Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DER6XYF)

DME Name Tryptophan 5-hydroxylase 2 (TPH2)
Synonyms Tryptophan 5-monooxygenase 2; Neuronal tryptophan hydroxylase; NTPH; TPH2
Gene Name TPH2
UniProt ID
TPH2_HUMAN
INTEDE ID
DME0174
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Gene ID
121278
EC Number EC: 1.14.16.4
Oxidoreductase
Oxygen paired donor oxidoreductase
Pteridine donor oxidoreductase
EC: 1.14.16.4
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MQPAMMMFSSKYWARRGFSLDSAVPEEHQLLGSSTLNKPNSGKNDDKGNKGSSKREAATE
SGKTAVVFSLKNEVGGLVKALRLFQEKRVNMVHIESRKSRRRSSEVEIFVDCECGKTEFN
ELIQLLKFQTTIVTLNPPENIWTEEEELEDVPWFPRKISELDKCSHRVLMYGSELDADHP
GFKDNVYRQRRKYFVDVAMGYKYGQPIPRVEYTEEETKTWGVVFRELSKLYPTHACREYL
KNFPLLTKYCGYREDNVPQLEDVSMFLKERSGFTVRPVAGYLSPRDFLAGLAYRVFHCTQ
YIRHGSDPLYTPEPDTCHELLGHVPLLADPKFAQFSQEIGLASLGASDEDVQKLATCYFF
TIEFGLCKQEGQLRAYGAGLLSSIGELKHALSDKACVKAFDPKTTCLQECLITTFQEAYF
VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTRSIENVVQDLRSDLNTVCDA
LNKMNQYLGI
Function This enzyme catalyzes the rate-limiting step in 5-HT synthesis.
KEGG Pathway
Folate biosynthesis (hsa00790 )
Metabolic pathways (hsa01100 )
Serotonergic synapse (hsa04726 )
Tryptophan metabolism (hsa00380 )
Reactome Pathway
Serotonin and melatonin biosynthesis (R-HSA-209931 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
2 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [3]
Tetrahydrobiopterin DMINZ4W Malnutrition 5B50-5B71 Approved [4]
1 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sapropterin DM6GE21 Phenylketonuria 5C50.0 Investigative [4]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
L-Tryptophan Depression [6A70-6A7Z] Approved Km = 0.0186 microM [4]
Tetrahydrobiopterin Malnutrition [5B50-5B71] Approved Km = 0.0147 microM [4]

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 3.66E-03 -6.61E-03 -3.86E-02
Alopecia ED70 Skin from scalp 8.92E-01 5.77E-02 2.78E-01
Alzheimer's disease 8A20 Entorhinal cortex 1.55E-05 -1.10E-01 -4.78E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 3.25E-01 -9.90E-02 -8.31E-01
Aortic stenosis BB70 Calcified aortic valve 8.78E-01 -2.30E-01 -4.26E-01
Apnea 7A40 Hyperplastic tonsil 3.47E-01 -2.12E-02 -1.35E-01
Arthropathy FA00-FA5Z Peripheral blood 2.16E-01 2.99E-02 2.25E-01
Asthma CA23 Nasal and bronchial airway 9.62E-01 3.41E-02 1.12E-01
Atopic dermatitis EA80 Skin 9.31E-03 4.57E-02 5.12E-01
Autism 6A02 Whole blood 1.64E-01 -6.47E-02 -3.27E-01
Autoimmune uveitis 9A96 Peripheral monocyte 5.21E-01 -6.42E-02 -3.10E-01
Autosomal dominant monocytopenia 4B04 Whole blood 6.02E-01 5.19E-02 3.68E-01
Bacterial infection of gingival 1C1H Gingival tissue 4.86E-04 -1.03E-01 -5.75E-01
Batten disease 5C56.1 Whole blood 4.76E-01 -1.24E-02 -8.94E-02
Behcet's disease 4A62 Peripheral blood 4.56E-01 -4.09E-02 -1.71E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 5.61E-01 3.34E-02 1.60E-01
Bladder cancer 2C94 Bladder tissue 6.63E-04 5.34E-01 2.54E+00
Breast cancer 2C60-2C6Z Breast tissue 1.56E-09 -6.84E-02 -2.89E-01
Cardioembolic stroke 8B11.20 Whole blood 6.21E-01 6.93E-02 2.47E-01
Cervical cancer 2C77 Cervical tissue 7.05E-03 -1.85E-01 -9.72E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 2.69E-01 -2.72E-02 -2.18E-01
Chronic hepatitis C 1E51.1 Whole blood 3.22E-01 1.25E-01 5.68E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 4.01E-02 7.93E-02 6.06E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.82E-02 -5.14E-02 -3.35E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 3.42E-01 1.86E-02 1.85E-01
Colon cancer 2B90 Colon tissue 3.99E-03 5.06E-02 3.09E-01
Coronary artery disease BA80-BA8Z Peripheral blood 2.79E-02 -1.29E-01 -1.66E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 9.77E-01 -4.33E-02 -4.33E-01
Endometriosis GA10 Endometrium tissue 9.49E-01 3.96E-02 2.19E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 8.67E-01 5.13E-04 4.00E-03
Familial hypercholesterolemia 5C80.00 Whole blood 4.47E-01 -6.06E-02 -3.71E-01
Gastric cancer 2B72 Gastric tissue 9.02E-01 -1.26E-01 -5.86E-01
Glioblastopma 2A00.00 Nervous tissue 4.44E-08 -1.12E-01 -2.22E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 2.59E-02 -2.13E-01 -4.01E+00
Glioma 2A00.0Y-2A00.0Z White matter tissue 2.44E-01 -1.84E-01 -5.92E-01
Head and neck cancer 2D42 Head and neck tissue 1.30E-01 -3.44E-02 -2.58E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 1.04E-01 -2.35E-04 -8.24E-04
Huntington's disease 8A01.10 Whole blood 2.89E-01 -1.49E-02 -1.22E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 9.42E-01 5.44E-02 2.06E-01
Immunodeficiency 4A00-4A20 Peripheral blood 6.84E-01 -2.27E-02 -2.94E-01
Influenza 1E30 Whole blood 2.51E-02 3.37E-01 2.22E+00
Interstitial cystitis GC00.3 Bladder tissue 3.13E-01 5.34E-02 6.20E-01
Intracranial aneurysm 8B01.0 Intracranial artery 3.82E-02 -9.46E-02 -6.00E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 6.04E-02 7.92E-02 2.02E-01
Ischemic stroke 8B11 Peripheral blood 4.63E-01 -2.37E-03 -2.20E-02
Juvenile idiopathic arthritis FA24 Peripheral blood 8.04E-01 4.18E-02 1.11E-01
Lateral sclerosis 8B60.4 Skin 1.34E-02 2.65E-01 2.60E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 9.03E-01 -2.39E-02 -7.18E-02
Liver cancer 2C12.0 Liver tissue 1.38E-01 -4.29E-02 -2.35E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.40E-01 -2.99E-02 -2.72E-01
Lung cancer 2C25 Lung tissue 2.82E-02 -2.46E-03 -1.56E-02
Lupus erythematosus 4A40 Whole blood 4.68E-07 1.55E-01 4.34E-01
Major depressive disorder 6A70-6A7Z Hippocampus 1.16E-01 6.78E-02 3.28E-01
Major depressive disorder 6A70-6A7Z Whole blood 8.70E-01 2.51E-02 1.18E-01
Melanoma 2C30 Skin 2.40E-01 3.20E-02 4.79E-02
Multiple myeloma 2A83.1 Peripheral blood 9.66E-02 1.55E-01 2.02E+00
Multiple myeloma 2A83.1 Bone marrow 8.42E-03 -2.41E-01 -1.07E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 8.59E-01 5.88E-02 2.49E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 1.44E-01 7.01E-02 4.76E-01
Myelofibrosis 2A20.2 Whole blood 2.18E-02 5.06E-02 4.33E-01
Myocardial infarction BA41-BA50 Peripheral blood 6.27E-01 -4.23E-02 -4.13E-02
Myopathy 8C70.6 Muscle tissue 4.50E-01 9.76E-03 8.38E-02
Neonatal sepsis KA60 Whole blood 1.17E-02 5.85E-02 2.91E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 4.76E-02 -2.03E-01 -5.19E-01
Non-alcoholic fatty liver disease DB92 Liver tissue 9.47E-01 6.76E-02 7.34E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 7.04E-01 8.43E-03 2.03E-01
Olive pollen allergy CA08.00 Peripheral blood 8.05E-01 -1.82E-02 -1.44E-01
Oral cancer 2B6E Oral tissue 1.61E-01 -8.66E-02 -3.03E-01
Osteoarthritis FA00-FA0Z Synovial tissue 2.11E-01 1.16E-02 7.98E-02
Osteoporosis FB83.1 Bone marrow 9.71E-01 -7.81E-03 -2.22E-01
Ovarian cancer 2C73 Ovarian tissue 8.34E-02 -1.41E-01 -9.21E-01
Pancreatic cancer 2C10 Pancreas 3.72E-02 -1.47E-01 -5.54E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 6.46E-01 -5.97E-02 -5.03E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.67E-01 7.40E-02 6.75E-01
Pituitary cancer 2D12 Pituitary tissue 1.01E-01 -1.43E-01 -6.95E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 8.59E-01 -2.04E-02 -1.30E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 9.28E-01 2.21E-03 1.77E-02
Polycythemia vera 2A20.4 Whole blood 2.68E-01 2.65E-03 2.13E-02
Pompe disease 5C51.3 Biceps muscle 6.83E-01 -3.40E-02 -3.15E-01
Preterm birth KA21.4Z Myometrium 4.85E-01 0.00E+00 0.00E+00
Prostate cancer 2C82 Prostate 1.02E-01 -2.11E-01 -4.50E-01
Psoriasis EA90 Skin 1.43E-07 -2.16E-01 -7.35E-01
Rectal cancer 2B92 Rectal colon tissue 1.92E-01 -8.06E-02 -4.07E-01
Renal cancer 2C90-2C91 Kidney 1.64E-01 -8.84E-02 -4.44E-01
Retinoblastoma 2D02.2 Uvea 1.29E-02 -1.72E-01 -1.08E+00
Rheumatoid arthritis FA20 Synovial tissue 8.31E-01 -4.56E-02 -2.55E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 9.22E-01 -1.06E-02 -1.21E-01
Schizophrenia 6A20 Prefrontal cortex 1.24E-01 -3.77E-02 -1.50E-01
Schizophrenia 6A20 Superior temporal cortex 7.15E-01 -2.09E-02 -2.45E-01
Scleroderma 4A42.Z Whole blood 8.76E-02 1.12E-01 9.77E-01
Seizure 8A60-8A6Z Whole blood 1.99E-01 -2.59E-02 -1.81E-01
Sensitive skin EK0Z Skin 5.70E-01 0.00E+00 0.00E+00
Sepsis with septic shock 1G41 Whole blood 1.49E-05 7.59E-02 3.29E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 5.42E-01 2.31E-01 8.26E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.88E-02 5.47E-02 7.13E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 7.87E-01 5.93E-02 6.03E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 8.46E-01 -2.59E-02 -5.94E-01
Skin cancer 2C30-2C3Z Skin 2.94E-02 -1.04E-01 -3.16E-01
Thrombocythemia 3B63 Whole blood 4.99E-01 1.65E-02 1.27E-01
Thrombocytopenia 3B64 Whole blood 3.34E-01 0.00E+00 0.00E+00
Thyroid cancer 2D10 Thyroid 2.48E-01 -3.48E-02 -1.77E-01
Tibial muscular dystrophy 8C75 Muscle tissue 7.89E-01 8.11E-02 4.35E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 7.86E-01 -3.86E-02 -4.34E-01
Type 2 diabetes 5A11 Liver tissue 9.71E-01 6.39E-02 2.80E-01
Ureter cancer 2C92 Urothelium 7.30E-01 -3.66E-02 -2.41E-01
Uterine cancer 2C78 Endometrium tissue 1.86E-07 -1.24E-01 -4.94E-01
Vitiligo ED63.0 Skin 1.26E-01 -1.99E-01 -9.92E-01
------------------------------------------------------------------------------------
⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name L-Tryptophan hydroxylase 2 (TPH2) DTT Info
DME DTT Type Literature-reported
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
6-fluorotryptophan DM6YD3U Discovery agent N.A. Investigative [1]
alpha-propyldopacetamide DMQKMX3 Discovery agent N.A. Investigative [2]
fenclonine DMUBO3E Discovery agent N.A. Investigative [2]

References

1 (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology. 1981 Apr;20(4):335-9.
2 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: 1242).
3 Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity. J Neurochem. 2007 Nov;103(3):1111-20.
4 Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2. J Neurochem. 2007 Mar;100(6):1648-57.