Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKF6AEB)

• DOT Name: Myelin regulatory factor (MYRF)
• Synonyms: EC 3.4.-.-; Myelin gene regulatory factor
• Gene Name: MYRF
• Related Disease:
  Autosomal dominant polycystic kidney disease
  Chronic kidney disease
  Chronic renal failure
  Cockayne syndrome type 1
  46,XX disorder of sex development
  Abdominal aortic aneurysm
  Angle-closure glaucoma
  Cardiac-urogenital syndrome
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Congenital diaphragmatic hernia
  Invasive candidiasis
  Microphthalmia
  Multiple sclerosis
  Nasal polyp
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Respiratory failure
  Moyamoya disease
  Ankylosing spondylitis
  Asthma
  Crohn disease
  Encephalitis/encephalopathy, mild, with reversible myelin vacuolization
  Lung cancer
  Psoriasis
  Rectal carcinoma
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: MYRF_HUMAN
• PDB ID: 5YHU; 5ZHU
• EC Number: 3.4.-.-
• Pfam ID: PF13888 ; PF13887 ; PF05224 ; PF13884
• Sequence:
  MEVVDETEALQRFFEGHDINGALEPSNIDTSILEEYISKEDASDLCFPDISAPASSASYS
  HGQPAMPGSSGVHHLSPPGGGPSPGRHGPLPPPGYGTPLNCNNNNGMGAAPKPFPGGTGP
  PIKAEPKAPYAPGTLPDSPPDSGSEAYSPQQVNEPHLLRTITPETLCHVGVPSRLEHPPP
  PPAHLPGPPPPPPPPPHYPVLQRDLYMKAEPPIPHYAAMGQGLVPTDLHHTQQSQMLHQL
  LQQHGAELPTHPSKKRKHSESPPSTLNAQMLNGMIKQEPGTVTALPLHPTRAPSPPWPPQ
  GPLSPGPGSLPLSIARVQTPPWHPPGAPSPGLLQDSDSLSGSYLDPNYQSIKWQPHQQNK
  WATLYDANYKELPMLTYRVDADKGFNFSVGDDAFVCQKKNHFQVTVYIGMLGEPKYVKTP
  EGLKPLDCFYLKLHGVKLEALNQSINIEQSQSDRSKRPFNPVTVNLPPEQVTKVTVGRLH
  FSETTANNMRKKGKPNPDQRYFMLVVALQAHAQNQNYTLAAQISERIIVRASNPGQFESD
  SDVLWQRAQVPDTVFHHGRVGINTDRPDEALVVHGNVKVMGSLMHPSDLRAKEHVQEVDT
  TEQLKRISRMRLVHYRYKPEFAASAGIEATAPETGVIAQEVKEILPEAVKDTGDMVFANG
  KTIENFLVVNKERIFMENVGAVKELCKLTDNLETRIDELERWSHKLAKLRRLDSLKSTGS
  SGAFSHAGSQFSRAGSVPHKKRPPKVASKSSSVVPDQACISQRFLQGTIIALVVVMAFSV
  VSMSTLYVLSLRTEEDLVDTDGSFAVSTSCLLALLRPQPPGGSEALCPWSSQSFGTTQLR
  QSPLTTGLPGIQPSLLLVTTSLTSSAPGSAVRTLDMCSSHPCPVICCSSPTTNPTTGPSL
  GPSFNPGHVLSPSPSPSTNRSGPSQMALLPVTNIRAKSWGLSVNGIGHSKHHKSLEPLAS
  PAVPFPGGQGKAKNSPSLGFHGRARRGALQSSVGPAEPTWAQGQSASLLAEPVPSLTSIQ
  VLENSMSITSQYCAPGDACRPGNFTYHIPVSSGTPLHLSLTLQMNSSSPVSVVLCSLRSK
  EEPCEEGSLPQSLHTHQDTQGTSHRWPITILSFREFTYHFRVALLGQANCSSEALAQPAT
  DYHFHFYRLCD
• Function: [Myelin regulatory factor]: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes ; [Myelin regulatory factor, C-terminal]: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage; [Myelin regulatory factor, N-terminal]: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype.
• Tissue Specificity: Expressed in lung, ARPE-19 cell line, brainstem, uterus and, to a lesser extent, in basal ganglion and liver. Weakly expressed in cerebellum and retina.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant polycystic kidney disease	DISBHWUI	Definitive	Genetic Variation	[1]
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[2]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
Cockayne syndrome type 1	DIS9JFVY	Definitive	Biomarker	[3]
46,XX disorder of sex development	DISJOG7M	Strong	Biomarker	[4]
Abdominal aortic aneurysm	DISD06OF	Strong	Altered Expression	[5]
Angle-closure glaucoma	DISZ95KY	Strong	Biomarker	[6]
Cardiac-urogenital syndrome	DISZMQV4	Strong	Autosomal dominant	[7]
Colon cancer	DISVC52G	Strong	Genetic Variation	[8]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[8]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[9]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[8]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[8]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[8]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[8]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[8]
Congenital diaphragmatic hernia	DIS0IPVU	Strong	Genetic Variation	[10]
Invasive candidiasis	DIS5EI0L	Strong	Genetic Variation	[11]
Microphthalmia	DISGEBES	Strong	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[13]
Nasal polyp	DISLP3XE	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Respiratory failure	DISVMYJO	Strong	Genetic Variation	[17]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[18]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[19]
Asthma	DISW9QNS	Limited	Genetic Variation	[20]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[19]
Encephalitis/encephalopathy, mild, with reversible myelin vacuolization	DIS4VEZH	Limited	Autosomal dominant	[7]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[21]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[19]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[22]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[19]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[19]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Myelin regulatory factor (MYRF) affects the response to substance of Cisplatin.	[33]
Capecitabine	DMTS85L	Approved	Myelin regulatory factor (MYRF) increases the response to substance of Capecitabine.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myelin regulatory factor (MYRF).	[23]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Myelin regulatory factor (MYRF).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Myelin regulatory factor (MYRF).	[26]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Myelin regulatory factor (MYRF).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin regulatory factor (MYRF).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myelin regulatory factor (MYRF).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myelin regulatory factor (MYRF).	[32]

3 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 Myelin regulatory factor (MYRF).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myelin regulatory factor (MYRF).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Myelin regulatory factor (MYRF).	[31]

References

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