Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7W3Q87)

• DOT Name: Collagen alpha-1(XIX) chain (COL19A1)
• Synonyms: Collagen alpha-1(Y) chain
• Gene Name: COL19A1
• Related Disease:
  Amyotrophic lateral sclerosis
  Parkinson disease
• UniProt ID: COJA1_HUMAN
• Pfam ID: PF01391
• Sequence:
  MRLTGPWKLWLWMSIFLLPASTSVTVRDKTEESCPILRIEGHQLTYDNINKLEVSGFDLG
  DSFSLRRAFCESDKTCFKLGSALLIRDTIKIFPKGLPEEYSVAAMFRVRRNAKKERWFLW
  QVLNQQNIPQISIVVDGGKKVVEFMFQATEGDVLNYIFRNRELRPLFDRQWHKLGISIQS
  QVISLYMDCNLIARRQTDEKDTVDFHGRTVIATRASDGKPVDIELHQLKIYCSANLIAQE
  TCCEISDTKCPEQDGFGNIASSWVTAHASKMSSYLPAKQELKDQCQCIPNKGEAGLPGAP
  GSPGQKGHKGEPGENGLHGAPGFPGQKGEQGFEGSKGETGEKGEQGEKGDPALAGLNGEN
  GLKGDLGPHGPPGPKGEKGDTGPPGPPALPGSLGIQGPQGPPGKEGQRGRRGKTGPPGKP
  GPPGPPGPPGIQGIHQTLGGYYNKDNKGNDEHEAGGLKGDKGETGLPGFPGSVGPKGQKG
  EPGEPFTKGEKGDRGEPGVIGSQGVKGEPGDPGPPGLIGSPGLKGQQGSAGSMGPRGPPG
  DVGLPGEHGIPGKQGIKGEKGDPGGIIGPPGLPGPKGEAGPPGKSLPGEPGLDGNPGAPG
  PRGPKGERGLPGVHGSPGDIGPQGIGIPGRTGAQGPAGEPGIQGPRGLPGLPGTPGTPGN
  DGVPGRDGKPGLPGPPGDPIALPLLGDIGALLKNFCGNCQASVPGLKSNKGEEGGAGEPG
  KYDSMARKGDIGPRGPPGIPGREGPKGSKGERGYPGIPGEKGDEGLQGIPGIPGAPGPTG
  PPGLMGRTGHPGPTGAKGEKGSDGPPGKPGPPGPPGIPFNERNGMSSLYKIKGGVNVPSY
  PGPPGPPGPKGDPGPVGEPGAMGLPGLEGFPGVKGDRGPAGPPGIAGMSGKPGAPGPPGV
  PGEPGERGPVGDIGFPGPEGPSGKPGINGKDGIPGAQGIMGKPGDRGPKGERGDQGIPGD
  RGSQGERGKPGLTGMKGAIGPMGPPGNKGSMGSPGHQGPPGSPGIPGIPADAVSFEEIKK
  YINQEVLRIFEERMAVFLSQLKLPAAMLAAQAYGRPGPPGKDGLPGPPGDPGPQGYRGQK
  GERGEPGIGLPGSPGLPGTSALGLPGSPGAPGPQGPPGPSGRCNPEDCLYPVSHAHQRTG
  GN
• Function: May act as a cross-bridge between fibrils and other extracellular matrix molecules. Involved in skeletal myogenesis in the developing esophagus. May play a role in organization of the pericellular matrix or the sphinteric smooth muscle.
• Tissue Specificity: Localized to vascular, neuronal, mesenchymal, and some epithelial basement membrane zones in umbilical cord.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Definitive	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Collagen alpha-1(XIX) chain (COL19A1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(XIX) chain (COL19A1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Collagen alpha-1(XIX) chain (COL19A1).	[5]

References

• [1] Collagen XIX Alpha 1 Improves Prognosis in Amyotrophic Lateral Sclerosis.Aging Dis. 2019 Apr 1;10(2):278-292. doi: 10.14336/AD.2018.0917. eCollection 2019 Apr.
• [2] Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.Neurobiol Aging. 2015 Feb;36(2):1105-9. doi: 10.1016/j.neurobiolaging.2014.10.039. Epub 2014 Nov 5.
• [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] 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.
• [5] 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.