Details of Protein

General Information of Protein (ID: PRT01249)
Name Sphingosine kinase 1 (SPHK1)
Synonyms   Click to Show/Hide Synonyms of This Protein
SK 1; SPK 1; Acetyltransferase SPHK1; Sphk1; Sk1
Gene Name Sphk1 Gene ID
20698
UniProt ID
Q8CI15
Family Transferases (EC 2)
EC Number   EC: 2.7.1.91  (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Phosphotransferase
EC: 2.7.1.91
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MEPVECPRGLLPRPCRVLVLLNPQGGKGKALQLFQSRVQPFLEEAEITFKLILTERKNHA
RELVCAEELGHWDALAVMSGDGLMHEVVNGLMERPDWETAIQKPLCSLPGGSGNALAASV
NHYAGYEQVTNEDLLINCTLLLCRRRLSPMNLLSLHTASGLRLYSVLSLSWGFVADVDLE
SEKYRRLGEIRFTVGTFFRLASLRIYQGQLAYLPVGTVASKRPASTLVQKGPVDTHLVPL
EEPVPSHWTVVPEQDFVLVLVLLHTHLSSELFAAPMGRCEAGVMHLFYVRAGVSRAALLR
LFLAMQKGKHMELDCPYLVHVPVVAFRLEPRSQRGVFSVDGELMVCEAVQGQVHPNYLWM
VCGSRDAPSGRDSRRGPPPEEP
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. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. 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. In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway. 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. In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA.; 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.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Lipids and lipid-like molecules
            Sphingosine 1-phosphate Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Sphk1
                      Induced Change Sphingosine 1-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Chronic kidney disease [ICD-11: GB61]
                      Details It is reported that knockout of Sphk1 leads to the decrease of sphingosine 1-phosphate levels compared with control group.
      Organic oxygen compounds
            2,3-Bisphosphoglycerate Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Sphk1
                      Induced Change 2,3-Bisphosphoglycerate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Chronic kidney disease [ICD-11: GB61]
                      Details It is reported that knockout of Sphk1 leads to the decrease of 2,3-bisphosphoglycerate levels compared with control group.
            2-Phosphoglyceric acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of Sphk1
                      Induced Change 2-Phosphoglyceric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Chronic kidney disease [ICD-11: GB61]
                      Details It is reported that knockout of Sphk1 leads to the decrease of 2-phosphoglyceric acid levels compared with control group.
References
1 Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies. Circ Res. 2020 Jul 17;127(3):360-375.

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