UniProt functional annotation for Q8VCQ6



	UniProt functional annotation for Q8VCQ6

UniProt code: Q8VCQ6.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Major sphingomyelin synthase at the Golgi apparatus (By similarity). 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 depends on the levels of CER and DAG in Golgi membranes (By similarity). Does not use free phosphorylcholine or CDP- choline as donor. 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:22580896, PubMed:16879426) (By similarity). Plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (By similarity). {ECO:0000250|UniProtKB:Q86VZ5, ECO:0000269|PubMed:16879426, ECO:0000269|PubMed:22580896}.

Function: (Microbial infection) Contributes to the brain SM production for Japanese encephalitis virus attachment and infection. {ECO:0000269|PubMed:27892528}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4- enine = a 1,2-diacyl-sn-glycerol + a sphingomyelin; Xref=Rhea:RHEA:18765, ChEBI:CHEBI:17636, ChEBI:CHEBI:17815, ChEBI:CHEBI:52639, ChEBI:CHEBI:57643; EC=2.7.8.27; Evidence={ECO:0000269|PubMed:27892528}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18766; Evidence={ECO:0000305|PubMed:27892528}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18767; Evidence={ECO:0000250|UniProtKB:Q86VZ5};

Catalytic activity: Reaction=1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N- acylsphing-4-enine; Xref=Rhea:RHEA:43320, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639, ChEBI:CHEBI:78421, ChEBI:CHEBI:82983; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43321; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43322; Evidence={ECO:0000250|UniProtKB:Q86VZ5};

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N- hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl- sphinganine-1-phosphocholine; Xref=Rhea:RHEA:41796, ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:67042, ChEBI:CHEBI:78647; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41797; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41798; Evidence={ECO:0000250|UniProtKB:Q86VZ5};

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoyl- (4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl- (4R)-hydroxysphinganine-phosphocholine; Xref=Rhea:RHEA:42140, ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:65107, ChEBI:CHEBI:78650; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42141; Evidence={ECO:0000250|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42142; Evidence={ECO:0000250|UniProtKB:Q86VZ5};

Pathway: Sphingolipid metabolism. {ECO:0000269|PubMed:27892528}.

Subcellular location: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q86VZ5}; Multi-pass membrane protein {ECO:0000255}.

Tissue specificity: Isoform 1 is widely expressed, isoform 2 shows a more narrow distribution and isoform 3 is detected only in testis and heart. {ECO:0000269|PubMed:16226406}.

Induction: [Isoform 1]: Induced by TNF-alpha. {ECO:0000269|PubMed:16226406}.

Induction: [Isoform 2]: Induced by TNF-alpha. {ECO:0000269|PubMed:16226406}.

Disruption phenotype: Null mice have hearing impairments with stria vascularis (SV) in these mice exhibiting atrophy and disorganized marginal cells resulting in significantly smaller endocochlear potentials (EPs). These decreased EPs, together with abnormal KCNQ1 expression patterns, increase with age. There is a decrease in plasma, liver, and macrophage sphingomyelin (59%, 45%, and 54%, respectively) and a dramatic increase in glycosphingolipids. No change in ceramide, total cholesterol, phospholipids nor triglycerides levels. Diminished macrophage MAP kinase and NFKB1 activation is observed. Atherosclerosis in SMS1(-/-)/LDLR(-/-) mice is significantly decreased. {ECO:0000269|PubMed:22580896, ECO:0000269|PubMed:22641779}.

Similarity: Belongs to the sphingomyelin synthase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Major sphingomyelin synthase at the Golgi apparatus (By similarity). 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 depends on the levels of CER and DAG in Golgi membranes (By similarity). Does not use free phosphorylcholine or CDP- choline as donor. 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:22580896, PubMed:16879426) (By similarity). Plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (By similarity). {ECO:0000250\|UniProtKB:Q86VZ5, ECO:0000269\|PubMed:16879426, ECO:0000269\|PubMed:22580896}.



Function:		(Microbial infection) Contributes to the brain SM production for Japanese encephalitis virus attachment and infection. {ECO:0000269\|PubMed:27892528}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4- enine = a 1,2-diacyl-sn-glycerol + a sphingomyelin; Xref=Rhea:RHEA:18765, ChEBI:CHEBI:17636, ChEBI:CHEBI:17815, ChEBI:CHEBI:52639, ChEBI:CHEBI:57643; EC=2.7.8.27; Evidence={ECO:0000269\|PubMed:27892528}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18766; Evidence={ECO:0000305\|PubMed:27892528}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18767; Evidence={ECO:0000250\|UniProtKB:Q86VZ5};
Catalytic activity:		Reaction=1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N- acylsphing-4-enine; Xref=Rhea:RHEA:43320, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639, ChEBI:CHEBI:78421, ChEBI:CHEBI:82983; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43321; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43322; Evidence={ECO:0000250\|UniProtKB:Q86VZ5};
Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N- hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl- sphinganine-1-phosphocholine; Xref=Rhea:RHEA:41796, ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:67042, ChEBI:CHEBI:78647; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41797; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41798; Evidence={ECO:0000250\|UniProtKB:Q86VZ5};
Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoyl- (4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl- (4R)-hydroxysphinganine-phosphocholine; Xref=Rhea:RHEA:42140, ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:65107, ChEBI:CHEBI:78650; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42141; Evidence={ECO:0000250\|UniProtKB:Q86VZ5}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42142; Evidence={ECO:0000250\|UniProtKB:Q86VZ5};
Pathway:		Sphingolipid metabolism. {ECO:0000269\|PubMed:27892528}.
Subcellular location:		Golgi apparatus membrane {ECO:0000250\|UniProtKB:Q86VZ5}; Multi-pass membrane protein {ECO:0000255}.
Tissue specificity:		Isoform 1 is widely expressed, isoform 2 shows a more narrow distribution and isoform 3 is detected only in testis and heart. {ECO:0000269\|PubMed:16226406}.
Induction:		[Isoform 1]: Induced by TNF-alpha. {ECO:0000269\|PubMed:16226406}.
Induction:		[Isoform 2]: Induced by TNF-alpha. {ECO:0000269\|PubMed:16226406}.
Disruption phenotype:		Null mice have hearing impairments with stria vascularis (SV) in these mice exhibiting atrophy and disorganized marginal cells resulting in significantly smaller endocochlear potentials (EPs). These decreased EPs, together with abnormal KCNQ1 expression patterns, increase with age. There is a decrease in plasma, liver, and macrophage sphingomyelin (59%, 45%, and 54%, respectively) and a dramatic increase in glycosphingolipids. No change in ceramide, total cholesterol, phospholipids nor triglycerides levels. Diminished macrophage MAP kinase and NFKB1 activation is observed. Atherosclerosis in SMS1(-/-)/LDLR(-/-) mice is significantly decreased. {ECO:0000269\|PubMed:22580896, ECO:0000269\|PubMed:22641779}.
Similarity:		Belongs to the sphingomyelin synthase family. {ECO:0000305}.