Q86VZ5 (SMS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	419 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Lipid metabolism Sphingolipid metabolism
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell growth Inferred from direct assay Ref.1. Source: HGNC sphingomyelin biosynthetic process Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	Golgi trans cisterna Inferred from direct assay Ref.10. Source: MGI endoplasmic reticulum Traceable author statement Ref.1. Source: HGNC integral to 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_function	ceramide 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 419	419	Phosphatidylcholine:ceramide cholinephosphotransferase 1		PRO_0000221068
Regions
	Transmembrane	142 – 162	21	Helical; Potential
	Transmembrane	190 – 210	21	Helical; Potential
	Transmembrane	221 – 241	21	Helical; Potential
	Transmembrane	282 – 302	21	Helical; Potential
	Transmembrane	310 – 330	21	Helical; Potential
	Topological domain	331 – 419	89	Cytoplasmic Potential
	Domain	13 – 76	64	SAM
Sites
	Active site	291	1	Ref.13
	Active site	334	1	Ref.13
	Active site	338	1	Ref.13
Natural variations
	Alternative sequence	1 – 205	205	Missing in isoform 2.		VSP_027223
	Alternative sequence	206 – 214	9	IQWLLLKYK → MTRMFLNNP in isoform 2.		VSP_027224
Experimental info
	Mutagenesis	289	1	S → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
	Mutagenesis	291	1	H → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
	Mutagenesis	334	1	H → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
	Mutagenesis	338	1	D → A: Completely abolishes enzyme activity. No change in subcellular location. Ref.13
	Sequence conflict	168	1	P → L in AAQ82051. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 16, 2004. Version 2. Checksum: 52C2A985E3F27E44	FASTA	419	49,208
	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
	Isoform 2 [UniParc]. Checksum: 1683928AB57C2FB2	FASTA	214	25,602
	10 20 30 40 50 60 MTRMFLNNPS IISRRFFCIV GTLYLYRCIT MYVTTLPVPG MHFNCSPKLF GDWEAQLRRI 70 80 90 100 110 120 MKLIAGGGLS ITGSHNMCGD YLYSGHTVML TLTYLFIKEY SPRRLWWYHW ICWLLSVVGI 130 140 150 160 170 180 FCILLAHDHY TVDVVVAYYI TTRLFWWYHT MANQQVLKEA SQMNLLARVW WYRPFQYFEK 190 200 210 NVQGIVPRSY HWPFPWPVVH LSRQVKYSRL VNDT

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00014863. IPI00910188.
RefSeq	NP_671512.1. NM_147156.3.
UniGene	Hs.654698.
3D structure databases
ProteinModelPortal	Q86VZ5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86VZ5. 1 interaction.
MINT	MINT-2879302.
STRING	9606.ENSP00000354829.
PTM databases
PhosphoSite	Q86VZ5.
Polymorphism databases
DMDM	44888473.
Proteomic databases
PaxDb	Q86VZ5.
PRIDE	Q86VZ5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361543; ENSP00000355235; ENSG00000198964.
GeneID	259230.
KEGG	hsa:259230.
UCSC	uc001jje.3. human.
Organism-specific databases
CTD	259230.
GeneCards	GC10M052065.
HGNC	HGNC:29799. SGMS1.
HPA	HPA045191.
MIM	611573. gene.
neXtProt	NX_Q86VZ5.
PharmGKB	PA162403042.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG259509.
HOGENOM	HOG000233822.
HOVERGEN	HBG048216.
InParanoid	Q86VZ5.
KO	K04714.
Enzyme and pathway databases
BRENDA	2.7.8.27. 2681.
Pathway_Interaction_DB	il2_pi3kpathway. IL2 signaling events mediated by PI3K.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q86VZ5.
Bgee	Q86VZ5.
CleanEx	HS_SGMS1.
Genevestigator	Q86VZ5.
GermOnline	ENSG00000198964. 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]
SUPFAM	SSF47769. SAM_homology. 1 hit.
PROSITE	PS50105. SAM_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SGMS1. human.
GenomeRNAi	259230.
NextBio	93062.
SOURCE	Search...

Entry information

Entry name

SMS1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 95 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.