Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2)
• Synonyms: EC 2.3.2.27; Adapter protein CIKS; Connection to IKK and SAPK/JNK; E3 ubiquitin-protein ligase CIKS; Nuclear factor NF-kappa-B activator 1; ACT1; TRAF3-interacting protein 2
• Gene Name: TRAF3IP2
• Related Disease:
  Neoplasm
  Acute myocardial infarction
  Advanced cancer
  Atopic dermatitis
  Autoimmune disease
  Behcet disease
  Candidiasis, familial, 8
  Capillary malformation
  Cardiovascular disease
  Cluster headache
  Colonic disorder
  Dermatitis
  Glioma
  Hirschsprung disease
  Inflammatory bowel disease
  Irritable bowel syndrome
  Malaria
  Myocardial infarction
  Nasal polyp
  Palmoplantar pustulosis
  Pneumonia
  Pneumonitis
  Polyp
  Psoriasis
  Pyoderma gangrenosum
  Rheumatoid arthritis
  Schwartz-Jampel syndrome
  Sjogren syndrome
  Systemic lupus erythematosus
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Toxic epidermal necrolysis
  Ulcerative colitis
  Vascular disease
  Mycetoma
  Myocardial ischemia
  Chronic mucocutaneous candidiasis
  Arteriosclerosis
  Atherosclerosis
  Bronchiectasis
  Crohn disease
  Glioblastoma multiforme
  Headache
  Migraine disorder
  Oral candidiasis
  Psoriatic arthritis
  Type-1/2 diabetes
• UniProt ID: CIKS_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF08357
• Sequence:
  MPPQLQETRMNRSIPVEVDESEPYPSQLLKPIPEYSPEEESEPPAPNIRNMAPNSLSAPT
  MLHNSSGDFSQAHSTLKLANHQRPVSRQVTCLRTQVLEDSEDSFCRRHPGLGKAFPSGCS
  AVSEPASESVVGALPAEHQFSFMEKRNQWLVSQLSAASPDTGHDSDKSDQSLPNASADSL
  GGSQEMVQRPQPHRNRAGLDLPTIDTGYDSQPQDVLGIRQLERPLPLTSVCYPQDLPRPL
  RSREFPQFEPQRYPACAQMLPPNLSPHAPWNYHYHCPGSPDHQVPYGHDYPRAAYQQVIQ
  PALPGQPLPGASVRGLHPVQKVILNYPSPWDHEERPAQRDCSFPGLPRHQDQPHHQPPNR
  AGAPGESLECPAELRPQVPQPPSPAAVPRPPSNPPARGTLKTSNLPEELRKVFITYSMDT
  AMEVVKFVNFLLVNGFQTAIDIFEDRIRGIDIIKWMERYLRDKTVMIIVAISPKYKQDVE
  GAESQLDEDEHGLHTKYIHRMMQIEFIKQGSMNFRFIPVLFPNAKKEHVPTWLQNTHVYS
  WPKNKKNILLRLLREEEYVAPPRGPLPTLQVVPL
• Function: E3 ubiquitin ligase that catalyzes 'Lys-63'-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling. Transfers ubiquitin from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein. Essential adapter molecule in IL17A-mediated signaling. Upon IL17A stimulation, interacts with IL17RA and IL17RC receptor chains through SEFIR domains and catalyzes 'Lys-63'-linked polyubiquitination of TRAF6, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Cellular senescence (hsa04218)
  IL-17 sig.ling pathway (hsa04657)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[6]
Candidiasis, familial, 8	DISMCSDG	Strong	Autosomal recessive	[7]
Capillary malformation	DISR6ZSG	Strong	Genetic Variation	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Cluster headache	DISKAXY9	Strong	Biomarker	[10]
Colonic disorder	DISXXS3L	Strong	Genetic Variation	[11]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Hirschsprung disease	DISUUSM1	Strong	Altered Expression	[13]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[14]
Irritable bowel syndrome	DIS27206	Strong	Genetic Variation	[15]
Malaria	DISQ9Y50	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[9]
Nasal polyp	DISLP3XE	Strong	Biomarker	[17]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[18]
Pneumonia	DIS8EF3M	Strong	Biomarker	[19]
Pneumonitis	DIS88E0K	Strong	Biomarker	[19]
Polyp	DISRSLYF	Strong	Altered Expression	[17]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[20]
Pyoderma gangrenosum	DIS8QVTT	Strong	Genetic Variation	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[21]
Schwartz-Jampel syndrome	DIS3HCR8	Strong	Genetic Variation	[22]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[25]
Toxic epidermal necrolysis	DISIWPFR	Strong	Genetic Variation	[22]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[26]
Vascular disease	DISVS67S	Strong	Biomarker	[27]
Mycetoma	DIST5UFZ	moderate	Biomarker	[28]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[29]
Chronic mucocutaneous candidiasis	DISPSGYF	Supportive	Autosomal dominant	[30]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[31]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[31]
Bronchiectasis	DIS5MYEE	Limited	Genetic Variation	[8]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[32]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[33]
Headache	DISK4TGU	Limited	Biomarker	[34]
Migraine disorder	DISFCQTG	Limited	Biomarker	[34]
Oral candidiasis	DISAVKAH	Limited	Genetic Variation	[8]
Psoriatic arthritis	DISLWTG2	Limited	Genetic Variation	[35]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[31]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[43]
Menadione	DMSJDTY	Approved	Menadione affects the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of E3 ubiquitin ligase TRAF3IP2 (TRAF3IP2).	[46]

References

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