Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DES1RUQ)

DME Name Sphingosine kinase 2 (SPHK2)
Synonyms Acetyltransferase SPHK2; Sphingosine protein kinase 2; SK 2; SK2; SPHK2; SPK 2
Gene Name SPHK2
UniProt ID
SPHK2_HUMAN
INTEDE ID
DME0483
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
56848
EC Number EC: 2.7.1.91
Transferase
Kinase
Phosphotransferase
EC: 2.7.1.91
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPA
RGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTY
PRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRP
PRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDG
IVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDL
LLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTL
GTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSV
SDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKA
ALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVL
MLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQL
GYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP
Function
This enzyme catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions and it also acts on D-erythro-dihydrosphingosine, D- erythro-sphingosine and L-threo-dihydrosphingosine.
KEGG Pathway
Apelin signaling pathway (hsa04371 )
Calcium signaling pathway (hsa04020 )
Fc gamma R-mediated phagocytosis (hsa04666 )
Metabolic pathways (hsa01100 )
Phospholipase D signaling pathway (hsa04072 )
Sphingolipid metabolism (hsa00600 )
Sphingolipid signaling pathway (hsa04071 )
Tuberculosis (hsa05152 )
VEGF signaling pathway (hsa04370 )
Reactome Pathway
Sphingolipid de novo biosynthesis (R-HSA-1660661 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sphingosine-1-phosphate DMJCQKA Acne vulgaris ED80 Phase 1 [5]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
Sphingosine-1-phosphate Acne vulgaris [ED80] Phase 1 Km = 0.014 microM [5]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 9.07E-14 1.48E-01 6.85E-01
Alopecia ED70 Skin from scalp 5.23E-01 -5.22E-03 -1.10E-02
Alzheimer's disease 8A20 Entorhinal cortex 4.32E-01 2.80E-03 1.03E-02
Ankylosing spondylitis FA92.0 Pheripheral blood 2.45E-01 7.51E-02 8.37E-01
Aortic stenosis BB70 Calcified aortic valve 8.84E-01 1.93E-01 5.33E-01
Apnea 7A40 Hyperplastic tonsil 5.65E-01 1.60E-01 5.89E-01
Arthropathy FA00-FA5Z Peripheral blood 7.37E-01 -8.84E-02 -4.72E-01
Asthma CA23 Nasal and bronchial airway 1.13E-01 1.55E-01 1.68E-01
Atopic dermatitis EA80 Skin 7.81E-08 2.80E-01 1.25E+00
Autism 6A02 Whole blood 1.54E-01 -1.64E-01 -6.42E-01
Autoimmune uveitis 9A96 Peripheral monocyte 5.85E-01 1.38E-01 6.27E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.58E-01 1.52E-03 2.69E-02
Bacterial infection of gingival 1C1H Gingival tissue 1.35E-09 2.65E-01 1.10E+00
Batten disease 5C56.1 Whole blood 5.27E-01 -3.59E-02 -2.37E-01
Behcet's disease 4A62 Peripheral blood 6.43E-01 5.68E-02 2.63E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 9.28E-01 -3.83E-02 -1.95E-01
Bladder cancer 2C94 Bladder tissue 1.03E-01 -1.32E-01 -5.04E-01
Breast cancer 2C60-2C6Z Breast tissue 1.29E-02 -1.27E-01 -4.39E-01
Cardioembolic stroke 8B11.20 Whole blood 5.78E-06 2.98E-01 1.11E+00
Cervical cancer 2C77 Cervical tissue 2.05E-01 -4.88E-02 -1.23E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 6.06E-01 -7.28E-02 -3.34E-01
Chronic hepatitis C 1E51.1 Whole blood 3.96E-02 6.30E-02 9.47E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 4.85E-01 -3.76E-02 -1.92E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 2.18E-01 -6.11E-02 -1.95E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 3.88E-01 -1.52E-02 -1.40E-01
Colon cancer 2B90 Colon tissue 1.67E-13 -2.44E-01 -8.47E-01
Coronary artery disease BA80-BA8Z Peripheral blood 8.19E-04 2.74E-01 5.16E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 9.08E-01 1.16E-01 2.97E-01
Endometriosis GA10 Endometrium tissue 8.07E-01 -2.40E-02 -8.10E-02
Familial hypercholesterolemia 5C80.00 Peripheral blood 1.39E-01 1.28E-01 8.60E-01
Familial hypercholesterolemia 5C80.00 Whole blood 5.72E-03 4.33E-01 2.57E+00
Gastric cancer 2B72 Gastric tissue 3.89E-02 4.61E-02 1.09E+00
Glioblastopma 2A00.00 Nervous tissue 1.09E-91 -7.00E-01 -1.55E+00
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 2.29E-02 -9.25E-01 -5.82E+00
Glioma 2A00.0Y-2A00.0Z White matter tissue 6.14E-02 2.74E-01 5.03E-01
Head and neck cancer 2D42 Head and neck tissue 7.46E-12 -2.83E-01 -5.91E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 7.34E-01 6.86E-02 1.65E-01
Huntington's disease 8A01.10 Whole blood 4.59E-01 9.04E-02 4.31E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 4.31E-01 -1.47E-01 -5.10E-01
Immunodeficiency 4A00-4A20 Peripheral blood 1.27E-01 2.00E-01 1.05E+00
Influenza 1E30 Whole blood 2.68E-01 1.58E-01 8.82E-01
Interstitial cystitis GC00.3 Bladder tissue 9.97E-01 -7.92E-02 -3.23E-01
Intracranial aneurysm 8B01.0 Intracranial artery 2.69E-03 3.82E-01 1.40E+00
Irritable bowel syndrome DD91.0 Rectal colon tissue 4.82E-02 -1.79E-01 -4.05E-01
Ischemic stroke 8B11 Peripheral blood 6.11E-01 4.86E-03 4.06E-02
Juvenile idiopathic arthritis FA24 Peripheral blood 9.11E-01 9.81E-04 2.90E-03
Lateral sclerosis 8B60.4 Skin 1.30E-03 1.85E-01 3.39E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 2.99E-01 3.82E-02 6.31E-02
Liver cancer 2C12.0 Liver tissue 7.07E-04 -2.30E-01 -6.43E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.20E-02 -3.14E-01 -9.17E-01
Lung cancer 2C25 Lung tissue 4.29E-10 1.01E-01 4.45E-01
Lupus erythematosus 4A40 Whole blood 2.25E-02 1.48E-02 3.08E-02
Major depressive disorder 6A70-6A7Z Hippocampus 4.23E-01 9.62E-02 4.84E-01
Major depressive disorder 6A70-6A7Z Whole blood 6.69E-01 -6.32E-04 -1.97E-03
Melanoma 2C30 Skin 1.78E-02 4.77E-01 6.35E-01
Multiple myeloma 2A83.1 Peripheral blood 4.85E-01 -1.35E-01 -3.20E-01
Multiple myeloma 2A83.1 Bone marrow 2.38E-05 7.97E-01 3.22E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 3.76E-01 -1.13E-01 -3.06E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 2.98E-01 2.75E-02 1.03E-01
Myelofibrosis 2A20.2 Whole blood 1.11E-01 -9.05E-02 -7.64E-01
Myocardial infarction BA41-BA50 Peripheral blood 4.85E-01 -2.40E-01 -4.15E-01
Myopathy 8C70.6 Muscle tissue 2.63E-01 -1.09E-01 -6.58E-01
Neonatal sepsis KA60 Whole blood 1.61E-03 5.64E-02 2.93E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 1.63E-06 -7.56E-01 -2.95E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 2.25E-01 -1.24E-01 -3.66E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 5.39E-01 -6.97E-02 -5.71E-01
Olive pollen allergy CA08.00 Peripheral blood 1.89E-01 3.36E-02 2.09E-01
Oral cancer 2B6E Oral tissue 2.10E-01 -1.36E-01 -3.95E-01
Osteoarthritis FA00-FA0Z Synovial tissue 6.41E-02 4.24E-01 1.19E+00
Osteoporosis FB83.1 Bone marrow 7.43E-01 3.72E-02 2.19E-01
Ovarian cancer 2C73 Ovarian tissue 8.34E-01 -3.79E-02 -2.27E-01
Pancreatic cancer 2C10 Pancreas 6.97E-01 -1.11E-01 -2.62E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.60E-01 -4.95E-02 -1.55E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 4.77E-02 8.69E-02 8.91E-01
Pituitary cancer 2D12 Pituitary tissue 1.45E-01 2.16E-01 1.16E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 2.57E-02 2.83E-01 1.27E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 8.86E-01 -3.15E-02 -3.72E-01
Polycythemia vera 2A20.4 Whole blood 7.69E-07 -1.13E-01 -8.84E-01
Pompe disease 5C51.3 Biceps muscle 1.85E-01 1.36E-01 6.95E-01
Preterm birth KA21.4Z Myometrium 8.89E-01 -3.98E-03 -1.56E-02
Prostate cancer 2C82 Prostate 1.39E-02 -3.43E-01 -7.18E-01
Psoriasis EA90 Skin 4.65E-05 -3.24E-01 -7.25E-01
Rectal cancer 2B92 Rectal colon tissue 2.79E-02 -2.85E-01 -1.23E+00
Renal cancer 2C90-2C91 Kidney 1.64E-05 -8.95E-01 -2.31E+00
Retinoblastoma 2D02.2 Uvea 3.91E-01 1.17E-01 6.74E-01
Rheumatoid arthritis FA20 Synovial tissue 3.70E-02 1.63E-01 6.60E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 9.72E-01 1.20E-02 8.24E-02
Schizophrenia 6A20 Prefrontal cortex 3.25E-02 -7.14E-02 -1.63E-01
Schizophrenia 6A20 Superior temporal cortex 1.60E-01 -1.44E-01 -1.02E+00
Scleroderma 4A42.Z Whole blood 3.66E-02 1.43E-01 1.07E+00
Seizure 8A60-8A6Z Whole blood 3.25E-01 -9.78E-02 -4.89E-01
Sensitive skin EK0Z Skin 5.18E-01 5.38E-02 6.96E-01
Sepsis with septic shock 1G41 Whole blood 3.79E-02 1.98E-02 8.82E-02
Shwachman-Diamond syndrome 3A70.0 Bone marrow 7.83E-01 -1.04E-01 -6.53E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.58E-01 -1.43E-02 -8.94E-02
Simpson golabi behmel syndrome LD2C Adipose tissue 4.71E-01 -2.23E-02 -4.74E-02
Sjogren's syndrome 4A43.2 Salivary gland tissue 6.76E-01 1.17E-01 4.01E-01
Skin cancer 2C30-2C3Z Skin 6.66E-04 1.52E-01 3.23E-01
Thrombocythemia 3B63 Whole blood 7.04E-03 -1.14E-01 -9.80E-01
Thrombocytopenia 3B64 Whole blood 4.61E-01 4.44E-01 5.35E-01
Thyroid cancer 2D10 Thyroid 6.38E-18 -3.19E-01 -1.17E+00
Tibial muscular dystrophy 8C75 Muscle tissue 6.22E-01 4.55E-02 2.98E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 8.77E-02 -2.23E-01 -1.65E+00
Type 2 diabetes 5A11 Liver tissue 2.15E-01 -2.76E-01 -9.54E-01
Ureter cancer 2C92 Urothelium 7.47E-01 -3.69E-02 -2.42E-01
Uterine cancer 2C78 Endometrium tissue 3.95E-02 1.85E-03 2.86E-03
Vitiligo ED63.0 Skin 6.09E-01 2.71E-02 9.40E-02
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Sphingosine kinase 2 (SPHK2) DTT Info
DME DTT Type Clinical trial
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ABC294640 DMCKPG4 Advanced solid tumour 2A00-2F9Z Phase 3 [1]
6 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(R)-2-amino-3-(4-octylphenylamino)propan-1-ol DMZXT34 Discovery agent N.A. Investigative [2]
(R)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide DMA1EFL Discovery agent N.A. Investigative [2]
(S)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide DM8A1HG Discovery agent N.A. Investigative [2]
(S)-2-amino-6-hydroxy-N-(4-octylphenyl)hexanamide DMG0CSZ Discovery agent N.A. Investigative [2]
DIMETHYLSPINGOSINE DM1OKN0 N. A. N. A. Investigative [3]
ROMe DMAROW1 Discovery agent N.A. Investigative [4]
⏷ Show the Full List of 6 Investigative Drug(s)

References

1 Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
2 Discovery of novel sphingosine kinase 1 inhibitors. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6119-21.
3 Synthesis and evaluation of sphingosine analogues as inhibitors of sphingosine kinases. J Med Chem. 2009 Jun 25;52(12):3618-26.
4 (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. Cell Signal. 2011 Oct;23(10):1590-5.
5 Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. J Biol Chem. 2003 Nov 28;278(48):47408-15.