Details of Drug Off-Target (DOT)

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

• DOT Name: Intercellular adhesion molecule 5 (ICAM5)
• Synonyms: ICAM-5; Telencephalin
• Gene Name: ICAM5
• Related Disease:
  Colorectal carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Fragile X syndrome
  Head and neck neoplasm
  Hematologic disease
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Colorectal neoplasm
  Enterovirus infection
  Psoriasis
• UniProt ID: ICAM5_HUMAN
• PDB ID: 3BN3; 4OI9; 4OIA; 4OIB
• Pfam ID: PF21146 ; PF03921 ; PF13927
• Sequence:
  MPGPSPGLRRALLGLWAALGLGLFGLSAVSQEPFWADLQPRVAFVERGGSLWLNCSTNCP
  RPERGGLETSLRRNGTQRGLRWLARQLVDIREPETQPVCFFRCARRTLQARGLIRTFQRP
  DRVELMPLPPWQPVGENFTLSCRVPGAGPRASLTLTLLRGAQELIRRSFAGEPPRARGAV
  LTATVLARREDHGANFSCRAELDLRPHGLGLFENSSAPRELRTFSLSPDAPRLAAPRLLE
  VGSERPVSCTLDGLFPASEARVYLALGDQNLSPDVTLEGDAFVATATATASAEQEGARQL
  VCNVTLGGENRETRENVTIYSFPAPLLTLSEPSVSEGQMVTVTCAAGAQALVTLEGVPAA
  VPGQPAQLQLNATENDDRRSFFCDATLDVDGETLIKNRSAELRVLYAPRLDDSDCPRSWT
  WPEGPEQTLRCEARGNPEPSVHCARSDGGAVLALGLLGPVTRALSGTYRCKAANDQGEAV
  KDVTLTVEYAPALDSVGCPERITWLEGTEASLSCVAHGVPPPDVICVRSGELGAVIEGLL
  RVAREHAGTYRCEATNPRGSAAKNVAVTVEYGPRFEEPSCPSNWTWVEGSGRLFSCEVDG
  KPQPSVKCVGSGGATEGVLLPLAPPDPSPRAPRIPRVLAPGIYVCNATNRHGSVAKTVVV
  SAESPPEMDESTCPSHQTWLEGAEASALACAARGRPSPGVRCSREGIPWPEQQRVSREDA
  GTYHCVATNAHGTDSRTVTVGVEYRPVVAELAASPPGGVRPGGNFTLTCRAEAWPPAQIS
  WRAPPGALNIGLSSNNSTLSVAGAMGSHGGEYECAATNAHGRHARRITVRVAGPWLWVAV
  GGAAGGAALLAAGAGLAFYVQSTACKKGEYNVQEAESSGEAVCLNGAGGGAGGAAGAEGG
  PEAAGGAAESPAEGEVFAIQLTSA
• Function: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2).
• Tissue Specificity: Expressed on neurons in the most rostral segment of the mammalian brain, the telencephalon.
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[5]
Head and neck neoplasm	DIS1OB2G	Strong	Altered Expression	[2]
Hematologic disease	DIS9XD9A	Strong	Genetic Variation	[6]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[8]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[10]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[1]
Enterovirus infection	DISH2UDP	Limited	Altered Expression	[11]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Intercellular adhesion molecule 5 (ICAM5).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Intercellular adhesion molecule 5 (ICAM5).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Intercellular adhesion molecule 5 (ICAM5).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Intercellular adhesion molecule 5 (ICAM5).	[16]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Intercellular adhesion molecule 5 (ICAM5).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Intercellular adhesion molecule 5 (ICAM5).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Intercellular adhesion molecule 5 (ICAM5).	[20]

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 decreases the methylation of Intercellular adhesion molecule 5 (ICAM5).	[18]

References

• [1] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [2] ICAM-5 (telencephalin) gene expression in head and neck squamous carcinoma tumorigenesis and perineural invasion!.Oral Oncol. 2005 Jul;41(6):580-8. doi: 10.1016/j.oraloncology.2005.01.002. Epub 2005 Apr 9.
• [3] The genetic polymorphisms of intercellular cell adhesion molecules and breast cancer susceptibility: a meta-analysis.Mol Biol Rep. 2013 Feb;40(2):1855-60. doi: 10.1007/s11033-012-2241-4. Epub 2012 Oct 19.
• [4] Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis.PLoS Med. 2008 May 27;5(5):e114. doi: 10.1371/journal.pmed.0050114.
• [5] Calsyntenin-1 Negatively Regulates ICAM5 Accumulation in Postsynaptic Membrane and Influences Dendritic Spine Maturation in a Mouse Model of Fragile X Syndrome.Front Neurosci. 2019 Oct 18;13:1098. doi: 10.3389/fnins.2019.01098. eCollection 2019.
• [6] Genetic association study of systemic lupus erythematosus and disease subphenotypes in European populations.Clin Rheumatol. 2016 May;35(5):1161-8. doi: 10.1007/s10067-016-3235-8. Epub 2016 Mar 28.
• [7] Neuronal ICAM-5 Plays a Neuroprotective Role in Progressive Neurodegeneration.Front Neurol. 2019 Mar 12;10:205. doi: 10.3389/fneur.2019.00205. eCollection 2019.
• [8] Metastatic lymph node ratio as a prognostic indicator in patients with stage IV colon cancer undergoing resection.J Cancer. 2019 Jun 2;10(11):2534-2540. doi: 10.7150/jca.29216. eCollection 2019.
• [9] ICAM gene cluster SNPs and prostate cancer risk in African Americans.Hum Genet. 2006 Aug;120(1):69-76. doi: 10.1007/s00439-006-0184-3. Epub 2006 May 30.
• [10] Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries.Ann Rheum Dis. 2012 Nov;71(11):1809-14. doi: 10.1136/annrheumdis-2011-201110. Epub 2012 Apr 20.
• [11] Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid.J Virol. 2019 Jul 30;93(16):e00578-19. doi: 10.1128/JVI.00578-19. Print 2019 Aug 15.
• [12] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [13] Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [17] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [18] 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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.