Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHLTV53)

• DOT Name: Collagen alpha-1(XII) chain (COL12A1)
• Synonyms: Collagen alpha-1(XII) chain
• Gene Name: COL12A1
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Bethlem myopathy 2
  Colon cancer
  Colon carcinoma
  Congenital myopathy
  Ehlers-Danlos syndrome
  Exostosis
  Lung cancer
  Malignant mesothelioma
  Microcephaly, epilepsy, and diabetes syndrome
  Myopathy
  Neoplasm
  Obesity
  Obsolete Bethlem myopathy 2
  Prostate cancer
  Prostate carcinoma
  Ullrich congenital muscular dystrophy 1A
  Ullrich congenital muscular dystrophy 2
  Breast cancer
  Colorectal carcinoma
  Endometriosis
  Bethlem myopathy
  Ullrich congenital muscular dystrophy
  Breast carcinoma
  Gastric cancer
  Rheumatoid arthritis
  Stomach cancer
• UniProt ID: COCA1_HUMAN
• Pfam ID: PF01391 ; PF00041 ; PF00092
• Sequence:
  MRSRLPPALAALGAALLLSSIEAEVDPPSDLNFKIIDENTVHMSWAKPVDPIVGYRITVD
  PTTDGPTKEFTLSASTTETLLSELVPETEYVVTITSYDEVEESVPVIGQLTIQTGSSTKP
  VEKKPGKTEIQKCSVSAWTDLVFLVDGSWSVGRNNFKYILDFIAALVSAFDIGEEKTRVG
  VVQYSSDTRTEFNLNQYYQRDELLAAIKKIPYKGGNTMTGDAIDYLVKNTFTESAGARVG
  FPKVAIIITDGKSQDEVEIPARELRNVGVEVFSLGIKAADAKELKQIASTPSLNHVFNVA
  NFDAIVDIQNEIISQVCSGVDEQLGELVSGEEVVEPPSNLIAMEVSSKYVKLNWNPSPSP
  VTGYKVILTPMTAGSRQHALSVGPQTTTLSVRDLSADTEYQISVSAMKGMTSSEPISIME
  KTQPMKVQVECSRGVDIKADIVFLVDGSYSIGIANFVKVRAFLEVLVKSFEISPNRVQIS
  LVQYSRDPHTEFTLKKFTKVEDIIEAINTFPYRGGSTNTGKAMTYVREKIFVPSKGSRSN
  VPKVMILITDGKSSDAFRDPAIKLRNSDVEIFAVGVKDAVRSELEAIASPPAETHVFTVE
  DFDAFQRISFELTQSICLRIEQELAAIKKKAYVPPKDLSFSEVTSYGFKTNWSPAGENVF
  SYHITYKEAAGDDEVTVVEPASSTSVVLSSLKPETLYLVNVTAEYEDGFSIPLAGEETTE
  EVKGAPRNLKVTDETTDSFKITWTQAPGRVLRYRIIYRPVAGGESREVTTPPNQRRRTLE
  NLIPDTKYEVSVIPEYFSGPGTPLTGNAATEEVRGNPRDLRVSDPTTSTMKLSWSGAPGK
  VKQYLVTYTPVAGGETQEVTVRGDTTNTVLQGLKEGTQYALSVTALYASGAGDALFGEGT
  TLEERGSPQDLVTKDITDTSIGAYWTSAPGMVRGYRVSWKSLYDDVDTGEKNLPEDAIHT
  MIENLQPETKYRISVFATYSSGEGEPLTGDATTELSQDSKTLKVDEETENTMRVTWKPAP
  GKVVNYRVVYRPHGRGKQMVAKVPPTVTSTVLKRLQPQTTYDITVLPIYKMGEGKLRQGS
  GTTASRFKSPRNLKTSDPTMSSFRVTWEPAPGEVKGYKVTFHPTGDDRRLGELVVGPYDN
  TVVLEELRAGTTYKVNVFGMFDGGESSPLVGQEMTTLSDTTVMPILSSGMECLTRAEADI
  VLLVDGSWSIGRANFRTVRSFISRIVEVFDIGPKRVQIALAQYSGDPRTEWQLNAHRDKK
  SLLQAVANLPYKGGNTLTGMALNFIRQQNFRTQAGMRPRARKIGVLITDGKSQDDVEAPS
  KKLKDEGVELFAIGIKNADEVELKMIATDPDDTHAYNVADFESLSRIVDDLTINLCNSVK
  GPGDLEAPSNLVISERTHRSFRVSWTPPSDSVDRYKVEYYPVSGGKRQEFYVSRMETSTV
  LKDLKPETEYVVNVYSVVEDEYSEPLKGTEKTLPVPVVSLNIYDVGPTTMHVQWQPVGGA
  TGYILSYKPVKDTEPTRPKEVRLGPTVNDMQLTDLVPNTEYAVTVQAVLHDLTSEPVTVR
  EVTLPLPRPQDLKLRDVTHSTMNVFWEPVPGKVRKYIVRYKTPEEDVKEVEVDRSETSTS
  LKDLFSQTLYTVSVSAVHDEGESPPVTAQETTRPVPAPTNLKITEVTSEGFRGTWDHGAS
  DVSLYRITWAPFGSSDKMETILNGDENTLVFENLNPNTIYEVSITAIYPDESESDDLIGS
  ERTLPILTTQAPKSGPRNLQVYNATSNSLTVKWDPASGRVQKYRITYQPSTGEGNEQTTT
  IGGRQNSVVLQKLKPDTPYTITVSSLYPDGEGGRMTGRGKTKPLNTVRNLRVYDPSTSTL
  NVRWDHAEGNPRQYKLFYAPAAGGPEELVPIPGNTNYAILRNLQPDTSYTVTVVPVYTEG
  DGGRTSDTGRTLMRGLARNVQVYNPTPNSLDVRWDPAPGPVLQYRVVYSPVDGTRPSESI
  VVPGNTRMVHLERLIPDTLYSVNLVALYSDGEGNPSPAQGRTLPRSGPRNLRVFGETTNS
  LSVAWDHADGPVQQYRIIYSPTVGDPIDEYTTVPGRRNNVILQPLQPDTPYKITVIAVYE
  DGDGGHLTGNGRTVGLLPPQNIHISDEWYTRFRVSWDPSPSPVLGYKIVYKPVGSNEPME
  AFVGEMTSYTLHNLNPSTTYDVNVYAQYDSGLSVPLTDQGTTLYLNVTDLKTYQIGWDTF
  CVKWSPHRAATSYRLKLSPADGTRGQEITVRGSETSHCFTGLSPDTDYGVTVFVQTPNLE
  GPGVSVKEHTTVKPTEAPTEPPTPPPPPTIPPARDVCKGAKADIVFLTDASWSIGDDNFN
  KVVKFIFNTVGGFDEISPAGIQVSFVQYSDEVKSEFKLNTYNDKALALGALQNIRYRGGN
  TRTGKALTFIKEKVLTWESGMRKNVPKVLVVVTDGRSQDEVKKAALVIQQSGFSVFVVGV
  ADVDYNELANIASKPSERHVFIVDDFESFEKIEDNLITFVCETATSSCPLIYLDGYTSPG
  FKMLEAYNLTEKNFASVQGVSLESGSFPSYSAYRIQKNAFVNQPTADLHPNGLPPSYTII
  LLFRLLPETPSDPFAIWQITDRDYKPQVGVIADPSSKTLSFFNKDTRGEVQTVTFDTEEV
  KTLFYGSFHKVHIVVTSKSVKIYIDCYEIIEKDIKEAGNITTDGYEILGKLLKGERKSAA
  FQIQSFDIVCSPVWTSRDRCCDIPSRRDEGKCPAFPNSCTCTQDSVGPPGPPGPAGGPGA
  KGPRGERGISGAIGPPGPRGDIGPPGPQGPPGPQGPNGLSIPGEQGRQGMKGDAGEPGLP
  GRTGTPGLPGPPGPMGPPGDRGFTGKDGAMGPRGPPGPPGSPGSPGVTGPSGKPGKPGDH
  GRPGPSGLKGEKGDRGDIASQNMMRAVARQVCEQLISGQMNRFNQMLNQIPNDYQSSRNQ
  PGPPGPPGPPGSAGARGEPGPGGRPGFPGTPGMQGPPGERGLPGEKGERGTGSSGPRGLP
  GPPGPQGESRTGPPGSTGSRGPPGPPGRPGNSGIRGPPGPPGYCDSSQCASIPYNGQGYP
  GSG
• Function: Type XII collagen interacts with type I collagen-containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix.
• Tissue Specificity: Found in collagen I-containing tissues: both isoform 1 and isoform 2 appear in amnion, chorion, skeletal muscle, small intestine, and in cell culture of dermal fibroblasts, keratinocytes and endothelial cells. Only isoform 2 is found in lung, placenta, kidney and a squamous cell carcinoma cell line. Isoform 1 is also present in the corneal epithelial Bowman's membrane (BM) and the interfibrillar matrix of the corneal stroma, but it is not detected in the limbal BM.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Bethlem myopathy 2	DISDC4S5	Strong	Autosomal dominant	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Congenital myopathy	DISLSK9G	Strong	Genetic Variation	[6]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[7]
Exostosis	DIS3VKEI	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[9]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[10]
Microcephaly, epilepsy, and diabetes syndrome	DISMC1NE	Strong	Biomarker	[6]
Myopathy	DISOWG27	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Altered Expression	[11]
Obsolete Bethlem myopathy 2	DISLOP71	Strong	Autosomal dominant	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Ullrich congenital muscular dystrophy 1A	DISFHHF0	Strong	GermlineCausalMutation	[4]
Ullrich congenital muscular dystrophy 2	DIS9T7C6	Strong	Autosomal recessive	[4]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[14]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[15]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[16]
Bethlem myopathy	DISVF5K2	Supportive	Autosomal dominant	[17]
Ullrich congenital muscular dystrophy	DISJWD0V	Supportive	Autosomal dominant	[4]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[14]
Gastric cancer	DISXGOUK	Limited	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[18]
Stomach cancer	DISKIJSX	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Collagen alpha-1(XII) chain (COL12A1).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Collagen alpha-1(XII) chain (COL12A1).	[30]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[23]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[31]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[32]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Collagen alpha-1(XII) chain (COL12A1).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[35]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Collagen alpha-1(XII) chain (COL12A1).	[33]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[37]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Collagen alpha-1(XII) chain (COL12A1).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Collagen alpha-1(XII) chain (COL12A1).	[28]

References

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