Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJFUH6O)

• DOT Name: Collagen alpha-1(XVIII) chain (COL18A1)
• Synonyms: Collagen alpha-1(XVIII) chain
• Gene Name: COL18A1
• Related Disease:
  Knobloch syndrome 1
  Obsolete Knobloch syndrome
• UniProt ID: COIA1_HUMAN
• PDB ID: 1BNL; 3HON; 3HSH
• Pfam ID: PF01391 ; PF20010 ; PF06121 ; PF06482 ; PF01392
• Sequence:
  MAPYPCGCHILLLLFCCLAAARANLLNLNWLWFNNEDTSHAATTIPEPQGPLPVQPTADT
  TTHVTPRNGSTEPATAPGSPEPPSELLEDGQDTPTSAESPDAPEENIAGVGAEILNVAKG
  IRSFVQLWNDTVPTESLARAETLVLETPVGPLALAGPSSTPQENGTTLWPSRGIPSSPGA
  HTTEAGTLPAPTPSPPSLGRPWAPLTGPSVPPPSSGRASLSSLLGGAPPWGSLQDPDSQG
  LSPAAAAPSQQLQRPDVRLRTPLLHPLVMGSLGKHAAPSAFSSGLPGALSQVAVTTLTRD
  SGAWVSHVANSVGPGLANNSALLGADPEAPAGRCLPLPPSLPVCGHLGISRFWLPNHLHH
  ESGEQVRAGARAWGGLLQTHCHPFLAWFFCLLLVPPCGSVPPPAPPPCCQFCEALQDACW
  SRLGGGRLPVACASLPTQEDGYCVLIGPAAERISEEVGLLQLLGDPPPQQVTQTDDPDVG
  LAYVFGPDANSGQVARYHFPSLFFRDFSLLFHIRPATEGPGVLFAITDSAQAMVLLGVKL
  SGVQDGHQDISLLYTEPGAGQTHTAASFRLPAFVGQWTHLALSVAGGFVALYVDCEEFQR
  MPLARSSRGLELEPGAGLFVAQAGGADPDKFQGVIAELKVRRDPQVSPMHCLDEEGDDSD
  GASGDSGSGLGDARELLREETGAALKPRLPAPPPVTTPPLAGGSSTEDSRSEEVEEQTTV
  ASLGAQTLPGSDSVSTWDGSVRTPGGRVKEGGLKGQKGEPGVPGPPGRAGPPGSPCLPGP
  PGLPCPVSPLGPAGPALQTVPGPQGPPGPPGRDGTPGRDGEPGDPGEDGKPGDTGPQGFP
  GTPGDVGPKGDKGDPGVGERGPPGPQGPPGPPGPSFRHDKLTFIDMEGSGFGGDLEALRG
  PRGFPGPPGPPGVPGLPGEPGRFGVNSSDVPGPAGLPGVPGREGPPGFPGLPGPPGPPGR
  EGPPGRTGQKGSLGEAGAPGHKGSKGAPGPAGARGESGLAGAPGPAGPPGPPGPPGPPGP
  GLPAGFDDMEGSGGPFWSTARSADGPQGPPGLPGLKGDPGVPGLPGAKGEVGADGVPGFP
  GLPGREGIAGPQGPKGDRGSRGEKGDPGKDGVGQPGLPGPPGPPGPVVYVSEQDGSVLSV
  PGPEGRPGFAGFPGPAGPKGNLGSKGERGSPGPKGEKGEPGSIFSPDGGALGPAQKGAKG
  EPGFRGPPGPYGRPGYKGEIGFPGRPGRPGMNGLKGEKGEPGDASLGFGMRGMPGPPGPP
  GPPGPPGTPVYDSNVFAESSRPGPPGLPGNQGPPGPKGAKGEVGPPGPPGQFPFDFLQLE
  AEMKGEKGDRGDAGQKGERGEPGGGGFFGSSLPGPPGPPGPPGPRGYPGIPGPKGESIRG
  QPGPPGPQGPPGIGYEGRQGPPGPPGPPGPPSFPGPHRQTISVPGPPGPPGPPGPPGTMG
  ASSGVRLWATRQAMLGQVHEVPEGWLIFVAEQEELYVRVQNGFRKVQLEARTPLPRGTDN
  EVAALQPPVVQLHDSNPYPRREHPHPTARPWRADDILASPPRLPEPQPYPGAPHHSSYVH
  LRPARPTSPPAHSHRDFQPVLHLVALNSPLSGGMRGIRGADFQCFQQARAVGLAGTFRAF
  LSSRLQDLYSIVRRADRAAVPIVNLKDELLFPSWEALFSGSEGPLKPGARIFSFDGKDVL
  RHPTWPQKSVWHGSDPNGRRLTESYCETWRTEAPSATGQASSLLGGRLLGQSAASCHHAY
  IVLCIENSFMTASK
• Function: Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube; [Non-collagenous domain 1]: May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling; [Endostatin]: Potently inhibits endothelial cell proliferation and angiogenesis. May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling. Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5. May negatively regulate the activity of homotrimeric non-collagenous domain 1.
• Tissue Specificity: Detected in placenta (at protein level) . Present in multiple organs with highest levels in liver, lung and kidney.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Integrin cell surface interactions (R-HSA-216083)
  Laminin interactions (R-HSA-3000157)
  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
Knobloch syndrome 1	DIS6C0UT	Definitive	Autosomal recessive	[1]
Obsolete Knobloch syndrome	DISVI56Q	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[17]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[18]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[19]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[25]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[27]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[28]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[29]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Collagen alpha-1(XVIII) chain (COL18A1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Collagen alpha-1(XVIII) chain (COL18A1).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Collagen alpha-1(XVIII) chain (COL18A1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Collagen alpha-1(XVIII) chain (COL18A1).	[23]

References

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