Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVG0P58)

DOT Name	Procollagen galactosyltransferase 1 (COLGALT1)
Synonyms	EC 2.4.1.50; Collagen beta(1-O)galactosyltransferase 1; ColGalT 1; Glycosyltransferase 25 family member 1; Hydroxylysine galactosyltransferase 1
Gene Name	COLGALT1
Related Disease	Brain small vessel disease 3 ( ) Narcolepsy ( ) Porencephaly ( ) Bone osteosarcoma ( ) Osteosarcoma ( ) Simpson-Golabi-Behmel syndrome type 1 ( )
UniProt ID	GT251_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.4.1.50
Pfam ID	PF13704 ; PF01755
Sequence	MAAAPRAGRRRGQPLLALLLLLLAPLPPGAPPGADAYFPEERWSPESPLQAPRVLIALLA RNAAHALPTTLGALERLRHPRERTALWVATDHNMDNTSTVLREWLVAVKSLYHSVEWRPA EEPRSYPDEEGPKHWSDSRYEHVMKLRQAALKSARDMWADYILFVDADNLILNPDTLSLL IAENKTVVAPMLDSRAAYSNFWCGMTSQGYYKRTPAYIPIRKRDRRGCFAVPMVHSTFLI DLRKAASRNLAFYPPHPDYTWSFDDIIVFAFSCKQAEVQMYVCNKEEYGFLPVPLRAHST LQDEAESFMHVQLEVMVKHPPAEPSRFISAPTKTPDKMGFDEVFMINLRRRQDRRERMLR ALQAQEIECRLVEAVDGKAMNTSQVEALGIQMLPGYRDPYHGRPLTKGELGCFLSHYNIW KEVVDRGLQKSLVFEDDLRFEIFFKRRLMNLMRDVEREGLDWDLIYVGRKRMQVEHPEKA VPRVRNLVEADYSYWTLAYVISLQGARKLLAAEPLSKMLPVDEFLPVMFDKHPVSEYKAH FSLRNLHAFSVEPLLIYPTHYTGDDGYVSDTETSVVWNNEHVKTDWDRAKSQKMREQQAL SREAKNSDVLQSPLDSAARDEL
Function	Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen. By acting on collagen glycosylation, facilitates the formation of collagen triple helix. Also involved in the biosynthesis of collagen type IV.
Tissue Specificity	Ubiquitous with higher levels in placenta, heart, lung and spleen.
KEGG Pathway	Lysine degradation (hsa00310 ) Other types of O-glycan biosynthesis (hsa00514 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Collagen biosynthesis and modifying enzymes (R-HSA-1650814 )
BioCyc Pathway	MetaCyc:ENSG00000130309-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Brain small vessel disease 3	DISUOEMC	Strong	Autosomal recessive	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]
Porencephaly	DISXBWXN	Strong	Genetic Variation	[3]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[4]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[4]
Simpson-Golabi-Behmel syndrome type 1	DISYV73N	Limited	Altered Expression	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[10]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Procollagen galactosyltransferase 1 (COLGALT1).	[14]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Procollagen galactosyltransferase 1 (COLGALT1).	[9]
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References

1	Biallelic COLGALT1 variants are associated with cerebral small vessel disease. Ann Neurol. 2018 Dec;84(6):843-853. doi: 10.1002/ana.25367. Epub 2018 Nov 30.
2	Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
3	Collagen glycosylation.Curr Opin Struct Biol. 2019 Jun;56:131-138. doi: 10.1016/j.sbi.2019.01.015. Epub 2019 Feb 26.
4	Collagen Accumulation in Osteosarcoma Cells lacking GLT25D1 Collagen Galactosyltransferase.J Biol Chem. 2016 Aug 26;291(35):18514-24. doi: 10.1074/jbc.M116.723379. Epub 2016 Jul 11.
5	Collagen beta (1-O) galactosyltransferase 1 (GLT25D1) is required for the secretion of high molecular weight adiponectin and affects lipid accumulation.Biosci Rep. 2017 May 17;37(3):BSR20170105. doi: 10.1042/BSR20170105. Print 2017 Jun 30.
6	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
8	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
9	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
10	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
11	Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
12	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
13	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
14	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.