Contents

Search

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

Interactions

molecular events

Related

myelin basic protein (MBP) in CSF

General

calmodulin binding protein myelin protein phosphoprotein

Properties

SIZE: entity length = 304 aa MW = 33 kD COMPARTMENT: cytoplasm MOTIF: Ser phosphorylation site {S96} Ser phosphorylation site {S141} Ser phosphorylation site {S146} Thr phosphorylation site {T169} Ser phosphorylation site {S174} Induces experimental autoimmune encephalomyelitis (EAE) 1 {179-222} MOTIF: Tyr phosphorylation site {Y203} Ser phosphorylation site {S205} Thr phosphorylation site {T229} Thr phosphorylation site {T232} Induces experimental autoimmune encephalomyelitis (EAE) 2 {246-256} MOTIF: Ser phosphorylation site {S249} Ser phosphorylation site {S295} Ser phosphorylation site {S299}

Database Correlations

OMIM 159430 UniProt P02686 Pfam PF01669 Entrez Gene 4155 Kegg hsa:4155

References

  1. UniProt :accession P02686
  2. Wikipedia; Note: myelin basic protein entry http://en.wikipedia.org/wiki/myelin_basic_protein
  3. Wang KK et al Calmodulin-binding proteins as calpain substrates. Biochem J 262:693 1989 PMID: 2556106
  4. Entrez Gene :accession 4155