42635)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 78232 MW; E65F61DF1AC2E455 CRC64;
MANSKMAFLA FLAVSFLCGL VSATYKVGVG RADITGPPVE INFMGYANIK QVGRGIHTRV
FARAFVVEDE KGNRVAFVSA DAGMMGYGLK REVIKRLQAR YGNIYHNDNV AISGTHTHGA
PGGFLMHLLY DISILGFVPQ TFEVMAQGLY LCIKRATDNL VDGRILLSKT TVLNVNINRS
PSSYLRNPAE ERAQYEHDTD KTLTQLRFVD LENNLLGAFN WYAVHATSMN NTNRLVTSDN
VGYAALLLEK EYNPNKMPGK GKFVGAFCSS NLGDVSPNIM GPKCSISGNE CDLLTSRCPT
GEGDCFASGP GKDMFESTQI LGQRLADAAL GLLNEQSQES TAREVTGDVR FIHQFVDMPN
YNGSTYNPLS RKVDKIRGCQ PAMGYSFAAG TTDGPGAFSF EQGTTTDNPM WNFVRDFIAA
PTQEDIKCHE PKPILLATGR ATFPYEWQPK IVSDQLLKIG DVIIAAVPCE FTTMAGRRLR
NQIRAAASAV GGIDTEVIIA GLTNIYTSYT VTPEEYQAQR YEAASTIFGP HTHSIYMDVF
ERLTKAMMRN ETVDAGPSPP YMNDVMLSLN TGVLFDGHPI NTDFGYVKSQ PNKEYGINET
VKVTYISGNP RNNLFTEKTY FTIERKINED RWKVAYTDAS WETKMVWHRT NTILGFSEMD
IYWDISPQTL PGEYRIRHSG EYKYILGGKY PYEGLTHSFT VKED
