Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH4V7VQ)

• DOT Name: Actin, cytoplasmic 2 (ACTG1)
• Synonyms: EC 3.6.4.-; Gamma-actin
• Gene Name: ACTG1
• Related Disease:
  Baraitser-winter syndrome 2
  Nonsyndromic genetic hearing loss
  Autosomal dominant nonsyndromic hearing loss 20
  Autosomal dominant nonsyndromic hearing loss
  Baraitser-Winter cerebrofrontofacial syndrome
• UniProt ID: ACTG_HUMAN
• PDB ID: 5JLH; 6CXI; 6CXJ; 6G2T; 6V62; 6V63; 6WK1; 6WK2; 7NVM; 8DNF
• EC Number: 3.6.4.-
• Pfam ID: PF00022
• Sequence:
  MEEEIAALVIDNGSGMCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQS
  KRGILTLKYPIEHGIVTNWDDMEKIWHHTFYNELRVAPEEHPVLLTEAPLNPKANREKMT
  QIMFETFNTPAMYVAIQAVLSLYASGRTTGIVMDSGDGVTHTVPIYEGYALPHAILRLDL
  AGRDLTDYLMKILTERGYSFTTTAEREIVRDIKEKLCYVALDFEQEMATAASSSSLEKSY
  ELPDGQVITIGNERFRCPEALFQPSFLGMESCGIHETTFNSIMKCDVDIRKDLYANTVLS
  GGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQ
  EYDESGPSIVHRKCF
• Function: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Rap1 sig.ling pathway (hsa04015)
  Phagosome (hsa04145)
  Apoptosis (hsa04210)
  Hippo sig.ling pathway (hsa04390)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Leukocyte transendothelial migration (hsa04670)
  Thermogenesis (hsa04714)
  Regulation of actin cytoskeleton (hsa04810)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  Thyroid hormone sig.ling pathway (hsa04919)
  Oxytocin sig.ling pathway (hsa04921)
  Gastric acid secretion (hsa04971)
  Amyotrophic lateral sclerosis (hsa05014)
  Bacterial invasion of epithelial cells (hsa05100)
  Vibrio cholerae infection (hsa05110)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Yersinia infection (hsa05135)
  Influenza A (hsa05164)
  Proteoglycans in cancer (hsa05205)
  Hepatocellular carcinoma (hsa05225)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Viral myocarditis (hsa05416)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Gap junction degradation (R-HSA-190873)
  Formation of annular gap junctions (R-HSA-196025)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  EPHB-mediated forward signaling (R-HSA-3928662)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Adherens junctions interactions (R-HSA-418990)
  Recycling pathway of L1 (R-HSA-437239)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Interaction between L1 and Ankyrins (R-HSA-445095)
  Cell-extracellular matrix interactions (R-HSA-446353)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  RHO GTPases Activate Formins (R-HSA-5663220)
  MAP2K and MAPK activation (R-HSA-5674135)
  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)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Baraitser-winter syndrome 2	DISE1WFL	Definitive	Autosomal dominant	[1]
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	Autosomal dominant	[1]
Autosomal dominant nonsyndromic hearing loss 20	DIS3GZXU	Strong	Autosomal dominant	[2]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[3]
Baraitser-Winter cerebrofrontofacial syndrome	DISN13U9	Supportive	Autosomal dominant	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Actin, cytoplasmic 2 (ACTG1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Actin, cytoplasmic 2 (ACTG1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Actin, cytoplasmic 2 (ACTG1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Actin, cytoplasmic 2 (ACTG1).	[14]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[15]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Actin, cytoplasmic 2 (ACTG1).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Actin, cytoplasmic 2 (ACTG1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Actin, cytoplasmic 2 (ACTG1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Actin, cytoplasmic 2 (ACTG1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Actin, cytoplasmic 2 (ACTG1).	[24]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Actin, cytoplasmic 2 (ACTG1).	[25]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Investigative	9-hydroxyoctadecadienoic acid increases the expression of Actin, cytoplasmic 2 (ACTG1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Actin, cytoplasmic 2 (ACTG1).	[16]

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 Actin, cytoplasmic 2 (ACTG1).	[19]

References

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• [2] Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26). Am J Hum Genet. 2003 Nov;73(5):1082-91. doi: 10.1086/379286. Epub 2003 Sep 16.
• [3] Genetic Hearing Loss Overview. 1999 Feb 14 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
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