Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0C7YUD)

• DOT Name: Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4)
• Synonyms: CEA cell adhesion molecule 4; Carcinoembryonic antigen CGM7; Non-specific cross-reacting antigen W236
• Gene Name: CEACAM4
• Related Disease:
  LambertEaton myasthenic syndrome
  Acute lymphocytic leukaemia
  Advanced cancer
  Candidemia
  Carcinoma
  Colon cancer
  Colon carcinoma
  Pancreatic adenocarcinoma
  Adenocarcinoma
  Amyotrophic lateral sclerosis
  Cognitive impairment
  Colorectal carcinoma
  Frontotemporal dementia
  Neoplasm
  Pick disease
• UniProt ID: CEAM4_HUMAN
• Pfam ID: PF07686
• Sequence:
  MGPPSAAPRGGHRPWQGLLITASLLTFWHPPTTVQFTIEALPSSAAEGKDVLLLACNISE
  TIQAYYWHKGKTAEGSPLIAGYITDIQANIPGAAYSGRETVYPNGSLLFQNITLEDAGSY
  TLRTINASYDSDQATGQLHVHQNNVPGLPVGAVAGIVTGVLVGVALVAALVCFLLLSRTG
  RASIQRDLREQPPPASTPGHGPSHRSTFSAPLPSPRTATPIYEELLYSDANIYCQIDHKA
  DVVS
• Function: Granulocyte orphan receptor that acts as an trigger efficient phagocytosis of attached particles.
• Tissue Specificity: Granulocytes.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
LambertEaton myasthenic syndrome	DISN0Q7Q	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Candidemia	DISVKFN7	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[7]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[7]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[8]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[9]
Frontotemporal dementia	DISKYHXL	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[10]
Pick disease	DISP6X50	Limited	Biomarker	[8]

3 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 4 (CEACAM4).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4).	[14]

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 4 (CEACAM4).	[13]

References

• [1] Increased frequency of HLA class II alleles DRB1*0301 and DQB1*0201 in Lambert-Eaton myasthenic syndrome without associated cancer.Hum Immunol. 2000 Aug;61(8):828-33. doi: 10.1016/s0198-8859(00)00135-x.
• [2] Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin.Leukemia. 1994 Dec;8(12):2127-33.
• [3] Synthesis and characterization of a hyperbranched grafting copolymer PEI-g-PLeu for gene and drug co-delivery.J Mater Sci Mater Med. 2018 Apr 17;29(5):47. doi: 10.1007/s10856-018-6057-1.
• [4] The emergence of non-albicans candidemia and evaluation of HiChrome Candida differential agar and VITEK2 YST platform for differentiation of Candida bloodstream isolates in teaching hospital Kandy, Sri Lanka.BMC Microbiol. 2019 Jun 21;19(1):136. doi: 10.1186/s12866-019-1518-3.
• [5] Dysregulation of carcinoembryonic antigen group members CGM2, CD66a (biliary glycoprotein), and nonspecific cross-reacting antigen in colorectal carcinomas. Comparative analysis by northern blot and in situ hybridization.Am J Pathol. 1997 Aug;151(2):521-30.
• [6] Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells.J Gastroenterol. 1997 Apr;32(2):200-5. doi: 10.1007/BF02936368.
• [7] The protein core of the NCA-related pancreatic adenocarcinoma-associated antigen (DD9-Ag) is NCA-50.Pancreas. 1993 Mar;8(2):166-70. doi: 10.1097/00006676-199303000-00005.
• [8] Visual encoding, consolidation, and retrieval in amyotrophic lateral sclerosis: executive function as a mediator, and predictor of performance.Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):193-201. doi: 10.1080/21678421.2016.1272615. Epub 2017 Jan 13.
• [9] Cis-acting elements required for expression of the nonspecific cross-reacting antigen gene in colorectal carcinoma.Gastroenterology. 1997 Mar;112(3):776-82. doi: 10.1053/gast.1997.v112.pm9041239.
• [10] The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos oncogenes in vitro and is spontaneously metastatic in vivo.Cell Mol Biol (Noisy-le-grand). 1998 May;44(3):493-504.
• [11] 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.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] 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.
• [14] 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.