Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DHQ1P)

• DOT Name: Interferon regulatory factor 4 (IRF4)
• Synonyms: IRF-4; Lymphocyte-specific interferon regulatory factor; LSIRF; Multiple myeloma oncogene 1; NF-EM5
• Gene Name: IRF4
• Related Disease:
  Classic Hodgkin lymphoma
  Cutaneous squamous cell carcinoma
  Melanocytic nevus
  Melanoma
  Neoplasm
  Skin carcinoma
  Adult lymphoma
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Anaplastic large cell lymphoma
  Asthma
  Burkitt lymphoma
  Coeliac disease
  Erectile dysfunction
  Gonorrhea
  Hypothyroidism
  Inflammatory bowel disease
  Kaposi sarcoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Osteoarthritis
  Pediatric lymphoma
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Primary cutaneous T-cell lymphoma
  Progressive supranuclear palsy
  Skin cancer
  Squamous cell carcinoma
  T-cell leukaemia
  Vitiligo
  Waldenstrom macroglobulinemia
  AIDS-related lymphoma
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
  Basal cell carcinoma
  Basal cell neoplasm
  Colitis
  Lymphoproliferative syndrome
  Rheumatoid arthritis
  Stroke
• UniProt ID: IRF4_HUMAN
• PDB ID: 2DLL; 6TD4; 7JM4; 7O56; 7OGS; 7OOT; 7RH2
• Pfam ID: PF00605 ; PF10401
• Sequence:
  MNLEGGGRGGEFGMSAVSCGNGKLRQWLIDQIDSGKYPGLVWENEEKSIFRIPWKHAGKQ
  DYNREEDAALFKAWALFKGKFREGIDKPDPPTWKTRLRCALNKSNDFEELVERSQLDISD
  PYKVYRIVPEGAKKGAKQLTLEDPQMSMSHPYTMTTPYPSLPAQQVHNYMMPPLDRSWRD
  YVPDQPHPEIPYQCPMTFGPRGHHWQGPACENGCQVTGTFYACAPPESQAPGVPTEPSIR
  SAEALAFSDCRLHICLYYREILVKELTTSSPEGCRISHGHTYDASNLDQVLFPYPEDNGQ
  RKNIEKLLSHLERGVVLWMAPDGLYAKRLCQSRIYWDGPLALCNDRPNKLERDQTCKLFD
  TQQFLSELQAFAHHGRSLPRFQVTLCFGEEFPDPQRQRKLITAHVEPLLARQLYYFAQQN
  SGHFLRGYDLPEHISNPEDYHRSIRHSSIQE
• Function: Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes.
• Tissue Specificity: Lymphoid cells.
• KEGG Pathway: Th17 cell differentiation (hsa04659)
• Reactome Pathway:
  Interferon gamma signaling (R-HSA-877300)
  Interferon alpha/beta signaling (R-HSA-909733)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Altered Expression	[1]
Cutaneous squamous cell carcinoma	DIS3LXUG	Definitive	Genetic Variation	[2]
Melanocytic nevus	DISYS32D	Definitive	Genetic Variation	[3]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[3]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Skin carcinoma	DISUZREN	Definitive	Genetic Variation	[5]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[6]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Biomarker	[9]
Asthma	DISW9QNS	Strong	Genetic Variation	[10]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[6]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[11]
Erectile dysfunction	DISD8MTH	Strong	Genetic Variation	[12]
Gonorrhea	DISQ5AO6	Strong	Altered Expression	[13]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[14]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[15]
Kaposi sarcoma	DISC1H1Z	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Altered Expression	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[17]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[18]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[6]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Altered Expression	[22]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Altered Expression	[23]
Progressive supranuclear palsy	DISO5KRQ	Strong	Genetic Variation	[24]
Skin cancer	DISTM18U	Strong	Genetic Variation	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[26]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[27]
Vitiligo	DISR05SL	Strong	Genetic Variation	[28]
Waldenstrom macroglobulinemia	DIS9O23I	Strong	Genetic Variation	[29]
AIDS-related lymphoma	DISSLRAU	Limited	Altered Expression	[16]
Alopecia	DIS37HU4	Limited	Genetic Variation	[30]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[31]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[31]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[26]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[26]
Colitis	DISAF7DD	Limited	Biomarker	[32]
Lymphoproliferative syndrome	DISMVL8O	Limited	Biomarker	[9]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[33]
Stroke	DISX6UHX	Limited	Altered Expression	[34]

11 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 Interferon regulatory factor 4 (IRF4).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon regulatory factor 4 (IRF4).	[36]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Interferon regulatory factor 4 (IRF4).	[39]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Interferon regulatory factor 4 (IRF4).	[40]
Rigosertib	DMOSTXF	Phase 3	Rigosertib affects the expression of Interferon regulatory factor 4 (IRF4).	[41]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Interferon regulatory factor 4 (IRF4).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon regulatory factor 4 (IRF4).	[44]
T-5224	DMD3CUJ	Discontinued in Phase 2	T-5224 decreases the expression of Interferon regulatory factor 4 (IRF4).	[39]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Interferon regulatory factor 4 (IRF4).	[46]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Interferon regulatory factor 4 (IRF4).	[47]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of Interferon regulatory factor 4 (IRF4).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Interferon regulatory factor 4 (IRF4).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the methylation of Interferon regulatory factor 4 (IRF4).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon regulatory factor 4 (IRF4).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interferon regulatory factor 4 (IRF4).	[45]

References

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