Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT167PR5)

• DOT Name: ETS-related transcription factor Elf-4 (ELF4)
• Synonyms: E74-like factor 4; Myeloid Elf-1-like factor
• Gene Name: ELF4
• Related Disease:
  Parkinson disease
  Poliomyelitis
  Acute erythroid leukemia
  Adult lymphoma
  Adult teratoma
  Advanced cancer
  Autoinflammatory syndrome, familial, X-linked, Behcet-like 2
  Breast cancer
  Breast carcinoma
  Epithelial neoplasm
  Familial Mediterranean fever
  Glioma
  Haematological malignancy
  Isolated growth hormone deficiency type III
  Lymphoma
  Malaria
  Neoplasm
  Pediatric lymphoma
  Plasma cell myeloma
  Retinoblastoma
  Systemic lupus erythematosus
  Teratoma
  Encephalitis
  Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
  Extranodal NK/T-cell Lymphoma
  Neuroblastoma
  Acute myelogenous leukaemia
  Adult glioblastoma
  Glioblastoma multiforme
  Lysosomal storage disease
  Neurofibromatosis type 2
• UniProt ID: ELF4_HUMAN
• Pfam ID: PF12310 ; PF00178
• Sequence:
  MAITLQPSDLIFEFASNGMDDDIHQLEDPSVFPAVIVEQVPYPDLLHLYSGLELDDVHNG
  IITDGTLCMTQDQILEGSFLLTDDNEATSHTMSTAEVLLNMESPSDILDEKQIFSTSEML
  PDSDPAPAVTLPNYLFPASEPDALNRAGDTSDQEGHSLEEKASREESAKKTGKSKKRIRK
  TKGNRSTSPVTDPSIPIRKKSKDGKGSTIYLWEFLLALLQDRNTCPKYIKWTQREKGIFK
  LVDSKAVSKLWGKQKNKPDMNYETMGRALRYYYQRGILAKVEGQRLVYQFKEMPKDLVVI
  EDEDESSEATAAPPQASTASVASASTTRRTSSRVSSRSAPQGKGSSSWEKPKIQHVGLQP
  SASLELGPSLDEEIPTTSTMLVSPAEGQVKLTKAVSASSVPSNIHLGVAPVGSGSALTLQ
  TIPLTTVLTNGPPASTTAPTQLVLQSVPAASTFKDTFTLQASFPLNASFQDSQVAAPGAP
  LILSGLPQLLAGANRPTNPAPPTVTGAGPAGPSSQPPGTVIAAFIRTSGTTAAPRVKEGP
  LRSSSYVQGMVTGAPMEGLLVPEETLRELLRDQAHLQPLPTQVVSRGSHNPSLLGNQTLS
  PPSRPTVGLTPVAELELSSGSGSLLMAEPSVTTSGSLLTRSPTPAPFSPFNPTSLIKMEP
  HDI
• Function: Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme gene. Acts synergistically with RUNX1 to transactivate the IL3 promoter. Transactivates the PRF1 promoter in natural killer (NK) cells and CD8+ T cells. Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T-cells via the Kruppel-like factors KLF4 and KLF2. Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. Is a transcriptional regulator of inflammation, controlling T-helper 17 (Th17) cells and macrophage inflammatory responses. Required for sustained transcription of anti-inflammatory genes, including IL1RN. Is a negative regulator of pro-inflammatory cytokines expression including IL17A, IL1B, IL6, TNFA and CXCL1. Down-regulates expression of TREM1, a cell surface receptor involved in the amplification of inflammatory responses.
• Tissue Specificity: Abundantly expressed in the placenta and in a variety of myeloid leukemia cell lines. Moderate levels of expression in heart, lung, spleen, thymus, peripheral blood lymphocytes, ovary and colon. Lower levels of expression in Jurkat T-cells and other T-cell lines and no expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Poliomyelitis	DISANFJN	Definitive	Biomarker	[2]
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[4]
Adult teratoma	DISBY81U	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2	DIS9HYUL	Strong	X-linked	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[9]
Familial Mediterranean fever	DISVP5WP	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[9]
Isolated growth hormone deficiency type III	DISRZSTR	Strong	GermlineCausalMutation	[12]
Lymphoma	DISN6V4S	Strong	Altered Expression	[4]
Malaria	DISQ9Y50	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[4]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[15]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[17]
Teratoma	DIS6ICY4	Strong	Biomarker	[5]
Encephalitis	DISLD1RL	moderate	Biomarker	[18]
Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia	DIS32FL3	Supportive	X-linked	[12]
Extranodal NK/T-cell Lymphoma	DIS72GCL	Disputed	Genetic Variation	[19]
Neuroblastoma	DISVZBI4	Disputed	Altered Expression	[20]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[21]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[8]
Lysosomal storage disease	DIS6QM6U	Limited	Biomarker	[22]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[23]

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 ETS-related transcription factor Elf-4 (ELF4).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ETS-related transcription factor Elf-4 (ELF4).	[40]

20 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 ETS-related transcription factor Elf-4 (ELF4).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of ETS-related transcription factor Elf-4 (ELF4).	[29]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[30]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[31]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ETS-related transcription factor Elf-4 (ELF4).	[33]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of ETS-related transcription factor Elf-4 (ELF4).	[29]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[34]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[35]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[35]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ETS-related transcription factor Elf-4 (ELF4).	[37]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of ETS-related transcription factor Elf-4 (ELF4).	[41]

References

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