Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGPZHR9)

DOT Name	Gamma-glutamylaminecyclotransferase (GGACT)
Synonyms	GGACT; EC 4.3.2.8; AIG2-like domain-containing protein 1; Gamma-glutamylamine cyclotransferase
Gene Name	GGACT
Related Disease	Alzheimer disease ( ) Asthma ( )
UniProt ID	GGACT_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3JUB; 3JUC; 3JUD
EC Number	4.3.2.8
Pfam ID	PF06094
Sequence	MALVFVYGTLKRGQPNHRVLRDGAHGSAAFRARGRTLEPYPLVIAGEHNIPWLLHLPGSG RLVEGEVYAVDERMLRFLDDFESCPALYQRTVLRVQLLEDRAPGAEEPPAPTAVQCFVYS RATFPPEWAQLPHHDSYDSEGPHGLRYNPRENR
Function	Contributes to degradation of proteins cross-linked by transglutaminases by degrading the cross-link between a lysine and a glutamic acid residue. Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine. Inactive with L-gamma-glutamyl-alpha-amino acid substrates such as L-gamma-glutamyl-L-alpha-cysteine and L-gamma-glutamyl-L-alpha-alanine.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[2]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gamma-glutamylaminecyclotransferase (GGACT).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Gamma-glutamylaminecyclotransferase (GGACT).	[4]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Gamma-glutamylaminecyclotransferase (GGACT).	[5]
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References

1	Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
2	Association of ADAM33 gene polymorphisms with asthma in Indian children.J Hum Genet. 2011 Mar;56(3):188-95. doi: 10.1038/jhg.2010.157. Epub 2010 Dec 23.
3	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
4	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.
5	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.