Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYB6PXZ)

DOT Name	Betaine--homocysteine S-methyltransferase 1 (BHMT)
Synonyms	EC 2.1.1.5
Gene Name	BHMT
Related Disease	Cervical cancer ( ) Cervical carcinoma ( ) Primary biliary cholangitis ( ) Alcohol dependence ( ) Attention deficit hyperactivity disorder ( ) Cardiovascular disease ( ) Cleft lip/palate ( ) Cleft palate ( ) Colorectal adenoma ( ) Fatty liver disease ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Isolated cleft palate ( ) Large cell lymphoma ( ) Lymphoma, non-Hodgkin, familial ( ) Lymphosarcoma ( ) Neoplasm ( ) Non-hodgkin lymphoma ( ) Obesity ( ) Polycystic ovarian syndrome ( ) Wilson disease ( ) Fetal growth restriction ( ) Stroke ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Inflammation ( ) Nervous system inflammation ( ) Non-insulin dependent diabetes ( )
UniProt ID	BHMT1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1LT7; 1LT8; 4M3P; 8D45
EC Number	2.1.1.5
Pfam ID	PF02574
Sequence	MPPVGGKKAKKGILERLNAGEIVIGDGGFVFALEKRGYVKAGPWTPEAAVEHPEAVRQLH REFLRAGSNVMQTFTFYASEDKLENRGNYVLEKISGQEVNEAACDIARQVADEGDALVAG GVSQTPSYLSCKSETEVKKVFLQQLEVFMKKNVDFLIAEYFEHVEEAVWAVETLIASGKP VAATMCIGPEGDLHGVPPGECAVRLVKAGASIIGVNCHFDPTISLKTVKLMKEGLEAARL KAHLMSQPLAYHTPDCNKQGFIDLPEFPFGLEPRVATRWDIQKYAREAYNLGVRYIGGCC GFEPYHIRAIAEELAPERGFLPPASEKHGSWGSGLDMHTKPWVRARARKEYWENLRIASG RPYNPSMSKPDGWGVTKGTAELMQQKEATTEQQLKELFEKQKFKSQ
Function	Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.
Tissue Specificity	Found exclusively in liver and kidney.
KEGG Pathway	Glycine, serine and threonine metabolism (hsa00260 ) Cysteine and methionine metabolism (hsa00270 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Choline catabolism (R-HSA-6798163 ) Sulfur amino acid metabolism (R-HSA-1614635 )
BioCyc Pathway	MetaCyc:HS07273-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cervical cancer	DISFSHPF	Definitive	Genetic Variation	[1]
Cervical carcinoma	DIST4S00	Definitive	Genetic Variation	[1]
Primary biliary cholangitis	DIS43E0O	Definitive	Altered Expression	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[4]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[5]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[6]
Cleft palate	DIS6G5TF	Strong	Genetic Variation	[7]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[7]
Large cell lymphoma	DISYZHCP	Strong	Biomarker	[12]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[12]
Lymphosarcoma	DISGYV3F	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[12]
Obesity	DIS47Y1K	Strong	Genetic Variation	[14]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[15]
Wilson disease	DISVS9H7	Strong	Biomarker	[16]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[17]
Stroke	DISX6UHX	moderate	Genetic Variation	[18]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[19]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[19]
Inflammation	DISJUQ5T	Limited	Altered Expression	[20]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[21]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[22]
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⏷ Show the Full List of 28 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Betaine	DMGRZW2	Approved	Betaine--homocysteine S-methyltransferase 1 (BHMT) increases the metabolism of Betaine.	[35]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[26]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[28]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[29]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[34]
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⏷ Show the Full List of 11 Drug(s)

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Betaine--homocysteine S-methyltransferase 1 (BHMT).	[31]
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References

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19	Folate gene polymorphisms MTR A2756G, MTRR A66G, and BHMT G742A and risk for coronary artery disease: a meta-analysis.Genet Test Mol Biomarkers. 2012 Jun;16(6):471-5. doi: 10.1089/gtmb.2011.0237. Epub 2012 Feb 17.
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21	1,25-Dihydroxyvitamin D(3) increases the methionine cycle, CD4(+) T cell DNA methylation and Helios(+)Foxp3(+) T regulatory cells to reverse autoimmune neurodegenerative disease.J Neuroimmunol. 2018 Nov 15;324:100-114. doi: 10.1016/j.jneuroim.2018.09.008. Epub 2018 Sep 21.
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33	Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
34	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
35	Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase. J Biol Chem. 2008 Apr 4;283(14):8939-45. doi: 10.1074/jbc.M710449200. Epub 2008 Jan 29.