SPHK2

Protein-coding gene in the species Homo sapiens

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

Gene location (Human)

Chr.	Chromosome 19 (human)^[1]

Band	19q13.33	Start	48,619,291 bp^[1]
Band	19q13.33	End	48,630,717 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 7 (mouse)^[2]

Band	7\|7 B3	Start	45,358,891 bp^[2]
Band	7\|7 B3	End	45,367,426 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

cingulate gyrus

prefrontal cortex

right lobe of liver

Brodmann area 9

hypothalamus

substantia nigra

hippocampus proper

amygdala

right lobe of thyroid gland

body of stomach

Top expressed in

saccule

otic placode

aortic valve

epithelium of stomach

duodenum

ascending aorta

crypt of lieberkuhn of small intestine

jejunum

esophagus

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

^[3]

^[4]

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000063176 – Ensembl, May 2017
^ ^a ^b ^c 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.
^ ^a ^b "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. 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.

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase
2.7.2: COOH acceptor	Phosphoglycerate Aspartate kinase
2.7.3: N acceptor	Creatine
2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I/A γ θ ν T7 Taq II/B α δ ε ζ Pfu III/C IV/X β λ μ TDT V/Y η ι κ RNA-directed DNA polymerase Reverse transcriptase Telomerase
RNA polymerase	Template-directed RNA polymerase I II III IV V ssRNAP POLRMT Primase 1 2 PrimPol RNA-dependent RNA polymerase Polyadenylation PAP PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase
Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases
2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases
2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases
2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

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)