SPHK2

SPHK2
Identifiers
Aliases	SPHK2, SK 2, SK-2, SPK 2, SPK-2, sphingosine kinase 2
External IDs	OMIM: 607092; MGI: 1861380; HomoloGene: 32456; GeneCards: SPHK2; OMA:SPHK2 - orthologs
Enzyme activity
Gene location (Human)
Chr.	Chromosome 19 (human)
End	48,630,717 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	45,367,426 bp
RNA expression pattern
	Top expressed in
	mucosa of transverse colon; ; right frontal lobe; ; cingulate gyrus; ; anterior cingulate cortex; ; prefrontal cortex; ; C1 segment; ; right lobe of liver; ; right hemisphere of cerebellum; ; Brodmann area 9; ; mucosa of ileum;
	Top expressed in
	saccule; ; otic placode; ; aortic valve; ; otic vesicle; ; granulocyte; ; lip; ; epithelium of stomach; ; duodenum; ; ascending aorta; ; crypt of lieberkuhn of small intestine;
	More reference expression data
	n/a
Gene ontology
Molecular function	sphingosine-1-phosphate receptor activity; transferase activity; nucleotide binding; kinase activity; protein binding; ATP binding; D-erythro-sphingosine kinase activity; sphinganine kinase activity; NAD+ kinase activity;
Cellular component	cytoplasm; lysosome; membrane; lysosomal membrane; cytosol; intracellular membrane-bounded organelle; nucleosome; nucleus; mitochondrion; mitochondrial inner membrane; endoplasmic reticulum;
Biological process	phosphorylation; sphinganine-1-phosphate biosynthetic process; female pregnancy; sphingosine metabolic process; sphingosine biosynthetic process; negative regulation of apoptotic process; sphingolipid biosynthetic process; brain development; blood vessel development; positive regulation of cell population proliferation; cell population proliferation; lipid phosphorylation; sphingosine-1-phosphate receptor signaling pathway; metabolism; negative regulation of cell growth; negative regulation of histone deacetylation; positive regulation of mast cell activation involved in immune response; positive regulation of apoptotic process; regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of mast cell degranulation; histone H2A-K5 acetylation; histone H2B-K12 acetylation; epigenetic maintenance of chromatin in transcription-competent conformation; positive regulation of protein kinase C signaling; positive regulation of calcium ion import; negative regulation of histone deacetylase activity; regulation of reactive oxygen species biosynthetic process; cellular response to phorbol 13-acetate 12-myristate; regulation of cytochrome-c oxidase activity; positive regulation of ceramide biosynthetic process; positive regulation of histone H3-K9 acetylation; regulation of ATP biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	56848
	56632
	ENSG00000063176
	ENSMUSG00000057342
	Q9NRA0
	Q9JIA7
	NM_001204158; NM_001204159; NM_001204160; NM_001243876; NM_020126
	NM_001172561; NM_020011; NM_203280
	NP_001191087; NP_001191088; NP_001191089; NP_001230805; NP_064511
	NP_001166032; NP_064395; NP_975009
	Wikidata
View/Edit Human	View/Edit Mouse

Sphingosine kinase 2 is a protein that in humans is encoded by the SPHK2 gene.^[5]

This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.^[5]^[6]

The researchers also found that the expression of sphingosine kinase 2 (SphK2) and the secretion of sphingosine-1-phosphate (S1P) were significantly upregulated in the lungs of CS-exposed mice with COPD-like symptoms.^[7]

Inhibitors

Opaganib

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000063176 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000057342 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: Sphingosine kinase 2". Retrieved 2011-12-22.
↑ [provided by RefSeq, Aug 2011].
↑ Chen Y, Zhang Y, Rao C, Huang J, Qing Q (2023-03-16). "Deletion of sphingosine kinase 2 attenuates cigarette smoke-mediated chronic obstructive pulmonary disease-like symptoms by reducing lung inflammation". Biomolecules and Biomedicine. 23 (2): 259–270. doi:10.17305/bjbms.2022.8034. ISSN 2831-090X. PMC 10113950. PMID 36226596.

Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S (June 2000). "Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform". The Journal of Biological Chemistry. 275 (26): 19513–20. doi:10.1074/jbc.M002759200. PMID 10751414.
Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA (March 2002). "Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling". The Journal of Biological Chemistry. 277 (10): 7996–8003. doi:10.1074/jbc.M111423200. PMID 11777919.
Shu X, Wu W, Mosteller RD, Broek D (November 2002). "Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases". Molecular and Cellular Biology. 22 (22): 7758–68. doi:10.1128/mcb.22.22.7758-7768.2002. PMC 134718. PMID 12391145.
Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S (November 2003). "The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2". FEBS Letters. 554 (1–2): 189–93. Bibcode:2003FEBSL.554..189P. doi:10.1016/S0014-5793(03)01168-2. PMID 14596938. S2CID 41465940.
Hait NC, Sarkar S, Le Stunff H, Mikami A, Maceyka M, Milstien S, Spiegel S (August 2005). "Role of sphingosine kinase 2 in cell migration toward epidermal growth factor". The Journal of Biological Chemistry. 280 (33): 29462–9. doi:10.1074/jbc.M502922200. PMID 15951439.
Okada T, Ding G, Sonoda H, Kajimoto T, Haga Y, Khosrowbeygi A, Gao S, Miwa N, Jahangeer S, Nakamura S (October 2005). "Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis". The Journal of Biological Chemistry. 280 (43): 36318–25. doi:10.1074/jbc.M504507200. PMID 16103110.
Olivera A, Urtz N, Mizugishi K, Yamashita Y, Gilfillan AM, Furumoto Y, Gu H, Proia RL, Baumruker T, Rivera J (February 2006). "IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses". The Journal of Biological Chemistry. 281 (5): 2515–25. doi:10.1074/jbc.M508931200. PMID 16316995.
Sun J, Yan G, Ren A, You B, Liao JK (September 2006). "FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1". Circulation Research. 99 (5): 468–76. doi:10.1161/01.RES.0000239410.65551.b3. PMC 2614439. PMID 16888242.
Hait NC, Bellamy A, Milstien S, Kordula T, Spiegel S (April 2007). "Sphingosine kinase type 2 activation by ERK-mediated phosphorylation". The Journal of Biological Chemistry. 282 (16): 12058–65. doi:10.1074/jbc.M609559200. PMID 17311928.
Ding G, Sonoda H, Yu H, Kajimoto T, Goparaju SK, Jahangeer S, Okada T, Nakamura S (September 2007). "Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2". The Journal of Biological Chemistry. 282 (37): 27493–502. doi:10.1074/jbc.M701641200. PMID 17635916.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000063176 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000057342 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: Sphingosine kinase 2". Retrieved 2011-12-22.

[6] [provided by RefSeq, Aug 2011].

[7] Chen Y, Zhang Y, Rao C, Huang J, Qing Q (2023-03-16). "Deletion of sphingosine kinase 2 attenuates cigarette smoke-mediated chronic obstructive pulmonary disease-like symptoms by reducing lung inflammation". Biomolecules and Biomedicine. 23 (2): 259–270. doi:10.17305/bjbms.2022.8034. ISSN 2831-090X. PMC 10113950. PMID 36226596.

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[2]

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[5]

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[7]

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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SPHK2

Inhibitors

References

Further reading