SPHK1 phosphorylates sphingoid

Stable Identifier
Reaction [transition]
Homo sapiens
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The cytosolic enzyme sphingosine kinase 1 (SPHK1) catalyzes the phosphorylation of sphingoids (SPG) to sphingoid 1-phosphate (S1P). The main product is sphingosine 1-phoshate, a bioactive lipid that acts extracellularly on G protein-coupled receptors of the S1P1/EDG-1 subfamily (Nava et al., 2000; Pitson et al., 2000; Wang et al., 2013; reviewed by Siow & Wattenberg, 2011). The isoforms SK1a, SK1b, and SK1c are produced through alternative splicing and show functional differences in their activity (reviewed by Hatoum et al., 2017). SPHK1 is regulated transcriptionally by transcription factors, cytokines, and micro-RNAs (reviewed by Bonica et al., 2020). Its activity is also modulated by posttranslational modifications and interactions with other proteins (reviewed by Pulkoski-Gross & Obeid, 2018). Through its product S1P, which is a multifunctional signaling lipid, SPHK1 is essential in inflammation processes (reviewed by Rauch, 2014). SPHK1 was also shown to be associated with cancer genesis, progression, and metastasic processes (Zhang et al., 2014).
Literature References
PubMed ID Title Journal Year
10802064 Functional characterization of human sphingosine kinase-1

Sugiura, M, Poulton, S, Liu, H, Nava, VE, Spiegel, S, Kohama, T, Milstien, S, Kono, K, Lacana, E

FEBS Lett 2000
28415564 Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget

Hatoum, D, McGowan, EM, Nassif, NT, Lin, Y, Haddadi, N

Oncotarget 2017
23602659 Molecular basis of sphingosine kinase 1 substrate recognition and catalysis

Romanow, W, Walker, N, Dai, J, Xiao, SH, Johnstone, S, Thibault, S, An, S, Xu, H, Meininger, D, Min, X, Liu, J, Wang, Z

Structure 2013
24977491 Sphingosine 1-phosphate as a link between blood coagulation and inflammation

Rauch, BH

Cell Physiol Biochem 2014
30591148 Molecular mechanisms of regulation of sphingosine kinase 1

Pulkoski-Gross, MJ, Obeid, LM

Biochim Biophys Acta Mol Cell Biol Lipids 2018
33171624 Transcriptional Regulation of Sphingosine Kinase 1

Mao, C, Bonica, J, Hannun, YA, Obeid, LM

Cells 2020
10947957 Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes

D'Andrea, RJ, Pitson, SM, Gamble, JR, Vadas, MA, Wattenberg, BW, Moretti, PA, Vandeleur, L, Xia, P

Biochem J 2000
21864225 The compartmentalization and translocation of the sphingosine kinases: mechanisms and functions in cell signaling and sphingolipid metabolism

Siow, D, Wattenberg, B

Crit Rev Biochem Mol Biol 2011
Catalyst Activity

lipid kinase activity of SPHK1 [cytosol]

Orthologous Events
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