Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCGC4DM)

• DOT Name: Collagen alpha-3(V) chain (COL5A3)
• Synonyms: Collagen alpha-3(V) chain
• Gene Name: COL5A3
• Related Disease:
  Ehlers-Danlos syndrome
  Prostate cancer
  Prostate neoplasm
• UniProt ID: CO5A3_HUMAN
• Pfam ID: PF01410 ; PF01391
• Sequence:
  MGNRRDLGQPRAGLCLLLAALQLLPGTQADPVDVLKALGVQGGQAGVPEGPGFCPQRTPE
  GDRAFRIGQASTLGIPTWELFPEGHFPENFSLLITLRGQPANQSVLLSIYDERGARQLGL
  ALGPALGLLGDPFRPLPQQVNLTDGRWHRVAVSIDGEMVTLVADCEAQPPVLGHGPRFIS
  IAGLTVLGTQDLGEKTFEGDIQELLISPDPQAAFQACERYLPDCDNLAPAATVAPQGEPE
  TPRPRRKGKGKGRKKGRGRKGKGRKKNKEIWTSSPPPDSAENQTSTDIPKTETPAPNLPP
  TPTPLVVTSTVTTGLNATILERSLDPDSGTELGTLETKAAREDEEGDDSTMGPDFRAAEY
  PSRTQFQIFPGAGEKGAKGEPAVIEKGQQFEGPPGAPGPQGVVGPSGPPGPPGFPGDPGP
  PGPAGLPGIPGIDGIRGPPGTVIMMPFQFAGGSFKGPPVSFQQAQAQAVLQQTQLSMKGP
  PGPVGLTGRPGPVGLPGHPGLKGEEGAEGPQGPRGLQGPHGPPGRVGKMGRPGADGARGL
  PGDTGPKGDRGFDGLPGLPGEKGQRGDFGHVGQPGPPGEDGERGAEGPPGPTGQAGEPGP
  RGLLGPRGSPGPTGRPGVTGIDGAPGAKGNVGPPGEPGPPGQQGNHGSQGLPGPQGLIGT
  PGEKGPPGNPGIPGLPGSDGPLGHPGHEGPTGEKGAQGPPGSAGPPGYPGPRGVKGTSGN
  RGLQGEKGEKGEDGFPGFKGDVGLKGDQGKPGAPGPRGEDGPEGPKGQAGQAGEEGPPGS
  AGEKGKLGVPGLPGYPGRPGPKGSIGFPGPLGPIGEKGKSGKTGQPGLEGERGPPGSRGE
  RGQPGATGQPGPKGDVGQDGAPGIPGEKGLPGLQGPPGFPGPKGPPGHQGKDGRPGHPGQ
  RGELGFQGQTGPPGPAGVLGPQGKTGEVGPLGERGPPGPPGPPGEQGLPGLEGREGAKGE
  LGPPGPLGKEGPAGLRGFPGPKGGPGDPGPTGLKGDKGPPGPVGANGSPGERGPLGPAGG
  IGLPGQSGSEGPVGPAGKKGSRGERGPPGPTGKDGIPGPLGPLGPPGAAGPSGEEGDKGD
  VGAPGHKGSKGDKGDAGPPGQPGIRGPAGHPGPPGADGAQGRRGPPGLFGQKGDDGVRGF
  VGVIGPPGLQGLPGPPGEKGEVGDVGSMGPHGAPGPRGPQGPTGSEGTPGLPGGVGQPGA
  VGEKGERGDAGDPGPPGAPGIPGPKGDIGEKGDSGPSGAAGPPGKKGPPGEDGAKGSVGP
  TGLPGDLGPPGDPGVSGIDGSPGEKGDPGDVGGPGPPGASGEPGAPGPPGKRGPSGHMGR
  EGREGEKGAKGEPGPDGPPGRTGPMGARGPPGRVGPEGLRGIPGPVGEPGLLGAPGQMGP
  PGPLGPSGLPGLKGDTGPKGEKGHIGLIGLIGPPGEAGEKGDQGLPGVQGPPGPKGDPGP
  PGPIGSLGHPGPPGVAGPLGQKGSKGSPGSMGPRGDTGPAGPPGPPGAPAELHGLRRRRR
  FVPVPLPVVEGGLEEVLASLTSLSLELEQLRRPPGTAERPGLVCHELHRNHPHLPDGEYW
  IDPNQGCARDSFRVFCNFTAGGETCLYPDKKFEIVKLASWSKEKPGGWYSTFRRGKKFSY
  VDADGSPVNVVQLNFLKLLSATARQNFTYSCQNAAAWLDEATGDYSHSARFLGTNGEELS
  FNQTTAATVSVPQDGCRLRKGQTKTLFEFSSSRAGFLPLWDVAATDFGQTNQKFGFELGP
  VCFSS
• Function: Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin.
• Tissue Specificity: Detected in fibroblasts (at protein level) . Detected in urine (at protein level) .
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Extracellular matrix organization (R-HSA-1474244)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Signaling by PDGF (R-HSA-186797)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Integrin cell surface interactions (R-HSA-216083)
  Syndecan interactions (R-HSA-3000170)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  NCAM1 interactions (R-HSA-419037)
  MET activates PTK2 signaling (R-HSA-8874081)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ehlers-Danlos syndrome	DISSVBRR	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]

1 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-3(V) chain (COL5A3).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-3(V) chain (COL5A3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-3(V) chain (COL5A3).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-3(V) chain (COL5A3).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Collagen alpha-3(V) chain (COL5A3).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Collagen alpha-3(V) chain (COL5A3).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Collagen alpha-3(V) chain (COL5A3).	[9]
Alendronate	DMY2KX9	Approved	Alendronate decreases the expression of Collagen alpha-3(V) chain (COL5A3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-3(V) chain (COL5A3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Collagen alpha-3(V) chain (COL5A3).	[11]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Collagen alpha-3(V) chain (COL5A3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Collagen alpha-3(V) chain (COL5A3).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-3(V) chain (COL5A3).	[13]

References

• [1] The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.J Biol Chem. 2000 Mar 24;275(12):8749-59. doi: 10.1074/jbc.275.12.8749.
• [2] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [10] Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Investig. 2010 Feb;14(1):51-8. doi: 10.1007/s00784-009-0312-2. Epub 2009 Jul 14.
• [11] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.