Details of the Target
General Information of Target
Target ID | LDTP12817 | |||||
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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.- |
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3D Structure | ||||||
Sequence |
MGTEGPPPPAASRGRQGCLLVPARTKTTIALLYDEESENAYDIRLKLTKEVLTIQKQDVV
CVGGSHQGRNRRTVTLRRQPVGGLGLSIKGGSEHNVPVVISKIFEDQAADQTGMLFVGDA VLQVNGIHVENATHEEVVHLLRNAGDEVTITVEYLREAPAFLKLPLGSPGPSSDHSSGAS SPLFDSGLHLNGNSSTTAPSSPSSPIAKDPRYEKRWLDTLSVPLSMARISRYKAGTEKLR WNAFEVLALDGVSSGILRFYTAQDGTDWLRAVSANIRELTLQNMKMANKCCSPSDQVVHM GWVNEKLQGADSSQTFRPKFLALKGPSFYVFSTPPVSTFDWVRAERTYHLCEVLFKVHKF WLTEDCWLQANLYLGLQDFDFEDQRPYCFSIVAGHGKSHVFNVELGSELAMWEKSFQRAT FMEVQRTGSRTYMCSWQGEMLCFTVDFALGFTCFESKTKNVLWRFKFSQLKGSSDDGKTR VKLLFQNLDTKQIETKELEFQDLRAVLHCIHSFIAAKVASVDPGFMDSQSLARKYMYSS |
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Target Type |
Clinical trial
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Target Bioclass |
Enzyme
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Subcellular location |
Cytoplasm
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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.
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TTD ID | ||||||
Uniprot ID | ||||||
DrugMap ID | ||||||
Ensemble ID | ||||||
HGNC ID | ||||||
ChEMBL ID |
Probe(s) Labeling This Target
ABPP Probe
Probe name | Structure | Binding Site(Ratio) | Interaction ID | Ref | |
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DBIA Probe Info |
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C366(2.48); C402(3.68) | LDD3332 | [1] | |
NAIA_4 Probe Info |
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N.A. | LDD2226 | [2] | |
TFBX Probe Info |
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N.A. | LDD0148 | [3] |
Competitor(s) Related to This Target
The Interaction Atlas With This Target
The Protein(s) Related To This Target
Enzyme
Transporter and channel
Protein name | Family | Uniprot ID | |||
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Endophilin-B1 (SH3GLB1) | Endophilin family | Q9Y371 |
Other
Protein name | Family | Uniprot ID | |||
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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
Drug Name | Drug Type | External ID | |||
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Fingolimod | Small molecular drug | DB08868 |
Phase 2
Drug Name | Drug Type | External ID | |||
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Phenoxodiol | Small molecular drug | D03YOS |
Phase 1
Drug Name | Drug Type | External ID | |||
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Gsk618334 | Small molecular drug | D0HI1K |
Investigative
Drug Name | Drug Type | External ID | |||
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Pf-543 | Small molecular drug | D08SND | |||
Sk1-i | Small molecular drug | D05SLY | |||
Vpc-94075 | Small molecular drug | D00YNY |
Patented
Discontinued
Drug Name | Drug Type | External ID | |||
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B-5354a | . | D02YQJ | |||
F-12509a | . | D0O0JH |
References