sphingosine kinase 2 | Sphingosine kinase | IUPHAR/BPS Guide to PHARMACOLOGY

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sphingosine kinase 2

target has curated data in GtoImmuPdb

Target id: 2205

Nomenclature: sphingosine kinase 2

Abbreviated Name: SPHK2

Family: Sphingosine kinase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 654 19q13.2 SPHK2 sphingosine kinase 2
Mouse - 617 7 B4 Sphk2 sphingosine kinase 2
Rat - 616 1 q22 Sphk2 sphingosine kinase 2
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.1.91 Sphingosine + ATP = sphingosine 1-phosphate + ADP
dihydrosphingosine + ATP = sphingosine 1-phosphate + ADP
Cofactors
Cofactor Species Comments Reference
Mg2+ None

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SLC4101431 Hs Inhibition 7.1 pKi 1
pKi 7.1 (Ki 9x10-8 M) [1]
MP-A08 Hs Inhibition 5.2 pKi 5
pKi 5.2 (Ki 6.9x10-6 M) [5]
Description: In vitro inhibition of substrate phosphorylation.
SKI II Hs Inhibition 5.1 pKi 3
pKi 5.1 (Ki 7.9x10-6 M) [3]
opaganib Hs Inhibition 5.0 pKi 2
pKi 5.0 (Ki 9.8x10-6 M) [2]
ROMe Hs Inhibition 4.8 pKi 4
pKi 4.8 (Ki 1.65x10-5 M) [4]
compound 27d [PMID: 28231433] Hs Inhibition 6.8 pIC50 8
pIC50 6.8 (IC50 1.45x10-7 M) [8]
PF-543 Hs Inhibition 6.4 pIC50 8
pIC50 6.4 (IC50 3.56x10-7 M) [8]
ROMe Hs Inhibition 4.6 pIC50 4
pIC50 4.6 (IC50 2.7x10-5 M) [4]
Immunopharmacology Comments
SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [6]. Selective SK2 inhibitors are being used to explore the feasibility of targeting SK2 [7].
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0033008 positive regulation of mast cell activation involved in immune response ISS
GO:0043306 positive regulation of mast cell degranulation ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 4 GO processes
GO:0002374 cytokine secretion involved in immune response ISS
GO:0072604 interleukin-6 secretion ISS
GO:0072611 interleukin-13 secretion ISS
GO:1990774 tumor necrosis factor secretion ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0033008 positive regulation of mast cell activation involved in immune response ISS
GO:0043306 positive regulation of mast cell degranulation ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0033008 positive regulation of mast cell activation involved in immune response ISS
GO:0043306 positive regulation of mast cell degranulation ISS

References

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1. Childress ES, Kharel Y, Brown AM, Bevan DR, Lynch KR, Santos WL. (2017) Transforming Sphingosine Kinase 1 Inhibitors into Dual and Sphingosine Kinase 2 Selective Inhibitors: Design, Synthesis, and in Vivo Activity. J. Med. Chem., 60 (9): 3933-3957. [PMID:28406646]

2. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. (2010) Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J. Pharmacol. Exp. Ther., 333 (1): 129-39. [PMID:20061445]

3. Gao P, Peterson YK, Smith RA, Smith CD. (2012) Characterization of isoenzyme-selective inhibitors of human sphingosine kinases. PLoS ONE, 7 (9): e44543. [PMID:22970244]

4. Lim KG, Sun C, Bittman R, Pyne NJ, Pyne S. (2011) (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells. Cell. Signal., 23 (10): 1590-5. [PMID:21620961]

5. Pitman MR, Powell JA, Coolen C, Moretti PA, Zebol JR, Pham DH, Finnie JW, Don AS, Ebert LM, Bonder CS et al.. (2015) A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties. Oncotarget, 6 (9): 7065-83. [PMID:25788259]

6. Pyne NJ, Adams DR, Pyne S. (2017) Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors. Trends Pharmacol. Sci., 38 (7): 581-591. [PMID:28606480]

7. Pyne S, Adams DR, Pyne NJ. (2018) Sphingosine Kinases as Druggable Targets. Handb Exp Pharmacol, [Epub ahead of print]. [PMID:29460151]

8. Schnute ME, McReynolds MD, Carroll J, Chrencik J, Highkin MK, Iyanar K, Jerome G, Rains JW, Saabye M, Scholten JA et al.. (2017) Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. J. Med. Chem., 60 (6): 2562-2572. [PMID:28231433]

How to cite this page

Sphingosine kinase: sphingosine kinase 2. Last modified on 05/02/2019. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2205.