Q96LT4 (SAMD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingomyelin synthase-related protein 1
Short name=SMSr
EC=2.7.8.-

Alternative name(s):
Ceramide phosphoethanolamine synthase
Short name=CPE synthase
Sterile alpha motif domain-containing protein 8
Short name=SAM domain-containing protein 8

Gene names

Name:

SAMD8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	415 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphoethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway. Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.8.
Domain	The SAM domain is required to retain SMAD8 in the endoplasmic reticulum.
Sequence similarities	Belongs to the sphingomyelin synthase family. Contains 1 SAM (sterile alpha motif) domain.
Sequence caution	The sequence AAH80593.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of ceramide biosynthetic process Inferred from direct assay Ref.8. Source: UniProtKB sphingomyelin biosynthetic process Non-traceable author statement Ref.7. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	transferase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96LT4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96LT4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     315-326: YTPRSWNFLHTL → CKYLFSASMRIR
     327-415: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 415	415	Sphingomyelin synthase-related protein 1		PRO_0000221080
Regions
	Transmembrane	153 – 173	21	Helical; Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Transmembrane	232 – 252	21	Helical; Potential
	Transmembrane	277 – 297	21	Helical; Potential
	Transmembrane	322 – 342	21	Helical; Potential
	Transmembrane	347 – 367	21	Helical; Potential
	Topological domain	368 – 415	48	Cytoplasmic Potential
	Domain	12 – 78	67	SAM
Sites
	Active site	301	1	By similarity
	Active site	344	1	By similarity
	Active site	348	1
Natural variations
	Alternative sequence	315 – 326	12	YTPRS…FLHTL → CKYLFSASMRIR in isoform 2.		VSP_038403
	Alternative sequence	327 – 415	89	Missing in isoform 2.		VSP_038404
Experimental info
	Mutagenesis	348	1	D → E: Abolishes CPE synthase activity. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: AAED366F56C9CDC9	FASTA	415	48,321
	10 20 30 40 50 60 MAGPNQLCIR RWTTKHVAVW LKDEGFFEYV DILCNKHRLD GITLLTLTEY DLRSPPLEIK 70 80 90 100 110 120 VLGDIKRLML SVRKLQKIHI DVLEEMGYNS DSPMGSMTPF ISALQSTDWL CNGELSHDCD 130 140 150 160 170 180 GPITDLNSDQ YQYMNGKNKH SVRRLDPEYW KTILSCIYVF IVFGFTSFIM VIVHERVPDM 190 200 210 220 230 240 QTYPPLPDIF LDSVPRIPWA FAMTEVCGMI LCYIWLLVLL LHKHRSILLR RLCSLMGTVF 250 260 270 280 290 300 LLRCFTMFVT SLSVPGQHLQ CTGKIYGSVW EKLHRAFAIW SGFGMTLTGV HTCGDYMFSG 310 320 330 340 350 360 HTVVLTMLNF FVTEYTPRSW NFLHTLSWVL NLFGIFFILA AHEHYSIDVF IAFYITTRLF 370 380 390 400 410 LYYHTLANTR AYQQSRRARI WFPMFSFFEC NVNGTVPNEY CWPFSKPAIM KRLIG
	Isoform 2 [UniParc]. Checksum: 3FA96772EDFB7486	FASTA	326	37,609
	10 20 30 40 50 60 MAGPNQLCIR RWTTKHVAVW LKDEGFFEYV DILCNKHRLD GITLLTLTEY DLRSPPLEIK 70 80 90 100 110 120 VLGDIKRLML SVRKLQKIHI DVLEEMGYNS DSPMGSMTPF ISALQSTDWL CNGELSHDCD 130 140 150 160 170 180 GPITDLNSDQ YQYMNGKNKH SVRRLDPEYW KTILSCIYVF IVFGFTSFIM VIVHERVPDM 190 200 210 220 230 240 QTYPPLPDIF LDSVPRIPWA FAMTEVCGMI LCYIWLLVLL LHKHRSILLR RLCSLMGTVF 250 260 270 280 290 300 LLRCFTMFVT SLSVPGQHLQ CTGKIYGSVW EKLHRAFAIW SGFGMTLTGV HTCGDYMFSG 310 320 HTVVLTMLNF FVTECKYLFS ASMRIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Huitema K. Submitted (FEB-2003) to UniProtKB Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cerebellum.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	Ebert L., Heil O., Hennig S., Neubert P., Partsch E., Peters M., Radelof U., Schneider D., Korn B. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 198-359 (ISOFORM 1).
[7]	"Identification of a family of animal sphingomyelin synthases." Huitema K., Van Den Dikkenberg J., Brouwers J.F.H.M., Holthuis J.C. EMBO J. 23:33-44(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[8]	"Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER." Vacaru A.M., Tafesse F.G., Ternes P., Kondylis V., Hermansson M., Brouwers J.F., Somerharju P., Rabouille C., Holthuis J.C. J. Cell Biol. 185:1013-1027(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF ASP-348.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK057811 mRNA. Translation: BAB71586.1. AL392111 Genomic DNA. Translation: CAI40906.1. AL392111 Genomic DNA. Translation: CAI40909.1. CH471083 Genomic DNA. Translation: EAW54566.1. CH471083 Genomic DNA. Translation: EAW54567.1. BC080593 mRNA. Translation: AAH80593.1. Different initiation. BX280496 mRNA. No translation available.
IPI	IPI00165639. IPI00550225.
RefSeq	NP_001167627.1. NM_001174156.1. NP_653261.1. NM_144660.2.
UniGene	Hs.727615.
3D structure databases
ProteinModelPortal	Q96LT4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96LT4. 1 interaction.
STRING	9606.ENSP00000361772.
PTM databases
PhosphoSite	Q96LT4.
Polymorphism databases
DMDM	44888529.
Proteomic databases
PaxDb	Q96LT4.
PRIDE	Q96LT4.
Protocols and materials databases
DNASU	142891.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372687; ENSP00000361772; ENSG00000156671. ENST00000372690; ENSP00000361775; ENSG00000156671. ENST00000542569; ENSP00000438042; ENSG00000156671.
GeneID	142891.
KEGG	hsa:142891.
UCSC	uc001jwx.2. human. uc001jwy.2. human.
Organism-specific databases
CTD	142891.
GeneCards	GC10P076859.
HGNC	HGNC:26320. SAMD8.
HPA	HPA044402.
MIM	611575. gene.
neXtProt	NX_Q96LT4.
PharmGKB	PA134868247.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG306737.
HOGENOM	HOG000233822.
HOVERGEN	HBG048216.
InParanoid	Q96LT4.
PhylomeDB	Q96LT4.
Gene expression databases
ArrayExpress	Q96LT4.
Bgee	Q96LT4.
CleanEx	HS_SAMD8.
Genevestigator	Q96LT4.
GermOnline	ENSG00000156671. Homo sapiens.
Family and domain databases
Gene3D	1.10.150.50. 1 hit.
InterPro	IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR025749. Sphingomyelin_synth-like_dom. [Graphical view]
Pfam	PF14360. PAP2_C. 1 hit. PF00536. SAM_1. 1 hit. [Graphical view]
SMART	SM00454. SAM. 1 hit. [Graphical view]
SUPFAM	SSF47769. SAM_homology. 1 hit.
PROSITE	PS50105. SAM_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	142891.
NextBio	84629.
SOURCE	Search...

Entry information

Entry name

SAMD8_HUMAN

Accession

Primary (citable) accession number: Q96LT4
Secondary accession number(s): Q5JSC5, Q5JSC8, Q66K52

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.