Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT27ZYKJ)

• DOT Name: Protein Wnt-5a
• Gene Name: WNT5A
• Related Disease:
  Autosomal dominant Robinow syndrome 1
  Autosomal dominant Robinow syndrome
• UniProt ID: WNT5A_HUMAN
• Pfam ID: PF00110
• Sequence:
  MKKSIGILSPGVALGMAGSAMSSKFFLVALAIFFSFAQVVIEANSWWSLGMNNPVQMSEV
  YIIGAQPLCSQLAGLSQGQKKLCHLYQDHMQYIGEGAKTGIKECQYQFRHRRWNCSTVDN
  TSVFGRVMQIGSRETAFTYAVSAAGVVNAMSRACREGELSTCGCSRAARPKDLPRDWLWG
  GCGDNIDYGYRFAKEFVDARERERIHAKGSYESARILMNLHNNEAGRRTVYNLADVACKC
  HGVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMRLNSRGKLVQVNSRFNSPTTQDLV
  YIDPSPDYCVRNESTGSLGTQGRLCNKTSEGMDGCELMCCGRGYDQFKTVQTERCHCKFH
  WCCYVKCKKCTEIVDQFVCK
• Function: Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression. Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells. Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes.
• Tissue Specificity: Expression is increased in differentiated thyroid carcinomas compared to normal thyroid tissue and anaplastic thyroid tumors where expression is low or undetectable. Expression is found in thyrocytes but not in stromal cells (at protein level) . Detected in neonate heart and lung .
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  Wnt sig.ling pathway (hsa04310)
  Axon guidance (hsa04360)
  Hippo sig.ling pathway (hsa04390)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Melanogenesis (hsa04916)
  Cushing syndrome (hsa04934)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Basal cell carcinoma (hsa05217)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  WNT ligand biogenesis and trafficking (R-HSA-3238698)
  Class B/2 (Secretin family receptors) (R-HSA-373080)
  Negative regulation of TCF-dependent signaling by WNT ligand antagonists (R-HSA-3772470)
  Ca2+ pathway (R-HSA-4086398)
  PCP/CE pathway (R-HSA-4086400)
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  WNT5A-dependent internalization of FZD4 (R-HSA-5099900)
  WNT5A-dependent internalization of FZD2, FZD5 and ROR2 (R-HSA-5140745)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  WNT5 (R-HSA-9673324)
  TCF dependent signaling in response to WNT (R-HSA-201681)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant Robinow syndrome 1	DISLYVHM	Definitive	Autosomal dominant	[1]
Autosomal dominant Robinow syndrome	DIS94N80	Moderate	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Protein Wnt-5a affects the response to substance of DTI-015.	[37]
Mitomycin	DMH0ZJE	Approved	Protein Wnt-5a affects the response to substance of Mitomycin.	[38]

38 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 Protein Wnt-5a.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Wnt-5a.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein Wnt-5a.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein Wnt-5a.	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein Wnt-5a.	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein Wnt-5a.	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein Wnt-5a.	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein Wnt-5a.	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein Wnt-5a.	[12]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Protein Wnt-5a.	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein Wnt-5a.	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein Wnt-5a.	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein Wnt-5a.	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein Wnt-5a.	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Protein Wnt-5a.	[17]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Protein Wnt-5a.	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Protein Wnt-5a.	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Protein Wnt-5a.	[18]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein Wnt-5a.	[19]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Protein Wnt-5a.	[20]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Protein Wnt-5a.	[21]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Protein Wnt-5a.	[22]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Protein Wnt-5a.	[5]
Ramelteon	DM7IW9J	Approved	Ramelteon increases the expression of Protein Wnt-5a.	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Protein Wnt-5a.	[23]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein Wnt-5a.	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein Wnt-5a.	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Wnt-5a.	[28]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 increases the expression of Protein Wnt-5a.	[5]
SB-431542	DM0YOXQ	Preclinical	SB-431542 decreases the expression of Protein Wnt-5a.	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein Wnt-5a.	[31]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein Wnt-5a.	[32]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Protein Wnt-5a.	[33]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Protein Wnt-5a.	[34]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Protein Wnt-5a.	[35]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Protein Wnt-5a.	[36]
U0126	DM31OGF	Investigative	U0126 increases the expression of Protein Wnt-5a.	[12]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Protein Wnt-5a.	[19]

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 acetylation of Protein Wnt-5a.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein Wnt-5a.	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein Wnt-5a.	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein Wnt-5a.	[30]

References

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