Details of Drug Off-Target (DOT)

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

• DOT Name: Myelin basic protein (MBP)
• Synonyms: MBP; Myelin A1 protein; Myelin membrane encephalitogenic protein
• Gene Name: MBP
• UniProt ID: MBP_HUMAN
• PDB ID: 1BX2; 1FV1; 1HQR; 1K2D; 1YMM; 1ZGL
• Pfam ID: PF01669
• Sequence:
  MGNHAGKRELNAEKASTNSETNRGESEKKRNLGELSRTTSEDNEVFGEADANQNNGTSSQ
  DTAVTDSKRTADPKNAWQDAHPADPGSRPHLIRLFSRDAPGREDNTFKDRPSESDELQTI
  QEDSAATSESLDVMASQKRPSQRHGSKYLATASTMDHARHGFLPRHRDTGILDSIGRFFG
  GDRGAPKRGSGKDSHHPARTAHYGSLPQKSHGRTQDENPVVHFFKNIVTPRTPPPSQGKG
  RGLSLSRFSWGAEGQRPGFGYGGRASDYKSAHKGFKGVDAQGTLSKIFKLGGRDSRSGSP
  MARR
• Function: The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation.
• Tissue Specificity: MBP isoforms are found in both the central and the peripheral nervous system, whereas Golli-MBP isoforms are expressed in fetal thymus, spleen and spinal cord, as well as in cell lines derived from the immune system.
• Reactome Pathway: EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Myelin basic protein (MBP) affects the response to substance of Etoposide.	[25]
Mitomycin	DMH0ZJE	Approved	Myelin basic protein (MBP) affects the response to substance of Mitomycin.	[25]
Topotecan	DMP6G8T	Approved	Myelin basic protein (MBP) affects the response to substance of Topotecan.	[25]
Aciclovir	DMYLOVR	Approved	Myelin basic protein (MBP) increases the Neurological symptom ADR of Aciclovir.	[26]

25 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 Myelin basic protein (MBP).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myelin basic protein (MBP).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myelin basic protein (MBP).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myelin basic protein (MBP).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Myelin basic protein (MBP).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Myelin basic protein (MBP).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Myelin basic protein (MBP).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Myelin basic protein (MBP).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Myelin basic protein (MBP).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Myelin basic protein (MBP).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Myelin basic protein (MBP).	[11]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Myelin basic protein (MBP).	[12]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Myelin basic protein (MBP).	[13]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Myelin basic protein (MBP).	[14]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Myelin basic protein (MBP).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myelin basic protein (MBP).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myelin basic protein (MBP).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin basic protein (MBP).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Myelin basic protein (MBP).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myelin basic protein (MBP).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Myelin basic protein (MBP).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Myelin basic protein (MBP).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Myelin basic protein (MBP).	[23]
Manganese	DMKT129	Investigative	Manganese increases the expression of Myelin basic protein (MBP).	[24]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Myelin basic protein (MBP).	[21]

References

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• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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