Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HXFCV)

• DOT Name: Histidine ammonia-lyase (HAL)
• Synonyms: Histidase; EC 4.3.1.3
• Gene Name: HAL
• Related Disease: Histidinemia
• UniProt ID: HUTH_HUMAN
• EC Number: 4.3.1.3
• Pfam ID: PF00221
• Sequence:
  MPRYTVHVRGEWLAVPCQDAQLTVGWLGREAVRRYIKNKPDNGGFTSVDDAHFLVRRCKG
  LGLLDNEDRLEVALENNEFVEVVIEGDAMSPDFIPSQPEGVYLYSKYREPEKYIELDGDR
  LTTEDLVNLGKGRYKIKLTPTAEKRVQKSREVIDSIIKEKTVVYGITTGFGKFARTVIPI
  NKLQELQVNLVRSHSSGVGKPLSPERCRMLLALRINVLAKGYSGISLETLKQVIEMFNAS
  CLPYVPEKGTVGASGDLAPLSHLALGLVGEGKMWSPKSGWADAKYVLEAHGLKPVILKPK
  EGLALINGTQMITSLGCEAVERASAIARQADIVAALTLEVLKGTTKAFDTDIHALRPHRG
  QIEVAFRFRSLLDSDHHPSEIAESHRFCDRVQDAYTLRCCPQVHGVVNDTIAFVKNIITT
  ELNSATDNPMVFANRGETVSGGNFHGEYPAKALDYLAIGIHELAAISERRIERLCNPSLS
  ELPAFLVAEGGLNSGFMIAHCTAAALVSENKALCHPSSVDSLSTSAATEDHVSMGGWAAR
  KALRVIEHVEQVLAIELLAACQGIEFLRPLKTTTPLEKVYDLVRSVVRPWIKDRFMAPDI
  EAAHRLLLEQKVWEVAAPYIEKYRMEHIPESRPLSPTAFSLQFLHKKSTKIPESEDL
• KEGG Pathway:
  Histidine metabolism (hsa00340)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Histidine catabolism (R-HSA-70921)
• BioCyc Pathway: MetaCyc:HS01466-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Histidinemia	DIS7LGS9	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Histidine ammonia-lyase (HAL).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histidine ammonia-lyase (HAL).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histidine ammonia-lyase (HAL).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histidine ammonia-lyase (HAL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Histidine ammonia-lyase (HAL).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histidine ammonia-lyase (HAL).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histidine ammonia-lyase (HAL).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Histidine ammonia-lyase (HAL).	[8]
Methoxsalen	DME8FZ9	Approved	Methoxsalen decreases the activity of Histidine ammonia-lyase (HAL).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histidine ammonia-lyase (HAL).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histidine ammonia-lyase (HAL).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histidine ammonia-lyase (HAL).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Histidine ammonia-lyase (HAL).	[12]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Histidine ammonia-lyase (HAL).	[13]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Histidine ammonia-lyase (HAL).	[7]

References

• [1] Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene. Hum Genet. 2005 Apr;116(5):340-6. doi: 10.1007/s00439-004-1232-5. Epub 2005 Jan 27.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J Steroid Biochem Mol Biol. 2003 May;85(1):1-8. doi: 10.1016/s0960-0760(03)00142-0.
• [9] Inhibition of histidine ammonia lyase by 8-methoxypsoralen and psoralen-oxidized photoproducts. Photochem Photobiol. 2010 Nov-Dec;86(6):1272-7. doi: 10.1111/j.1751-1097.2010.00807.x. Epub 2010 Sep 29.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Identification of palmitate-regulated genes in HepG2 cells by applying microarray analysis. Biochim Biophys Acta. 2007 Sep;1770(9):1283-8. doi: 10.1016/j.bbagen.2007.07.001. Epub 2007 Jul 10.