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Protein

Sphingomyelin synthase-related protein 1

Gene

SAMD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei301 – 3011By similarity
Active sitei344 – 3441By similarity
Active sitei348 – 3481

GO - Molecular functioni

GO - Biological processi

  • ceramide biosynthetic process Source: UniProtKB
  • regulation of ceramide biosynthetic process Source: UniProtKB
  • sphingomyelin biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Lipid metabolism, Sphingolipid metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin synthase-related protein 1 (EC:2.7.8.-)
Short name:
SMSr
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 namesi
Name:SAMD8
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:26320. SAMD8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei153 – 17321HelicalSequence AnalysisAdd
BLAST
Transmembranei201 – 22121HelicalSequence AnalysisAdd
BLAST
Transmembranei232 – 25221HelicalSequence AnalysisAdd
BLAST
Transmembranei277 – 29721HelicalSequence AnalysisAdd
BLAST
Transmembranei322 – 34221HelicalSequence AnalysisAdd
BLAST
Transmembranei347 – 36721HelicalSequence AnalysisAdd
BLAST
Topological domaini368 – 41548CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi348 – 3481D → E: Abolishes CPE synthase activity. 1 Publication

Organism-specific databases

PharmGKBiPA134868247.

Polymorphism and mutation databases

BioMutaiSAMD8.
DMDMi44888529.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 415415Sphingomyelin synthase-related protein 1PRO_0000221080Add
BLAST

Proteomic databases

MaxQBiQ96LT4.
PaxDbiQ96LT4.
PRIDEiQ96LT4.

PTM databases

PhosphoSiteiQ96LT4.

Expressioni

Gene expression databases

BgeeiQ96LT4.
CleanExiHS_SAMD8.
ExpressionAtlasiQ96LT4. baseline and differential.
GenevestigatoriQ96LT4.

Organism-specific databases

HPAiHPA044402.

Interactioni

Protein-protein interaction databases

BioGridi126778. 1 interaction.
IntActiQ96LT4. 1 interaction.
STRINGi9606.ENSP00000361772.

Structurei

3D structure databases

ProteinModelPortaliQ96LT4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 7867SAMPROSITE-ProRule annotationAdd
BLAST

Domaini

The SAM domain is required to retain SMAD8 in the endoplasmic reticulum.

Sequence similaritiesi

Belongs to the sphingomyelin synthase family.Curated
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG306737.
GeneTreeiENSGT00390000001630.
HOGENOMiHOG000233822.
HOVERGENiHBG048216.
InParanoidiQ96LT4.
PhylomeDBiQ96LT4.
TreeFamiTF314547.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR025749. Sphingomyelin_synth-like_dom.
[Graphical view]
PfamiPF14360. PAP2_C. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96LT4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGPNQLCIR RWTTKHVAVW LKDEGFFEYV DILCNKHRLD GITLLTLTEY
60 70 80 90 100
DLRSPPLEIK VLGDIKRLML SVRKLQKIHI DVLEEMGYNS DSPMGSMTPF
110 120 130 140 150
ISALQSTDWL CNGELSHDCD GPITDLNSDQ YQYMNGKNKH SVRRLDPEYW
160 170 180 190 200
KTILSCIYVF IVFGFTSFIM VIVHERVPDM QTYPPLPDIF LDSVPRIPWA
210 220 230 240 250
FAMTEVCGMI LCYIWLLVLL LHKHRSILLR RLCSLMGTVF LLRCFTMFVT
260 270 280 290 300
SLSVPGQHLQ CTGKIYGSVW EKLHRAFAIW SGFGMTLTGV HTCGDYMFSG
310 320 330 340 350
HTVVLTMLNF FVTEYTPRSW NFLHTLSWVL NLFGIFFILA AHEHYSIDVF
360 370 380 390 400
IAFYITTRLF LYYHTLANTR AYQQSRRARI WFPMFSFFEC NVNGTVPNEY
410
CWPFSKPAIM KRLIG
Length:415
Mass (Da):48,321
Last modified:March 1, 2004 - v2
Checksum:iAAED366F56C9CDC9
GO
Isoform 2 (identifier: Q96LT4-2) [UniParc]FASTAAdd to basket

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

Show »
Length:326
Mass (Da):37,609
Checksum:i3FA96772EDFB7486
GO

Sequence cautioni

The sequence AAH80593.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei315 – 32612YTPRS…FLHTL → CKYLFSASMRIR in isoform 2. 1 PublicationVSP_038403Add
BLAST
Alternative sequencei327 – 41589Missing in isoform 2. 1 PublicationVSP_038404Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS53543.1. [Q96LT4-1]
CCDS7347.1. [Q96LT4-2]
RefSeqiNP_001167627.1. NM_001174156.1. [Q96LT4-1]
NP_653261.1. NM_144660.2. [Q96LT4-2]
XP_005269598.1. XM_005269541.3. [Q96LT4-1]
UniGeneiHs.744986.

Genome annotation databases

GeneIDi142891.
KEGGihsa:142891.
UCSCiuc001jwx.2. human. [Q96LT4-1]
uc001jwy.2. human. [Q96LT4-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS53543.1. [Q96LT4-1]
CCDS7347.1. [Q96LT4-2]
RefSeqiNP_001167627.1. NM_001174156.1. [Q96LT4-1]
NP_653261.1. NM_144660.2. [Q96LT4-2]
XP_005269598.1. XM_005269541.3. [Q96LT4-1]
UniGeneiHs.744986.

3D structure databases

ProteinModelPortaliQ96LT4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126778. 1 interaction.
IntActiQ96LT4. 1 interaction.
STRINGi9606.ENSP00000361772.

PTM databases

PhosphoSiteiQ96LT4.

Polymorphism and mutation databases

BioMutaiSAMD8.
DMDMi44888529.

Proteomic databases

MaxQBiQ96LT4.
PaxDbiQ96LT4.
PRIDEiQ96LT4.

Protocols and materials databases

DNASUi142891.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi142891.
KEGGihsa:142891.
UCSCiuc001jwx.2. human. [Q96LT4-1]
uc001jwy.2. human. [Q96LT4-2]

Organism-specific databases

CTDi142891.
GeneCardsiGC10P076859.
HGNCiHGNC:26320. SAMD8.
HPAiHPA044402.
MIMi611575. gene.
neXtProtiNX_Q96LT4.
PharmGKBiPA134868247.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG306737.
GeneTreeiENSGT00390000001630.
HOGENOMiHOG000233822.
HOVERGENiHBG048216.
InParanoidiQ96LT4.
PhylomeDBiQ96LT4.
TreeFamiTF314547.

Miscellaneous databases

GenomeRNAii142891.
NextBioi84629.
PROiQ96LT4.
SOURCEiSearch...

Gene expression databases

BgeeiQ96LT4.
CleanExiHS_SAMD8.
ExpressionAtlasiQ96LT4. baseline and differential.
GenevestigatoriQ96LT4.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR025749. Sphingomyelin_synth-like_dom.
[Graphical view]
PfamiPF14360. PAP2_C. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: CerebellumImported.
  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. 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, MUTAGENESIS OF ASP-348, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiSAMD8_HUMAN
AccessioniPrimary (citable) accession number: Q96LT4
Secondary accession number(s): Q5JSC5, Q5JSC8, Q66K52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: April 29, 2015
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.