Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ5VDRH)

• DOT Name: Collagen alpha-1(XXVII) chain (COL27A1)
• Synonyms: Collagen alpha-1(XXVII) chain
• Gene Name: COL27A1
• Related Disease:
  Colorectal carcinoma
  Steel syndrome
  Tourette syndrome
  Type 2 collagenopathy
• UniProt ID: CORA1_HUMAN
• Pfam ID: PF01410 ; PF01391
• Sequence:
  MGAGSARGARGTAAAAAARGGGFLFSWILVSFACHLASTQGAPEDVDILQRLGLSWTKAG
  SPAPPGVIPFQSGFIFTQRARLQAPTGTVIPAALGTELALVLSLCSHRVNHAFLFAVRSQ
  KRKLQLGLQFLPGKTVVHLGSRRSVAFDLDMHDGRWHHLALELRGRTVTLVTACGQRRVP
  VLLPFHRDPALDPGGSFLFGKMNPHAVQFEGALCQFSIYPVTQVAHNYCTHLRKQCGQAD
  TYQSPLGPLFSQDSGRPFTFQSDLALLGLENLTTATPALGSLPAGRGPRGTVAPATPTKP
  QRTSPTNPHQHMAVGGPAQTPLLPAKLSASNALDPMLPASVGGSTRTPRPAAAQPSQKIT
  ATKIPKSLPTKPSAPSTSIVPIKSPHPTQKTAPSSFTKSALPTQKQVPPTSRPVPARVSR
  PAEKPIQRNPGMPRPPPPSTRPLPPTTSSSKKPIPTLARTEAKITSHASKPASARTSTHK
  PPPFTALSSSPAPTPGSTRSTRPPATMVPPTSGTSTPRTAPAVPTPGSAPTGSKKPIGSE
  ASKKAGPKSSPRKPVPLRPGKAARDVPLSDLTTRPSPRQPQPSQQTTPALVLAPAQFLSS
  SPRPTSSGYSIFHLAGSTPFPLLMGPPGPKGDCGLPGPPGLPGLPGIPGARGPRGPPGPY
  GNPGLPGPPGAKGQKGDPGLSPGKAHDGAKGDMGLPGLSGNPGPPGRKGHKGYPGPAGHP
  GEQGQPGPEGSPGAKGYPGRQGLPGPVGDPGPKGSRGYIGLPGLFGLPGSDGERGLPGVP
  GKRGKMGMPGFPGVFGERGPPGLDGNPGELGLPGPPGVPGLIGDLGVLGPIGYPGPKGMK
  GLMGSVGEPGLKGDKGEQGVPGVSGDPGFQGDKGSQGLPGFPGARGKPGPLGKVGDKGSI
  GFPGPPGPEGFPGDIGPPGDNGPEGMKGKPGARGLPGPRGQLGPEGDEGPMGPPGAPGLE
  GQPGRKGFPGRPGLDGVKGEPGDPGRPGPVGEQGFMGFIGLVGEPGIVGEKGDRGMMGPP
  GVPGPKGSMGHPGMPGGMGTPGEPGPQGPPGSRGPPGMRGAKGRRGPRGPDGPAGEQGSR
  GLKGPPGPQGRPGRPGQQGVAGERGHLGSRGFPGIPGPSGPPGTKGLPGEPGPQGPQGPI
  GPPGEMGPKGPPGAVGEPGLPGEAGMKGDLGPLGTPGEQGLIGQRGEPGLEGDSGPMGPD
  GLKGDRGDPGPDGEHGEKGQEGLMGEDGPPGPPGVTGVRGPEGKSGKQGEKGRTGAKGAK
  GYQGQLGEMGVPGDPGPPGTPGPKGSRGSLGPTGAPGRMGAQGEPGLAGYDGHKGIVGPL
  GPPGPKGEKGEQGEDGKAEGPPGPPGDRGPVGDRGDRGEPGDPGYPGQEGVQGLRGKPGQ
  QGQPGHPGPRGWPGPKGSKGAEGPKGKQGKAGAPGRRGVQGLQGLPGPRGVVGRQGLEGI
  AGPDGLPGRDGQAGQQGEQGDDGDPGPMGPAGKRGNPGVAGLPGAQGPPGFKGESGLPGQ
  LGPPGKRGTEGRTGLPGNQGEPGSKGQPGDSGEMGFPGMAGLFGPKGPPGDIGFKGIQGP
  RGPPGLMGKEGIVGPLGILGPSGLPGPKGDKGSRGDWGLQGPRGPPGPRGRPGPPGPPGG
  PIQLQQDDLGAAFQTWMDTSGALRPESYSYPDRLVLDQGGEIFKTLHYLSNLIQSIKTPL
  GTKENPARVCRDLMDCEQKMVDGTYWVDPNLGCSSDTIEVSCNFTHGGQTCLKPITASKV
  EFAISRVQMNFLHLLSSEVTQHITIHCLNMTVWQEGTGQTPAKQAVRFRAWNGQIFEAGG
  QFRPEVSMDGCKVQDGRWHQTLFTFRTQDPQQLPIISVDNLPPASSGKQYRLEVGPACFL
• Function: Plays a role during the calcification of cartilage and the transition of cartilage to bone.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  MET activates PTK2 signaling (R-HSA-8874081)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Steel syndrome	DISR2L1K	Strong	Autosomal recessive	[2]
Tourette syndrome	DISX9D54	moderate	Genetic Variation	[3]
Type 2 collagenopathy	DIS8WIDY	moderate	Biomarker	[4]

3 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(XXVII) chain (COL27A1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Collagen alpha-1(XXVII) chain (COL27A1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-1(XXVII) chain (COL27A1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-1(XXVII) chain (COL27A1).	[17]

References

• [1] Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population.PLoS One. 2018 Mar 16;13(3):e0193547. doi: 10.1371/journal.pone.0193547. eCollection 2018.
• [2] Collagen XXVII organises the pericellular matrix in the growth plate. PLoS One. 2011;6(12):e29422. doi: 10.1371/journal.pone.0029422. Epub 2011 Dec 19.
• [3] Support of positive association in family-based genetic analysis between COL27A1 and Tourette syndrome.Sci Rep. 2015 Aug 3;5:12687. doi: 10.1038/srep12687.
• [4] The expression and function of microRNAs in chondrogenesis and osteoarthritis.Arthritis Rheum. 2012 Jun;64(6):1909-19. doi: 10.1002/art.34314. Epub 2011 Dec 5.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] Expression of copper-responsive genes in HepG2 cells. Mol Cell Biochem. 2005 Nov;279(1-2):141-7.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] 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.
• [16] 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.
• [17] 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.