Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJK1LKN)

• DOT Name: Collagen alpha-2(IV) chain (COL4A2)
• Synonyms: Collagen alpha-2(IV) chain
• Gene Name: COL4A2
• Related Disease:
  Cerebrovascular disease
  Myopathy
  Nephropathy
  Non-insulin dependent diabetes
  Advanced cancer
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cerebral infarction
  Classic Hodgkin lymphoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Dementia
  Epithelial ovarian cancer
  Familial adenomatous polyposis
  Gastric cancer
  High blood pressure
  Huntington disease
  IgA nephropathy
  Lung cancer
  Lung carcinoma
  Myelodysplastic syndrome
  Myocardial infarction
  Neoplasm
  Nephrotic syndrome
  Porencephaly 2
  Stomach cancer
  Triple negative breast cancer
  Type-1 diabetes
  Uterine fibroids
  Acute myelogenous leukaemia
  Amyotrophic lateral sclerosis
  Cardiovascular disease
  Chronic renal failure
  End-stage renal disease
  Obsolete COL4A1 or COL4A2-related cerebral small vessel disease
  Pancreatic cancer
  Familial porencephaly
  Small-cell lung cancer
• UniProt ID: CO4A2_HUMAN
• PDB ID: 1LI1; 5NAX; 5NB2; 6MPX
• Pfam ID: PF01413 ; PF01391
• Sequence:
  MGRDQRAVAGPALRRWLLLGTVTVGFLAQSVLAGVKKFDVPCGGRDCSGGCQCYPEKGGR
  GQPGPVGPQGYNGPPGLQGFPGLQGRKGDKGERGAPGVTGPKGDVGARGVSGFPGADGIP
  GHPGQGGPRGRPGYDGCNGTQGDSGPQGPPGSEGFTGPPGPQGPKGQKGEPYALPKEERD
  RYRGEPGEPGLVGFQGPPGRPGHVGQMGPVGAPGRPGPPGPPGPKGQQGNRGLGFYGVKG
  EKGDVGQPGPNGIPSDTLHPIIAPTGVTFHPDQYKGEKGSEGEPGIRGISLKGEEGIMGF
  PGLRGYPGLSGEKGSPGQKGSRGLDGYQGPDGPRGPKGEAGDPGPPGLPAYSPHPSLAKG
  ARGDPGFPGAQGEPGSQGEPGDPGLPGPPGLSIGDGDQRRGLPGEMGPKGFIGDPGIPAL
  YGGPPGPDGKRGPPGPPGLPGPPGPDGFLFGLKGAKGRAGFPGLPGSPGARGPKGWKGDA
  GECRCTEGDEAIKGLPGLPGPKGFAGINGEPGRKGDRGDPGQHGLPGFPGLKGVPGNIGA
  PGPKGAKGDSRTITTKGERGQPGVPGVPGMKGDDGSPGRDGLDGFPGLPGPPGDGIKGPP
  GDPGYPGIPGTKGTPGEMGPPGLGLPGLKGQRGFPGDAGLPGPPGFLGPPGPAGTPGQID
  CDTDVKRAVGGDRQEAIQPGCIGGPKGLPGLPGPPGPTGAKGLRGIPGFAGADGGPGPRG
  LPGDAGREGFPGPPGFIGPRGSKGAVGLPGPDGSPGPIGLPGPDGPPGERGLPGEVLGAQ
  PGPRGDAGVPGQPGLKGLPGDRGPPGFRGSQGMPGMPGLKGQPGLPGPSGQPGLYGPPGL
  HGFPGAPGQEGPLGLPGIPGREGLPGDRGDPGDTGAPGPVGMKGLSGDRGDAGFTGEQGH
  PGSPGFKGIDGMPGTPGLKGDRGSPGMDGFQGMPGLKGRPGFPGSKGEAGFFGIPGLKGL
  AGEPGFKGSRGDPGPPGPPPVILPGMKDIKGEKGDEGPMGLKGYLGAKGIQGMPGIPGLS
  GIPGLPGRPGHIKGVKGDIGVPGIPGLPGFPGVAGPPGITGFPGFIGSRGDKGAPGRAGL
  YGEIGATGDFGDIGDTINLPGRPGLKGERGTTGIPGLKGFFGEKGTEGDIGFPGITGVTG
  VQGPPGLKGQTGFPGLTGPPGSQGELGRIGLPGGKGDDGWPGAPGLPGFPGLRGIRGLHG
  LPGTKGFPGSPGSDIHGDPGFPGPPGERGDPGEANTLPGPVGVPGQKGDQGAPGERGPPG
  SPGLQGFPGITPPSNISGAPGDKGAPGIFGLKGYRGPPGPPGSAALPGSKGDTGNPGAPG
  TPGTKGWAGDSGPQGRPGVFGLPGEKGPRGEQGFMGNTGPTGAVGDRGPKGPKGDPGFPG
  APGTVGAPGIAGIPQKIAVQPGTVGPQGRRGPPGAPGEMGPQGPPGEPGFRGAPGKAGPQ
  GRGGVSAVPGFRGDEGPIGHQGPIGQEGAPGRPGSPGLPGMPGRSVSIGYLLVKHSQTDQ
  EPMCPVGMNKLWSGYSLLYFEGQEKAHNQDLGLAGSCLARFSTMPFLYCNPGDVCYYASR
  NDKSYWLSTTAPLPMMPVAEDEIKPYISRCSVCEAPAIAIAVHSQDVSIPHCPAGWRSLW
  IGYSFLMHTAAGDEGGGQSLVSPGSCLEDFRATPFIECNGGRGTCHYYANKYSFWLTTIP
  EQSFQGSPSADTLKAGLIRTHISRCQVCMKNL
• Function: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.; Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cytoskeleton in muscle cells (hsa04820)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Protein digestion and absorption (hsa04974)
  Amoebiasis (hsa05146)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
• 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)
  Anchoring fibril formation (R-HSA-2214320)
  Crosslinking of collagen fibrils (R-HSA-2243919)
  Laminin interactions (R-HSA-3000157)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  Scavenging by Class A Receptors (R-HSA-3000480)
  NCAM1 interactions (R-HSA-419037)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebrovascular disease	DISAB237	Definitive	Genetic Variation	[1]
Myopathy	DISOWG27	Definitive	Genetic Variation	[2]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Cerebral infarction	DISR1WNP	Strong	Genetic Variation	[9]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Genetic Variation	[11]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[11]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[11]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[11]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[11]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[11]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[11]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[11]
Dementia	DISXL1WY	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Huntington disease	DISQPLA4	Strong	Biomarker	[10]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[18]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[21]
Porencephaly 2	DISXDCXB	Strong	Autosomal dominant	[22]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[24]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[25]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[26]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Altered Expression	[27]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[28]
Chronic renal failure	DISGG7K6	moderate	Biomarker	[29]
End-stage renal disease	DISXA7GG	moderate	Biomarker	[29]
Obsolete COL4A1 or COL4A2-related cerebral small vessel disease	DIS3BCSV	Moderate	Autosomal dominant	[22]
Pancreatic cancer	DISJC981	moderate	Biomarker	[30]
Familial porencephaly	DISTLT56	Supportive	Autosomal dominant	[31]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Collagen alpha-2(IV) chain (COL4A2) affects the response to substance of Mitomycin.	[55]

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-2(IV) chain (COL4A2).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Collagen alpha-2(IV) chain (COL4A2).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-2(IV) chain (COL4A2).	[52]

23 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-2(IV) chain (COL4A2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[35]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Collagen alpha-2(IV) chain (COL4A2).	[44]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[45]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[46]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Collagen alpha-2(IV) chain (COL4A2).	[47]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[48]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[49]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[50]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[50]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[50]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-2(IV) chain (COL4A2).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[53]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Collagen alpha-2(IV) chain (COL4A2).	[50]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	D-glucose affects the secretion of Collagen alpha-2(IV) chain (COL4A2).	[54]

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