Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT1EMLM)

• DOT Name: Collagen alpha-1(III) chain (COL3A1)
• Synonyms: Collagen alpha-1(III) chain
• Gene Name: COL3A1
• Related Disease:
  Abdominal aortic aneurysm
  Autosomal dominant Ehlers-Danlos syndrome, vascular type
  Ehlers-Danlos syndrome, vascular type
  Familial thoracic aortic aneurysm and aortic dissection
  Glioblastoma multiforme
  Adult glioblastoma
  Advanced cancer
  Alcoholic cirrhosis of liver
  Alzheimer disease
  Alzheimer disease 3
  Aortic aneurysm
  Cardiomyopathy
  Clear cell renal carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Ehlers-Danlos syndrome
  facioscapulohumeral muscular dystrophy
  Fatty liver disease
  Glioma
  Glomerulonephritis
  Glomerulosclerosis
  Hepatocellular carcinoma
  High blood pressure
  Keloid
  Liver cirrhosis
  Loeys-Dietz syndrome
  Lung adenocarcinoma
  Marfan syndrome
  Myocardial fibrosis
  Myocardial infarction
  Non-insulin dependent diabetes
  Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome
  Schizophrenia
  Stroke
  Subarachnoid hemorrhage
  Systemic sclerosis
  Hyperglycemia
  Hyperinsulinemia
  Mitral valve prolapse
  Neoplasm
  Pulmonary fibrosis
• UniProt ID: CO3A1_HUMAN
• PDB ID: 2V53; 3DMW; 4AE2; 4AEJ; 4AK3; 4GYX; 6FZV; 6FZW; 7WWR; 7WWS; 7XAN
• Pfam ID: PF01410 ; PF01391 ; PF00093
• Sequence:
  MMSFVQKGSWLLLALLHPTIILAQQEAVEGGCSHLGQSYADRDVWKPEPCQICVCDSGSV
  LCDDIICDDQELDCPNPEIPFGECCAVCPQPPTAPTRPPNGQGPQGPKGDPGPPGIPGRN
  GDPGIPGQPGSPGSPGPPGICESCPTGPQNYSPQYDSYDVKSGVAVGGLAGYPGPAGPPG
  PPGPPGTSGHPGSPGSPGYQGPPGEPGQAGPSGPPGPPGAIGPSGPAGKDGESGRPGRPG
  ERGLPGPPGIKGPAGIPGFPGMKGHRGFDGRNGEKGETGAPGLKGENGLPGENGAPGPMG
  PRGAPGERGRPGLPGAAGARGNDGARGSDGQPGPPGPPGTAGFPGSPGAKGEVGPAGSPG
  SNGAPGQRGEPGPQGHAGAQGPPGPPGINGSPGGKGEMGPAGIPGAPGLMGARGPPGPAG
  ANGAPGLRGGAGEPGKNGAKGEPGPRGERGEAGIPGVPGAKGEDGKDGSPGEPGANGLPG
  AAGERGAPGFRGPAGPNGIPGEKGPAGERGAPGPAGPRGAAGEPGRDGVPGGPGMRGMPG
  SPGGPGSDGKPGPPGSQGESGRPGPPGPSGPRGQPGVMGFPGPKGNDGAPGKNGERGGPG
  GPGPQGPPGKNGETGPQGPPGPTGPGGDKGDTGPPGPQGLQGLPGTGGPPGENGKPGEPG
  PKGDAGAPGAPGGKGDAGAPGERGPPGLAGAPGLRGGAGPPGPEGGKGAAGPPGPPGAAG
  TPGLQGMPGERGGLGSPGPKGDKGEPGGPGADGVPGKDGPRGPTGPIGPPGPAGQPGDKG
  EGGAPGLPGIAGPRGSPGERGETGPPGPAGFPGAPGQNGEPGGKGERGAPGEKGEGGPPG
  VAGPPGGSGPAGPPGPQGVKGERGSPGGPGAAGFPGARGLPGPPGSNGNPGPPGPSGSPG
  KDGPPGPAGNTGAPGSPGVSGPKGDAGQPGEKGSPGAQGPPGAPGPLGIAGITGARGLAG
  PPGMPGPRGSPGPQGVKGESGKPGANGLSGERGPPGPQGLPGLAGTAGEPGRDGNPGSDG
  LPGRDGSPGGKGDRGENGSPGAPGAPGHPGPPGPVGPAGKSGDRGESGPAGPAGAPGPAG
  SRGAPGPQGPRGDKGETGERGAAGIKGHRGFPGNPGAPGSPGPAGQQGAIGSPGPAGPRG
  PVGPSGPPGKDGTSGHPGPIGPPGPRGNRGERGSEGSPGHPGQPGPPGPPGAPGPCCGGV
  GAAAIAGIGGEKAGGFAPYYGDEPMDFKINTDEIMTSLKSVNGQIESLISPDGSRKNPAR
  NCRDLKFCHPELKSGEYWVDPNQGCKLDAIKVFCNMETGETCISANPLNVPRKHWWTDSS
  AEKKHVWFGESMDGGFQFSYGNPELPEDVLDVHLAFLRLLSSRASQNITYHCKNSIAYMD
  QASGNVKKALKLMGSNEGEFKAEGNSKFTYTVLEDGCTKHTGEWSKTVFEYRTRKAVRLP
  IVDIAPYDIGGPDQEFGVDVGPVCFL
• Function: Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of ADGRG1 in the developing brain and binding to ADGRG1 inhibits neuronal migration and activates the RhoA pathway by coupling ADGRG1 to GNA13 and possibly GNA12.
• KEGG Pathway:
  Platelet activation (hsa04611)
  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)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Extracellular matrix organization (R-HSA-1474244)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Signaling by PDGF (R-HSA-186797)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  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)
  Scavenging by Class A Receptors (R-HSA-3000480)
  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

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Definitive	Genetic Variation	[1]
Autosomal dominant Ehlers-Danlos syndrome, vascular type	DIST4JDL	Definitive	Autosomal dominant	[2]
Ehlers-Danlos syndrome, vascular type	DISTZ07K	Definitive	Autosomal dominant	[3]
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Definitive	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alcoholic cirrhosis of liver	DISQ1WRT	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[8]
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[9]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[12]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[13]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Biomarker	[14]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[16]
Glomerulosclerosis	DISJF20Z	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[17]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[18]
Keloid	DISV09JY	Strong	Biomarker	[19]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[17]
Loeys-Dietz syndrome	DIS4FUPZ	Strong	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[21]
Marfan syndrome	DISVEUWZ	Strong	Genetic Variation	[22]
Myocardial fibrosis	DISMOLYU	Strong	Biomarker	[23]
Myocardial infarction	DIS655KI	Strong	Biomarker	[24]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[25]
Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome	DISUCHDT	Strong	Autosomal recessive	[26]
Schizophrenia	DISSRV2N	Strong	Biomarker	[27]
Stroke	DISX6UHX	Strong	Genetic Variation	[28]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Genetic Variation	[29]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[30]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[25]
Hyperinsulinemia	DISIDWT6	Limited	Biomarker	[25]
Mitral valve prolapse	DISNCHQ3	Limited	Genetic Variation	[31]
Neoplasm	DISZKGEW	Limited	Altered Expression	[32]
Pulmonary fibrosis	DISQKVLA	Limited	Altered Expression	[33]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Collagen alpha-1(III) chain (COL3A1) decreases the response to substance of Doxorubicin.	[70]
Cisplatin	DMRHGI9	Approved	Collagen alpha-1(III) chain (COL3A1) decreases the response to substance of Cisplatin.	[70]
Methotrexate	DM2TEOL	Approved	Collagen alpha-1(III) chain (COL3A1) decreases the response to substance of Methotrexate.	[70]
Fluorouracil	DMUM7HZ	Approved	Collagen alpha-1(III) chain (COL3A1) affects the response to substance of Fluorouracil.	[71]
Paclitaxel	DMLB81S	Approved	Collagen alpha-1(III) chain (COL3A1) decreases the response to substance of Paclitaxel.	[70]
Topotecan	DMP6G8T	Approved	Collagen alpha-1(III) chain (COL3A1) decreases the response to substance of Topotecan.	[70]

36 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(III) chain (COL3A1).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collagen alpha-1(III) chain (COL3A1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Collagen alpha-1(III) chain (COL3A1).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[42]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Collagen alpha-1(III) chain (COL3A1).	[43]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[44]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Collagen alpha-1(III) chain (COL3A1).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[46]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[47]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Collagen alpha-1(III) chain (COL3A1).	[48]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Collagen alpha-1(III) chain (COL3A1).	[49]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Collagen alpha-1(III) chain (COL3A1).	[50]
Aldosterone	DM9S2JW	Approved	Aldosterone increases the expression of Collagen alpha-1(III) chain (COL3A1).	[51]
Spironolactone	DM2AQ5N	Approved	Spironolactone decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[23]
Lamivudine	DMI347A	Approved	Lamivudine decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[53]
Metoprolol	DMOJ0V6	Approved	Metoprolol increases the expression of Collagen alpha-1(III) chain (COL3A1).	[51]
Alendronate	DMY2KX9	Approved	Alendronate decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[54]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[55]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Collagen alpha-1(III) chain (COL3A1).	[56]
HMPL-004	DM29XGY	Phase 3	HMPL-004 decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[57]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[61]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[62]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Collagen alpha-1(III) chain (COL3A1).	[63]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[65]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[66]
NAPQI	DM8F5LR	Investigative	NAPQI increases the expression of Collagen alpha-1(III) chain (COL3A1).	[67]
Isoarnebin 4	DM0B7NO	Investigative	Isoarnebin 4 decreases the expression of Collagen alpha-1(III) chain (COL3A1).	[68]
CGS 21680	DMZ0TGY	Investigative	CGS 21680 increases the expression of Collagen alpha-1(III) chain (COL3A1).	[69]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(III) chain (COL3A1).	[58]

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-1(III) chain (COL3A1).	[64]

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