Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3M5P3G)

• DOT Name: Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP)
• Synonyms: TERF2-interacting telomeric protein 1; TRF2-interacting telomeric protein 1; Dopamine receptor-interacting protein 5; Repressor/activator protein 1 homolog; RAP1 homolog; hRap1
• Gene Name: TERF2IP
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Crohn disease
  Inflammatory bowel disease
  Ulcerative colitis
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Bone osteosarcoma
  Cerebral cavernous malformation
  Colitis
  Colon cancer
  Depression
  Diabetic kidney disease
  Familial atypical multiple mole melanoma syndrome
  Gastric cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Melanoma
  Myocardial infarction
  Neuroblastoma
  Non-insulin dependent diabetes
  Obesity
  Osteosarcoma
  Ovarian cancer
  Pancreatic cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Thyroid tumor
  Tuberous sclerosis
  Colon carcinoma
  Head-neck squamous cell carcinoma
  High blood pressure
  Renal fibrosis
  Carcinoma of liver and intrahepatic biliary tract
  Fatty liver disease
  Liver cancer
  Non-small-cell lung cancer
  Rheumatoid arthritis
  Stroke
• UniProt ID: TE2IP_HUMAN
• PDB ID: 1FEX; 3K6G; 4RQI; 7OZ0
• Pfam ID: PF16589 ; PF08914 ; PF11626
• Sequence:
  MAEAMDLGKDPNGPTHSSTLFVRDDGSSMSFYVRPSPAKRRLSTLILHGGGTVCRVQEPG
  AVLLAQPGEALAEASGDFISTQYILDCVERNERLELEAYRLGPASAADTGSEAKPGALAE
  GAAEPEPQRHAGRIAFTDADDVAILTYVKENARSPSSVTGNALWKAMEKSSLTQHSWQSL
  KDRYLKHLRGQEHKYLLGDAPVSPSSQKLKRKAEEDPEAADSGEPQNKRTPDLPEEEYVK
  EEIQENEEAVKKMLVEATREFEEVVVDESPPDFEIHITMCDDDPPTPEEDSETQPDEEEE
  EEEEKVSQPEVGAAIKIIRQLMEKFNLDLSTVTQAFLKNSGELEATSAFLASGQRADGYP
  IWSRQDDIDLQKDDEDTREALVKKFGAQNVARRIEFRKK
• Function: Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes.
• Tissue Specificity: Ubiquitous. Highly expressed.
• Reactome Pathway:
  Cleavage of the damaged pyrimidine (R-HSA-110329)
  Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330)
  Cleavage of the damaged purine (R-HSA-110331)
  Meiotic synapsis (R-HSA-1221632)
  Packaging Of Telomere Ends (R-HSA-171306)
  Telomere Extension By Telomerase (R-HSA-171319)
  Polymerase switching on the C-strand of the telomere (R-HSA-174411)
  Processive synthesis on the C-strand of the telomere (R-HSA-174414)
  Telomere C-strand (Lagging Strand) Synthesis (R-HSA-174417)
  Telomere C-strand synthesis initiation (R-HSA-174430)
  Removal of the Flap Intermediate from the C-strand (R-HSA-174437)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  Inhibition of DNA recombination at telomere (R-HSA-9670095)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[2]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[3]
Inflammatory bowel disease	DISGN23E	Definitive	Altered Expression	[3]
Ulcerative colitis	DIS8K27O	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Cerebral cavernous malformation	DISLKNYA	Strong	Biomarker	[8]
Colitis	DISAF7DD	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Depression	DIS3XJ69	Strong	Altered Expression	[11]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[12]
Familial atypical multiple mole melanoma syndrome	DIS2YEKP	Strong	SusceptibilityMutation	[13]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Altered Expression	[17]
Myocardial infarction	DIS655KI	Strong	Biomarker	[18]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[20]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[22]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[26]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[14]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[28]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[29]
Tuberous sclerosis	DISEMUGZ	Strong	Altered Expression	[30]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[10]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[31]
High blood pressure	DISY2OHH	moderate	Biomarker	[32]
Renal fibrosis	DISMHI3I	moderate	Biomarker	[12]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[15]
Fatty liver disease	DIS485QZ	Limited	Biomarker	[15]
Liver cancer	DISDE4BI	Limited	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[33]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[34]
Stroke	DISX6UHX	Limited	Altered Expression	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[41]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[42]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[48]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[49]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP).	[46]

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