Q8NHU3 · SMS2_HUMAN
- ProteinPhosphatidylcholine:ceramide cholinephosphotransferase 2
- GeneSGMS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids365 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane. Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction appears to depend on the levels of CER and DAG in the plasma membrane (PubMed:14685263, PubMed:17449912, PubMed:17982138, PubMed:18370930).
Does not use free phosphorylcholine or CDP-choline as donors (PubMed:14685263).
Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (PubMed:19454763).
Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:17449912, PubMed:17982138).
To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (PubMed:18370930, PubMed:21980337).
Required for normal bone matrix mineralization (PubMed:30779713).
Does not use free phosphorylcholine or CDP-choline as donors (PubMed:14685263).
Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (PubMed:19454763).
Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:17449912, PubMed:17982138).
To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (PubMed:18370930, PubMed:21980337).
Required for normal bone matrix mineralization (PubMed:30779713).
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 the atherogenic potential of non-HDL lipoprotein particles.
Catalytic activity
- a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine = a 1,2-diacyl-sn-glycerol + a sphingomyelinThis reaction proceeds in the forward and the backward directions.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine = 1,2-dihexadecanoyl-sn-glycerol + a sphingomyelinThis reaction proceeds in the forward and the backward directions.
- 1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enineThis reaction proceeds in the forward and the backward directions.
- a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-sphinganine-1-phosphocholineThis reaction proceeds in the forward and the backward directions.
- a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-(4R)-hydroxysphinganine-phosphocholineThis reaction proceeds in the forward and the backward directions.
- a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-sphinganine-1-phosphoethanolamineThis reaction proceeds in the forward direction.
- a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-(4R)-hydroxysphinganine-1-phosphoethanolamineThis reaction proceeds in the forward direction.
Activity regulation
Inhibited by bacterial PC-phospholipase C inhibitor D609.
Pathway
Sphingolipid metabolism.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 229 | |||||
Sequence: H | ||||||
Active site | 272 | |||||
Sequence: H | ||||||
Active site | 276 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | nucleoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | ceramide cholinephosphotransferase activity | |
Molecular Function | ceramide phosphoethanolamine synthase activity | |
Molecular Function | kinase activity | |
Molecular Function | sphingomyelin synthase activity | |
Biological Process | ceramide biosynthetic process | |
Biological Process | ceramide phosphoethanolamine biosynthetic process | |
Biological Process | regulation of bone mineralization | |
Biological Process | sphingolipid biosynthetic process | |
Biological Process | sphingomyelin biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended namePhosphatidylcholine:ceramide cholinephosphotransferase 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8NHU3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Note: Primarily localized at the plasma membrane with a small fraction at the Golgi apparatus.
Features
Showing features for transmembrane, topological domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 80-100 | Helical | ||||
Sequence: GIAFIYAVFNLVLTTVMITVV | ||||||
Transmembrane | 128-148 | Helical | ||||
Sequence: FSVSEINGIILVGLWITQWLF | ||||||
Transmembrane | 159-179 | Helical | ||||
Sequence: FCFIIGTLYLYRCITMYVTTL | ||||||
Transmembrane | 206-226 | Helical | ||||
Sequence: LISGGGLSITGSHILCGDFLF | ||||||
Transmembrane | 248-268 | Helical | ||||
Sequence: FWWYHLICWLLSAAGIICILV | ||||||
Transmembrane | 275-295 | Helical | ||||
Sequence: IDVIIAYYITTRLFWWYHSMA | ||||||
Topological domain | 296-365 | Cytoplasmic | ||||
Sequence: NEKNLKVSSQTNFLSRAWWFPIFYFFEKNVQGSIPCCFSWPLSWPPGCFKSSCKKYSRVQKIGEDNEKST |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Calvarial doughnut lesions with bone fragility (CDL)
- Note
- DescriptionA rare autosomal dominant bone disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. Patients present with childhood onset of primary osteoporosis and typical sclerotic doughnut-shaped lesions in the cranial bones.
- See alsoMIM:126550
Natural variants in CDL
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_082674 | 50-365 | missing | in CDL; loss of enzymatic activity; does not localize to plasma membrane |
Calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia (CDLSMD)
- Note
- DescriptionA severe form of calvarial doughnut lesions with bone fragility, a rare autosomal dominant disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. CDLSMD patients show neonatal onset of fractures, severe short stature, marked cranial sclerosis, and spondylometaphyseal dysplasia.
- See alsoMIM:126550
Natural variants in CDLSMD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_082675 | 62 | I>S | in CDLSMD; uncertain significance; no effect on enzymatic activity; does not localize to plasma membrane; accumulates in the endoplasmic reticulum | |
VAR_082676 | 64 | M>R | in CDLSMD; uncertain significance; no effect on enzymatic activity; does not localize to plasma membrane; accumulates in the endoplasmic reticulum |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_052025 | 21 | in dbSNP:rs17038204 | |||
Sequence: T → M | ||||||
Natural variant | VAR_082674 | 50-365 | in CDL; loss of enzymatic activity; does not localize to plasma membrane | |||
Sequence: Missing | ||||||
Natural variant | VAR_082675 | 62 | in CDLSMD; uncertain significance; no effect on enzymatic activity; does not localize to plasma membrane; accumulates in the endoplasmic reticulum | |||
Sequence: I → S | ||||||
Natural variant | VAR_082676 | 64 | in CDLSMD; uncertain significance; no effect on enzymatic activity; does not localize to plasma membrane; accumulates in the endoplasmic reticulum | |||
Sequence: M → R | ||||||
Mutagenesis | 227 | Abolishes enzyme activity by about 70%. No change in subcellular location. | ||||
Sequence: S → A | ||||||
Mutagenesis | 229 | Completely abolishes enzyme activity. No change in subcellular location. | ||||
Sequence: H → A | ||||||
Mutagenesis | 272 | Completely abolishes enzyme activity. No change in subcellular location. | ||||
Sequence: H → A | ||||||
Mutagenesis | 276 | Completely abolishes enzyme activity. No change in subcellular location. | ||||
Sequence: D → E or A | ||||||
Mutagenesis | 331-332 | Little effect on palmitoylation; when associated with A-343 or A-348. Abolishes palmitoylation and dramatically reduces plasma membrane localization; when associated with A-343 and A-348. | ||||
Sequence: CC → AA | ||||||
Mutagenesis | 343 | Strongly decreases palmitoylation; when associated with A-348. Abolishes palmitoylation and dramatically reduces plasma membrane localization; when associated with 331-A-A-332 and A-348. | ||||
Sequence: C → A | ||||||
Mutagenesis | 348 | Strongly decreases palmitoylation; when associated with A-343. Abolishes palmitoylation and dramatically reduces plasma membrane localization; when associated with 331-A-A-332 and A-343. | ||||
Sequence: C → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 386 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), lipidation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000221072 | 1-365 | UniProt | Phosphatidylcholine:ceramide cholinephosphotransferase 2 | |||
Sequence: MDIIETAKLEEHLENQPSDPTNTYARPAEPVEEENKNGNGKPKSLSSGLRKGTKKYPDYIQIAMPTESRNKFPLEWWKTGIAFIYAVFNLVLTTVMITVVHERVPPKELSPPLPDKFFDYIDRVKWAFSVSEINGIILVGLWITQWLFLRYKSIVGRRFCFIIGTLYLYRCITMYVTTLPVPGMHFQCAPKLNGDSQAKVQRILRLISGGGLSITGSHILCGDFLFSGHTVTLTLTYLFIKEYSPRHFWWYHLICWLLSAAGIICILVAHEHYTIDVIIAYYITTRLFWWYHSMANEKNLKVSSQTNFLSRAWWFPIFYFFEKNVQGSIPCCFSWPLSWPPGCFKSSCKKYSRVQKIGEDNEKST | |||||||
Modified residue (large scale data) | 56 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 59 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Lipidation | 331 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 332 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 343 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 348 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C |
Post-translational modification
Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Brain, heart, kidney, liver, muscle and stomach. Also expressed in a number of cell lines such as carcinoma HeLa cells, hepatoma Hep-G2 cells, and colon carcinoma Caco-2 cells.
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8NHU3 | GPX8 Q8TED1 | 3 | EBI-10977284, EBI-11721746 | |
BINARY | Q8NHU3 | LPAR3 Q9UBY5 | 3 | EBI-10977284, EBI-12033434 | |
BINARY | Q8NHU3 | PPGB Q59EV6 | 3 | EBI-10977284, EBI-14210385 | |
BINARY | Q8NHU3 | VAMP1 P23763-3 | 3 | EBI-10977284, EBI-12097582 | |
BINARY | Q8NHU3 | ZFPL1 O95159 | 3 | EBI-10977284, EBI-718439 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Basic and acidic residues | ||||
Sequence: MDIIETAKLEEHLEN | ||||||
Region | 1-52 | Disordered | ||||
Sequence: MDIIETAKLEEHLENQPSDPTNTYARPAEPVEEENKNGNGKPKSLSSGLRKG |
Sequence similarities
Belongs to the sphingomyelin synthase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length365
- Mass (Da)42,280
- Last updated2002-10-01 v1
- Checksum49B3560AFB87CF40
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Basic and acidic residues | ||||
Sequence: MDIIETAKLEEHLEN | ||||||
Sequence conflict | 313 | in Ref. 2; BAF83033 | ||||
Sequence: W → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF452717 EMBL· GenBank· DDBJ | AAP13352.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290344 EMBL· GenBank· DDBJ | BAF83033.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314049 EMBL· GenBank· DDBJ | BAG36758.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471057 EMBL· GenBank· DDBJ | EAX06211.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC028705 EMBL· GenBank· DDBJ | AAH28705.1 EMBL· GenBank· DDBJ | mRNA | ||
BC041369 EMBL· GenBank· DDBJ | AAH41369.1 EMBL· GenBank· DDBJ | mRNA | ||
AC096564 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |