UniProt functional annotation for Q8C172



	UniProt functional annotation for Q8C172

UniProt code: Q8C172.

Organism: Mus musculus (Mouse).

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

Function: Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) as acyl donor (PubMed:15823095, PubMed:18541923, PubMed:23760501, PubMed:31150623). Can use other acyl donors, but with less efficiency (PubMed:18541923). Ceramides generated by CERS6 play a role in inflammatory response (PubMed:22544924). Acts as a regulator of metabolism and hepatic lipid accumulation (PubMed:25295788, PubMed:30655217, PubMed:31150623). Under high fat diet, palmitoyl- (C16:0-) ceramides generated by CERS6 specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to the development of obesity (PubMed:31150623). {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:22544924, ECO:0000269|PubMed:23760501, ECO:0000269|PubMed:25295788, ECO:0000269|PubMed:30655217, ECO:0000269|PubMed:31150623}.

Catalytic activity: Reaction=hexadecanoyl-CoA + sphinganine = CoA + H(+) + N- hexadecanoylsphinganine; Xref=Rhea:RHEA:36539, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57817, ChEBI:CHEBI:67042; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:31150623}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36540; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:31150623};

Catalytic activity: Reaction=octadecanoyl-CoA + sphinganine = CoA + H(+) + N- (octadecanoyl)-sphinganine; Xref=Rhea:RHEA:36547, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57817, ChEBI:CHEBI:67033; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923};

Catalytic activity: Reaction=sphinganine + tetradecanoyl-CoA = CoA + H(+) + N- (tetradecanoyl)-sphinganine; Xref=Rhea:RHEA:36571, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57817, ChEBI:CHEBI:67045; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36572; Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923};

Catalytic activity: Reaction=hexadecanoyl-CoA + hexadecasphinganine = CoA + H(+) + N- hexadecanoylhexadecasphinganine; Xref=Rhea:RHEA:43040, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:71009, ChEBI:CHEBI:82810; Evidence={ECO:0000250|UniProtKB:Q6ZMG9}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43041; Evidence={ECO:0000250|UniProtKB:Q6ZMG9};

Catalytic activity: Reaction=hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N- hexadecanoylsphing-4-enine; Xref=Rhea:RHEA:36687, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57756, ChEBI:CHEBI:72959; Evidence={ECO:0000250|UniProtKB:Q6ZMG9}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36688; Evidence={ECO:0000250|UniProtKB:Q6ZMG9};

Pathway: Lipid metabolism; sphingolipid metabolism. {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:31150623}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15823095}; Multi-pass membrane protein {ECO:0000269|PubMed:15823095}.

Tissue specificity: Broadly expressed, with highest levels in kidney and brain (at protein level). {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:23760501}.

Induction: Up-regulated in liver in response to high-fat diet. {ECO:0000269|PubMed:25295788}.

Ptm: N-glycosylated (PubMed:15823095, PubMed:23760501). Glycosylation on Asn-18 is not necessary for function (PubMed:15823095). {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:23760501}.

Ptm: Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563). {ECO:0000269|PubMed:26620563}.

Ptm: Phosphorylated at the C-terminus by CK2. {ECO:0000250|UniProtKB:Q6ZMG9}.

Disruption phenotype: Mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit (PubMed:23760501). Knockout mice are protected against high fat diet- induced obesity and glucose intolerance (PubMed:25295788, PubMed:31150623). Mice show decreased palmitoyl (C16:0) ceramide pools and increased energy expenditure (PubMed:25295788, PubMed:31150623). Conditional deletion in brown adipose tissue or liver also protects mice against high fat diet-induced obesity, while it is not the case with specific deletion in myeloid cells (PubMed:25295788). {ECO:0000269|PubMed:23760501, ECO:0000269|PubMed:25295788, ECO:0000269|PubMed:31150623}.

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:		Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) as acyl donor (PubMed:15823095, PubMed:18541923, PubMed:23760501, PubMed:31150623). Can use other acyl donors, but with less efficiency (PubMed:18541923). Ceramides generated by CERS6 play a role in inflammatory response (PubMed:22544924). Acts as a regulator of metabolism and hepatic lipid accumulation (PubMed:25295788, PubMed:30655217, PubMed:31150623). Under high fat diet, palmitoyl- (C16:0-) ceramides generated by CERS6 specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to the development of obesity (PubMed:31150623). {ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923, ECO:0000269\|PubMed:22544924, ECO:0000269\|PubMed:23760501, ECO:0000269\|PubMed:25295788, ECO:0000269\|PubMed:30655217, ECO:0000269\|PubMed:31150623}.


Catalytic activity:		Reaction=hexadecanoyl-CoA + sphinganine = CoA + H(+) + N- hexadecanoylsphinganine; Xref=Rhea:RHEA:36539, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57817, ChEBI:CHEBI:67042; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923, ECO:0000269\|PubMed:31150623}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36540; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923, ECO:0000269\|PubMed:31150623};
Catalytic activity:		Reaction=octadecanoyl-CoA + sphinganine = CoA + H(+) + N- (octadecanoyl)-sphinganine; Xref=Rhea:RHEA:36547, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57817, ChEBI:CHEBI:67033; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923};
Catalytic activity:		Reaction=sphinganine + tetradecanoyl-CoA = CoA + H(+) + N- (tetradecanoyl)-sphinganine; Xref=Rhea:RHEA:36571, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57817, ChEBI:CHEBI:67045; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36572; Evidence={ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923};
Catalytic activity:		Reaction=hexadecanoyl-CoA + hexadecasphinganine = CoA + H(+) + N- hexadecanoylhexadecasphinganine; Xref=Rhea:RHEA:43040, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:71009, ChEBI:CHEBI:82810; Evidence={ECO:0000250\|UniProtKB:Q6ZMG9}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43041; Evidence={ECO:0000250\|UniProtKB:Q6ZMG9};
Catalytic activity:		Reaction=hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N- hexadecanoylsphing-4-enine; Xref=Rhea:RHEA:36687, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57756, ChEBI:CHEBI:72959; Evidence={ECO:0000250\|UniProtKB:Q6ZMG9}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36688; Evidence={ECO:0000250\|UniProtKB:Q6ZMG9};
Pathway:		Lipid metabolism; sphingolipid metabolism. {ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:18541923, ECO:0000269\|PubMed:31150623}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:15823095}; Multi-pass membrane protein {ECO:0000269\|PubMed:15823095}.
Tissue specificity:		Broadly expressed, with highest levels in kidney and brain (at protein level). {ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:23760501}.
Induction:		Up-regulated in liver in response to high-fat diet. {ECO:0000269\|PubMed:25295788}.
Ptm:		N-glycosylated (PubMed:15823095, PubMed:23760501). Glycosylation on Asn-18 is not necessary for function (PubMed:15823095). {ECO:0000269\|PubMed:15823095, ECO:0000269\|PubMed:23760501}.
Ptm:		Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563). {ECO:0000269\|PubMed:26620563}.
Ptm:		Phosphorylated at the C-terminus by CK2. {ECO:0000250\|UniProtKB:Q6ZMG9}.
Disruption phenotype:		Mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit (PubMed:23760501). Knockout mice are protected against high fat diet- induced obesity and glucose intolerance (PubMed:25295788, PubMed:31150623). Mice show decreased palmitoyl (C16:0) ceramide pools and increased energy expenditure (PubMed:25295788, PubMed:31150623). Conditional deletion in brown adipose tissue or liver also protects mice against high fat diet-induced obesity, while it is not the case with specific deletion in myeloid cells (PubMed:25295788). {ECO:0000269\|PubMed:23760501, ECO:0000269\|PubMed:25295788, ECO:0000269\|PubMed:31150623}.