SMSR1_DROME
ID SMSR1_DROME Reviewed; 600 AA.
AC Q9VS60; Q961G5; Q9VS61;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-FEB-2004, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Ceramide phosphoethanolamine synthase;
DE Short=CPE synthase;
DE EC=2.7.8.- {ECO:0000269|PubMed:19506037};
DE AltName: Full=Sphingomyelin synthase-related 1;
DE Short=SMSr {ECO:0000303|PubMed:19506037};
GN Name=SMSr; ORFNames=CG32380;
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:0000312|EMBL:AAO24929.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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] {ECO:0000305}
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-600.
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569}, and
RC Head {ECO:0000269|PubMed:12537569};
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).
RN [4] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=14685263; DOI=10.1038/sj.emboj.7600034;
RA Huitema K., Van Den Dikkenberg J., Brouwers J.F.H.M., Holthuis J.C.;
RT "Identification of a family of animal sphingomyelin synthases.";
RL EMBO J. 23:33-44(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-514; SER-525 AND THR-548, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-401 AND ASP-405.
RX PubMed=19506037; DOI=10.1083/jcb.200903152;
RA Vacaru A.M., Tafesse F.G., Ternes P., Kondylis V., Hermansson M.,
RA Brouwers J.F., Somerharju P., Rabouille C., Holthuis J.C.;
RT "Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis
RT in the ER.";
RL J. Cell Biol. 185:1013-1027(2009).
CC -!- FUNCTION: A phosphatidylethanolamine (PE)/ceramide ethanolamine
CC phosphotransferase that catalyzes the synthesis of ceramide
CC phosphoethanolamines (CPE), a class of lipids that is a sphingomyelin
CC analog and a major membrane constituent in Drosophila. Transfers the
CC head group from PE (1,2-diacyl-sn-glycero-3-phosphoethanolamine) on to
CC different ceramides such as N-acylsphinganine (dihydroceramide) and N-
CC acyl-(4R)-hydroxysphinganine (phytoceramide) to form N-acyl-
CC sphinganine-1-phosphoethanolamine and N-acyl-(4R)-hydroxysphinganine-1-
CC phosphoethanolamine, respectively. Operates as a ceramide sensor to
CC control ceramide homeostasis in the endoplasmic reticulum, which is
CC critical for the integrity of the early secretory pathway.
CC {ECO:0000269|PubMed:19506037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + an N-
CC acylsphinganine = a 1,2-diacyl-sn-glycerol + an N-acylsphinganine-1-
CC phosphoethanolamine; Xref=Rhea:RHEA:42136, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:31488, ChEBI:CHEBI:64612, ChEBI:CHEBI:78655;
CC Evidence={ECO:0000269|PubMed:19506037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42137;
CC Evidence={ECO:0000269|PubMed:19506037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-
CC hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-
CC sphinganine-1-phosphoethanolamine; Xref=Rhea:RHEA:42128,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:64612, ChEBI:CHEBI:67042,
CC ChEBI:CHEBI:78654; Evidence={ECO:0000269|PubMed:19506037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42129;
CC Evidence={ECO:0000269|PubMed:19506037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + an N-acyl-
CC (4R)-4-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + an N-acyl-
CC (4R)-4-hydroxysphinganine-1-phosphoethanolamine;
CC Xref=Rhea:RHEA:42148, ChEBI:CHEBI:17815, ChEBI:CHEBI:31998,
CC ChEBI:CHEBI:64612, ChEBI:CHEBI:78657;
CC Evidence={ECO:0000269|PubMed:19506037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42149;
CC Evidence={ECO:0000269|PubMed:19506037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-
CC hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-
CC hexadecanoyl-(4R)-hydroxysphinganine-1-phosphoethanolamine;
CC Xref=Rhea:RHEA:42144, ChEBI:CHEBI:17815, ChEBI:CHEBI:64612,
CC ChEBI:CHEBI:65107, ChEBI:CHEBI:78656;
CC Evidence={ECO:0000269|PubMed:19506037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42145;
CC Evidence={ECO:0000269|PubMed:19506037};
CC -!- PATHWAY: Sphingolipid metabolism. {ECO:0000305|PubMed:19506037}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19506037}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19506037}.
CC -!- DOMAIN: The SAM domain is required to retain SMSR in the endoplasmic
CC reticulum. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO24929.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AE014296; AAF50567.2; -; Genomic_DNA.
DR EMBL; AY051605; AAK93029.1; -; mRNA.
DR EMBL; BT003174; AAO24929.1; ALT_SEQ; mRNA.
DR RefSeq; NP_648114.1; NM_139857.3.
DR AlphaFoldDB; Q9VS60; -.
DR SMR; Q9VS60; -.
DR BioGRID; 64262; 5.
DR STRING; 7227.FBpp0076580; -.
DR SwissLipids; SLP:000001115; -.
DR iPTMnet; Q9VS60; -.
DR PaxDb; Q9VS60; -.
DR PRIDE; Q9VS60; -.
DR DNASU; 38823; -.
DR EnsemblMetazoa; FBtr0076870; FBpp0076580; FBgn0052380.
DR GeneID; 38823; -.
DR KEGG; dme:Dmel_CG32380; -.
DR UCSC; CG32380-RA; d. melanogaster.
DR CTD; 38823; -.
DR FlyBase; FBgn0052380; SMSr.
DR VEuPathDB; VectorBase:FBgn0052380; -.
DR eggNOG; KOG3058; Eukaryota.
DR GeneTree; ENSGT00940000155540; -.
DR HOGENOM; CLU_027104_1_1_1; -.
DR InParanoid; Q9VS60; -.
DR OMA; FNMCEIT; -.
DR OrthoDB; 599210at2759; -.
DR PhylomeDB; Q9VS60; -.
DR BioCyc; FLY:FBGN0052380-MON; -.
DR Reactome; R-DME-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 38823; 0 hits in 3 CRISPR screens.
DR ChiTaRS; SMSr; fly.
DR GenomeRNAi; 38823; -.
DR PRO; PR:Q9VS60; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0052380; Expressed in cleaving embryo and 22 other tissues.
DR Genevisible; Q9VS60; DM.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0047493; F:ceramide cholinephosphotransferase activity; IDA:UniProtKB.
DR GO; GO:0033188; F:sphingomyelin synthase activity; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; NAS:UniProtKB.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR045221; Sphingomyelin_synth-like.
DR InterPro; IPR025749; Sphingomyelin_synth-like_dom.
DR PANTHER; PTHR21290; PTHR21290; 1.
DR Pfam; PF14360; PAP2_C; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid metabolism; Membrane; Phosphoprotein;
KW Reference proteome; Sphingolipid metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..600
FT /note="Ceramide phosphoethanolamine synthase"
FT /id="PRO_0000221079"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..600
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 58..129
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..566
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 358
FT /evidence="ECO:0000305"
FT ACT_SITE 401
FT ACT_SITE 405
FT MOD_RES 514
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 548
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 401
FT /note="H->A: Abolishes CPE synthase activity."
FT /evidence="ECO:0000269|PubMed:19506037"
FT MUTAGEN 405
FT /note="D->E: Abolishes CPE synthase activity."
FT /evidence="ECO:0000269|PubMed:19506037"
SQ SEQUENCE 600 AA; 67063 MW; 4A0BF06BBA4D779E CRC64;
MCDGEIGDPV TQPRSEGGGL VTMDQETRTH YLDAATDKHL TNGSPDPEPV DPLLVAQWSI
ENVTSWATCM EHFSRTLLDC LRQEAIDGEV LLSLTEEDVR DMRYKLGYKL TFGELKKFWI
AVLKLQLLVK NSSAESVILG IECHGNGNSV YMPLASTGCG PPSSSTCPCP QAECPSYVSD
CDTYLRMGGR YVPPEYFKTA MSLGYSFVVT WITSLTMVIV HERVPDMKRY PPLPDIFLDN
VPHIPWAFNM CEITGSLLFT IWVVVLTFHK YRLVLLRRFF ALAGTVFLLR CVTMLITSLS
VPGTHLQCSQ KDFAIDDPNV DMVGALIIRM SRAYRIWSGL GMSIQGVRTC GDYMFSGHTV
ALTLLNFFIT EYTPRNLYFL HTLTWLLNMF GIFFILAAHE HYSIDVFVAF YITSRLFLYY
HTLANNRALM QSDSKRTRVW FPMFSYFESS VDGMVPNEYD TLGSLIDGII EQIFKAKDQL
AISVKRCWLD APLSGNSSAH MFGGESEQCL RNGTASAAFF SPHQSLIGGL GGQRSQTHLN
SAQSGSSTPT PATSAPTKSL PTQKKTFRDA SVDPFSRTTF AAVQQAENVK DSPMKEKKHL
