Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF7WRSX)

• DOT Name: Carnosine synthase 1 (CARNS1)
• Synonyms: EC 6.3.2.11; ATP-grasp domain-containing protein 1
• Gene Name: CARNS1
• UniProt ID: CRNS1_HUMAN
• EC Number: 6.3.2.11
• Pfam ID: PF18130 ; PF15632
• Sequence:
  MLLCLSPAWLMKVPAPGQPGEAALLVSKAVSFHPGGLTFLDDFVPPRRATYFLAGLGLGP
  GRGREAAELARDLTCPTGASAELARLLEDRLLTRQLLAQQGGVAVPATLAFTYKPPGLLR
  GGDASLGLRLVELSGKEGQETLVKEEVEAFLRSEALGDILQVAVKLSGWRWRGRQAWRLH
  PRAELGAVVDTVLALLEKLEEEESVLVEAVYPPAQLPCSDGPSPGPGLAVRICAVVCRTQ
  GDRPLLSKVVCGVGRGDRPLRHHNSLPRTLEVALAQCGLGEEAQVAAVRQRVKAAAEAAL
  AAVLALEAGLSAEQRGGRRAHTDFLGVDFALTAAGGVLTPVALELNGGLCLEACGALEGL
  WAAPRLGPAADEAVAAPLVETMLRRSARCLMEGKQLLVVGAGGVSKKFVWEAARDYGLQL
  HLVESDPNHFASQLVQTFIHFDMTEHRRDEENARLLAELVRARGLKLDGCFSYWDDCLVL
  TALLCQELGLPCSSPAAMRLAKQKSLTQLHLLHHHGPPWPAPSLHAVPCCPLESEADVER
  AVHQVPLPGVMKLEFGAGAVGVRLVEDAPQCHEHFSRITRDLQGEADHPGIGLGWGNAML
  LMEFVEGTEHDVDLVLFGGRLLAAFVSDNGPTRLPGFTETAACMPTGLAPEQEAQMVQAA
  FRCCLGCGLLDGVFNVELKLTGAGPRLIEINPRMGGFYLRDWILELYGVDLLLAAVMVAC
  GLRPALPTRPRARGHLVGVMCLVSQHLQALSSTASRETLQALHDRGLLRLNLLEEALVPG
  EYEEPYCSVACAGPSPTEARLRLLGLCQGLGIDGPSYPVAHFLSHFK
• Function: Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Histidine metabolism (hsa00340)
  beta-Alanine metabolism (hsa00410)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Histidine catabolism (R-HSA-70921)
• BioCyc Pathway: MetaCyc:MONOMER66-34422

Molecular Interaction Atlas (MIA) 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 Carnosine synthase 1 (CARNS1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carnosine synthase 1 (CARNS1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carnosine synthase 1 (CARNS1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carnosine synthase 1 (CARNS1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Carnosine synthase 1 (CARNS1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carnosine synthase 1 (CARNS1).	[6]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] 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.