Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZG1W8W)

• DOT Name: Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3)
• Synonyms: Carcinoembryonic antigen CGM1; CD antigen CD66d
• Gene Name: CEACAM3
• UniProt ID: CEAM3_HUMAN
• PDB ID: 6AVZ; 6AW0; 6AW1; 6AW3
• Pfam ID: PF07686
• Sequence:
  MGPPSASPHRECIPWQGLLLTASLLNFWNPPTTAKLTIESMPLSVAEGKEVLLLVHNLPQ
  HLFGYSWYKGERVDGNSLIVGYVIGTQQATPGAAYSGRETIYTNASLLIQNVTQNDIGFY
  TLQVIKSDLVNEEATGQFHVYQENAPGLPVGAVAGIVTGVLVGVALVAALVCFLLLAKTG
  RTSIQRDLKEQQPQALAPGRGPSHSSAFSMSPLSTAQAPLPNPRTAASIYEELLKHDTNI
  YCRMDHKAEVAS
• Function: Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis.
• Tissue Specificity: CGM1a, the predominant CGM1 transcript, is granulocyte-specific. Not detected out of the granulocytic lineage, such as monocytes, lymphocytes, spleen, testis, colon, brain, liver, pancreas, thymus, ovary, placenta, skeletal muscle, prostate, small intestine, heart, lung and kidney.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[4]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[8]

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 increases the methylation of Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3).	[7]

References

• [1] 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.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.