General Information of Target

Target ID LDTP12817
Target Name Sphingosine kinase 1 (SPHK1)
Gene Name SPHK1
Gene ID 8877
Synonyms
SK1; SPHK; SPK; Sphingosine kinase 1; SK 1; SPK 1; EC 2.7.1.91; Acetyltransferase SPHK1; EC 2.3.1.-
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGTEGPPPPAASRGRQGCLLVPARTKTTIALLYDEESENAYDIRLKLTKEVLTIQKQDVV
CVGGSHQGRNRRTVTLRRQPVGGLGLSIKGGSEHNVPVVISKIFEDQAADQTGMLFVGDA
VLQVNGIHVENATHEEVVHLLRNAGDEVTITVEYLREAPAFLKLPLGSPGPSSDHSSGAS
SPLFDSGLHLNGNSSTTAPSSPSSPIAKDPRYEKRWLDTLSVPLSMARISRYKAGTEKLR
WNAFEVLALDGVSSGILRFYTAQDGTDWLRAVSANIRELTLQNMKMANKCCSPSDQVVHM
GWVNEKLQGADSSQTFRPKFLALKGPSFYVFSTPPVSTFDWVRAERTYHLCEVLFKVHKF
WLTEDCWLQANLYLGLQDFDFEDQRPYCFSIVAGHGKSHVFNVELGSELAMWEKSFQRAT
FMEVQRTGSRTYMCSWQGEMLCFTVDFALGFTCFESKTKNVLWRFKFSQLKGSSDDGKTR
VKLLFQNLDTKQIETKELEFQDLRAVLHCIHSFIAAKVASVDPGFMDSQSLARKYMYSS
Target Type
Clinical trial
Target Bioclass
Enzyme
Subcellular location
Cytoplasm
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-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion. In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway. Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity. In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA.; Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.
TTD ID
T86014
Uniprot ID
Q9NYA1
DrugMap ID
TTOHFIY
Ensemble ID
ENST00000323374.8
HGNC ID
HGNC:11240
ChEMBL ID
CHEMBL4394

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C366(2.48); C402(3.68)  LDD3332  [1]
NAIA_4
 Probe Info 
N.A.  LDD2226  [2]
TFBX
 Probe Info 
N.A.  LDD0148  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A2780 C366(1.70)  LDD2254  [1]
 LDCM0023  KB03 A2780 C366(1.76)  LDD2671  [1]
 LDCM0024  KB05 MKN45 C366(2.48); C402(3.68)  LDD3332  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cathepsin B (CTSB) Peptidase C1 family P07858
TNF receptor-associated factor 6 (TRAF6) TNF receptor-associated factor family Q9Y4K3
Elongation factor 1-alpha 1 (EEF1A1) Classic translation factor GTPase family P68104
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Endophilin-B1 (SH3GLB1) Endophilin family Q9Y371
Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
A-kinase anchor protein SPHKAP (SPHKAP) AKAP110 family Q2M3C7
Four and a half LIM domains protein 2 (FHL2) . Q14192

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fingolimod Small molecular drug DB08868
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phenoxodiol Small molecular drug D03YOS
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Gsk618334 Small molecular drug D0HI1K
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pf-543 Small molecular drug D08SND
Sk1-i Small molecular drug D05SLY
Vpc-94075 Small molecular drug D00YNY
Patented
Click To Hide/Show 11 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Methylbenzenesulfonamide Derivative 1 Small molecular drug D04VDD
Pmid27539678-compound-10 Small molecular drug D0DG7E
Pmid27539678-compound-11 Small molecular drug D0QT5B
Pmid27539678-compound-12 Small molecular drug D07QBL
Pmid27539678-compound-13 Small molecular drug D0HM6Q
Pmid27539678-compound-14 Small molecular drug D0H1BQ
Pmid27539678-compound-16 Small molecular drug D0G2TX
Pmid27539678-compound-17 Small molecular drug D0TR9T
Pmid27539678-compound-6 Small molecular drug D02DLL
Pmid27539678-compound-7 Small molecular drug D0RE9W
Pmid27539678-compound-9 Small molecular drug D0VB2X
Discontinued
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
B-5354a . D02YQJ
F-12509a . D0O0JH

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255