MAG/GMA

Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination. Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2. Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (By similarity). Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides. In cerebellar granule cells the inhibition is mediated primarily via binding to neuronal gangliosides. In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides. Inhibits axon longitudinal growth (By similarity). Inhibits axon outgrowth by binding to RTN4R (By similarity). Preferentially binds to alpha-2,3-linked sialic acid. Binds ganglioside Gt1b (By similarity).

Spastic paraplegia 75, autosomal recessive

SPG75

A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG75 is characterized by onset in early childhood and is associated with mild to moderate cognitive impairment.

None

The disease is caused by variants affecting the gene represented in this entry.

N-glycosylated.

Phosphorylated on tyrosine residues.

Ubiquitinated, leading to proteasomal degradation.

Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Both isoform 1 and isoform 2 are detected in myelinated structures in the central and peripheral nervous system, in periaxonal myelin and at Schmidt-Lanterman incisures (PubMed:6200494, PubMed:9495552). Detected in optic nerve, in oligodendroglia and in periaxonal myelin sheaths (PubMed:6200494). Detected in compact myelin (at protein level) (PubMed:6200494). Both isoform 1 and isoform 2 are detected in the central and peripheral nervous system (PubMed:9495552).

• Cell membrane
• Single-pass type I membrane protein
• Membrane raft

GMA, MAG, Myelin-associated glycoprotein, Siglec-4a

• entrezGene:4099
• omim:159460
• swissprot:P20916

Proteins

Immunology & Infectious Disease

69069Da