Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related C3 botulinum toxin substrate 2 (RAC2)
• Synonyms: GX; Small G protein; p21-Rac2
• Gene Name: RAC2
• Related Disease:
  Acute myelogenous leukaemia
  Glioma
  Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia
  Alzheimer disease
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Autoimmune disease
  Bone osteosarcoma
  Brain neoplasm
  Chronic kidney disease
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Crohn disease
  Fatty liver disease
  Hepatocellular carcinoma
  High blood pressure
  Immunodeficiency
  Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Lymphoma
  Melanoma
  Multiple sclerosis
  Neoplasm
  Neutrophil immunodeficiency syndrome
  Non-small-cell lung cancer
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Thyroid gland carcinoma
  Clear cell renal carcinoma
  Rheumatoid arthritis
  Chronic myelomonocytic leukaemia
  Pneumonia
  Type-1/2 diabetes
  Adult glioblastoma
  Advanced cancer
  Cardiac disease
  Glioblastoma multiforme
  Graves disease
  Inflammatory bowel disease
  Small lymphocytic lymphoma
  Type-1 diabetes
• UniProt ID: RAC2_HUMAN
• PDB ID: 1DS6; 2W2T; 2W2V; 2W2X
• Pfam ID: PF00071
• Sequence:
  MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDSKPVNLGLWDTAG
  QEDYDRLRPLSYPQTDVFLICFSLVSPASYENVRAKWFPEVRHHCPSTPIILVGTKLDLR
  DDKDTIEKLKEKKLAPITYPQGLALAKEIDSVKYLECSALTQRGLKTVFDEAIRAVLCPQ
  PTRQQKRACSLL
• Function: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase.
• Tissue Specificity: Hematopoietic specific.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  Sphingolipid sig.ling pathway (hsa04071)
  Wnt sig.ling pathway (hsa04310)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Neutrophil extracellular trap formation (hsa04613)
  .tural killer cell mediated cytotoxicity (hsa04650)
  B cell receptor sig.ling pathway (hsa04662)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Prion disease (hsa05020)
  Yersinia infection (hsa05135)
  Human cytomegalovirus infection (hsa05163)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Choline metabolism in cancer (hsa05231)
  Diabetic cardiomyopathy (hsa05415)
  Viral myocarditis (hsa05416)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  ROS and RNS production in phagocytes (R-HSA-1222556)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  PCP/CE pathway (R-HSA-4086400)
  RHO GTPases Activate NADPH Oxidases (R-HSA-5668599)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  RAC2 GTPase cycle (R-HSA-9013404)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Genetic Variation	[2]
Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia	DISOXIIW	Definitive	Autosomal dominant	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[6]
Chronic kidney disease	DISW82R7	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[11]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[11]
Immunodeficiency	DIS093I0	Strong	Biomarker	[15]
Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia	DISHCVKX	Strong	Autosomal recessive	[16]
leukaemia	DISS7D1V	Strong	Altered Expression	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Lymphoma	DISN6V4S	Strong	Biomarker	[19]
Melanoma	DIS1RRCY	Strong	Biomarker	[20]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Neutrophil immunodeficiency syndrome	DISTXP5J	Strong	Autosomal dominant	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[25]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[26]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[22]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[27]
Chronic myelomonocytic leukaemia	DISDN5P7	Disputed	Biomarker	[28]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[29]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[30]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[31]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[32]
Cardiac disease	DISVO1I5	Limited	Biomarker	[33]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[31]
Graves disease	DISU4KOQ	Limited	Genetic Variation	[34]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[35]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[36]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[37]

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 Ras-related C3 botulinum toxin substrate 2 (RAC2).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[43]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[45]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[47]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[48]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[49]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[50]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[51]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[48]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[56]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin affects the localization of Ras-related C3 botulinum toxin substrate 2 (RAC2).	[53]

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 Ras-related C3 botulinum toxin substrate 2 (RAC2).	[55]

References

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