General Information of the Protein
Protein ID
PT01765
Protein Name
Sphingosine kinase 2
Gene Name
SPHK2
Secondarily
Gene Name
SK2
Sequence
MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPARGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTYPRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRPPRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDGIVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDLLLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTLGTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSVSDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKAALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVLMLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQLGYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP
    Show/Hide
Organism
Homo sapiens, Human
Protein Classification
Enzyme
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. Up-regulates 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).
    Show/Hide
Uniprot ID
Primary ID:
Q9NRA0

Secondarily ID:
A0T4C8
B4DU87
Q9BRN1
Q9H0Q2
Q9NWU7
    Show/Hide
HGNC ID
HGNC:18859
Subcellular Location
Cytoplasm
Nucleus
Endoplasmic reticulum
Mitochondrion inner membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Compound ID Compound Name Compound Formula
CP0424577
4-methyl-N-[3-[[2-[(4-methylphenyl)sulfonylamino]phenyl]iminomethyl]phenyl]benzenesulfonamide
   Show/Hide
C27H25N3O4S2
 1
1
Ki = 6900 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0067907
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol
   Show/Hide
C24H26F3N3O2S
 2
1 IC50 = 20 nM
2 IC50 = 100 nM
CP0109512
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol
   Show/Hide
C27H31NO4S
 6
1 IC50 = 356 nM
2 IC50 = 5400 nM
3 IC50 = 17000 nM
4 IC50 > 5000 nM
5 IC50 > 10000 nM
6 Ki = 3.6 nM
CP0079039
(5Z)-3-(2-aminoethyl)-5-[3-(4-butoxyphenyl)propylidene]-1,3-thiazolidine-2,4-dione
   Show/Hide
C18H24N2O3S
 3
1 IC50 = 4300 nM
2 Ki = 4300 nM
3 Ki = 6400 nM
CP0058280
(E)-(2S,3R)-2-Dimethylamino-octadec-4-ene-1,3-diol
   Show/Hide
C20H41NO2
 4
1 IC50 = 16300 nM
2 IC50 = 20000 nM
3 IC50 > 80000 nM
4 Ki = 12000 nM
CP0015606
4-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol
   Show/Hide
C15H11ClN2OS
 4
1 IC50 = 20000 nM
2 Ki = 6700 nM
3 Ki = 7900 nM
4 Ki = 50000 nM
CP0067976
3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide
   Show/Hide
C23H25ClN2O
 3
1 IC50 = 60000 nM
2 Ki = 9800 nM
3 Ki = 10000 nM
CP0519380
(2S)-2-[3-[3-(trifluoromethyl)-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide;hydrochloride
   Show/Hide
C22H20ClF6N5O2
 1
1 Ki = 89 nM
CP0541492
(2S)-2-[[3-[4-[[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]-1,2,4-oxadiazol-5-yl]methyl]pyrrolidine-1-carboximidamide;hydrochloride
   Show/Hide
C24H23ClF3N7OS
 1
1 Ki = 90 nM
CP0709550
(S)-2-(3-(4-Octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide Hydrochloride
   Show/Hide
C21H32ClN5O
 2
1 Ki = 1300 nM
2 Ki = 1400 nM
CP0352767
4-methyl-N-[2-[[2-[(4-methylphenyl)sulfonylamino]phenyl]iminomethyl]phenyl]benzenesulfonamide
   Show/Hide
C27H25N3O4S2
 1
1 Ki = 6900 nM
CP0847908
(S)-2-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)pyrrolidine-1-carboximidamide hydrochloride
   Show/Hide
C22H34ClN5O
 1
1 Ki > 10000 nM
Clinical Information about the Protein
Target 1 ( Sphingosine kinase 2 (SPHK2) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Advanced solid tumour [ICD-11: 2A00-2F9Z]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 ABC294640 Phase 3
Advanced solid tumour