{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9NYA1","secondaryAccessions":["Q8N632","Q96GK1","Q9HD92","Q9NY70","Q9NYL3"],"uniProtkbId":"SPHK1_HUMAN","entryAudit":{"firstPublicDate":"2001-10-24","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2000-10-01","entryVersion":205,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Sphingosine kinase 1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23935096"}],"value":"SK 1"},{"value":"SPK 1"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20577214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23602659"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24929359"}],"value":"2.7.1.91"}]},"alternativeNames":[{"fullName":{"value":"Acetyltransferase SPHK1"},"ecNumbers":[{"value":"2.3.1.-"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:11240"}],"value":"SPHK1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23935096"}],"value":"SK1"},{"value":"SPHK"},{"value":"SPK"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16118219"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20577214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23602659"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23935096"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24929359"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25417698"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28049734"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29662056"}],"value":"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:11923095, PubMed:20577214, PubMed:23602659, PubMed:24929359, PubMed:29662056). In contrast to pro-apoptotic 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:24929359, PubMed:28049734). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CI15"}],"value":"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"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:51496"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:76941"},{"database":"ChEBI","id":"CHEBI:84410"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.1.91","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20577214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23602659"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24929359"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25417698"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:51497"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24929359"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25417698"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[protein] + acetyl-CoA = O-acetyl-L-seryl-[protein] + CoA","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:59392"},{"database":"Rhea","id":"RHEA-COMP:9863"},{"database":"Rhea","id":"RHEA-COMP:15352"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:57287"},{"database":"ChEBI","id":"CHEBI:57288"},{"database":"ChEBI","id":"CHEBI:141128"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CI15"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:59393"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CI15"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"sphinganine + ATP = sphinganine 1-phosphate + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:15465"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:57817"},{"database":"ChEBI","id":"CHEBI:57939"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.1.91","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:15466"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"sphing-4-enine + ATP = sphing-4-enine 1-phosphate + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:35847"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:57756"},{"database":"ChEBI","id":"CHEBI:60119"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.1.91","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:35848"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10802064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"1-O-hexadecyl-2-amino-sn-glycerol + ATP = 1-O-hexadecyl-2-desoxy-2-amino-sn-glycero-3-phosphate + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:41163"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:77786"},{"database":"ChEBI","id":"CHEBI:77787"},{"database":"ChEBI","id":"CHEBI:456216"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:41164"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10947957"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CI15"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q91V26"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25417698"}],"value":"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)"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":14.0,"unit":"uM","substrate":"sphingosine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10947957"}]},{"constant":20.0,"unit":"uM","substrate":"dihydrosphingosine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10947957"}]},{"constant":77.0,"unit":"uM","substrate":"ATP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10947957"}]},{"constant":3.8,"unit":"uM","substrate":"1-O-hexadecyl-2-amino-sn-glycerol","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},{"constant":15.7,"unit":"uM","substrate":"sphing-4-enine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},{"constant":46.0,"unit":"uM","substrate":"sphinganine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11923095"}]},{"constant":24.0,"unit":"uM","substrate":"sphingosine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18263879"}]},{"constant":89.0,"unit":"uM","substrate":"ATP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18263879"}]}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18263879"}],"value":"kcat is 124 sec(-1) for sphingosine and increases to 304 sec(-1) upon interaction with EEF1A1."}]}},"phDependence":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10947957"}],"value":"Optimum pH is 7.4."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CI15"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12080051"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18263879"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19854831"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20577214"}],"value":"Interacts with ACY1 (By similarity). 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