Myelin basic protein

MBP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZGL, 1BX2, 1FV1, 1HQR, 1K2D, 1YMM
Identifiers
Aliases	MBP, entrez:4155, myelin basic protein
External IDs	OMIM: 159430 MGI: 96925 HomoloGene: 1788 GeneCards: MBP
Gene location (Human) Chr. Chromosome 18 (human)[1] Band No data available Start 76,978,827 bp[1] End 77,133,683 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band No data available Start 82,475,146 bp[2] End 82,585,637 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein binding • protease binding • calmodulin binding • structural constituent of myelin sheath Cellular component • nucleus • cell projection • membrane • plasma membrane • intracellular • internode region of axon • neuronal cell body • myelin sheath • compact myelin • protein complex • cell periphery Biological process • chemical synaptic transmission • membrane organization • central nervous system development • axon ensheathment • substantia nigra development • response to toxic substance • immune response • sensory perception of sound • MAPK cascade • negative regulation of heterotypic cell-cell adhesion • maintenance of permeability of blood-brain barrier • myelination • positive regulation of chemokine (C-C motif) ligand 2 secretion • positive regulation of metalloendopeptidase activity • positive regulation of interleukin-6 secretion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4155	17196
Ensembl	ENSG00000197971	ENSMUSG00000041607
UniProt	P02686	P04370
RefSeq (mRNA)	NM_001025081 NM_001025090 NM_001025092 NM_001025094 NM_001025098 NM_001025100 NM_001025101 NM_002385	NM_001025245 NM_001025251 NM_001025254 NM_001025255 NM_001025256 NM_001025258 NM_001025259 NM_010777
RefSeq (protein)	NP_001020252 NP_001020261 NP_001020263 NP_001020271 NP_001020272 NP_002376	NP_001020416 NP_001020422 NP_001020425 NP_001020426 NP_001020427 NP_001020429 NP_001020430 NP_034907
Location (UCSC)	Chr 18: 76.98 – 77.13 Mb	Chr 18: 82.48 – 82.59 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction.^[5] MBP maintains the correct structure of myelin, interacting with the lipids in the myelin membrane.^[6][7]

MBP was initially sequenced in 1971 after isolation from myelin membranes.^[8] Since that time, knockout mice deficient in MBP that showed decreased amounts of CNS myelination and a progressive disorder characterized by tremors, seizures, and early death have been developed. The human gene for MBP is on chromosome 18;^[9] the protein localizes to the CNS and to various cells of the hematopoietic system.

The pool of MBP in the central nervous system is very diverse, with several splice variants being expressed and a large number of post-translational modifications on the protein, which include phosphorylation, methylation, deamidation, and citrullination. These forms differ by the presence or the absence of short (10 to 20 residues) peptides in various internal locations in the sequence. In general, the major form of MBP is a protein of about 18.5 Kd (170 residues).

In melanocytic cell types, MBP gene expression may be regulated by MITF.^[10]

Gene expression

The protein encoded by the classic MBP gene is a major constituent of the myelin sheath of oligodendrocytes and Schwann cells in the nervous system. However, MBP-related transcripts are also present in the bone marrow and the immune system. These mRNAs arise from the long MBP gene (otherwise called "Golli-MBP") that contains 3 additional exons located upstream of the classic MBP exons. Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that have N-terminal Golli aa sequence linked to MBP aa sequence. The second family of transcripts contain only MBP exons and produce the well-characterized myelin basic proteins. This complex gene structure is conserved among species, suggesting that the MBP transcription unit is an integral part of the Golli transcription unit and that this arrangement is important for the function and/or regulation of these genes.^[11]

Role in disease

Interest in MBP has centered on its role in demyelinating diseases, in particular, multiple sclerosis (MS). Several studies have shown a role for antibodies against MBP in the pathogenesis of MS.^[12] Some studies have linked a genetic predisposition to MS to the MBP gene, though a majority have not.

Some recent works have shown that inoculating an animal with MBP to generate an immune response against it increases blood–brain barrier permeability.

A targeted immune response to MBP has been researched in lethal rabies infection. The inoculation of MBP generates increases the permeability of the blood–brain barrier (BBB), allowing immune cells to enter the brain, the primary site of rabies virus replication. In a study of mice infected with Silver-haired bat rabies virus (SHBRV), the mortality rate of mice treated with MBP improved 20%-30% over the untreated control group. It is significant to note that healthy uninfected mice treated with MBP showed an increase in mortality rate between 0% and 40%.^[13]

A "molecular mimicry" hypothesis of multiple sclerosis has been suggested, in which T cells are, in essence, confusing MBP with human herpesvirus-6. Researchers in the United States created a synthetic peptide with a sequence identical to that of an HHV-6 peptide. They were able to show that T cells were activated by this peptide. These activated T cells also recognized and initiated an immune response against a synthetically created peptide sequence that is identical to part of human MBP. During their research, they found that the levels of these cross-reactive T cells are significantly elevated in multiple sclerosis patients.^[14]

Interactions

Myelin basic protein has been shown to interact in vivo with Proteolipid protein 1,^[15][16] and in vitro with Calmodulin, Actin, Tropomyosin, Tubulin, Clathrin, 2',3'-Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system.^[17]

References

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.