SAMD8_HUMAN
ID SAMD8_HUMAN Reviewed; 415 AA.
AC Q96LT4; Q5JSC5; Q5JSC8; Q66K52;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Sphingomyelin synthase-related protein 1 {ECO:0000305};
DE Short=SMSr;
DE EC=2.7.8.- {ECO:0000269|PubMed:19506037};
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|HGNC:HGNC:26320};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:BAB71586.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Huitema K.;
RL Submitted (FEB-2003) to UniProtKB.
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum {ECO:0000312|EMBL:BAB71586.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 198-359 (ISOFORM 1).
RA Ebert L., Heil O., Hennig S., Neubert P., Partsch E., Peters M.,
RA Radelof U., Schneider D., Korn B.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [7] {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 [8]
RP SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF
RP ASP-348, IDENTIFICATION BY MASS SPECTROMETRY, AND CATALYTIC ACTIVITY.
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: 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 phosphoethanolamine (CPE) albeit with low product yield. Appears to
CC 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.
CC {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:0000305|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:0000305|PubMed:19506037};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19506037}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19506037}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96LT4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96LT4-2; Sequence=VSP_038403, VSP_038404;
CC -!- DOMAIN: The SAM domain is required to retain SMAD8 in the endoplasmic
CC reticulum.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH80593.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK057811; BAB71586.1; -; mRNA.
DR EMBL; AL392111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54566.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54567.1; -; Genomic_DNA.
DR EMBL; BC080593; AAH80593.1; ALT_INIT; mRNA.
DR EMBL; BX280496; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS53543.1; -. [Q96LT4-1]
DR CCDS; CCDS7347.1; -. [Q96LT4-2]
DR RefSeq; NP_001167627.1; NM_001174156.1. [Q96LT4-1]
DR RefSeq; NP_653261.1; NM_144660.2. [Q96LT4-2]
DR RefSeq; XP_005269598.1; XM_005269541.4. [Q96LT4-1]
DR RefSeq; XP_011537613.1; XM_011539311.1.
DR RefSeq; XP_011537614.1; XM_011539312.2. [Q96LT4-1]
DR RefSeq; XP_016871228.1; XM_017015739.1. [Q96LT4-1]
DR AlphaFoldDB; Q96LT4; -.
DR SMR; Q96LT4; -.
DR BioGRID; 126778; 8.
DR IntAct; Q96LT4; 4.
DR STRING; 9606.ENSP00000438042; -.
DR SwissLipids; SLP:000000704; -.
DR iPTMnet; Q96LT4; -.
DR PhosphoSitePlus; Q96LT4; -.
DR BioMuta; SAMD8; -.
DR DMDM; 44888529; -.
DR EPD; Q96LT4; -.
DR jPOST; Q96LT4; -.
DR MassIVE; Q96LT4; -.
DR MaxQB; Q96LT4; -.
DR PaxDb; Q96LT4; -.
DR PeptideAtlas; Q96LT4; -.
DR PRIDE; Q96LT4; -.
DR ProteomicsDB; 77245; -. [Q96LT4-1]
DR ProteomicsDB; 77246; -. [Q96LT4-2]
DR Antibodypedia; 29663; 117 antibodies from 23 providers.
DR DNASU; 142891; -.
DR Ensembl; ENST00000372687.4; ENSP00000361772.3; ENSG00000156671.15. [Q96LT4-2]
DR Ensembl; ENST00000542569.6; ENSP00000438042.1; ENSG00000156671.15. [Q96LT4-1]
DR Ensembl; ENST00000671800.1; ENSP00000500411.1; ENSG00000156671.15. [Q96LT4-1]
DR GeneID; 142891; -.
DR KEGG; hsa:142891; -.
DR MANE-Select; ENST00000542569.6; ENSP00000438042.1; NM_001174156.2; NP_001167627.1.
DR UCSC; uc001jwx.2; human. [Q96LT4-1]
DR CTD; 142891; -.
DR DisGeNET; 142891; -.
DR GeneCards; SAMD8; -.
DR HGNC; HGNC:26320; SAMD8.
DR HPA; ENSG00000156671; Low tissue specificity.
DR MIM; 611575; gene.
DR neXtProt; NX_Q96LT4; -.
DR OpenTargets; ENSG00000156671; -.
DR PharmGKB; PA134868247; -.
DR VEuPathDB; HostDB:ENSG00000156671; -.
DR eggNOG; KOG3058; Eukaryota.
DR GeneTree; ENSGT00940000155540; -.
DR HOGENOM; CLU_027104_1_1_1; -.
DR InParanoid; Q96LT4; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q96LT4; -.
DR TreeFam; TF314547; -.
DR PathwayCommons; Q96LT4; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q96LT4; -.
DR BioGRID-ORCS; 142891; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; SAMD8; human.
DR GenomeRNAi; 142891; -.
DR Pharos; Q96LT4; Tbio.
DR PRO; PR:Q96LT4; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96LT4; protein.
DR Bgee; ENSG00000156671; Expressed in medial globus pallidus and 187 other tissues.
DR ExpressionAtlas; Q96LT4; baseline and differential.
DR Genevisible; Q96LT4; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
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; IBA:GO_Central.
DR GO; GO:0002950; F:ceramide phosphoethanolamine synthase activity; TAS:Reactome.
DR GO; GO:0033188; F:sphingomyelin synthase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:1905373; P:ceramide phosphoethanolamine biosynthetic process; IEA:Ensembl.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
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 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Reference proteome; Sphingolipid metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..415
FT /note="Sphingomyelin synthase-related protein 1"
FT /id="PRO_0000221080"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 322..342
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 12..78
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ACT_SITE 301
FT /evidence="ECO:0000250"
FT ACT_SITE 344
FT /evidence="ECO:0000250"
FT ACT_SITE 348
FT VAR_SEQ 315..326
FT /note="YTPRSWNFLHTL -> CKYLFSASMRIR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038403"
FT VAR_SEQ 327..415
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038404"
FT MUTAGEN 348
FT /note="D->E: Abolishes CPE synthase activity."
FT /evidence="ECO:0000269|PubMed:19506037"
SQ SEQUENCE 415 AA; 48321 MW; AAED366F56C9CDC9 CRC64;
MAGPNQLCIR RWTTKHVAVW LKDEGFFEYV DILCNKHRLD GITLLTLTEY DLRSPPLEIK
VLGDIKRLML SVRKLQKIHI DVLEEMGYNS DSPMGSMTPF ISALQSTDWL CNGELSHDCD
GPITDLNSDQ YQYMNGKNKH SVRRLDPEYW KTILSCIYVF IVFGFTSFIM VIVHERVPDM
QTYPPLPDIF LDSVPRIPWA FAMTEVCGMI LCYIWLLVLL LHKHRSILLR RLCSLMGTVF
LLRCFTMFVT SLSVPGQHLQ CTGKIYGSVW EKLHRAFAIW SGFGMTLTGV HTCGDYMFSG
HTVVLTMLNF FVTEYTPRSW NFLHTLSWVL NLFGIFFILA AHEHYSIDVF IAFYITTRLF
LYYHTLANTR AYQQSRRARI WFPMFSFFEC NVNGTVPNEY CWPFSKPAIM KRLIG
