| Kinesin Family Member 5A | |
|---|---|
| Gene | [KIF5A](/genes/kif5a) |
| UniProt | Q9BVI5 |
| PDB | 6R9L, 6RAU |
| Mol. Weight | 103 kDa (956 amino acids) |
| Localization | Axon, dendrites, neuronal soma |
| Family | Kinesin-1 family (KHC) |
| Diseases | [Amyotrophic Lateral Sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis), [Hereditary Spastic Paraplegia (HSP)](/diseases/hereditary-spastic-paraplegia), [Charcot-Marie-Tooth Disease](/diseases/charcot-marie-tooth) |
Kinesin Family Member 5A (KIF5A) is a neuronal-specific kinesin motor protein encoded by the KIF5A gene that functions as a molecular motor transporting cargo along microtubules in an ATP-dependent manner. KIF5A is essential for axonal and dendritic transport, playing critical roles in neuronal development, synaptic function, and neuronal survival. Mutations in KIF5A are causally linked to amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), and Charcot-Marie-Tooth disease, highlighting its importance in neurodegeneration.
KIF5A is a member of the kinesin-1 family (also known as conventional kinesin or KHC). The protein consists of:
Available structural data includes PDB entries 6R9L and 6RAU, which reveal the motor domain structure in various nucleotide-bound states.
The protein's three-dimensional structure can also be explored via the AlphaFold Protein Structure Database.
Under physiological conditions, KIF5A performs essential functions in the nervous system:
KIF5A mediates anterograde transport of cargo from the neuronal soma to synaptic terminals along axonal microtubules. Key cargoes include:
In dendrites, KIF5A transports cargo to support dendritic arborization, spine formation, and synaptic plasticity.
KIF5A activity is regulated by:
KIF5A dysfunction contributes to multiple neurodegenerative diseases through several mechanisms:
ALS-associated KIF5A mutations (e.g., p.Arg1006Gly, p.Asn1065Lys, p.Ala1067Val) disrupt axonal transport, leading to:
HSP-causing KIF5A mutations (primarily in the stalk domain) result in:
CMT mutations in KIF5A affect peripheral nerve function through:
KIF5A represents an important therapeutic target for neurodegenerative disorders. Current strategies include: