Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5RH6TI)

• DOT Name: Ras-related protein Rap-1A (RAP1A)
• Synonyms: EC 3.6.5.2; C21KG; G-22K; GTP-binding protein smg p21A; Ras-related protein Krev-1
• Gene Name: RAP1A
• Related Disease:
  Acute myelogenous leukaemia
  Multiple sclerosis
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cerebral cavernous malformation
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Crohn disease
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Kabuki syndrome
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Neuroblastoma
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Osteosarcoma
  Ovarian cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Tuberous sclerosis
  Colorectal carcinoma
  Ductal breast carcinoma in situ
  Head-neck squamous cell carcinoma
  High blood pressure
  Renal fibrosis
  Liver cancer
  Melanoma
  Plasma cell myeloma
  Rheumatoid arthritis
  Schizophrenia
  Stroke
• UniProt ID: RAP1A_HUMAN
• PDB ID: 1C1Y; 1GUA; 3KUC; 4KVG
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MREYKLVVLGSGGVGKSALTVQFVQGIFVEKYDPTIEDSYRKQVEVDCQQCMLEILDTAG
  TEQFTAMRDLYMKNGQGFALVYSITAQSTFNDLQDLREQILRVKDTEDVPMILVGNKCDL
  EDERVVGKEQGQNLARQWCNCAFLESSAKSKINVNEIFYDLVRQINRKTPVEKKKPKKKS
  CLLL
• Function: Induces morphological reversion of a cell line transformed by a Ras oncogene. Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes. Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions.
• 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)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Platelet activation (hsa04611)
  Leukocyte transendothelial migration (hsa04670)
  Long-term potentiation (hsa04720)
  Neurotrophin sig.ling pathway (hsa04722)
  Cushing syndrome (hsa04934)
  Pancreatic secretion (hsa04972)
  Re.l cell carcinoma (hsa05211)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  ARMS-mediated activation (R-HSA-170984)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676)
  Rap1 signalling (R-HSA-392517)
  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)
  MET activates RAP1 and RAC1 (R-HSA-8875555)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Frs2-mediated activation (R-HSA-170968)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Cerebral cavernous malformation	DISLKNYA	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Kabuki syndrome	DISZN97H	Strong	GermlineCausalMutation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Myocardial infarction	DIS655KI	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Osteoporosis	DISF2JE0	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[23]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[14]
Tuberous sclerosis	DISEMUGZ	Strong	Altered Expression	[27]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[28]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[29]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[30]
High blood pressure	DISY2OHH	moderate	Biomarker	[31]
Renal fibrosis	DISMHI3I	moderate	Biomarker	[32]
Liver cancer	DISDE4BI	Limited	Biomarker	[15]
Melanoma	DIS1RRCY	Limited	Altered Expression	[33]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[34]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[35]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[36]
Stroke	DISX6UHX	Limited	Altered Expression	[37]

20 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 protein Rap-1A (RAP1A).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rap-1A (RAP1A).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rap-1A (RAP1A).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-related protein Rap-1A (RAP1A).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rap-1A (RAP1A).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ras-related protein Rap-1A (RAP1A).	[44]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Ras-related protein Rap-1A (RAP1A).	[41]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Ras-related protein Rap-1A (RAP1A).	[45]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Ras-related protein Rap-1A (RAP1A).	[46]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Ras-related protein Rap-1A (RAP1A).	[47]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Ras-related protein Rap-1A (RAP1A).	[48]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Ras-related protein Rap-1A (RAP1A).	[49]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Ras-related protein Rap-1A (RAP1A).	[50]
Pitavastatin	DMJH792	Approved	Pitavastatin decreases the expression of Ras-related protein Rap-1A (RAP1A).	[47]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Ras-related protein Rap-1A (RAP1A).	[41]
Perillyl alcohol	DMFWC3O	Discontinued in Phase 2	Perillyl alcohol increases the expression of Ras-related protein Rap-1A (RAP1A).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rap-1A (RAP1A).	[55]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Ras-related protein Rap-1A (RAP1A).	[56]
[3H]cAMP	DMZRQU7	Investigative	[3H]cAMP increases the activity of Ras-related protein Rap-1A (RAP1A).	[57]
Perillaldehyde	DMZA0VD	Investigative	Perillaldehyde increases the expression of Ras-related protein Rap-1A (RAP1A).	[46]

7 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 Ras-related protein Rap-1A (RAP1A).	[43]
Pamidronate	DMB4AVP	Approved	Pamidronate decreases the prenylation of Ras-related protein Rap-1A (RAP1A).	[51]
Alendronate	DMY2KX9	Approved	Alendronate decreases the prenylation of Ras-related protein Rap-1A (RAP1A).	[51]
Minodronate	DM50PMY	Approved	Minodronate decreases the prenylation of Ras-related protein Rap-1A (RAP1A).	[52]
Risedronate	DM5FLTY	Approved	Risedronate decreases the prenylation of Ras-related protein Rap-1A (RAP1A).	[51]
Ibandronate	DM0QZBN	Approved	Ibandronate decreases the prenylation of Ras-related protein Rap-1A (RAP1A).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ras-related protein Rap-1A (RAP1A).	[54]

References

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