Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJT8O80)

• DOT Name: Collagen alpha-5(VI) chain (COL6A5)
• Synonyms: Collagen alpha-1(XXIX) chain; von Willebrand factor A domain-containing protein 4
• Gene Name: COL6A5
• Related Disease:
  Atopic dermatitis
  Chronic kidney disease
  High blood pressure
  Myocardial infarction
  Acute myelogenous leukaemia
  Bethlem myopathy
  Diabetic neuropathy
  Keratosis pilaris
  Ullrich congenital muscular dystrophy 1A
  Asthma
• UniProt ID: CO6A5_HUMAN
• Pfam ID: PF01391 ; PF00092
• Sequence:
  MKILLIIFVLIIWTETLADQSPGPGPVYADVVFLVDSSDHLGPKSFPFVKTFINKMINSL
  PIEANKYRVALAQYSDEFHSEFHLSTFKGRSPMLNHLKKNFQFIGGSLQIGKALQEAHRT
  YFSAPINGRDRKQFPPILVVLASAESEDEVEEASKALQKDGVKIISVGVQKASEENLKAM
  ATSHFHFNLRTIRDLSTFSQNMTQIIKDVTKYKEGAVDADMQVHFPISCQKDSLADLVFL
  VDESLGTGGNLRHLQTFLENITSSMDVKENCMRLGLMSYSNSAKTISFLKSSTTQSEFQQ
  QIKNLSIQVGKSNTGAAIDQMRRDGFSESYGSRRAQGVPQIAVLVTHRPSDDEVHDAALN
  LRLEDVNVFALSIQGANNTQLEEIVSYPPEQTISTLKSYADLETYSTKFLKKLQNEIWSQ
  ISTYAEQRNLDKTGCVDTKEADIHFLIDGSSSIQEKQFEQIKRFMLEVTEMFSIGPDKVR
  VGVVQYSDDTEVEFYITDYSNDIDLRKAIFNIKQLTGGTYTGKALDYILQIIKNGMKDRM
  SKVPCYLIVLTDGMSTDRVVEPAKRLRAEQITVHAVGIGAANKIELQEIAGKEERVSFGQ
  NFDALKSIKNEVVREICAEKGCEDMKADIMFLVDSSWSIGNENFRKMKIFMKNLLTKIQI
  GADKTQIGVVQFSDKTKEEFQLNRYFTQQEISDAIDRMSLINEGTLTGKALNFVGQYFTH
  SKGARLGAKKFLILITDGVAQDDVRDPARILRGKDVTIFSVGVYNANRSQLEEISGDSSL
  VFHVENFDHLKALERKLIFRVCALHDCKRITLLDVVFVLDHSGSIKKQYQDHMINLTIHL
  VKKADVGRDRVQFGALKYSDQPNILFYLNTYSNRSAIIENLRKRRDTGGNTYTAKALKHA
  NALFTEEHGSRIKQNVKQMLIVITDGESHDHDQLNDTALELRNKGITIFAVGVGKANQKE
  LEGMAGNKNNTIYVDNFDKLKDVFTLVQERMCTEAPEVCHLQEADVIFLCDGSDRVSNSD
  FVTMTTFLSDLIDNFDIQSQRMKIGMAQFGSNYQSIIELKNSLTKTQWKTQIQNVSKSGG
  FPRIDFALKKVSNMFNLHAGGRRNAGVPQTLVVITSGDPRYDVADAVKTLKDLGICVLVL
  GIGDVYKEHLLPITGNSEKIITFQDFDKLKNVDVKKRIIREICQSCGKTNCFMDIVVGFD
  ISTHVQGQPLFQGHPQLESYLPGILEDISSIKGVSCGAGTEAQVSLAFKVNSDQGFPAKF
  QIYQKAVFDSLLQVNVSGPTHLNAQFLRSLWDTFKDKSASRGQVLLIFSDGLQSESNIML
  ENQSDRLREAGLDALLVVSLNTTAHHEFSSFEFGKRFDYRTHLTIGMRELGKKLSQYLGN
  IAERTCCCTFCKCPGIPGPHGTRGLQAMKGSQGLKGSRGHRGEDGNPGVRGDTGPQGDKG
  IAGCPGAWGQKGLKGFSGPKGGHGDDGIDGLDGEEGCHGFPGIKGEKGDPGSQGSPGSRG
  APGQYGEKGFPGDPGNPGQNNNIKGQKGSKGEQGRQGRSGQKGVQGSPSSRGSRGREGQR
  GLRGVSGEPGNPGPTGTLGAEGLQGPQGSQGNPGRKGEKGSQGQKGPQGSPGLMGAKGST
  GRPGLLGKKGEPGLPGDLGPVGQTGQRGRQGDSGIPGYGQMGRKGVKGPRGFPGDAGQKG
  DIGNPGIPGGPGPKGFRGLALTVGLKGEEGSRGLPGPPGQRGIKGMAGQPVYSQCDLIRF
  LREHSPCWKEKCPAYPTELVFALDNSYDVTEESFNKTRDIITSIVNDLNIRENNCPVGAR
  VAMVSYNSGTSYLIRWSDYNRKKQLLQQLSQIKYQDTTEPRDVGNAMRFVTRNVFKRTYA
  GANVRRVAVFFSNGQTASRSSIITATMEFSALDISPTVFAFDERVFLEAFGFDNTGTFQV
  IPVPPNGENQTLERLRRCALCYDKCFPNACIREAFLPEDSYMDVVFLIDNSRNIAKDEFK
  AVKALVSSVIDNFNIASDPLISDSGDRIALLSYSPWESSRRKMGTVKTEFDFITYDNQLL
  MKNHIQTSFQQLNGEATIGRALLWTTENLFPETPYLRKHKVIFVVSAGENYERKEFVKMM
  ALRAKCQGYVIFVISLGSTRKDDMEELASYPLDQHLIQLGRIHKPDLNYIAKFLKPFLYS
  VRRGFNQYPPPMLEDACRLINLGGENIQNDGFQFVTELQEDFLGGNGFIGQELNSGRESP
  FVKTEDNGSDYLVYLPSQMFEPQKLMINYEKDQKSAEIASLTSGHENYGRKEEPDHTYEP
  GDVSLQEYYMDVAFLIDASQRVGSDEFKEVKAFITSVLDYFHIAPTPLTSTLGDRVAVLS
  YSPPGYMPNTEECPVYLEFDLVTYNSIHQMKHHLQDSQQLNGDVFIGHALQWTIDNVFVG
  TPNLRKNKVIFVISAGETNSLDKDVLRNVSLRAKCQGYSIFVFSFGPKHNDKELEELASH
  PLDHHLVQLGRTHKPDWNYIIKFVKPFVHLIRRAINKYPTEDMKATCVNMTSPNPENGGT
  ENTVLLLPGIYEIKTENGDLFDEFDSQAQHLLVLGNNHSSGSETATDLMQKLYLLFSTEK
  LAMKDKEKAHLEEISALVVDKQQEKEDKEMEATDI
• Function: Collagen VI acts as a cell-binding protein.
• Tissue Specificity: Expressed in skin, followed by lung, small intestine, colon and testis. In skin, it is expressed in the epidermis with strongest staining in suprabasal viable layers. In ATOD patients, it is absent in the most differentiated upper spinous and granular layers (at protein level).
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cytoskeleton in muscle cells (hsa04820)
  Protein digestion and absorption (hsa04974)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  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)
  ECM proteoglycans (R-HSA-3000178)
  NCAM1 interactions (R-HSA-419037)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Biomarker	[1]
Chronic kidney disease	DISW82R7	Strong	Genetic Variation	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[2]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Bethlem myopathy	DISVF5K2	moderate	Genetic Variation	[4]
Diabetic neuropathy	DISX6VF8	moderate	Genetic Variation	[5]
Keratosis pilaris	DISKOBPU	moderate	Genetic Variation	[4]
Ullrich congenital muscular dystrophy 1A	DISFHHF0	moderate	Genetic Variation	[4]
Asthma	DISW9QNS	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-5(VI) chain (COL6A5).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Collagen alpha-5(VI) chain (COL6A5).	[8]

2 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 affects the methylation of Collagen alpha-5(VI) chain (COL6A5).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Collagen alpha-5(VI) chain (COL6A5).	[10]

References

• [1] Atopic Eczema: Genetic Analysis of COL6A5, COL8A1, and COL10A1 in Mediterranean Populations.Biomed Res Int. 2019 Jun 4;2019:3457898. doi: 10.1155/2019/3457898. eCollection 2019.
• [2] Identification of 13 novel susceptibility loci for early-onset myocardial infarction, hypertension, or chronic kidney disease.Int J Mol Med. 2018 Nov;42(5):2415-2436. doi: 10.3892/ijmm.2018.3852. Epub 2018 Sep 4.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] Expression of the collagen VI 5 and 6 chains in normal human skin and in skin of patients with collagen VI-related myopathies.J Invest Dermatol. 2011 Jan;131(1):99-107. doi: 10.1038/jid.2010.284. Epub 2010 Sep 30.
• [5] COL6A5 variants in familial neuropathic chronic itch.Brain. 2017 Mar 1;140(3):555-567. doi: 10.1093/brain/aww343.
• [6] Rule-based models of the interplay between genetic and environmental factors in childhood allergy.PLoS One. 2013 Nov 19;8(11):e80080. doi: 10.1371/journal.pone.0080080. eCollection 2013.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] 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.