UniProt functional annotation for P02686



	UniProt functional annotation for P02686

UniProt code: P02686.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:8544862}.

Subunit: Homodimer. Isoform 3 exists as a homodimer. {ECO:0000269|PubMed:11080454, ECO:0000269|PubMed:11163233, ECO:0000269|PubMed:16079912}.

Subcellular location: Myelin membrane; Peripheral membrane protein; Cytoplasmic side. Note=Cytoplasmic side of myelin.

Subcellular location: [Isoform 3]: Nucleus {ECO:0000269|PubMed:22609403}. Note=Targeted to nucleus in oligodendrocytes.

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. {ECO:0000269|PubMed:7504278}.

Developmental stage: Expression begins abruptly in 14-16 week old fetuses. Even smaller isoforms seem to be produced during embryogenesis; some of these persisting in the adult. Isoform 4 expression is more evident at 16 weeks and its relative proportion declines thereafter.

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. {ECO:0000269|PubMed:23828821, ECO:0000269|PubMed:2466844, ECO:0000269|PubMed:5128665}.

Ptm: The N-terminal alanine is acetylated (isoform 3, isoform 4, isoform 5 and isoform 6).

Ptm: Arg-241 was found to be 6% monomethylated and 60% symmetrically dimethylated.

Ptm: Phosphorylated by TAOK2, VRK2, MAPK11, MAPK12, MAPK14 and MINK1.

Disease: Note=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).

Miscellaneous: [Isoform 3]: Contains a non-traditional PY nuclear localization signal. Mutagenesis of Cys-81 to Ser prevents dimerization. {ECO:0000305}.

Similarity: Belongs to the myelin basic protein family. {ECO:0000305}.

Sequence caution: Sequence=AAC41944.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The C-terminus contains a Histidine tag.; Evidence={ECO:0000305}; Sequence=BAD92223.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAH10359.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:8544862}.


Subunit:		Homodimer. Isoform 3 exists as a homodimer. {ECO:0000269\|PubMed:11080454, ECO:0000269\|PubMed:11163233, ECO:0000269\|PubMed:16079912}.
Subcellular location:		Myelin membrane; Peripheral membrane protein; Cytoplasmic side. Note=Cytoplasmic side of myelin.
Subcellular location:		[Isoform 3]: Nucleus {ECO:0000269\|PubMed:22609403}. Note=Targeted to nucleus in oligodendrocytes.
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. {ECO:0000269\|PubMed:7504278}.
Developmental stage:		Expression begins abruptly in 14-16 week old fetuses. Even smaller isoforms seem to be produced during embryogenesis; some of these persisting in the adult. Isoform 4 expression is more evident at 16 weeks and its relative proportion declines thereafter.
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. {ECO:0000269\|PubMed:23828821, ECO:0000269\|PubMed:2466844, ECO:0000269\|PubMed:5128665}.
Ptm:		The N-terminal alanine is acetylated (isoform 3, isoform 4, isoform 5 and isoform 6).
Ptm:		Arg-241 was found to be 6% monomethylated and 60% symmetrically dimethylated.
Ptm:		Phosphorylated by TAOK2, VRK2, MAPK11, MAPK12, MAPK14 and MINK1.
Disease:		Note=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).
Miscellaneous:		[Isoform 3]: Contains a non-traditional PY nuclear localization signal. Mutagenesis of Cys-81 to Ser prevents dimerization. {ECO:0000305}.
Similarity:		Belongs to the myelin basic protein family. {ECO:0000305}.
Sequence caution:		Sequence=AAC41944.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The C-terminus contains a Histidine tag.; Evidence={ECO:0000305}; Sequence=BAD92223.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAH10359.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305};