Sphingosine kinase 2

Details

Name
Sphingosine kinase 2
Synonyms
  • 2.7.1.91
  • SK 2
  • SK2
Gene Name
SPHK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052519|Sphingosine kinase 2
MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPA
RGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTY
PRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRP
PRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDG
IVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDL
LLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTL
GTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSV
SDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKA
ALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVL
MLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQL
GYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP
Number of residues
654
Molecular Weight
69216.375
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / D-erythro-sphingosine kinase activity / lipid kinase activity / NAD+ kinase activity / nucleosomal histone binding / Ras GTPase binding / sphinganine kinase activity / sphingosine-1-phosphate receptor activity
Processes
blood vessel development / brain development / cellular response to phorbol 13-acetate 12-myristate / cytokine secretion involved in immune response / female pregnancy / histone H2A-K5 acetylation / histone H2B-K12 acetylation / interleukin-13 production / interleukin-6 production / negative regulation of cell growth / negative regulation of histone deacetylase activity / negative regulation of histone deacetylation / phosphorylation / positive regulation of apoptotic process / positive regulation of calcium ion import / positive regulation of cell population proliferation / positive regulation of ceramide biosynthetic process / positive regulation of gene expression, epigenetic / positive regulation of histone H3-K9 acetylation / positive regulation of mast cell activation involved in immune response / positive regulation of mast cell degranulation / positive regulation of protein kinase C signaling / regulation of ATP biosynthetic process / regulation of cytochrome-c oxidase activity / regulation of I-kappaB kinase/NF-kappaB signaling / regulation of reactive oxygen species biosynthetic process / sphinganine-1-phosphate biosynthetic process / sphingolipid biosynthetic process / sphingolipid metabolic process / sphingosine biosynthetic process / sphingosine metabolic process / tumor necrosis factor secretion
Components
cytoplasm / cytosol / endoplasmic reticulum / intracellular membrane-bounded organelle / lysosomal membrane / membrane / mitochondrial inner membrane / mitochondrion / nucleosome / nucleus
General Function
Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:19168031, PubMed:12954646). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Upregulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0052520|Sphingosine kinase 2 (SPHK2)
ATGAATGGACACCTTGAAGCAGAGGAGCAGCAGGACCAGAGGCCAGACCAGGAGCTGACC
GGGAGCTGGGGCCACGGGCCTAGGAGCACCCTGGTCAGGGCTAAGGCCATGGCCCCGCCC
CCACCGCCACTGGCTGCCAGCACCCCGCTCCTCCATGGCGAGTTTGGCTCCTACCCAGCC
CGAGGCCCACGCTTTGCCCTCACCCTTACATCGCAGGCCCTGCACATACAGCGGCTGCGC
CCCAAACCTGAAGCCAGGCCCCGGGGTGGCCTGGTCCCGTTGGCCGAGGTCTCAGGCTGC
TGCACCCTGCGAAGCCGCAGCCCCTCAGACTCAGCGGCCTACTTCTGCATCTACACCTAC
CCTCGGGGCCGGCGCGGGGCCCGGCGCAGAGCCACTCGCACCTTCCGGGCAGATGGGGCC
GCCACCTACGAAGAGAACCGTGCCGAGGCCCAGCGCTGGGCCACTGCCCTCACCTGTCTG
CTCCGAGGACTGCCACTGCCCGGGGATGGGGAGATCACCCCTGACCTGCTACCTCGGCCG
CCCCGGTTGCTTCTATTGGTCAATCCCTTTGGGGGTCGGGGCCTGGCCTGGCAGTGGTGT
AAGAACCACGTGCTTCCCATGATCTCTGAAGCTGGGCTGTCCTTCAACCTCATCCAGACA
GAACGACAGAACCACGCCCGGGAGCTGGTCCAGGGGCTGAGCCTGAGTGAGTGGGATGGC
ATCGTCACGGTCTCGGGAGACGGGCTGCTCCATGAGGTGCTGAACGGGCTCCTAGATCGC
CCTGACTGGGAGGAAGCTGTGAAGATGCCTGTGGGCATCCTCCCCTGCGGCTCGGGCAAC
GCGCTGGCCGGAGCAGTGAACCAGCACGGGGGATTTGAGCCAGCCCTGGGCCTCGACCTG
TTGCTCAACTGCTCACTGTTGCTGTGCCGGGGTGGTGGCCACCCACTGGACCTGCTCTCC
GTGACGCTGGCCTCGGGCTCCCGCTGTTTCTCCTTCCTGTCTGTGGCCTGGGGCTTCGTG
TCAGATGTGGATATCCAGAGCGAGCGCTTCAGGGCCTTGGGCAGTGCCCGCTTCACACTG
GGCACGGTGCTGGGCCTCGCCACACTGCACACCTACCGCGGACGCCTCTCCTACCTCCCC
GCCACTGTGGAACCTGCCTCGCCCACCCCTGCCCATAGCCTGCCTCGTGCCAAGTCGGAG
CTGACCCTAACCCCAGACCCAGCCCCGCCCATGGCCCACTCACCCCTGCATCGTTCTGTG
TCTGACCTGCCTCTTCCCCTGCCCCAGCCTGCCCTGGCCTCTCCTGGCTCGCCAGAACCC
CTGCCCATCCTGTCCCTCAACGGTGGGGGCCCAGAGCTGGCTGGGGACTGGGGTGGGGCT
GGGGATGCTCCGCTGTCCCCGGACCCACTGCTGTCTTCACCTCCTGGCTCTCCCAAGGCA
GCTCTACACTCACCCGTCTCCGAAGGGGCCCCCGTAATTCCCCCATCCTCTGGGCTCCCA
CTTCCCACCCCTGATGCCCGGGTAGGGGCCTCCACCTGCGGCCCGCCCGACCACCTGCTG
CCTCCGCTGGGCACCCCGCTGCCCCCAGACTGGGTGACGCTGGAGGGGGACTTTGTGCTC
ATGTTGGCCATCTCGCCCAGCCACCTAGGCGCTGACCTGGTGGCAGCTCCGCATGCGCGC
TTCGACGACGGCCTGGTGCACCTGTGCTGGGTGCGTAGCGGCATCTCGCGGGCTGCGCTG
CTGCGCCTTTTCTTGGCCATGGAGCGTGGTAGCCACTTCAGCCTGGGCTGTCCGCAGCTG
GGCTACGCCGCGGCCCGTGCCTTCCGCCTAGAGCCGCTCACACCACGCGGCGTGCTCACA
GTGGACGGGGAGCAGGTGGAGTATGGGCCGCTACAGGCACAGATGCACCCTGGCATCGGT
ACACTGCTCACTGGGCCTCCTGGCTGCCCGGGGCGGGAGCCCTGA
Chromosome Location
19
Locus
19q13.33
External Identifiers
ResourceLink
UniProtKB IDQ9NRA0
UniProtKB Entry NameSPHK2_HUMAN
HGNC IDHGNC:18859
General References
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  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Igarashi N, Okada T, Hayashi S, Fujita T, Jahangeer S, Nakamura S: Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. J Biol Chem. 2003 Nov 21;278(47):46832-9. doi: 10.1074/jbc.M306577200. Epub 2003 Sep 2. [Article]
  7. Okada T, Ding G, Sonoda H, Kajimoto T, Haga Y, Khosrowbeygi A, Gao S, Miwa N, Jahangeer S, Nakamura S: Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis. J Biol Chem. 2005 Oct 28;280(43):36318-25. doi: 10.1074/jbc.M504507200. Epub 2005 Aug 15. [Article]
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  11. Schroder B, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H, Elsasser HP, Mann M, Hasilik A: Integral and associated lysosomal membrane proteins. Traffic. 2007 Dec;8(12):1676-86. Epub 2007 Sep 26. [Article]
  12. Leclercq TM, Moretti PA, Vadas MA, Pitson SM: Eukaryotic elongation factor 1A interacts with sphingosine kinase and directly enhances its catalytic activity. J Biol Chem. 2008 Apr 11;283(15):9606-14. doi: 10.1074/jbc.M708782200. Epub 2008 Feb 8. [Article]
  13. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
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  16. Weigert A, Cremer S, Schmidt MV, von Knethen A, Angioni C, Geisslinger G, Brune B: Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells. Blood. 2010 Apr 29;115(17):3531-40. doi: 10.1182/blood-2009-10-243444. Epub 2010 Mar 2. [Article]
  17. Strub GM, Paillard M, Liang J, Gomez L, Allegood JC, Hait NC, Maceyka M, Price MM, Chen Q, Simpson DC, Kordula T, Milstien S, Lesnefsky EJ, Spiegel S: Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J. 2011 Feb;25(2):600-12. doi: 10.1096/fj.10-167502. Epub 2010 Oct 19. [Article]
  18. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  20. Dominguez G, Maddelein ML, Pucelle M, Nicaise Y, Maurage CA, Duyckaerts C, Cuvillier O, Delisle MB: Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer's disease brain. Acta Neuropathol Commun. 2018 Apr 3;6(1):25. doi: 10.1186/s40478-018-0527-z. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12764OpaganibinvestigationalyesinhibitorDetails