Details of Drug-Metabolizing Enzyme (DME)

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

• DME Name: Sulfotransferase 1A1 (SULT1A1)
• Synonyms: Sulfotransferase family cytosolic 1A member 1; Aryl sulfotransferase 1A1; Aryl sulfotransferase 1; Thermostable phenol sulfotransferase; Phenol sulfotransferase 1; Phenol-sulfating phenol sulfotransferase 1; Ts-PST; HAST1/HAST2; OK/SW-cl.88; P-PST 1; ST1A1; STP; STP1; SULT1A1
• Gene Name: SULT1A1
• UniProt ID: ST1A1_HUMAN
• INTEDE ID: DME0008
• Gene ID: 6817
• EC Number:
  EC: 2.8.2.1
  Transferase
  Sulfotransferase
  Sulfotransferase
  EC: 2.8.2.1
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MELIQDTSRPPLEYVKGVPLIKYFAEALGPLQSFQARPDDLLISTYPKSGTTWVSQILDM
  IYQGGDLEKCHRAPIFMRVPFLEFKAPGIPSGMETLKDTPAPRLLKTHLPLALLPQTLLD
  QKVKVVYVARNAKDVAVSYYHFYHMAKVHPEPGTWDSFLEKFMVGEVSYGSWYQHVQEWW
  ELSRTHPVLYLFYEDMKENPKREIQKILEFVGRSLPEETVDFVVQHTSFKEMKKNPMTNY
  TTVPQEFMDHSISPFMRKGMAGDWKTTFTVAQNERFDADYAEKMAGCSLSFRSEL
• Function: This enzyme utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. It also has estrogen sulfotransferase activity and is responsible for the sulfonation and activation of minoxidil. It mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products.
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)

Molecular Interaction Atlas (MIA) of This DME

24 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[1]
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[2]
Apomorphine	DMX38HQ	Parkinson disease	8A00.0	Approved	[3]
Aspirin	DM672AH	Myocardial infarction	BA41-BA43	Approved	[4]
Benzyl alcohol	DMBVYDI	Head and body lice	1G00.0	Approved	[5]
Budesonide	DMJIBAW	Asthma	CA23	Approved	[6]
Celecoxib	DM6LOQU	Rheumatoid arthritis	FA20	Approved	[7]
Cholic acid	DM7OKQV	Peroxisomal disorder	5C57	Approved	[8]
Digitoxin	DMWVIGP	Arrhythmia	BC9Z	Approved	[9]
Ephedrine	DMMV0KW	Asthma	CA23	Approved	[10]
Epinephrine	DM3KJBC	Allergy	4A80-4A85	Approved	[11]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[12]
Liothyronine	DM6IR3P	Hypothyroidism	5A00	Approved	[13]
Methyldopa	DM5I621	Hypertension	BA00-BA04	Approved	[14]
Minoxidil	DMA2Z4F	Hypertension	BA00-BA04	Approved	[15]
Pantoprazole	DMSVOCZ	Gastroesophageal reflux disease	DA22.Z	Approved	[16]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[17]
Pseudoephedrine	DMIVJ0D	Nasal congestion	MD11.9	Approved	[10]
Ritodrine	DM4V6RL	Premature labour	JB00	Approved	[18]
Rotigotine	DMP7X6Q	Parkinson disease	8A00.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Teicoplanin	DMAQ2LK	Bacterial infection	1A00-1C4Z	Approved	[21]
Tibolone	DM78XFG	Anabolic metabolism	5C50-5C8Z	Approved	[22]
Warfarin	DMJYCVW	Atrial fibrillation	BC81.3	Approved	[23]

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CERC-801	DM3SZ7P	N. A.	N. A.	Phase 2	[24]

1 Discontinued Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clioquinol	DM746BZ	N. A.	N. A.	Withdrawn from market	[25]

4 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminobenzoic acid	DMNGW2M	N. A.	N. A.	Investigative	[26]
Diiodo-l-thyronine	DM917FE	Discovery agent	N.A.	Investigative	[13]
L-thyroxine	DM83HWL	Hypogonadism	5A61.0	Investigative	[13]
Triiodo-l-thyronine	DMVJD1A	Discovery agent	N.A.	Investigative	[13]

Experimental Enzyme Kinetic Data of Drugs

Drug Name	Indication	Highest Status	Kinetic Data	REF
Benzyl alcohol	Head and body lice [1G00.0]	Approved	Km = 0.0685 microM	[5]
Liothyronine	Hypothyroidism [5A00]	Approved	Km = 0.084 microM	[13]

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	1.68E-09	-5.32E-01	-8.75E-01
Alopecia	ED70	Skin from scalp	3.88E-01	-5.34E-02	-1.38E-01
Alzheimer's disease	8A20	Entorhinal cortex	8.47E-01	3.57E-02	1.73E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.49E-02	4.31E-01	1.22E+00
Aortic stenosis	BB70	Calcified aortic valve	6.88E-01	3.80E-02	3.18E-02
Apnea	7A40	Hyperplastic tonsil	4.16E-01	2.24E-01	4.55E-01
Arthropathy	FA00-FA5Z	Peripheral blood	6.36E-01	1.20E-02	3.27E-02
Asthma	CA23	Nasal and bronchial airway	2.85E-02	1.23E-01	1.51E-01
Atopic dermatitis	EA80	Skin	9.94E-04	3.59E-01	2.58E+00
Autism	6A02	Whole blood	6.77E-01	-1.14E-01	-2.77E-01
Autoimmune uveitis	9A96	Peripheral monocyte	9.40E-01	-2.44E-02	-4.27E-02
Autosomal dominant monocytopenia	4B04	Whole blood	1.56E-02	-7.60E-01	-1.33E+00
Bacterial infection of gingival	1C1H	Gingival tissue	4.93E-08	3.74E-01	9.66E-01
Batten disease	5C56.1	Whole blood	1.36E-02	-7.37E-01	-4.41E+00
Behcet's disease	4A62	Peripheral blood	9.21E-01	1.16E-01	3.06E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	8.90E-01	-2.90E-02	-1.34E-01
Bladder cancer	2C94	Bladder tissue	1.30E-03	-4.62E-01	-1.61E+00
Breast cancer	2C60-2C6Z	Breast tissue	1.86E-04	2.54E-01	5.19E-01
Cardioembolic stroke	8B11.20	Whole blood	4.53E-01	-1.33E-02	-3.86E-02
Cervical cancer	2C77	Cervical tissue	1.99E-01	2.42E-01	3.18E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	6.58E-01	1.21E-03	2.57E-03
Chronic hepatitis C	1E51.1	Whole blood	7.66E-01	-1.06E-01	-1.98E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.62E-02	-1.87E-01	-4.46E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	6.72E-01	6.81E-02	1.62E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	9.19E-01	9.00E-02	1.84E-01
Colon cancer	2B90	Colon tissue	3.08E-122	-1.86E+00	-4.11E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.80E-01	1.16E-01	3.20E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	8.24E-01	1.10E-01	1.58E-01
Endometriosis	GA10	Endometrium tissue	2.58E-01	-3.40E-01	-4.65E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	1.06E-01	-1.41E-01	-4.50E-01
Familial hypercholesterolemia	5C80.00	Whole blood	1.61E-12	1.01E+00	1.51E+00
Gastric cancer	2B72	Gastric tissue	5.41E-01	-5.26E-01	-8.08E-01
Glioblastopma	2A00.00	Nervous tissue	4.66E-98	-6.77E-01	-1.73E+00
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	1.92E-09	-7.60E-01	-9.59E+01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.12E-02	8.26E-01	9.43E-01
Head and neck cancer	2D42	Head and neck tissue	1.33E-13	-5.98E-01	-6.06E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	5.72E-01	2.42E-02	7.36E-02
Huntington's disease	8A01.10	Whole blood	7.58E-01	3.02E-02	1.04E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	4.10E-01	2.08E-01	5.26E-01
Immunodeficiency	4A00-4A20	Peripheral blood	1.34E-02	-1.61E-01	-8.65E-01
Influenza	1E30	Whole blood	4.30E-01	2.36E-01	5.81E-01
Interstitial cystitis	GC00.3	Bladder tissue	8.76E-01	9.79E-02	2.74E-01
Intracranial aneurysm	8B01.0	Intracranial artery	1.66E-03	6.24E-01	1.39E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.00E-02	-5.31E-01	-8.17E-01
Ischemic stroke	8B11	Peripheral blood	8.20E-01	-1.78E-01	-3.50E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.74E-08	-6.09E-01	-9.05E-01
Lateral sclerosis	8B60.4	Skin	1.33E-02	1.73E-01	2.66E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	7.37E-01	-1.61E-01	-5.99E-01
Liver cancer	2C12.0	Liver tissue	1.59E-12	-1.21E+00	-1.58E+00
Liver failure	DB99.7-DB99.8	Liver tissue	5.18E-01	2.57E-01	4.12E-01
Lung cancer	2C25	Lung tissue	4.57E-88	-1.17E+00	-2.60E+00
Lupus erythematosus	4A40	Whole blood	1.16E-08	5.39E-01	6.44E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	8.72E-02	6.46E-02	2.89E-01
Major depressive disorder	6A70-6A7Z	Whole blood	4.30E-01	-4.93E-02	-6.94E-02
Melanoma	2C30	Skin	3.67E-01	-6.97E-01	-5.48E-01
Multiple myeloma	2A83.1	Peripheral blood	2.30E-01	1.89E-01	5.25E-01
Multiple myeloma	2A83.1	Bone marrow	1.21E-01	3.91E-01	7.16E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	6.22E-02	1.64E-01	5.58E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	8.07E-05	3.02E-01	8.70E-01
Myelofibrosis	2A20.2	Whole blood	1.69E-01	-2.25E-01	-5.39E-01
Myocardial infarction	BA41-BA50	Peripheral blood	2.62E-02	2.51E-01	3.65E-01
Myopathy	8C70.6	Muscle tissue	1.93E-04	4.88E-01	2.67E+00
Neonatal sepsis	KA60	Whole blood	2.91E-07	4.72E-01	6.99E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.38E-07	-7.65E-01	-2.96E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	6.16E-02	-3.96E-01	-6.27E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	6.86E-01	-1.80E-01	-2.64E-01
Olive pollen allergy	CA08.00	Peripheral blood	6.22E-01	1.02E-01	3.01E-01
Oral cancer	2B6E	Oral tissue	5.33E-03	-4.99E-01	-7.60E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	6.74E-01	-5.26E-02	-2.14E-01
Osteoporosis	FB83.1	Bone marrow	8.23E-01	6.63E-03	1.33E-02
Ovarian cancer	2C73	Ovarian tissue	5.19E-02	7.69E-02	1.83E-01
Pancreatic cancer	2C10	Pancreas	1.31E-02	7.29E-01	9.19E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	2.45E-01	1.10E-01	2.25E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.62E-03	4.42E-01	7.42E-01
Pituitary cancer	2D12	Pituitary tissue	1.38E-02	-3.57E-01	-7.63E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	6.08E-01	4.96E-02	1.45E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	4.13E-01	9.76E-02	6.56E-01
Polycythemia vera	2A20.4	Whole blood	7.62E-03	-1.11E-01	-2.49E-01
Pompe disease	5C51.3	Biceps muscle	4.01E-04	9.76E-01	1.57E+00
Preterm birth	KA21.4Z	Myometrium	4.49E-01	-4.54E-02	-9.42E-02
Prostate cancer	2C82	Prostate	3.87E-01	3.66E-01	4.21E-01
Psoriasis	EA90	Skin	2.30E-01	-6.03E-02	-1.32E-01
Rectal cancer	2B92	Rectal colon tissue	7.87E-07	-1.63E+00	-5.54E+00
Renal cancer	2C90-2C91	Kidney	4.58E-02	-8.78E-02	-2.11E-01
Retinoblastoma	2D02.2	Uvea	8.18E-05	1.15E+00	5.93E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.36E-04	6.73E-01	3.00E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	2.97E-02	-1.15E-01	-3.70E-01
Schizophrenia	6A20	Prefrontal cortex	1.78E-01	1.06E-01	1.65E-01
Schizophrenia	6A20	Superior temporal cortex	5.69E-01	-3.98E-02	-1.90E-01
Scleroderma	4A42.Z	Whole blood	1.94E-01	2.30E-01	4.10E-01
Seizure	8A60-8A6Z	Whole blood	8.82E-01	-2.93E-02	-8.27E-02
Sensitive skin	EK0Z	Skin	8.48E-01	5.79E-02	3.07E-01
Sepsis with septic shock	1G41	Whole blood	1.37E-03	2.13E-01	3.00E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	1.60E-02	-5.24E-01	-1.40E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	4.92E-01	-3.10E-01	-7.59E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.76E-01	-2.82E-02	-2.35E-02
Sjogren's syndrome	4A43.2	Salivary gland tissue	5.95E-02	-2.25E-01	-1.69E+00
Skin cancer	2C30-2C3Z	Skin	1.66E-02	-8.90E-02	-1.64E-01
Thrombocythemia	3B63	Whole blood	3.04E-01	1.91E-02	4.46E-02
Thrombocytopenia	3B64	Whole blood	3.67E-01	2.61E-01	2.10E-01
Thyroid cancer	2D10	Thyroid	1.82E-04	-1.89E-01	-4.65E-01
Tibial muscular dystrophy	8C75	Muscle tissue	5.41E-05	6.69E-01	1.57E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	1.62E-02	-5.50E-01	-3.85E+00
Type 2 diabetes	5A11	Liver tissue	9.67E-01	2.92E-01	5.33E-01
Ureter cancer	2C92	Urothelium	5.66E-02	1.05E-01	4.66E-01
Uterine cancer	2C78	Endometrium tissue	1.61E-03	-2.57E-01	-3.75E-01
Vitiligo	ED63.0	Skin	7.75E-01	1.30E-02	3.91E-02

References

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• [2] Regulation of sulfate assimilation in plants: 7. Cysteine inactivation of adenosine 5'-phosphosulfate sulfotransferase in Lemna minor L. Plant Physiol. 1978 Mar;61(3):342-7.
• [3] Sulfation of apomorphine by human sulfotransferases: evidence of a major role for the polymorphic phenol sulfotransferase, SULT1A1. Xenobiotica. 2003 Nov;33(11):1139-48.
• [4] Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents. Curr Drug Metab. 2006 Oct;7(7):745-53.
• [5] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
• [6] Sulfation of budesonide by human cytosolic sulfotransferase, dehydroepiandrosterone-sulfotransferase (DHEA-ST). Drug Metab Dispos. 2002 May;30(5):582-5.
• [7] Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Aquat Toxicol. 2007 Mar 10;81(3):286-92.
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• [9] Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man. Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):226-33.
• [10] Benzylic alcohols as stereospecific substrates and inhibitors for aryl sulfotransferase. Chirality. 1991;3(2):104-11.
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• [12] Proposed role of the sulfotransferase/sulfatase pathway in modulating yolk steroid effects. Integr Comp Biol. 2008 Sep;48(3):419-27.
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• [14] Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities: correlation with methyldopa metabolism. Clin Pharmacol Ther. 1984 Jan;35(1):55-63.
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• [16] Interaction of proton pump inhibitors with cytochromes P450: consequences for drug interactions. Yale J Biol Med. 1996 May-Jun;69(3):203-9.
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• [18] Inhibitory effects of various beverages on ritodrine sulfation by recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3. Pharm Res. 2005 Aug;22(8):1406-10.
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• [20] Tamoxifen-induced adduct formation and cell stress in human endometrial glands. Drug Metab Dispos. 2010 Jan;38(1):200-7.
• [21] The 2.7 A resolution structure of the glycopeptide sulfotransferase Teg14. Acta Crystallogr D Biol Crystallogr. 2010 Dec;66(Pt 12):1278-86.
• [22] Sulfation of tibolone metabolites by human postmenopausal liver and small intestinal sulfotransferases (SULTs). Steroids. 2006 May;71(5):343-51.
• [23] Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine. 2001 Nov;8(6):481-8.
• [24] Sulfation of the galactose residues in the glycosaminoglycan-protein linkage region by recombinant human chondroitin 6-O-sulfotransferase-1. J Biol Chem. 2008 Oct 10;283(41):27438-43.
• [25] Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase. Toxicol Lett. 2011 Oct 10;206(2):229-33.
• [26] Activities of drug metabolizing enzymes in bovine colon epithelial cell cultures. Arch Toxicol. 2003 Nov;77(11):621-9.