Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPQ0JYS)

• DOT Name: Vinculin
• Synonyms: Metavinculin; MV
• Gene Name: VCL
• Related Disease:
  Dilated cardiomyopathy 1W
  Dilated cardiomyopathy
  Obsolete familial isolated dilated cardiomyopathy
  Hypertrophic cardiomyopathy
  Hypertrophic cardiomyopathy 15
• UniProt ID: VINC_HUMAN
• PDB ID: 1RKC ; 1RKE ; 1SYQ ; 1TR2 ; 1YDI ; 2GWW ; 2HSQ ; 2IBF ; 3H2U ; 3H2V ; 3JBK ; 3MYI ; 3RF3 ; 3S90 ; 3TJ5 ; 3TJ6 ; 3VF0 ; 4DJ9 ; 4EHP ; 4LN2 ; 4LNP ; 4PR9 ; 5L0C ; 5L0D ; 5L0F ; 5L0G ; 5L0H ; 5L0I ; 5L0J ; 5O2Q ; 6FUY ; 6UPW ; 7KTT ; 7KTU ; 7KTV ; 7KTW
• Pfam ID: PF01044
• Sequence:
  MPVFHTRTIESILEPVAQQISHLVIMHEEGEVDGKAIPDLTAPVAAVQAAVSNLVRVGKE
  TVQTTEDQILKRDMPPAFIKVENACTKLVQAAQMLQSDPYSVPARDYLIDGSRGILSGTS
  DLLLTFDEAEVRKIIRVCKGILEYLTVAEVVETMEDLVTYTKNLGPGMTKMAKMIDERQQ
  ELTHQEHRVMLVNSMNTVKELLPVLISAMKIFVTTKNSKNQGIEEALKNRNFTVEKMSAE
  INEIIRVLQLTSWDEDAWASKDTEAMKRALASIDSKLNQAKGWLRDPSASPGDAGEQAIR
  QILDEAGKVGELCAGKERREILGTCKMLGQMTDQVADLRARGQGSSPVAMQKAQQVSQGL
  DVLTAKVENAARKLEAMTNSKQSIAKKIDAAQNWLADPNGGPEGEEQIRGALAEARKIAE
  LCDDPKERDDILRSLGEISALTSKLADLRRQGKGDSPEARALAKQVATALQNLQTKTNRA
  VANSRPAKAAVHLEGKIEQAQRWIDNPTVDDRGVGQAAIRGLVAEGHRLANVMMGPYRQD
  LLAKCDRVDQLTAQLADLAARGEGESPQARALASQLQDSLKDLKARMQEAMTQEVSDVFS
  DTTTPIKLLAVAATAPPDAPNREEVFDERAANFENHSGKLGATAEKAAAVGTANKSTVEG
  IQASVKTARELTPQVVSAARILLRNPGNQAAYEHFETMKNQWIDNVEKMTGLVDEAIDTK
  SLLDASEEAIKKDLDKCKVAMANIQPQMLVAGATSIARRANRILLVAKREVENSEDPKFR
  EAVKAASDELSKTISPMVMDAKAVAGNISDPGLQKSFLDSGYRILGAVAKVREAFQPQEP
  DFPPPPPDLEQLRLTDELAPPKPPLPEGEVPPPRPPPPEEKDEEFPEQKAGEVINQPMMM
  AARQLHDEARKWSSKPGIPAAEVGIGVVAEADAADAAGFPVPPDMEDDYEPELLLMPSNQ
  PVNQPILAAAQSLHREATKWSSKGNDIIAAAKRMALLMAEMSRLVRGGSGTKRALIQCAK
  DIAKASDEVTRLAKEVAKQCTDKRIRTNLLQVCERIPTISTQLKILSTVKATMLGRTNIS
  DEESEQATEMLVHNAQNLMQSVKETVREAEAASIKIRTDAGFTLRWVRKTPWYQ
• Function: Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.
• Tissue Specificity: Metavinculin is muscle-specific.
• KEGG Pathway:
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Amoebiasis (hsa05146)
• Reactome Pathway:
  Smooth Muscle Contraction (R-HSA-445355)
  MAP2K and MAPK activation (R-HSA-5674135)
  Neutrophil degranulation (R-HSA-6798695)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy 1W	DISCYA3B	Strong	Autosomal dominant	[1]
Dilated cardiomyopathy	DISX608J	Moderate	Autosomal dominant	[2]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[1]
Hypertrophic cardiomyopathy	DISQG2AI	Disputed	Autosomal dominant	[2]
Hypertrophic cardiomyopathy 15	DIS0J29O	Limited	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Vinculin increases the Cytology abnormal ADR of Menadione.	[32]
Fluorouracil	DMUM7HZ	Approved	Vinculin affects the response to substance of Fluorouracil.	[33]

28 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 Vinculin.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vinculin.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Vinculin.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Vinculin.	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Vinculin.	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Vinculin.	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vinculin.	[10]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Vinculin.	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Vinculin.	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Vinculin.	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Vinculin.	[14]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Vinculin.	[15]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Vinculin.	[13]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Vinculin.	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Vinculin.	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Vinculin.	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Vinculin.	[19]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Vinculin.	[20]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Vinculin.	[21]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Vinculin.	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Vinculin.	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vinculin.	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Vinculin.	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Vinculin.	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Vinculin.	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Vinculin.	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Vinculin.	[29]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Vinculin.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Vinculin.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Vinculin.	[30]

References

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