UniProt functional annotation for Q9NYA1



	UniProt functional annotation for Q9NYA1

UniProt code: Q9NYA1.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (PubMed:20577214, PubMed:23602659, PubMed:29662056, PubMed:24929359, PubMed:11923095). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF- kappa-B in response to TNF signaling leading to IL17 secretion (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:28049734, PubMed:24929359). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698). {ECO:0000269|PubMed:11923095, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23602659, ECO:0000269|PubMed:23935096, ECO:0000269|PubMed:24929359, ECO:0000269|PubMed:25417698, ECO:0000269|PubMed:28049734, ECO:0000269|PubMed:29662056}.

Function: Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15- R-lipoxin A4, which results in an increase of phagocytic microglia. {ECO:0000250|UniProtKB:Q8CI15}.

Catalytic activity: Reaction=a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+); Xref=Rhea:RHEA:51496, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:76941, ChEBI:CHEBI:84410, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23602659, ECO:0000269|PubMed:24929359, ECO:0000269|PubMed:25417698}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51497; Evidence={ECO:0000269|PubMed:24929359, ECO:0000269|PubMed:25417698};

Catalytic activity: Reaction=acetyl-CoA + L-seryl-[protein] = CoA + O-acetyl-L-seryl- [protein]; Xref=Rhea:RHEA:59392, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:15352, ChEBI:CHEBI:29999, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:141128; Evidence={ECO:0000250|UniProtKB:Q8CI15}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59393; Evidence={ECO:0000250|UniProtKB:Q8CI15};

Catalytic activity: Reaction=ATP + sphinganine = ADP + H(+) + sphinganine 1-phosphate; Xref=Rhea:RHEA:15465, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57817, ChEBI:CHEBI:57939, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15466; Evidence={ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:11923095};

Catalytic activity: Reaction=ATP + sphing-4-enine = ADP + H(+) + sphing-4-enine 1- phosphate; Xref=Rhea:RHEA:35847, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57756, ChEBI:CHEBI:60119, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35848; Evidence={ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:11923095};

Catalytic activity: Reaction=1-O-hexadecyl-2-amino-sn-glycerol + ATP = 1-O-hexadecyl-2- desoxy-2-amino-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41163, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77786, ChEBI:CHEBI:77787, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41164; Evidence={ECO:0000269|PubMed:11923095};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10947957};

Activity regulation: Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (By similarity). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity). {ECO:0000250|UniProtKB:Q8CI15, ECO:0000250|UniProtKB:Q91V26, ECO:0000269|PubMed:25417698}.

Biophysicochemical properties: Kinetic parameters: KM=14 uM for sphingosine {ECO:0000269|PubMed:10947957}; KM=20 uM for dihydrosphingosine {ECO:0000269|PubMed:10947957}; KM=77 uM for ATP {ECO:0000269|PubMed:10947957}; KM=3.8 uM for 1-O-hexadecyl-2-amino-sn-glycerol {ECO:0000269|PubMed:11923095}; KM=15.7 uM for sphing-4-enine {ECO:0000269|PubMed:11923095}; KM=46 uM for sphinganine {ECO:0000269|PubMed:11923095}; KM=24 uM for sphingosine {ECO:0000269|PubMed:18263879}; KM=89 uM for ATP {ECO:0000269|PubMed:18263879}; Note=Kcat is 124 s(-1) for sphingosine and increases to 304 s(-1) upon interaction with EEF1A1. {ECO:0000269|PubMed:18263879}; pH dependence: Optimum pH is 7.4. {ECO:0000269|PubMed:10947957};

Subunit: Interacts with ACY1 (By similarity). Binds to calmodulin. Interacts with SPHKAP (PubMed:12080051). Interacts with CIB1, the interaction occurs in a calcium-dependent manner (PubMed:19854831). Interacts with TRAF2 (PubMed:20577214). Interacts with EEF1A1; the interaction enhances SPHK1 kinase activity (PubMed:18263879). {ECO:0000250|UniProtKB:Q8CI15, ECO:0000269|PubMed:12080051, ECO:0000269|PubMed:18263879, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:20577214}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:14575709, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:29662056}. Nucleus {ECO:0000269|PubMed:14575709, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:29662056}. Cell membrane {ECO:0000269|PubMed:19854831}. Endosome membrane {ECO:0000269|PubMed:24929359}; Peripheral membrane protein {ECO:0000269|PubMed:24929359}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:24929359}. Cell junction, synapse {ECO:0000250|UniProtKB:Q8CI15}. Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner (PubMed:19854831). Binds to membranes containing negatively charged lipids but not neutral lipids (PubMed:24929359). Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity). {ECO:0000250|UniProtKB:Q8CI15, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:24929359}.

Tissue specificity: Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Expressed in brain cortex (at protein level) (PubMed:29662056). {ECO:0000269|PubMed:10802064, ECO:0000269|PubMed:29662056}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (PubMed:20577214, PubMed:23602659, PubMed:29662056, PubMed:24929359, PubMed:11923095). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF- kappa-B in response to TNF signaling leading to IL17 secretion (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:28049734, PubMed:24929359). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698). {ECO:0000269\|PubMed:11923095, ECO:0000269\|PubMed:16118219, ECO:0000269\|PubMed:20577214, ECO:0000269\|PubMed:23602659, ECO:0000269\|PubMed:23935096, ECO:0000269\|PubMed:24929359, ECO:0000269\|PubMed:25417698, ECO:0000269\|PubMed:28049734, ECO:0000269\|PubMed:29662056}.



Function:		Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15- R-lipoxin A4, which results in an increase of phagocytic microglia. {ECO:0000250\|UniProtKB:Q8CI15}.


Catalytic activity:		Reaction=a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+); Xref=Rhea:RHEA:51496, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:76941, ChEBI:CHEBI:84410, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:20577214, ECO:0000269\|PubMed:23602659, ECO:0000269\|PubMed:24929359, ECO:0000269\|PubMed:25417698}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51497; Evidence={ECO:0000269\|PubMed:24929359, ECO:0000269\|PubMed:25417698};
Catalytic activity:		Reaction=acetyl-CoA + L-seryl-[protein] = CoA + O-acetyl-L-seryl- [protein]; Xref=Rhea:RHEA:59392, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:15352, ChEBI:CHEBI:29999, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:141128; Evidence={ECO:0000250\|UniProtKB:Q8CI15}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59393; Evidence={ECO:0000250\|UniProtKB:Q8CI15};
Catalytic activity:		Reaction=ATP + sphinganine = ADP + H(+) + sphinganine 1-phosphate; Xref=Rhea:RHEA:15465, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57817, ChEBI:CHEBI:57939, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15466; Evidence={ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:11923095};
Catalytic activity:		Reaction=ATP + sphing-4-enine = ADP + H(+) + sphing-4-enine 1- phosphate; Xref=Rhea:RHEA:35847, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57756, ChEBI:CHEBI:60119, ChEBI:CHEBI:456216; EC=2.7.1.91; Evidence={ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35848; Evidence={ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:11923095};
Catalytic activity:		Reaction=1-O-hexadecyl-2-amino-sn-glycerol + ATP = 1-O-hexadecyl-2- desoxy-2-amino-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41163, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77786, ChEBI:CHEBI:77787, ChEBI:CHEBI:456216; Evidence={ECO:0000269\|PubMed:11923095}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41164; Evidence={ECO:0000269\|PubMed:11923095};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:10947957};
Activity regulation:		Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (By similarity). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity). {ECO:0000250\|UniProtKB:Q8CI15, ECO:0000250\|UniProtKB:Q91V26, ECO:0000269\|PubMed:25417698}.
Biophysicochemical properties:		Kinetic parameters: KM=14 uM for sphingosine {ECO:0000269\|PubMed:10947957}; KM=20 uM for dihydrosphingosine {ECO:0000269\|PubMed:10947957}; KM=77 uM for ATP {ECO:0000269\|PubMed:10947957}; KM=3.8 uM for 1-O-hexadecyl-2-amino-sn-glycerol {ECO:0000269\|PubMed:11923095}; KM=15.7 uM for sphing-4-enine {ECO:0000269\|PubMed:11923095}; KM=46 uM for sphinganine {ECO:0000269\|PubMed:11923095}; KM=24 uM for sphingosine {ECO:0000269\|PubMed:18263879}; KM=89 uM for ATP {ECO:0000269\|PubMed:18263879}; Note=Kcat is 124 s(-1) for sphingosine and increases to 304 s(-1) upon interaction with EEF1A1. {ECO:0000269\|PubMed:18263879}; pH dependence: Optimum pH is 7.4. {ECO:0000269\|PubMed:10947957};
Subunit:		Interacts with ACY1 (By similarity). Binds to calmodulin. Interacts with SPHKAP (PubMed:12080051). Interacts with CIB1, the interaction occurs in a calcium-dependent manner (PubMed:19854831). Interacts with TRAF2 (PubMed:20577214). Interacts with EEF1A1; the interaction enhances SPHK1 kinase activity (PubMed:18263879). {ECO:0000250\|UniProtKB:Q8CI15, ECO:0000269\|PubMed:12080051, ECO:0000269\|PubMed:18263879, ECO:0000269\|PubMed:19854831, ECO:0000269\|PubMed:20577214}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:14575709, ECO:0000269\|PubMed:19854831, ECO:0000269\|PubMed:29662056}. Nucleus {ECO:0000269\|PubMed:14575709, ECO:0000269\|PubMed:19854831, ECO:0000269\|PubMed:29662056}. Cell membrane {ECO:0000269\|PubMed:19854831}. Endosome membrane {ECO:0000269\|PubMed:24929359}; Peripheral membrane protein {ECO:0000269\|PubMed:24929359}. Membrane, clathrin-coated pit {ECO:0000269\|PubMed:24929359}. Cell junction, synapse {ECO:0000250\|UniProtKB:Q8CI15}. Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner (PubMed:19854831). Binds to membranes containing negatively charged lipids but not neutral lipids (PubMed:24929359). Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity). {ECO:0000250\|UniProtKB:Q8CI15, ECO:0000269\|PubMed:19854831, ECO:0000269\|PubMed:24929359}.
Tissue specificity:		Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Expressed in brain cortex (at protein level) (PubMed:29662056). {ECO:0000269\|PubMed:10802064, ECO:0000269\|PubMed:29662056}.