MBP
MBIP (MAP3K12 Binding Inhibitory Protein 1) is a Protein Coding gene. Among its related pathways are Chromatin organization. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase inhibitor activity.
Full Name
MAP3K12 Binding Inhibitory Protein 1
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.
Biological Process
Aging Source: Ensembl
Axon ensheathment Source: ProtInc
Central nervous system development Source: ProtInc
Chemical synaptic transmission Source: ProtInc
Immune response Source: ProtInc
Maintenance of blood-brain barrier Source: CAFA
MAPK cascade Source: CAFA
Membrane organization Source: Ensembl
Myelination Source: GO_Central
Negative regulation of axonogenesis Source: Ensembl
Negative regulation of heterotypic cell-cell adhesion Source: CAFA
Positive regulation of chemokine (C-X-C motif) ligand 2 production Source: CAFA
Positive regulation of interleukin-6 production Source: CAFA
Positive regulation of metalloendopeptidase activity Source: CAFA
Response to fatty acid Source: Ensembl
Response to mercury ion Source: Ensembl
Response to progesterone Source: Ensembl
Response to toxic substance Source: Ensembl
Response to tumor necrosis factor Source: Ensembl
Sensory perception of sound Source: Ensembl
Substantia nigra development Source: UniProtKB
Cellular Location
Plasma membrane
Myelin membrane
Note: Cytoplasmic side of myelin.
Isoform 3:
Nucleus
Note: Targeted to nucleus in oligodendrocytes.
Involvement in disease
The reduction in the surface charge of citrullinated and/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), and fulminating MS (Marburg disease).
PTM
Several charge isomers of MBP; C1 (the most cationic, least modified, and most abundant form), C2, C3, C4, C5, C6, C7, C8-A and C8-B (the least cationic form); are produced as a result of optional PTM, such as phosphorylation, deamidation of glutamine or asparagine, arginine citrullination and methylation. C8-A and C8-B contain each two mass isoforms termed C8-A(H), C8-A(L), C8-B(H) and C8-B(L), (H) standing for higher and (L) for lower molecular weight. C3, C4 and C5 are phosphorylated. The ratio of methylated arginine residues decreases during aging, making the protein more cationic.
The N-terminal alanine is acetylated (isoform 3, isoform 4, isoform 5 and isoform 6).
Arg-241 was found to be 6% monomethylated and 60% symmetrically dimethylated.
Proteolytically cleaved in B cell lysosomes by cathepsin CTSG which degrades the major immunogenic MBP epitope and prevents the activation of MBP-specific autoreactive T cells.
Phosphorylated by TAOK2, VRK2, MAPK11, MAPK12, MAPK14 and MINK1.