Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPF7MQE)

• DOT Name: Guanine nucleotide exchange factor VAV3
• Synonyms: VAV-3
• Gene Name: VAV3
• UniProt ID: VAV3_HUMAN
• PDB ID: 2D86
• Pfam ID: PF00130 ; PF11971 ; PF00169 ; PF00621 ; PF00017 ; PF07653
• Sequence:
  MEPWKQCAQWLIHCKVLPTNHRVTWDSAQVFDLAQTLRDGVLLCQLLNNLRAHSINLKEI
  NLRPQMSQFLCLKNIRTFLTACCETFGMRKSELFEAFDLFDVRDFGKVIETLSRLSRTPI
  ALATGIRPFPTEESINDEDIYKGLPDLIDETLVEDEEDLYDCVYGEDEGGEVYEDLMKAE
  EAHQPKCPENDIRSCCLAEIKQTEEKYTETLESIEKYFMAPLKRFLTAAEFDSVFINIPE
  LVKLHRNLMQEIHDSIVNKNDQNLYQVFINYKERLVIYGQYCSGVESAISSLDYISKTKE
  DVKLKLEECSKRANNGKFTLRDLLVVPMQRVLKYHLLLQELVKHTTDPTEKANLKLALDA
  MKDLAQYVNEVKRDNETLREIKQFQLSIENLNQPVLLFGRPQGDGEIRITTLDKHTKQER
  HIFLFDLAVIVCKRKGDNYEMKEIIDLQQYKIANNPTTDKENKKWSYGFYLIHTQGQNGL
  EFYCKTKDLKKKWLEQFEMALSNIRPDYADSNFHDFKMHTFTRVTSCKVCQMLLRGTFYQ
  GYLCFKCGARAHKECLGRVDNCGRVNSGEQGTLKLPEKRTNGLRRTPKQVDPGLPKMQVI
  RNYSGTPPPALHEGPPLQLQAGDTVELLKGDAHSLFWQGRNLASGEVGFFPSDAVKPCPC
  VPKPVDYSCQPWYAGAMERLQAETELINRVNSTYLVRHRTKESGEYAISIKYNNEAKHIK
  ILTRDGFFHIAENRKFKSLMELVEYYKHHSLKEGFRTLDTTLQFPYKEPEHSAGQRGNRA
  GNSLLSPKVLGIAIARYDFCARDMRELSLLKGDVVKIYTKMSANGWWRGEVNGRVGWFPS
  TYVEEDE
• Function: Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2 (ITGB2)-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3 (ITGB3)-mediated adhesion. Does not affect integrin beta-1 (ITGB1)-mediated adhesion.
• Tissue Specificity: Isoform 1 and isoform 3 are widely expressed; both are expressed at very low levels in skeletal muscle. In keratinocytes, isoform 1 is less abundant than isoform 3. Isoform 3 is detected at very low levels, if any, in adrenal gland, bone marrow, spleen, fetal brain and spinal chord; in these tissues, isoform 1 is readily detectable.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  Focal adhesion (hsa04510)
  .tural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor sig.ling pathway (hsa04660)
  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)
  Yersinia infection (hsa05135)
  Proteoglycans in cancer (hsa05205)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  NRAGE signals death through JNK (R-HSA-193648)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  DAP12 signaling (R-HSA-2424491)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  G alpha (12/13) signalling events (R-HSA-416482)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  RHOA GTPase cycle (R-HSA-8980692)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOG GTPase cycle (R-HSA-9013408)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Azathioprine ADME (R-HSA-9748787)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Guanine nucleotide exchange factor VAV3 affects the response to substance of Cisplatin.	[27]

27 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 Guanine nucleotide exchange factor VAV3.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Guanine nucleotide exchange factor VAV3.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Guanine nucleotide exchange factor VAV3.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Guanine nucleotide exchange factor VAV3.	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Guanine nucleotide exchange factor VAV3.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Guanine nucleotide exchange factor VAV3.	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Guanine nucleotide exchange factor VAV3.	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Guanine nucleotide exchange factor VAV3.	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Guanine nucleotide exchange factor VAV3.	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Guanine nucleotide exchange factor VAV3.	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Guanine nucleotide exchange factor VAV3.	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Guanine nucleotide exchange factor VAV3.	[13]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Guanine nucleotide exchange factor VAV3.	[14]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Guanine nucleotide exchange factor VAV3.	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanine nucleotide exchange factor VAV3.	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Guanine nucleotide exchange factor VAV3.	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Guanine nucleotide exchange factor VAV3.	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Guanine nucleotide exchange factor VAV3.	[15]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Guanine nucleotide exchange factor VAV3.	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Guanine nucleotide exchange factor VAV3.	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Guanine nucleotide exchange factor VAV3.	[21]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Guanine nucleotide exchange factor VAV3.	[19]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the expression of Guanine nucleotide exchange factor VAV3.	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Guanine nucleotide exchange factor VAV3.	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Guanine nucleotide exchange factor VAV3.	[26]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Guanine nucleotide exchange factor VAV3.	[26]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Guanine nucleotide exchange factor VAV3.	[26]

4 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 Guanine nucleotide exchange factor VAV3.	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Guanine nucleotide exchange factor VAV3.	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Guanine nucleotide exchange factor VAV3.	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Guanine nucleotide exchange factor VAV3.	[24]

References

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