SAMD8_MOUSE
ID SAMD8_MOUSE Reviewed; 478 AA.
AC Q9DA37;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Sphingomyelin synthase-related protein 1 {ECO:0000305};
DE Short=SMSr;
DE EC=2.7.8.-;
DE AltName: Full=Ceramide phosphoethanolamine synthase;
DE Short=CPE synthase;
DE AltName: Full=Sterile alpha motif domain-containing protein 8;
DE Short=SAM domain-containing protein 8;
GN Name=Samd8 {ECO:0000312|MGI:MGI:1914880};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:BAB24461.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|EMBL:AAQ01515.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RA Brathwaite M.E., Waeltz P., Qian Y., Dudekula D., Schlessinger D.,
RA Nagaraja R.;
RT "Genomic sequence analysis in the mouse T-complex region.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {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).
CC -!- FUNCTION: sphingomyelin synthases synthesize sphingolipids through
CC transfer of a phosphatidyl head group on to the primary hydroxyl of
CC ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has
CC no sphingomyelin synthase activity but can convert
CC phosphatidylethanolamine (PE) and ceramide to ceramide
CC phosphatidylethanolamine (CPE) albeit with low product yield. Appears
CC to operate as a ceramide sensor to control ceramide homeostasis in the
CC endoplasmic reticulum rather than a converter of ceramides. Seems to be
CC critical for the integrity of the early secretory pathway (By
CC similarity). {ECO:0000250}.
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:0000250|UniProtKB:Q96LT4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42129;
CC Evidence={ECO:0000250|UniProtKB:Q96LT4};
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:0000250|UniProtKB:Q96LT4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42145;
CC Evidence={ECO:0000250|UniProtKB:Q96LT4};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- DOMAIN: The SAM domain is required to retain SMAD8 in the endoplasmic
CC reticulum. membrane protein (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-64 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AK006211; BAB24461.1; -; mRNA.
DR EMBL; AK075749; BAC35929.1; -; mRNA.
DR EMBL; AY294423; AAQ01515.1; -; Genomic_DNA.
DR CCDS; CCDS26866.1; -.
DR RefSeq; NP_080559.1; NM_026283.2.
DR AlphaFoldDB; Q9DA37; -.
DR SMR; Q9DA37; -.
DR BioGRID; 212321; 1.
DR STRING; 10090.ENSMUSP00000022292; -.
DR iPTMnet; Q9DA37; -.
DR PhosphoSitePlus; Q9DA37; -.
DR MaxQB; Q9DA37; -.
DR PaxDb; Q9DA37; -.
DR PRIDE; Q9DA37; -.
DR ProteomicsDB; 255458; -.
DR Antibodypedia; 29663; 117 antibodies from 23 providers.
DR Ensembl; ENSMUST00000022292; ENSMUSP00000022292; ENSMUSG00000021770.
DR GeneID; 67630; -.
DR KEGG; mmu:67630; -.
DR UCSC; uc007slp.1; mouse.
DR CTD; 142891; -.
DR MGI; MGI:1914880; Samd8.
DR VEuPathDB; HostDB:ENSMUSG00000021770; -.
DR eggNOG; KOG3058; Eukaryota.
DR GeneTree; ENSGT00940000155540; -.
DR InParanoid; Q9DA37; -.
DR OrthoDB; 599210at2759; -.
DR PhylomeDB; Q9DA37; -.
DR TreeFam; TF314547; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 67630; 3 hits in 60 CRISPR screens.
DR ChiTaRS; Samd8; mouse.
DR PRO; PR:Q9DA37; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9DA37; protein.
DR Bgee; ENSMUSG00000021770; Expressed in mucous cell of stomach and 238 other tissues.
DR ExpressionAtlas; Q9DA37; baseline and differential.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS: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; IBA:GO_Central.
DR GO; GO:0002950; F:ceramide phosphoethanolamine synthase activity; IDA:MGI.
DR GO; GO:0033188; F:sphingomyelin synthase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:MGI.
DR GO; GO:1905373; P:ceramide phosphoethanolamine biosynthetic process; IDA:MGI.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; ISS: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 Pfam; PF00536; SAM_1; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid metabolism; Membrane; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..478
FT /note="Sphingomyelin synthase-related protein 1"
FT /id="PRO_0000221081"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..478
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 75..141
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 478 AA; 54713 MW; 5FE31E342E146A29 CRC64;
MPAGSRAGSR LRSGSLPRPS RLTLKALRPA YAPRTPDSNG DLDTGSELGP GSPAPTAEEV
EKEMAGPSQL CIRRWTTKHV AVWLKDEGFF EYVDILCNKH RLDGITLLTL TEYDLRSPPL
EIKVLGDIKR LMLSVRKLQK IHTDVLEEMG YNSDSPMSPM TPFLSALQSA DWLCNGEPTH
SCDGPIPDLS SDQYQYMNGK NKHSARRLDP EYWKTILSCV YVFIVFGFTS FIMVIVHERV
PDMQTYPPLP DIFLDSVPRI PWAFSMTEVC GVILCYIWIL VLLLHKHRSI LLRRLCSLMG
TVFLLRCFTM FVTSLSVPGQ HLQCTGKIYG SVWEKLRRAF AIWSGFGMTL TGVHTCGDYM
FSGHTVVLTM LNFFVTEYTP RSWNFLHTLS WVLNLFGIFF ILAAHEHYSI DVFIAFYITT
RLFLYYHTLA NTRAYHQSRR ARIWFPMFSF FECNVNGTVP NEYCWPFSKP AIMKRLIG
