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Nefh

Function

Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that is not subserved by the two smaller NF proteins. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (By similarity).

Involvement in disease

Amyotrophic lateral sclerosis

ALS

A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Charcot-Marie-Tooth disease 2CC

CMT2CC

An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.

None

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

Post-translational modifications

There are a number of repeats of the tripeptide K-S-P, NFH is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFH results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber.

Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincidentally with a change in the neurofilament function.

Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.

Sequence similarities

Belongs to the intermediate filament family.

Cellular localization

  • Cytoplasm
  • Cytoskeleton
  • Cell projection
  • Axon

Alternative names

  • Neurofilament heavy polypeptide
  • NF-H
  • 200 kDa neurofilament protein
  • Neurofilament triplet H protein
  • NFH
  • KIAA0845
  • NEFH

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

112479Da