Details of the Target

General Information of Target

Target ID LDTP12490
Target Name Sphingosine kinase 2 (SPHK2)
Gene Name SPHK2
Gene ID 56848
Synonyms
SK2; Sphingosine kinase 2; SK 2; SPK 2; EC 2.7.1.91
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPKRAHWGALSVVLILLWGHPRVALACPHPCACYVPSEVHCTFRSLASVPAGIAKHVERI
NLGFNSIQALSETSFAGLTKLELLMIHGNEIPSIPDGALRDLSSLQVFKFSYNKLRVITG
QTLQGLSNLMRLHIDHNKIEFIHPQAFNGLTSLRLLHLEGNLLHQLHPSTFSTFTFLDYF
RLSTIRHLYLAENMVRTLPASMLRNMPLLENLYLQGNPWTCDCEMRWFLEWDAKSRGILK
CKKDKAYEGGQLCAMCFSPKKLYKHEIHKLKDMTCLKPSIESPLRQNRSRSIEEEQEQEE
DGGSQLILEKFQLPQWSISLNMTDEHGNMVNLVCDIKKPMDVYKIHLNQTDPPDIDINAT
VALDFECPMTRENYEKLWKLIAYYSEVPVKLHRELMLSKDPRVSYQYRQDADEEALYYTG
VRAQILAEPEWVMQPSIDIQLNRRQSTAKKVLLSYYTQYSQTISTKDTRQARGRSWVMIE
PSGAVQRDQTVLEGGPCQLSCNVKASESPSIFWVLPDGSILKAPMDDPDSKFSILSSGWL
RIKSMEPSDSGLYQCIAQVRDEMDRMVYRVLVQSPSTQPAEKDTVTIGKNPGESVTLPCN
ALAIPEAHLSWILPNRRIINDLANTSHVYMLPNGTLSIPKVQVSDSGYYRCVAVNQQGAD
HFTVGITVTKKGSGLPSKRGRRPGAKALSRVREDIVEDEGGSGMGDEENTSRRLLHPKDQ
EVFLKTKDDAINGDKKAKKGRRKLKLWKHSEKEPETNVAEGRRVFESRRRINMANKQINP
ERWADILAKVRGKNLPKGTEVPPLIKTTSPPSLSLEVTPPFPAISPPSASPVQTVTSAEE
SSADVPLLGEEEHVLGTISSASMGLEHNHNGVILVEPEVTSTPLEEVVDDLSEKTEEITS
TEGDLKGTAAPTLISEPYEPSPTLHTLDTVYEKPTHEETATEGWSAADVGSSPEPTSSEY
EPPLDAVSLAESEPMQYFDPDLETKSQPDEDKMKEDTFAHLTPTPTIWVNDSSTSQLFED
STIGEPGVPGQSHLQGLTDNIHLVKSSLSTQDTLLIKKGMKEMSQTLQGGNMLEGDPTHS
RSSESEGQESKSITLPDSTLGIMSSMSPVKKPAETTVGTLLDKDTTTATTTPRQKVAPSS
TMSTHPSRRRPNGRRRLRPNKFRHRHKQTPPTTFAPSETFSTQPTQAPDIKISSQVESSL
VPTAWVDNTVNTPKQLEMEKNAEPTSKGTPRRKHGKRPNKHRYTPSTVSSRASGSKPSPS
PENKHRNIVTPSSETILLPRTVSLKTEGPYDSLDYMTTTRKIYSSYPKVQETLPVTYKPT
SDGKEIKDDVATNVDKHKSDILVTGESITNAIPTSRSLVSTMGEFKEESSPVGFPGTPTW
NPSRTAQPGRLQTGIPVTTSGENLTDPPLLKELEDVDFTSEFLSSLTVSTPFHQEEAGSS
TTLSSIKVEVASSQAETTTLDQDHLETTVAILLSETRPQNHTPTAARMKEPASSSPSTIL
MSLGQTTTTKPALPSPRISQASRDSKENVFLNYVGNPETEATPVNNEGTQHMSGPNELST
PSSDQDAFNLSTKLELEKQVFGSRSLPRGPDSQRQDGRVHASHQLTRVPAKPILPTATVR
LPEMSTQSASRYFVTSQSPRHWTNKPEITTYPSGALPENKQFTTPRLSSTTIPLPLHMSK
PSIPSKFTDRRTDQFNGYSKVFGNNNIPEARNPVGKPPSPRIPHYSNGRLPFFTNKTLSF
PQLGVTRRPQIPTSPAPVMRERKVIPGSYNRIHSHSTFHLDFGPPAPPLLHTPQTTGSPS
TNLQNIPMVSSTQSSISFITSSVQSSGSFHQSSSKFFAGGPPASKFWSLGEKPQILTKSP
QTVSVTAETDTVFPCEATGKPKPFVTWTKVSTGALMTPNTRIQRFEVLKNGTLVIRKVQV
QDRGQYMCTASNLHGLDRMVVLLSVTVQQPQILASHYQDVTVYLGDTIAMECLAKGTPAP
QISWIFPDRRVWQTVSPVEGRITLHENRTLSIKEASFSDRGVYKCVASNAAGADSLAIRL
HVAALPPVIHQEKLENISLPPGLSIHIHCTAKAAPLPSVRWVLGDGTQIRPSQFLHGNLF
VFPNGTLYIRNLAPKDSGRYECVAANLVGSARRTVQLNVQRAAANARITGTSPRRTDVRY
GGTLKLDCSASGDPWPRILWRLPSKRMIDALFSFDSRIKVFANGTLVVKSVTDKDAGDYL
CVARNKVGDDYVVLKVDVVMKPAKIEHKEENDHKVFYGGDLKVDCVATGLPNPEISWSLP
DGSLVNSFMQSDDSGGRTKRYVVFNNGTLYFNEVGMREEGDYTCFAENQVGKDEMRVRVK
VVTAPATIRNKTYLAVQVPYGDVVTVACEAKGEPMPKVTWLSPTNKVIPTSSEKYQIYQD
GTLLIQKAQRSDSGNYTCLVRNSAGEDRKTVWIHVNVQPPKINGNPNPITTVREIAAGGS
RKLIDCKAEGIPTPRVLWAFPEGVVLPAPYYGNRITVHGNGSLDIRSLRKSDSVQLVCMA
RNEGGEARLILQLTVLEPMEKPIFHDPISEKITAMAGHTISLNCSAAGTPTPSLVWVLPN
GTDLQSGQQLQRFYHKADGMLHISGLSSVDAGAYRCVARNAAGHTERLVSLKVGLKPEAN
KQYHNLVSIINGETLKLPCTPPGAGQGRFSWTLPNGMHLEGPQTLGRVSLLDNGTLTVRE
ASVFDRGTYVCRMETEYGPSVTSIPVIVIAYPPRITSEPTPVIYTRPGNTVKLNCMAMGI
PKADITWELPDKSHLKAGVQARLYGNRFLHPQGSLTIQHATQRDAGFYKCMAKNILGSDS
KTTYIHVF
Target Type
Clinical trial
Target Bioclass
Enzyme
Subcellular location
Cytoplasm; Lysosome membrane
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. In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis. 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. 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. In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle. 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. In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels. Also involved in the regulation of glucose and lipid metabolism.
TTD ID
T31989
Uniprot ID
Q9NRA0
DrugMap ID
TTCN0M9
Ensemble ID
ENST00000245222.9
HGNC ID
HGNC:18859
ChEMBL ID
CHEMBL3023

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C262(1.83)  LDD3314  [1]
IA-alkyne
 Probe Info  		C597(2.98)  LDD2184  [2]
NAIA_4
 Probe Info  		N.A.  LDD2226  [3]
IPM
 Probe Info  		N.A.  LDD0005  [4]
PAL-AfBPP Probe
Click To Hide/Show 17 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C055
 Probe Info  		13.18  LDD1752  [5]
C056
 Probe Info  		26.35  LDD1753  [5]
C070
 Probe Info  		11.79  LDD1766  [5]
C072
 Probe Info  		25.81  LDD1768  [5]
C107
 Probe Info  		8.11  LDD1794  [5]
C134
 Probe Info  		28.84  LDD1816  [5]
C135
 Probe Info  		9.58  LDD1817  [5]
C140
 Probe Info  		14.62  LDD1822  [5]
C143
 Probe Info  		13.64  LDD1825  [5]
C169
 Probe Info  		36.00  LDD1849  [5]
C173
 Probe Info  		7.01  LDD1853  [5]
C174
 Probe Info  		4.92  LDD1854  [5]
C225
 Probe Info  		5.94  LDD1898  [5]
C228
 Probe Info  		20.82  LDD1901  [5]
C346
 Probe Info  		16.68  LDD2007  [5]
C367
 Probe Info  		5.66  LDD2028  [5]
C400
 Probe Info  		6.87  LDD2059  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0575  Fragment13 Ramos C597(1.34)  LDD2192  [2]
 LDCM0576  Fragment14 Ramos C597(1.92)  LDD2193  [2]
 LDCM0580  Fragment21 Ramos C597(1.33)  LDD2195  [2]
 LDCM0582  Fragment23 Ramos C597(1.48)  LDD2196  [2]
 LDCM0578  Fragment27 Ramos C597(1.05)  LDD2197  [2]
 LDCM0586  Fragment28 Ramos C597(0.85)  LDD2198  [2]
 LDCM0588  Fragment30 Ramos C597(1.02)  LDD2199  [2]
 LDCM0589  Fragment31 Ramos C597(1.04)  LDD2200  [2]
 LDCM0468  Fragment33 Ramos C597(1.13)  LDD2202  [2]
 LDCM0596  Fragment38 Ramos C597(1.04)  LDD2203  [2]
 LDCM0566  Fragment4 Ramos C597(2.98)  LDD2184  [2]
 LDCM0610  Fragment52 Ramos C597(1.08)  LDD2204  [2]
 LDCM0614  Fragment56 Ramos C597(0.87)  LDD2205  [2]
 LDCM0022  KB02 42-MG-BA C262(2.25)  LDD2244  [1]
 LDCM0023  KB03 42-MG-BA C262(3.08)  LDD2661  [1]
 LDCM0024  KB05 IGR37 C262(1.83)  LDD3314  [1]
 LDCM0627  NUDT7-COV-1 HEK-293T C597(6.54)  LDD2206  [6]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Optineurin (OPTN) . Q96CV9

The Drug(s) Related To This Target

Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Abc294640 Small molecular drug D0X6BX
Investigative
Click To Hide/Show 7 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(R)-2-amino-3-(4-octylphenylamino)Propan-1-ol Small molecular drug D0E3LA
(R)-2-amino-4-hydroxy-n-(4-octylphenyl)Butanamide Small molecular drug D01UUZ
(S)-2-amino-4-hydroxy-n-(4-octylphenyl)Butanamide Small molecular drug D0TC4I
(S)-2-amino-6-hydroxy-n-(4-octylphenyl)Hexanamide Small molecular drug D01XSX
Dimethylspingosine Small molecular drug D0M9DT
Opaganib Small molecular drug DB12764
Rome Small molecular drug D0H2LN

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 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
3 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
4 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
5 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
6 Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening. J Am Chem Soc. 2019 Jun 5;141(22):8951-8968. doi: 10.1021/jacs.9b02822. Epub 2019 May 22.