Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC76KQM)

• DOT Name: CD2-associated protein (CD2AP)
• Synonyms: Adapter protein CMS; Cas ligand with multiple SH3 domains
• Gene Name: CD2AP
• Related Disease:
  B-cell neoplasm
  Glomerulosclerosis
  Rheumatoid arthritis
  Adult lymphoma
  Alzheimer disease
  Atrial fibrillation
  Chronic renal failure
  Congenital myasthenic syndrome
  Dementia
  Depression
  End-stage renal disease
  Familial Alzheimer disease
  Fatty liver disease
  Focal segmental glomerulosclerosis
  Focal segmental glomerulosclerosis 3, susceptibility to
  Hepatitis C virus infection
  Iatrogenic disease
  IgA nephropathy
  Kidney failure
  Lung cancer
  Lung carcinoma
  Lymphoma
  Myopathy
  Neoplasm
  Nephropathy
  Nephrotic syndrome
  Nephrotic syndrome, type 2
  Osteoarthritis
  Parkinson disease
  Pediatric lymphoma
  Precancerous condition
  Prion disease
  Schizophrenia
  Spinal muscular atrophy
  Steroid-resistant nephrotic syndrome
  Vascular dementia
  Wilms tumor
  Colorectal carcinoma
  Diabetic kidney disease
  High blood pressure
  Familial idiopathic steroid-resistant nephrotic syndrome
  Metastatic malignant neoplasm
  Amyotrophic lateral sclerosis
  Familial amyotrophic lateral sclerosis
  Metastatic melanoma
  Neuroblastoma
  Non-insulin dependent diabetes
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: CD2AP_HUMAN
• PDB ID: 2FEI; 2J6F; 2J6K; 2J6O; 2J7I; 3AA6; 3LK4; 3U23; 4WCI; 4X1V; 7DS6; 7DS8
• Pfam ID: PF00018 ; PF14604
• Sequence:
  MVDYIVEYDYDAVHDDELTIRVGEIIRNVKKLQEEGWLEGELNGRRGMFPDNFVKEIKRE
  TEFKDDSLPIKRERHGNVASLVQRISTYGLPAGGIQPHPQTKNIKKKTKKRQCKVLFEYI
  PQNEDELELKVGDIIDINEEVEEGWWSGTLNNKLGLFPSNFVKELEVTDDGETHEAQDDS
  ETVLAGPTSPIPSLGNVSETASGSVTQPKKIRGIGFGDIFKEGSVKLRTRTSSSETEEKK
  PEKPLILQSLGPKTQSVEITKTDTEGKIKAKEYCRTLFAYEGTNEDELTFKEGEIIHLIS
  KETGEAGWWRGELNGKEGVFPDNFAVQINELDKDFPKPKKPPPPAKAPAPKPELIAAEKK
  YFSLKPEEKDEKSTLEQKPSKPAAPQVPPKKPTPPTKASNLLRSSGTVYPKRPEKPVPPP
  PPIAKINGEVSSISSKFETEPVSKLKLDSEQLPLRPKSVDFDSLTVRTSKETDVVNFDDI
  ASSENLLHLTANRPKMPGRRLPGRFNGGHSPTHSPEKILKLPKEEDSANLKPSELKKDTC
  YSPKPSVYLSTPSSASKANTTAFLTPLEIKAKVETDDVKKNSLDELRAQIIELLCIVEAL
  KKDHGKELEKLRKDLEEEKTMRSNLEMEIEKLKKAVLSS
• Function: Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis. Plays a role in epithelial cell junctions formation.
• Tissue Specificity: Widely expressed in fetal and adult tissues.
• KEGG Pathway: Bacterial invasion of epithelial cells (hsa05100)
• Reactome Pathway: Nephrin family interactions (R-HSA-373753)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Glomerulosclerosis	DISJF20Z	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[3]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[6]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[7]
Congenital myasthenic syndrome	DISJLG2T	Strong	Genetic Variation	[8]
Dementia	DISXL1WY	Strong	Genetic Variation	[9]
Depression	DIS3XJ69	Strong	Biomarker	[10]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[7]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[11]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[4]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Genetic Variation	[7]
Focal segmental glomerulosclerosis 3, susceptibility to	DIS5XCZD	Strong	Autosomal dominant	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Iatrogenic disease	DISNZCYA	Strong	Biomarker	[13]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[14]
Kidney failure	DISOVQ9P	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[15]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[15]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Myopathy	DISOWG27	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[18]
Nephrotic syndrome	DISSPSC2	Strong	Altered Expression	[18]
Nephrotic syndrome, type 2	DISIRFO1	Strong	GermlineCausalMutation	[19]
Osteoarthritis	DIS05URM	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[9]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[4]
Precancerous condition	DISV06FL	Strong	Biomarker	[21]
Prion disease	DISOUMB0	Strong	Genetic Variation	[22]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[23]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[24]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Biomarker	[25]
Vascular dementia	DISVO82H	Strong	Biomarker	[5]
Wilms tumor	DISB6T16	Strong	Altered Expression	[26]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[27]
Diabetic kidney disease	DISJMWEY	moderate	Altered Expression	[28]
High blood pressure	DISY2OHH	moderate	Altered Expression	[29]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[19]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[17]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[30]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Limited	Biomarker	[30]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[31]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[32]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[33]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[33]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CD2-associated protein (CD2AP).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CD2-associated protein (CD2AP).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CD2-associated protein (CD2AP).	[37]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CD2-associated protein (CD2AP).	[40]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of CD2-associated protein (CD2AP).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CD2-associated protein (CD2AP).	[43]

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 CD2-associated protein (CD2AP).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of CD2-associated protein (CD2AP).	[39]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of CD2-associated protein (CD2AP).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of CD2-associated protein (CD2AP).	[39]

References

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