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Q86VZ5 (SMS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphatidylcholine:ceramide cholinephosphotransferase 1

EC=2.7.8.27
Alternative name(s):
Medulla oblongata-derived protein
Short name=Protein Mob
Sphingomyelin synthase 1
Transmembrane protein 23
Gene names
Name:SGMS1
Synonyms:MOB, SMS1, TMEM23
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length419 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Sphingomyelin synthases synthesize the sphingolipid, sphingomyelin, through transfer of the phosphatidyl head group, phosphatidylcholine, on to the primary hydroxyl of ceramide. The reaction is bidirectional depending on the respective levels of the sphingolipid and ceramide. Golgi apparatus SMS1 directly and specifically recognizes the choline head group on the substrate, requiring two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Major form in macrophages. Required for cell growth in certain cell types such as HeLa cells. Suppresses BAX-mediated apoptosis and also prevents cell death in response to stimuli such as hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. May protect against cell death by reversing the stress-inducible increase in levels of proapoptotic ceramide. Ref.10 Ref.12

Catalytic activity

A ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol.

Enzyme regulation

Inhibited by bacterial PC-phospholipase C inhibitor D609. Ref.10

Subcellular location

Golgi apparatus membrane; Multi-pass membrane protein Ref.10 Ref.12 Ref.13.

Tissue specificity

Brain, heart, kidney, liver, muscle and stomach. Ref.7 Ref.9 Ref.10

Miscellaneous

Overexpression of the human protein in mouse causes increased non-HDL-sphingomyelin and non-HDL cholesterol levels, decreased HDL-sphingomyelin and HDL-cholesterol levels and increases lipoprotein atherogenic potential.

Sequence similarities

Belongs to the sphingomyelin synthase family.

Contains 1 SAM (sterile alpha motif) domain.

Sequence caution

The sequence AAH42899.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence AAP37279.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence AAQ22363.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence AAQ82051.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence AK026683 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence BAD16809.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence CAD79708.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

Ontologies

Keywords
   Biological processApoptosis
Lipid metabolism
Sphingolipid metabolism
   Cellular componentGolgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell growth

Inferred from direct assay Ref.1. Source: HGNC

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid biosynthetic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

sphingomyelin biosynthetic process

Inferred from direct assay Ref.10. Source: UniProtKB

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

Golgi trans cisterna

Inferred from direct assay Ref.10. Source: MGI

endoplasmic reticulum

Traceable author statement Ref.1. Source: HGNC

integral component of Golgi membrane

Inferred from direct assay Ref.10. Source: UniProtKB

nucleus

Traceable author statement Ref.1. Source: HGNC

plasma membrane

Traceable author statement Ref.1. Source: HGNC

   Molecular_functionceramide cholinephosphotransferase activity

Inferred from direct assay Ref.10. Source: UniProtKB

kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

sphingomyelin synthase activity

Inferred from mutant phenotype Ref.1. Source: HGNC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q86VZ5-1)

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: Q86VZ5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-205: Missing.
     206-214: IQWLLLKYK → MTRMFLNNP

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 419419Phosphatidylcholine:ceramide cholinephosphotransferase 1
PRO_0000221068

Regions

Transmembrane142 – 16221Helical; Potential
Transmembrane190 – 21021Helical; Potential
Transmembrane221 – 24121Helical; Potential
Transmembrane282 – 30221Helical; Potential
Transmembrane310 – 33021Helical; Potential
Topological domain331 – 41989Cytoplasmic Potential
Domain13 – 7664SAM

Sites

Active site2911 Ref.13
Active site3341 Ref.13
Active site3381 Ref.13

Natural variations

Alternative sequence1 – 205205Missing in isoform 2.
VSP_027223
Alternative sequence206 – 2149IQWLLLKYK → MTRMFLNNP in isoform 2.
VSP_027224

Experimental info

Mutagenesis2891S → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
Mutagenesis2911H → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
Mutagenesis3341H → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
Mutagenesis3381D → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
Sequence conflict1681P → L in AAQ82051. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 16, 2004. Version 2.
Checksum: 52C2A985E3F27E44

FASTA41949,208
        10         20         30         40         50         60 
MLSASTMKEV VYWSPKKVAD WLLENAMPEY CEPLEHFTGQ DLINLTQEDF KKPPLCRVSS 

        70         80         90        100        110        120 
DNGQRLLDMI ETLKMEHHLE AHKNGHANGH LNIGVDIPTP DGSFSIKIKP NGMPNGYRKE 

       130        140        150        160        170        180 
MIKIPMPELE RSQYPMEWGK TFLAFLYALS CFVLTTVMIS VVHERVPPKE VQPPLPDTFF 

       190        200        210        220        230        240 
DHFNRVQWAF SICEINGMIL VGLWLIQWLL LKYKSIISRR FFCIVGTLYL YRCITMYVTT 

       250        260        270        280        290        300 
LPVPGMHFNC SPKLFGDWEA QLRRIMKLIA GGGLSITGSH NMCGDYLYSG HTVMLTLTYL 

       310        320        330        340        350        360 
FIKEYSPRRL WWYHWICWLL SVVGIFCILL AHDHYTVDVV VAYYITTRLF WWYHTMANQQ 

       370        380        390        400        410 
VLKEASQMNL LARVWWYRPF QYFEKNVQGI VPRSYHWPFP WPVVHLSRQV KYSRLVNDT 

« Hide

Isoform 2 [UniParc].

Checksum: 1683928AB57C2FB2
Show »

FASTA21425,602

References

« Hide 'large scale' references
[1]"Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells."
Yamaoka S., Miyaji M., Kitano T., Umehara H., Okazaki T.
J. Biol. Chem. 279:18688-18693(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete cDNA sequence of a novel gene, human mob."
Yuan H.F., Wang X., Wang D.M., Li H.M., Feng K., Bai C.X., Zhang R., Chen L., Li Y.H., Gao Y.H., Zhen M., Yue W., Xie C., Xie X.Y., Niu L.L., Gao W.J., Zhang J., Cao H., Pei X.T.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal liver.
[3]"A new spermatogenesis-related gene."
Zhao H., Miao S.Y., Zhang X.D., Liang G., Qiao Y., Wang L.F.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[4]"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. expand/collapse author list , 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 1).
Tissue: Lung.
[5]"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. expand/collapse author list , 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].
[6]"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: Lymph.
[7]"Human gene MOB: structure specification and aspects of transcriptional activity."
Vladychenskaya I.P., Dergunova L.V., Dmitrieva V.G., Limborska S.A.
Gene 338:257-265(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-296 (ISOFORM 2), IDENTIFICATION (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Cerebellum.
[8]"Structure and functional organization of a novel human brain-specific gene MOB encoding a phylogenetically conserved transmembrane protein."
Vladychenskaya I.P., Dergunova L.V., Limborska S.A., Dmitrieva V.G.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-283 (ISOFORM 1).
[9]"In vitro and in silico analysis of the predicted human MOB gene encoding a phylogenetically conserved transmembrane protein."
Vladychenskaya I.P., Dergunova L.V., Limborska S.A.
Biomol. Eng. 18:263-268(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 1), TISSUE SPECIFICITY.
[10]"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: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, TOPOLOGY OF C-TERMINUS.
[11]"Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice."
Dong J., Liu J., Lou B., Li Z., Ye X., Wu M., Jiang X.-C.
J. Lipid Res. 47:1307-1314(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: OVEREXPRESSION IN MOUSE.
[12]"Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells."
Tafesse F.G., Huitema K., Hermansson M., van der Poel S., van den Dikkenberg J., Uphoff A., Somerharju P., Holthuis J.C.M.
J. Biol. Chem. 282:17537-17547(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]"The domain responsible for sphingomyelin synthase (SMS) activity."
Yeang C., Varshney S., Wang R., Zhang Y., Ye D., Jiang X.C.
Biochim. Biophys. Acta 1781:610-617(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITES, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-289; HIS-291; HIS-334 AND ASP-338.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB154421 mRNA. Translation: BAD16809.1. Sequence problems.
AY280959 mRNA. Translation: AAP37279.1. Sequence problems.
AY312431 mRNA. Translation: AAQ82051.1. Sequence problems.
AK026683 mRNA. No translation available.
AC069547 Genomic DNA. No translation available.
AL117341 Genomic DNA. No translation available.
AL596137 Genomic DNA. No translation available.
BC042899 mRNA. Translation: AAH42899.1. Sequence problems.
AY364088 mRNA. Translation: AAR13294.1.
AY332650 mRNA. Translation: AAQ22363.1. Sequence problems.
BN000143 mRNA. Translation: CAD79708.1. Sequence problems.
RefSeqNP_671512.1. NM_147156.3.
XP_005269732.1. XM_005269675.1.
UniGeneHs.654698.

3D structure databases

ProteinModelPortalQ86VZ5.
SMRQ86VZ5. Positions 1-84.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid129227. 3 interactions.
IntActQ86VZ5. 1 interaction.
MINTMINT-2879302.
STRING9606.ENSP00000354829.

PTM databases

PhosphoSiteQ86VZ5.

Polymorphism databases

DMDM44888473.

Proteomic databases

PaxDbQ86VZ5.
PRIDEQ86VZ5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361543; ENSP00000355235; ENSG00000198964.
GeneID259230.
KEGGhsa:259230.
UCSCuc001jje.3. human. [Q86VZ5-1]

Organism-specific databases

CTD259230.
GeneCardsGC10M052065.
HGNCHGNC:29799. SGMS1.
HPAHPA045191.
MIM611573. gene.
neXtProtNX_Q86VZ5.
PharmGKBPA162403042.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259509.
HOGENOMHOG000233822.
HOVERGENHBG048216.
InParanoidQ86VZ5.
KOK04714.
PhylomeDBQ86VZ5.

Enzyme and pathway databases

BRENDA2.7.8.27. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ86VZ5.
BgeeQ86VZ5.
CleanExHS_SGMS1.
GenevestigatorQ86VZ5.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
InterProIPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR025749. Sphingomyelin_synth-like_dom.
[Graphical view]
PfamPF14360. PAP2_C. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
PROSITEPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSGMS1. human.
GeneWikiSGMS1.
GenomeRNAi259230.
NextBio93062.
PROQ86VZ5.
SOURCESearch...

Entry information

Entry nameSMS1_HUMAN
AccessionPrimary (citable) accession number: Q86VZ5
Secondary accession number(s): Q68U43, Q6EKK0, Q75SP1
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: February 16, 2004
Last modified: April 16, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM