SPHK2

Sphingosine kinase 2 is a protein that in humans is encoded by the SPHK2 gene.

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
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.33 Start 48,619,291 bp End 48,630,717 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 B3 Start 45,358,891 bp End 45,367,426 bp
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 56848 56632 Ensembl ENSG00000063176 ENSMUSG00000057342 UniProt Q9NRA0 Q9JIA7 RefSeq (mRNA) NM_001204158 NM_001204159 NM_001204160 NM_001243876 NM_020126 NM_001172561 NM_020011 NM_203280 RefSeq (protein) NP_001191087 NP_001191088 NP_001191089 NP_001230805 NP_064511 NP_001166032 NP_064395 NP_975009 Location (UCSC) Chr 19: 48.62 – 48.63 Mb Chr 7: 45.36 – 45.37 Mb PubMed search
Wikidata
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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.

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.

Inhibitors

• Opaganib

Further reading

• 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. 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.