Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAS6R6I)

• DOT Name: Collagen alpha-3(VI) chain (COL6A3)
• Synonyms: Collagen alpha-3(VI) chain
• Gene Name: COL6A3
• Related Disease:
  Bethlem myopathy 1A
  Collagen 6-related myopathy
  Ullrich congenital muscular dystrophy 1A
  Dystonia 27
  Bethlem myopathy
  Ullrich congenital muscular dystrophy
• UniProt ID: CO6A3_HUMAN
• PDB ID: 1KNT; 1KTH; 1KUN; 2KNT; 6SNK
• Pfam ID: PF01391 ; PF00014 ; PF00092
• Sequence:
  MRKHRHLPLVAVFCLFLSGFPTTHAQQQQADVKNGAAADIIFLVDSSWTIGEEHFQLVRE
  FLYDVVKSLAVGENDFHFALVQFNGNPHTEFLLNTYRTKQEVLSHISNMSYIGGTNQTGK
  GLEYIMQSHLTKAAGSRAGDGVPQVIVVLTDGHSKDGLALPSAELKSADVNVFAIGVEDA
  DEGALKEIASEPLNMHMFNLENFTSLHDIVGNLVSCVHSSVSPERAGDTETLKDITAQDS
  ADIIFLIDGSNNTGSVNFAVILDFLVNLLEKLPIGTQQIRVGVVQFSDEPRTMFSLDTYS
  TKAQVLGAVKALGFAGGELANIGLALDFVVENHFTRAGGSRVEEGVPQVLVLISAGPSSD
  EIRYGVVALKQASVFSFGLGAQAASRAELQHIATDDNLVFTVPEFRSFGDLQEKLLPYIV
  GVAQRHIVLKPPTIVTQVIEVNKRDIVFLVDGSSALGLANFNAIRDFIAKVIQRLEIGQD
  LIQVAVAQYADTVRPEFYFNTHPTKREVITAVRKMKPLDGSALYTGSALDFVRNNLFTSS
  AGYRAAEGIPKLLVLITGGKSLDEISQPAQELKRSSIMAFAIGNKGADQAELEEIAFDSS
  LVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEVHSNKRDIIFLLDGSANVGKTNFPYVRD
  FVMNLVNSLDIGNDNIRVGLVQFSDTPVTEFSLNTYQTKSDILGHLRQLQLQGGSGLNTG
  SALSYVYANHFTEAGGSRIREHVPQLLLLLTAGQSEDSYLQAANALTRAGILTFCVGASQ
  ANKAELEQIAFNPSLVYLMDDFSSLPALPQQLIQPLTTYVSGGVEEVPLAQPESKRDILF
  LFDGSANLVGQFPVVRDFLYKIIDELNVKPEGTRIAVAQYSDDVKVESRFDEHQSKPEIL
  NLVKRMKIKTGKALNLGYALDYAQRYIFVKSAGSRIEDGVLQFLVLLVAGRSSDRVDGPA
  SNLKQSGVVPFIFQAKNADPAELEQIVLSPAFILAAESLPKIGDLHPQIVNLLKSVHNGA
  PAPVSGEKDVVFLLDGSEGVRSGFPLLKEFVQRVVESLDVGQDRVRVAVVQYSDRTRPEF
  YLNSYMNKQDVVNAVRQLTLLGGPTPNTGAALEFVLRNILVSSAGSRITEGVPQLLIVLT
  ADRSGDDVRNPSVVVKRGGAVPIGIGIGNADITEMQTISFIPDFAVAIPTFRQLGTVQQV
  ISERVTQLTREELSRLQPVLQPLPSPGVGGKRDVVFLIDGSQSAGPEFQYVRTLIERLVD
  YLDVGFDTTRVAVIQFSDDPKVEFLLNAHSSKDEVQNAVQRLRPKGGRQINVGNALEYVS
  RNIFKRPLGSRIEEGVPQFLVLISSGKSDDEVDDPAVELKQFGVAPFTIARNADQEELVK
  ISLSPEYVFSVSTFRELPSLEQKLLTPITTLTSEQIQKLLASTRYPPPAVESDAADIVFL
  IDSSEGVRPDGFAHIRDFVSRIVRRLNIGPSKVRVGVVQFSNDVFPEFYLKTYRSQAPVL
  DAIRRLRLRGGSPLNTGKALEFVARNLFVKSAGSRIEDGVPQHLVLVLGGKSQDDVSRFA
  QVIRSSGIVSLGVGDRNIDRTELQTITNDPRLVFTVREFRELPNIEERIMNSFGPSAATP
  APPGVDTPPPSRPEKKKADIVFLLDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQVGL
  VQYNSDPTDEFFLKDFSTKRQIIDAINKVVYKGGRHANTKVGLEHLRVNHFVPEAGSRLD
  QRVPQIAFVITGGKSVEDAQDVSLALTQRGVKVFAVGVRNIDSEEVGKIASNSATAFRVG
  NVQELSELSEQVLETLHDAMHETLCPGVTDAAKACNLDVILGFDGSRDQNVFVAQKGFES
  KVDAILNRISQMHRVSCSGGRSPTVRVSVVANTPSGPVEAFDFDEYQPEMLEKFRNMRSQ
  HPYVLTEDTLKVYLNKFRQSSPDSVKVVIHFTDGADGDLADLHRASENLRQEGVRALILV
  GLERVVNLERLMHLEFGRGFMYDRPLRLNLLDLDYELAEQLDNIAEKACCGVPCKCSGQR
  GDRGPIGSIGPKGIPGEDGYRGYPGDEGGPGERGPPGVNGTQGFQGCPGQRGVKGSRGFP
  GEKGEVGEIGLDGLDGEDGDKGLPGSSGEKGNPGRRGDKGPRGEKGERGDVGIRGDPGNP
  GQDSQERGPKGETGDLGPMGVPGRDGVPGGPGETGKNGGFGRRGPPGAKGNKGGPGQPGF
  EGEQGTRGAQGPAGPAGPPGLIGEQGISGPRGSGGAAGAPGERGRTGPLGRKGEPGEPGP
  KGGIGNRGPRGETGDDGRDGVGSEGRRGKKGERGFPGYPGPKGNPGEPGLNGTTGPKGIR
  GRRGNSGPPGIVGQKGDPGYPGPAGPKGNRGDSIDQCALIQSIKDKCPCCYGPLECPVFP
  TELAFALDTSEGVNQDTFGRMRDVVLSIVNDLTIAESNCPRGARVAVVTYNNEVTTEIRF
  ADSKRKSVLLDKIKNLQVALTSKQQSLETAMSFVARNTFKRVRNGFLMRKVAVFFSNTPT
  RASPQLREAVLKLSDAGITPLFLTRQEDRQLINALQINNTAVGHALVLPAGRDLTDFLEN
  VLTCHVCLDICNIDPSCGFGSWRPSFRDRRAAGSDVDIDMAFILDSAETTTLFQFNEMKK
  YIAYLVRQLDMSPDPKASQHFARVAVVQHAPSESVDNASMPPVKVEFSLTDYGSKEKLVD
  FLSRGMTQLQGTRALGSAIEYTIENVFESAPNPRDLKIVVLMLTGEVPEQQLEEAQRVIL
  QAKCKGYFFVVLGIGRKVNIKEVYTFASEPNDVFFKLVDKSTELNEEPLMRFGRLLPSFV
  SSENAFYLSPDIRKQCDWFQGDQPTKNLVKFGHKQVNVPNNVTSSPTSNPVTTTKPVTTT
  KPVTTTTKPVTTTTKPVTIINQPSVKPAAAKPAPAKPVAAKPVATKMATVRPPVAVKPAT
  AAKPVAAKPAAVRPPAAAAAKPVATKPEVPRPQAAKPAATKPATTKPMVKMSREVQVFEI
  TENSAKLHWERAEPPGPYFYDLTVTSAHDQSLVLKQNLTVTDRVIGGLLAGQTYHVAVVC
  YLRSQVRATYHGSFSTKKSQPPPPQPARSASSSTINLMVSTEPLALTETDICKLPKDEGT
  CRDFILKWYYDPNTKSCARFWYGGCGGNENKFGSQKECEKVCAPVLAKPGVISVMGT
• Function: Collagen VI acts as a cell-binding protein.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bethlem myopathy 1A	DIS0ATYV	Definitive	Semidominant	[1]
Collagen 6-related myopathy	DISF4E3M	Definitive	Autosomal dominant	[2]
Ullrich congenital muscular dystrophy 1A	DISFHHF0	Definitive	Autosomal recessive	[3]
Dystonia 27	DISLJQWF	Strong	Autosomal recessive	[4]
Bethlem myopathy	DISVF5K2	Supportive	Autosomal dominant	[5]
Ullrich congenital muscular dystrophy	DISJWD0V	Supportive	Autosomal dominant	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Collagen alpha-3(VI) chain (COL6A3) affects the response to substance of Fluorouracil.	[27]
Paclitaxel	DMLB81S	Approved	Collagen alpha-3(VI) chain (COL6A3) affects the response to substance of Paclitaxel.	[27]

20 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-3(VI) chain (COL6A3).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[18]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[19]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[20]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[21]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Collagen alpha-3(VI) chain (COL6A3).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-3(VI) chain (COL6A3).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-3(VI) chain (COL6A3).	[14]

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-3(VI) chain (COL6A3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-3(VI) chain (COL6A3).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-3(VI) chain (COL6A3).	[26]

References

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• [3] Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002 Jun;70(6):1446-58. doi: 10.1086/340608. Epub 2002 Apr 24.
• [4] Recessive mutations in the 3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia. Am J Hum Genet. 2015 Jun 4;96(6):883-93. doi: 10.1016/j.ajhg.2015.04.010. Epub 2015 May 21.
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