Property Summary

NCBI Gene PubMed Count 50
PubMed Score 131.71
PubTator Score 145.60

Knowledge Summary

Patent (11,607)

TINX Plot

  Disease (3)

Disease Target Count
Infarction, Middle Cerebral Artery 25
Disease Target Count P-value
lung cancer 4473 5.7e-03
Disease Target Count Z-score Confidence
Lymphopenia 35 3.574 1.8
Multiple Sclerosis 498 3.492 1.7
Cancer 2346 3.353 1.7

Expression

  Differential Expression (1)

Disease log2 FC p
lung cancer 1.100 5.7e-03

Protein-protein Interaction (5)

Gene RIF (33)

PMID Text
26886371 increased SK and SPL mRNA expression along with reduced sphingosine 1-phosphate levels were more commonly observed in hepatocellular carcinoma tissues.
26494858 ABC294640 may reduce the proliferative capacity of castration-resistant prostate cancer cells through inhibition of both sphingosine kinase 2 and dihydroceramide desaturase.
26337959 Targeting of SphK2 by ABC294640 potently inhibits colorectal cancer cell growth both in vitro and in vivo.
26209696 results define new mechanistic insights for EGF-mediated invasion and novel actions of SK2
25808826 Because of the unique relationship observed after serum depletion, we examined effects of siRNA for SPHK2, and found the role of SPHK2 as a growth or survival factor but not a cell proliferation inhibitor in FCS(-) culture
25455157 Down-regulation of SphK2 increased the effects of all-trans-retinoic acid on colon cancer cells.
25010828 These data illuminate a novel survival mechanism and potential therapeutic target for KSHV-infected endothelial cells: SphK2-associated maintenance of viral latency
24903384 Data show that sphingosine kinase SphK1 and sphingosine-1-phosphate (S1P) receptors S1P1, S1P2, S1P3, and S1P5 were expressed from primary, up to recurrent and secondary glioblastomas, with sphingosine kinase SphK2 levels were highest in primary tumors.
24709100 SPHK2 regulates apoptosis in colon cancer cells.
24686171 Results demonstrated that SK2 regulates MYC, which has a pivotal role in hematologic malignancies.
24486401 SK2 prevents the nuclear translocation of Y416 phosphorylated c-Src and this appears to be independent of S1P4 and might involve an intracellular S1P-dependent mechanism, which is resistant to exogenously added S1P.
24422628 IGF1R mediates insulin-stimulated phosphorylation of both SphK1 and SphK2.
24385109 Silencing of sphingosine kinase 2 (SphK-2) also blocked HDL-induced COX-2/PGI-2 activation.
24140934 these results implicate interrelated mechanisms and SPHK2 inhibition in the induction of PEL cell death by ABC294640 and rationalize evaluation of ABC294640 in clinical trials for the treatment of KSHV-associated lymphoma.
23918304 the expression of SphK2 parallels the progression of NSCLC. The expression of SphK2 might represent a novel and potentially independent biomarker for the prognosis of patients with NSCLC.
23881266 SphK2 plays a controversial role in arthritis.
23359503 The function of SphK1 and SphK2 can be interchangeable in mast cells and is species and cell type determined.
23314175 Sphingosine kinase 2 might function simply to dynamically regulate sphingosine-S1P cycling.
21620961 SK2 functions as a pro-survival protein and is involved in promoting actin rearrangement into membrane ruffles/lamellipodia in response to sphingosine 1-phosphate in MCF-7 breast cancer cells.
21307639 pharmacological inhibition of Sphk2 with the orally bioavailable selective inhibitor, ABC294640, has therapeutic potential in the treatment of chemo- and endocrine therapy- resistant breast cancer.
20237496 Observational study of gene-disease association. (HuGE Navigator)
20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
19490468 SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to rheumatoid arthritis
19240026 Results indicate that SPHK1 and 2 isoforms and neutral sphingomyelinase contribute to the regulation of chemosensitivity by controlling ceramide formation and the downstream Akt pathway in human colon cancer cells.
19168031 A lipid binding domain in Sphk2 that is important for the enzyme's sub-cellular localisation was identified.
18263879 a novel mechanism of regulation of both SK1 and SK2 that is mediated by their interaction with eEF1A.
18178871 These data suggest that differential formation of sphingosine-1-phosphate by SphK1 and SphK2 has distinct and important actions in human mast cells.
17895250 Sphingosine kinase 2, but not sphingosine kinase 1, acted in concert with SPP-1 to regulate recycling of sphingosine into ceramide.
17635916 PKD is a physiologically relevant enzyme for SPHK2 phosphorylation, which leads to its nuclear export for subsequent cellular signaling.
17311928 hSphK2 is phosphorylated on Ser-351 and Thr-578 by ERK1 and phosphorylation of these residues is important for EGF-stimulated migration of MDA-MB-453 cells
16103110 the N-terminal-extended form of sphingosine kinase 2 has a role in serum-dependent regulation of cell proliferation and apoptosis
15951439 Sphingosine kinase 2 plays an important role in migration of MDA-MB-453 cells toward EGF.
14596938 although both sphingosine kinase type 1 (SphK1) and type 2 (SphK2) can phosphorylate FTY720 with low efficiency, SphK2 is much more effective than SphK1

AA Sequence

MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPARGPRFALTLT      1 - 70
SQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTYPRGRRGARRRATRTFRADGA     71 - 140
ATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRPPRLLLLVNPFGGRGLAWQWCKNHVLPMISE    141 - 210
AGLSFNLIQTERQNHARELVQGLSLSEWDGIVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGN    211 - 280
ALAGAVNQHGGFEPALGLDLLLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERF    281 - 350
RALGSARFTLGTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSV    351 - 420
SDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKAALHSPVSEGA    421 - 490
PVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVLMLAISPSHLGADLVAAPHAR    491 - 560
FDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQLGYAAARAFRLEPLTPRGVLTVDGEQVEYGP    561 - 630
LQAQMHPGIGTLLTGPPGCPGREP                                                  631 - 654
//

Text Mined References (54)

PMID Year Title
26886371 2016 Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.
26494858 2015 The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo.
26337959 2015 Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo.
26209696 2015 Intracellular sphingosine kinase 2-derived sphingosine-1-phosphate mediates epidermal growth factor-induced ezrin-radixin-moesin phosphorylation and cancer cell invasion.
25808826 2015 Increased SPHK2 Transcription of Human Colon Cancer Cells in Serum-Depleted Culture: The Involvement of CREB Transcription Factor.
25455157 2014 Down-regulation of sphingosine kinase 2 (SphK2) increases the effects of all-trans-retinoic acid (ATRA) on colon cancer cells.
25010828 2014 Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells.
24903384 2014 The role of sphingosine kinase isoforms and receptors S1P1, S1P2, S1P3, and S1P5 in primary, secondary, and recurrent glioblastomas.
24709100 2014 Sodium butyrate induces apoptosis of human colon cancer cells by modulating ERK and sphingosine kinase 2.
24686171 2014 Sphingosine kinase 2 promotes acute lymphoblastic leukemia by enhancing MYC expression.
24486401 2014 Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth: The role of sphingosine 1-phosphate receptor-4.
24422628 2014 Sphingosine kinase (SphK) 1 and SphK2 play equivalent roles in mediating insulin's mitogenic action.
24385109 2014 High-density lipoprotein induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through sphingosine kinase-2.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24140934 2014 Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV-associated primary effusion lymphoma.
23918304 2014 Prognostic significance of sphingosine kinase 2 expression in non-small cell lung cancer.
23881266 2014 Sphingosine kinase 2: a controversial role in arthritis.
23359503 2013 Usage of sphingosine kinase isoforms in mast cells is species and/or cell type determined.
23314175 2013 The roles of sphingosine kinases 1 and 2 in regulating the Warburg effect in prostate cancer cells.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
23106337 2013 Sphingosine 1-phosphate induces filopodia formation through S1PR2 activation of ERM proteins.
21926972 2011 Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
21707492 2011 Targeting sphingosine-1-phosphate in hematologic malignancies.
21706498 2011 Determination of sphingosine kinase 2 activity using fluorescent sphingosine by capillary electrophoresis.
21620961 2011 (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells.
21495716 2011 Development of amidine-based sphingosine kinase 1 nanomolar inhibitors and reduction of sphingosine 1-phosphate in human leukemia cells.
21307639 2011 Targeting NF?B mediated breast cancer chemoresistance through selective inhibition of sphingosine kinase-2.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20197547 2010 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
19490468 2009 Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720.
19240026 2009 Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and Akt activation.
19168031 2009 A lipid binding domain in sphingosine kinase 2.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18263879 2008 Eukaryotic elongation factor 1A interacts with sphingosine kinase and directly enhances its catalytic activity.
18178871 2008 Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions.
17897319 2007 Integral and associated lysosomal membrane proteins.
17895250 2007 Recycling of sphingosine is regulated by the concerted actions of sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2.
17635916 2007 Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2.
17311928 2007 Sphingosine kinase type 2 activation by ERK-mediated phosphorylation.
16888242 2006 FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16316995 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.
16103110 2005 Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis.
15951439 2005 Role of sphingosine kinase 2 in cell migration toward epidermal growth factor.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15057824 2004 The DNA sequence and biology of human chromosome 19.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14596938 2003 The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12391145 2002 Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.
11777919 2002 Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
10751414 2000 Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform.