Details of Drug-Metabolizing Enzyme (DME)

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

• DME Name: Sphingosine kinase 1 (SPHK1)
• Synonyms: Acetyltransferase SPHK1; Sphingosine protein kinase 1; SK 1; SK1; SPHK1; SPK 1
• Gene Name: SPHK1
• UniProt ID: SPHK1_HUMAN
• INTEDE ID: DME0484
• Gene ID: 8877
• 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:
  MDPAGGPRGVLPRPCRVLVLLNPRGGKGKALQLFRSHVQPLLAEAEISFTLMLTERRNHA
  RELVRSEELGRWDALVVMSGDGLMHEVVNGLMERPDWETAIQKPLCSLPAGSGNALAASL
  NHYAGYEQVTNEDLLTNCTLLLCRRLLSPMNLLSLHTASGLRLFSVLSLAWGFIADVDLE
  SEKYRRLGEMRFTLGTFLRLAALRTYRGRLAYLPVGRVGSKTPASPVVVQQGPVDAHLVP
  LEEPVPSHWTVVPDEDFVLVLALLHSHLGSEMFAAPMGRCAAGVMHLFYVRAGVSRAMLL
  RLFLAMEKGRHMEYECPYLVYVPVVAFRLEPKDGKGVFAVDGELMVSEAVQGQVHPNYFW
  MVSGCVEPPPSWKPQQMPPPEEPL
• Function: This enzyme catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. It 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.
• 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:
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Sphingolipid de novo biosynthesis (R-HSA-1660661)
  VEGFR2 mediated cell proliferation (R-HSA-5218921)
  Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)

Molecular Interaction Atlas (MIA) 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	[9]

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	[9]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	1.48E-01	-1.57E-01	-2.99E-01
Alopecia	ED70	Skin from scalp	1.55E-01	-1.20E-01	-2.92E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.88E-04	1.63E-01	5.74E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	9.17E-01	6.58E-02	2.11E-01
Aortic stenosis	BB70	Calcified aortic valve	6.92E-02	6.90E-01	1.08E+00
Apnea	7A40	Hyperplastic tonsil	1.78E-01	9.91E-01	1.97E+00
Arthropathy	FA00-FA5Z	Peripheral blood	6.22E-01	1.37E-01	6.05E-01
Asthma	CA23	Nasal and bronchial airway	7.99E-06	5.69E-01	5.78E-01
Atopic dermatitis	EA80	Skin	3.21E-06	3.12E-01	1.15E+00
Autism	6A02	Whole blood	4.88E-01	2.16E-02	8.47E-02
Autoimmune uveitis	9A96	Peripheral monocyte	9.79E-01	8.66E-02	6.75E-02
Autosomal dominant monocytopenia	4B04	Whole blood	3.72E-01	7.92E-01	6.42E-01
Bacterial infection of gingival	1C1H	Gingival tissue	1.85E-02	2.00E-01	4.13E-01
Batten disease	5C56.1	Whole blood	5.26E-01	1.05E-01	2.21E-01
Behcet's disease	4A62	Peripheral blood	6.30E-01	-8.07E-02	-2.35E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.48E-01	-6.58E-02	-4.07E-01
Bladder cancer	2C94	Bladder tissue	1.38E-09	1.36E+00	5.33E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.19E-14	2.52E-01	4.33E-01
Cardioembolic stroke	8B11.20	Whole blood	8.16E-01	-7.49E-02	-2.10E-01
Cervical cancer	2C77	Cervical tissue	2.98E-01	1.30E-01	2.04E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.17E-01	4.92E-02	1.91E-01
Chronic hepatitis C	1E51.1	Whole blood	3.58E-01	-3.59E-01	-3.27E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	6.08E-01	9.94E-02	1.91E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	7.09E-01	9.65E-02	2.78E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	3.76E-02	3.21E-01	1.22E+00
Colon cancer	2B90	Colon tissue	6.10E-82	6.94E-01	2.23E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.18E-01	-5.93E-02	-1.85E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	6.09E-01	8.17E-04	1.05E-03
Endometriosis	GA10	Endometrium tissue	5.93E-01	2.33E-01	2.05E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.48E-01	-8.59E-03	-6.37E-02
Familial hypercholesterolemia	5C80.00	Whole blood	1.33E-05	5.05E-01	1.50E+00
Gastric cancer	2B72	Gastric tissue	2.05E-02	1.02E+00	3.23E+00
Glioblastopma	2A00.00	Nervous tissue	6.72E-23	2.98E-01	6.03E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	3.59E-01	-6.61E-01	-9.67E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.04E-02	1.96E+00	1.55E+00
Head and neck cancer	2D42	Head and neck tissue	8.73E-24	1.26E+00	1.32E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	6.40E-01	5.07E-02	2.40E-01
Huntington's disease	8A01.10	Whole blood	6.86E-01	-1.05E-01	-4.00E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	5.64E-01	5.63E-03	6.94E-03
Immunodeficiency	4A00-4A20	Peripheral blood	4.14E-01	3.09E-02	3.70E-01
Influenza	1E30	Whole blood	2.10E-01	-3.40E-01	-1.26E+00
Interstitial cystitis	GC00.3	Bladder tissue	3.66E-03	6.90E-01	2.75E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.59E-01	2.94E-01	3.49E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	5.05E-01	1.01E-02	4.19E-02
Ischemic stroke	8B11	Peripheral blood	2.87E-01	2.20E-01	5.47E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.73E-01	5.63E-02	1.51E-01
Lateral sclerosis	8B60.4	Skin	4.84E-01	-1.57E-01	-3.53E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	1.87E-01	7.17E-02	2.19E-01
Liver cancer	2C12.0	Liver tissue	1.43E-07	7.67E-02	2.73E-01
Liver failure	DB99.7-DB99.8	Liver tissue	4.50E-03	4.68E-01	1.59E+00
Lung cancer	2C25	Lung tissue	2.29E-07	3.10E-01	5.63E-01
Lupus erythematosus	4A40	Whole blood	2.80E-01	4.30E-02	8.93E-02
Major depressive disorder	6A70-6A7Z	Hippocampus	9.63E-02	-6.89E-02	-4.17E-01
Major depressive disorder	6A70-6A7Z	Whole blood	1.08E-01	3.16E-02	8.03E-02
Melanoma	2C30	Skin	7.82E-02	2.31E-01	2.39E-01
Multiple myeloma	2A83.1	Peripheral blood	1.47E-01	7.12E-02	4.34E-01
Multiple myeloma	2A83.1	Bone marrow	1.16E-03	2.21E-01	9.79E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.97E-01	-1.10E-01	-2.17E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.02E-01	-2.24E-01	-3.45E-01
Myelofibrosis	2A20.2	Whole blood	1.23E-02	1.51E-01	7.25E-01
Myocardial infarction	BA41-BA50	Peripheral blood	7.61E-02	5.12E-01	4.63E-01
Myopathy	8C70.6	Muscle tissue	2.14E-03	1.61E-01	2.35E+00
Neonatal sepsis	KA60	Whole blood	4.88E-06	2.33E-01	7.33E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	4.66E-01	-5.72E-01	-9.89E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	4.60E-02	4.37E-01	1.37E+00
Obesity related type 2 diabetes	5A11	Omental adipose tissue	7.86E-01	-9.84E-02	-8.35E-02
Olive pollen allergy	CA08.00	Peripheral blood	9.33E-02	5.80E-01	6.12E-01
Oral cancer	2B6E	Oral tissue	6.24E-11	1.13E+00	1.95E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	1.23E-01	4.09E-01	4.27E-01
Osteoporosis	FB83.1	Bone marrow	5.69E-02	5.69E-01	1.02E+00
Ovarian cancer	2C73	Ovarian tissue	9.50E-01	-2.14E-01	-3.12E-01
Pancreatic cancer	2C10	Pancreas	8.79E-01	1.40E-01	1.92E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	7.93E-01	4.64E-02	1.45E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	3.94E-04	3.56E-01	1.81E+00
Pituitary cancer	2D12	Pituitary tissue	9.24E-02	-3.79E-01	-9.01E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.51E-02	-5.05E-01	-9.90E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	9.81E-01	1.38E-02	1.51E-01
Polycythemia vera	2A20.4	Whole blood	3.30E-03	1.97E-01	9.25E-01
Pompe disease	5C51.3	Biceps muscle	3.27E-01	6.69E-02	5.11E-01
Preterm birth	KA21.4Z	Myometrium	1.03E-01	-7.99E-01	-8.85E-01
Prostate cancer	2C82	Prostate	6.26E-11	-1.30E+00	-2.77E+00
Psoriasis	EA90	Skin	1.02E-02	-1.88E-01	-3.63E-01
Rectal cancer	2B92	Rectal colon tissue	6.88E-06	6.48E-01	2.96E+00
Renal cancer	2C90-2C91	Kidney	8.92E-03	2.09E-01	7.13E-01
Retinoblastoma	2D02.2	Uvea	2.52E-01	-1.53E-02	-2.67E-02
Rheumatoid arthritis	FA20	Synovial tissue	4.66E-07	2.29E+00	5.33E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	4.77E-01	1.69E-03	6.31E-03
Schizophrenia	6A20	Prefrontal cortex	2.66E-02	1.36E-01	3.71E-01
Schizophrenia	6A20	Superior temporal cortex	4.57E-01	4.78E-02	3.68E-01
Scleroderma	4A42.Z	Whole blood	4.89E-01	-6.10E-02	-3.38E-01
Seizure	8A60-8A6Z	Whole blood	2.61E-01	-2.12E-01	-7.28E-01
Sensitive skin	EK0Z	Skin	4.61E-01	1.25E-01	5.12E-01
Sepsis with septic shock	1G41	Whole blood	6.05E-14	2.17E-01	6.38E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.08E-01	1.35E-01	6.12E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	7.04E-02	4.00E-01	9.09E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	2.55E-01	3.27E-02	9.32E-02
Sjogren's syndrome	4A43.2	Salivary gland tissue	6.02E-01	-5.58E-01	-1.33E+00
Skin cancer	2C30-2C3Z	Skin	1.19E-02	3.19E-01	5.36E-01
Thrombocythemia	3B63	Whole blood	5.66E-03	2.17E-01	9.96E-01
Thrombocytopenia	3B64	Whole blood	2.12E-01	1.37E-01	5.57E-01
Thyroid cancer	2D10	Thyroid	4.37E-24	5.56E-01	1.51E+00
Tibial muscular dystrophy	8C75	Muscle tissue	2.13E-05	4.07E-01	1.89E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	5.44E-02	4.42E-01	1.44E+00
Type 2 diabetes	5A11	Liver tissue	4.22E-01	-6.33E-02	-5.27E-01
Ureter cancer	2C92	Urothelium	9.54E-01	-1.47E-02	-8.53E-02
Uterine cancer	2C78	Endometrium tissue	3.07E-01	-1.20E-01	-1.12E-01
Vitiligo	ED63.0	Skin	3.26E-02	1.04E-01	5.27E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Sphingosine kinase 1 (SPHK1) DTT Info
• DME DTT Type: Clinical trial

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenoxodiol	DMBUJVX	Ovarian cancer	2C73	Phase 1/2	[1]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[2]

11 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methylbenzenesulfonamide derivative 1	DMUNME2	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-10	DM61SR0	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-11	DMIKAJC	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-12	DMNIKTA	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-13	DM1J2V8	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-14	DMZ02LA	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-16	DMMDJH8	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-17	DMVG7A5	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-6	DMBKNDE	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-7	DMQAC4K	N. A.	N. A.	Patented	[3]
PMID27539678-Compound-9	DM0Y5NU	N. A.	N. A.	Patented	[3]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
B-5354a	DM8I5UF	Arteriosclerosis	BD40	Terminated	[4]
F-12509A	DM3786U	Arteriosclerosis	BD40	Terminated	[5]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-543	DMC4UHD	Discovery agent	N.A.	Investigative	[6]
SK1-I	DMMYX7C	Discovery agent	N.A.	Investigative	[7]
VPC-94075	DM20AJ4	Vascular disease	BE2Z	Investigative	[8]

References

• [1] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [2] Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.Oncotarget. 2016 Dec 6;7(49):80586-80598.
• [3] Sphingosine kinase inhibitors: a review of patent literature (2006-2015).Expert Opin Ther Pat. 2016 Dec;26(12):1409-1416.
• [4] Characterization of B-5354c, a new sphingosine kinase inhibitor, produced by a marine bacterium. J Antibiot (Tokyo). 2000 Aug;53(8):759-64.
• [5] F-12509A, a new sphingosine kinase inhibitor, produced by a discomycete. J Antibiot (Tokyo). 2000 May;53(5):459-66.
• [6] Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88.
• [7] A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood. 2008 Aug 15;112(4):1382-91.
• [8] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2204).
• [9] Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. J Biol Chem. 2003 Nov 28;278(48):47408-15.