myelin basic protein; MBP; myelin A1 protein; myelin membrane encephalitogenic protein (MBP)

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.
• role in both formation & stabilization of myelin
• 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, & may also be involved in signaling pathways in T-cells & 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
• several charge isomers of MBP; C1 (the most cationic, least modified, & most abundant form), C2, C3, C4, C5, C6, C7, C8-A& C8-B (the least cationic form); are produced as a result of optional post-translational modification, such as phosphorylation, deamidation of Glu or Asparagine, Arg citrullination & methylation
• C8-A & C8-B contain each two mass isoforms termed C8-A(H), C8-A(L), C8-B(H) & C8-B(L), (H) standing for higher & (L) for lower molecular weight
• C3, C4 & C5 are phosphorylated
• the N-terminal alanine is acetylated (isoform 3, isoform 4, isoform 5 & isoform 6)
• Arg-241 was found to be 6% monomethylated & 60% symmetrically dimethylated

Structure

• isoform 3 exists as a homodimer
• belongs to the myelin basic protein family

Compartment

• myelin membrane
• peripheral membrane protein; cytoplasmic side
• cytoplasmic side of myelin

Alternative splicing

named isoforms=7 Additional isoforms seem to exist

Expression

• MBP isoforms are found in both the central nervous system & the peripheral nervous system
• Golli-MBP isoforms are expressed in fetal thymus, spleen & spinal cord, as well as in cell lines derived from the immune system
• expression begins abruptly in 14-16 week old fetuses
• smaller isoforms seem to be produced during embryogenesis; some of these persisting in the adult
• expression of isoform MBP2 is more evident at 16 weeks & its relative proportion declines thereafter

Pathology

• the reduction in the surface charge of citrullinated &/or methylated MBP could result in a weakened attachment to the myelin membrane; this mechanism could be operative in demyelinating diseases such as chronical multiple sclerosis (MS), & fulminating MS (Marburg disease)
• smaller isoforms might have a role in remyelination of denuded axons in multiple sclerosis
• the ratio of methylated Arg decreases during aging, making the protein more cationic

Notes

• Met-1 is removed in at least some isoforms
• contains N-acetylalanine at position 2
• mutagenesis of Cys-81 to Ser prevents dimerization

More general terms

• myelin protein
• calmodulin binding protein
• phosphoprotein

Additional terms

• myelin basic protein (MBP) in CSF

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4155
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4155
• OMIM: https://mirror.omim.org/entry/159430
• UniProt: http://www.uniprot.org/uniprot/P02686.html