Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMS7RNF)

• DOT Name: Collagen alpha-1(XXVI) chain (COL26A1)
• Synonyms: Alpha-1 type XXVI collagen; EMI domain-containing protein 2; Emilin and multimerin domain-containing protein 2; Emu2
• Gene Name: COL26A1
• Related Disease:
  Asthma
  Ataxia-telangiectasia
  Nasal polyp
  Polyp
  Acute myelogenous leukaemia
• UniProt ID: COQA1_HUMAN
• PDB ID: 4AU2; 4AU3; 4BJ3; 7BDU; 7BEE; 7BFI
• Pfam ID: PF01391 ; PF07546
• Sequence:
  MKLALLLPWACCCLCGSALATGFLYPFSAAALQQHGYPEPGAGSPGSGYASRRHWCHHTV
  TRTVSCQVQNGSETVVQRVYQSCRWPGPCANLVSYRTLIRPTYRVSYRTVTVLEWRCCPG
  FTGSNCDEECMNCTRLSDMSERLTTLEAKVLLLEAAERPSSPDNDLPAPESTPPTWNEDF
  LPDAIPLAHPVPRQRRPTGPAGPPGQTGPPGPAGPPGSKGDRGQTGEKGPAGPPGLLGPP
  GPRGLPGEMGRPGPPGPPGPAGNPGPSPNSPQGALYSLQPPTDKDNGDSRLASAIVDTVL
  AGVPGPRGPPGPPGPPGPRGPPGPPGTPGSQGLAGERGTVGPSGEPGVKGEEGEKAATAE
  GEGVQQLREALKILAERVLILEHMIGIHDPLASPEGGSGQDAALRANLKMKRGGAQPDGV
  LAALLGPDPGQKSVDQASSRK
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Genetic Variation	[1]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[1]
Nasal polyp	DISLP3XE	Strong	Biomarker	[1]
Polyp	DISRSLYF	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Collagen alpha-1(XXVI) chain (COL26A1) affects the response to substance of Aspirin.	[11]

4 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 Collagen alpha-1(XXVI) chain (COL26A1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Collagen alpha-1(XXVI) chain (COL26A1).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Collagen alpha-1(XXVI) chain (COL26A1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(XXVI) chain (COL26A1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Collagen alpha-1(XXVI) chain (COL26A1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Collagen alpha-1(XXVI) chain (COL26A1).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Collagen alpha-1(XXVI) chain (COL26A1).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Collagen alpha-1(XXVI) chain (COL26A1).	[9]

References

• [1] Possible role of EMID2 on nasal polyps pathogenesis in Korean asthma patients.BMC Med Genet. 2012 Jan 4;13:2. doi: 10.1186/1471-2350-13-2.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] 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.
• [4] Differential regulation of native estrogen receptor-regulatory elements by estradiol, tamoxifen, and raloxifene. Mol Endocrinol. 2008 Feb;22(2):287-303. doi: 10.1210/me.2007-0340. Epub 2007 Oct 25.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] A possible association of EMID2 polymorphisms with aspirin hypersensitivity in asthma. Immunogenetics. 2011 Jan;63(1):13-21. doi: 10.1007/s00251-010-0490-8. Epub 2010 Nov 18.