Sphingosine kinase 1

Sphingosine kinase 1 is an enzyme that in humans is encoded by the SPHK1 gene.[5][6]

SPHK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3VZB, 3VZC, 3VZD, 4L02, 4V24
Identifiers
Aliases	SPHK1, SPHK, sphingosine kinase 1
External IDs	OMIM: 603730 MGI: 1316649 HomoloGene: 39748 GeneCards: SPHK1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q25.1 Start 76,376,584 bp[1] End 76,387,860 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 E2 Start 116,530,925 bp[2] End 116,536,674 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • sphingosine-1-phosphate receptor activity • transferase activity • nucleotide binding • DNA binding • calmodulin binding • kinase activity • GO:0001948 protein binding • protein phosphatase 2A binding • ATP binding • magnesium ion binding • sphinganine kinase activity • D-erythro-sphingosine kinase activity • NAD+ kinase activity • lipid binding • acetyltransferase activity Cellular component • cytoplasm • membrane • cell membrane • cell nucleus • cytosol • clathrin-coated pit • endocytic vesicle • early endosome membrane • presynapse • endosome • endosome membrane • cell junction • synapse Biological process • GO:0007243 intracellular signal transduction • positive regulation of fibroblast proliferation • sphingosine metabolic process • regulation of tumor necrosis factor-mediated signaling pathway • sphingosine biosynthetic process • positive regulation of mitotic cell cycle • sphingolipid biosynthetic process • positive regulation of angiogenesis • positive regulation of cell growth • brain development • blood vessel development • positive regulation of NF-kappaB transcription factor activity • positive regulation of peptidyl-threonine phosphorylation • protein folding • positive regulation of cell proliferation • regulation of interleukin-1 beta production • inflammatory response • sphingoid catabolic process • positive regulation of protein ubiquitination • positive regulation of smooth muscle contraction • calcium-mediated signaling • signal transduction • sphingosine-1-phosphate signaling pathway • lipid phosphorylation • positive regulation of cell migration • negative regulation of apoptotic process • phosphorylation • metabolism • positive regulation of NIK/NF-kappaB signaling • positive regulation of mitotic nuclear division • cellular response to hydrogen peroxide • DNA biosynthetic process • sphingolipid mediated signaling pathway • protein acetylation • regulation of endocytosis • positive regulation of interleukin-17 production • response to tumor necrosis factor • cellular response to vascular endothelial growth factor stimulus • regulation of phagocytosis • regulation of neuroinflammatory response • negative regulation of ceramide biosynthetic process • positive regulation of p38MAPK cascade • regulation of microglial cell activation • regulation of endosomal vesicle fusion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8877	20698
Ensembl	ENSG00000176170	ENSMUSG00000061878
UniProt	Q9NYA1	Q8CI15
RefSeq (mRNA)	NM_001142601 NM_001142602 NM_021972 NM_182965 NM_001355139	NM_001172472 NM_001172473 NM_001172475 NM_011451 NM_025367 NM_001372484 NM_001372485 NM_001372486 NM_001372487 NM_001372488 NM_001372489
RefSeq (protein)	NP_001136073 NP_001136074 NP_068807 NP_892010 NP_001342068	NP_001165943 NP_001165944 NP_001165946 NP_035581 NP_079643 NP_001359413 NP_001359414 NP_001359415 NP_001359416 NP_001359417 NP_001359418
Location (UCSC)	Chr 17: 76.38 – 76.39 Mb	Chr 11: 116.53 – 116.54 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P) SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate (PA), a product of Phospholipase D (PLD)

Sphingosine-1-phosphate (S1P) is a novel lipid messenger with both intracellular and extracellular functions. Intracellularly, it regulates proliferation and survival, and extracellularly, it is a ligand for EDG1. Various stimuli increase cellular levels of S1P by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. Competitive inhibitors of SPHK block formation of S1P and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor and serum.[6]

Interactions

SPHK1 has been shown to interact with TRAF2.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000176170 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061878 - 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.
5. Kohama T, Olivera A, Edsall L, Nagiec MM, Dickson R, Spiegel S (Sep 1998). "Molecular cloning and functional characterization of murine sphingosine kinase". The Journal of Biological Chemistry. 273 (37): 23722–8. doi:10.1074/jbc.273.37.23722. PMID 9726979.
6. "Entrez Gene: SPHK1 sphingosine kinase 1".
7. Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA (Mar 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.

Further reading

• Tsukahara T, Mizuno H, Igarashi Y (Mar 2002). "[Molecular diversity of sphingosine kinase]". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 47 (4 Suppl): 509–13. PMID 11915350.
• Sudo K, Chinen K, Nakamura Y (Nov 1994). "2058 expressed sequence tags (ESTs) from a human fetal lung cDNA library". Genomics. 24 (2): 276–9. doi:10.1006/geno.1994.1616. PMID 7698749.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M (Sep 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S (Jun 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.
• Nava VE, Lacana E, Poulton S, Liu H, Sugiura M, Kono K, Milstien S, Kohama T, Spiegel S (May 2000). "Functional characterization of human sphingosine kinase-1". FEBS Letters. 473 (1): 81–4. doi:10.1016/S0014-5793(00)01510-6. PMID 10802064.
• Melendez AJ, Carlos-Dias E, Gosink M, Allen JM, Takacs L (Jun 2000). "Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution". Gene. 251 (1): 19–26. doi:10.1016/S0378-1119(00)00205-5. PMID 10863092.
• Pitson SM, D'andrea RJ, Vandeleur L, Moretti PA, Xia P, Gamble JR, Vadas MA, Wattenberg BW (Sep 2000). "Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes". The Biochemical Journal. 350 Pt 2 (2): 429–41. doi:10.1042/0264-6021:3500429. PMC 1221270. PMID 10947957.
• Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA (Mar 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.
• Melendez AJ, Khaw AK (May 2002). "Dichotomy of Ca2+ signals triggered by different phospholipid pathways in antigen stimulation of human mast cells". The Journal of Biological Chemistry. 277 (19): 17255–62. doi:10.1074/jbc.M110944200. PMID 11856736.
• Hayashi S, Okada T, Igarashi N, Fujita T, Jahangeer S, Nakamura S (Sep 2002). "Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein". The Journal of Biological Chemistry. 277 (36): 33319–24. doi:10.1074/jbc.M201442200. PMID 12077123.
• Lacaná E, Maceyka M, Milstien S, Spiegel S (Sep 2002). "Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity". The Journal of Biological Chemistry. 277 (36): 32947–53. doi:10.1074/jbc.M202841200. PMID 12080051.
• Johnson KR, Becker KP, Facchinetti MM, Hannun YA, Obeid LM (Sep 2002). "PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA)". The Journal of Biological Chemistry. 277 (38): 35257–62. doi:10.1074/jbc.M203033200. PMID 12124383.
• Pitson SM, Moretti PA, Zebol JR, Zareie R, Derian CK, Darrow AL, Qi J, D'Andrea RJ, Bagley CJ, Vadas MA, Wattenberg BW (Dec 2002). "The nucleotide-binding site of human sphingosine kinase 1". The Journal of Biological Chemistry. 277 (51): 49545–53. doi:10.1074/jbc.M206687200. PMID 12393916.
• Nava VE, Hobson JP, Murthy S, Milstien S, Spiegel S (Nov 2002). "Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells". Experimental Cell Research. 281 (1): 115–27. doi:10.1006/excr.2002.5658. PMID 12441135.
• MacKinnon AC, Buckley A, Chilvers ER, Rossi AG, Haslett C, Sethi T (Dec 2002). "Sphingosine kinase: a point of convergence in the action of diverse neutrophil priming agents". Journal of Immunology. 169 (11): 6394–400. doi:10.4049/jimmunol.169.11.6394. PMID 12444147.

External links

• Paugh SW, Kapitonov D, Spiegel S (2007-11-08). "Sphingosine kinase 1". UCSD-Nature Molecule Pages. Signaling Gateway: University of California San Diego (UCSD) and Nature Publishing Group. doi:10.1038/mp.a002219.01. Retrieved 2008-09-15.