| Kinesin-1 Heavy Chain | |
|---|---|
| Protein Name | Kinesin-1 Heavy Chain |
| Gene | [KIF5A](/genes/kif5a) |
| UniProt ID | [Q9BQE3](https://www.uniprot.org/uniprot/Q9BQE3) |
| PDB Structures | 3ZFW, 4BMO |
| Molecular Weight | 115 kDa |
| Subcellular Localization | Axons, Dendrites |
| Protein Family | Kinesin-1 family |
| Aliases | KHC, KIF5A, conventional kinesin heavy chain |
Kinesin-1 Heavy Chain (KIF5A) is a motor protein that transports cargo along microtubules from the cell body toward the synaptic terminal (anterograde transport). KIF5A is essential for neuronal function, transporting synaptic vesicles, proteins, organelles, and RNA granules along axonal and dendritic microtubules[1]. Mutations in KIF5A cause hereditary spastic paraplegia type 10 (SPG10), a neurodegenerative disorder characterized by progressive lower limb spasticity, and have been implicated in amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Charcot-Marie-Tooth disease type 2 (CMT2)[2][3].
Kinesin-1 Heavy Chain is a 115 kDa protein composed of several distinct structural domains:
The protein forms a heterotetramer with two heavy chains and two light chains (KLC1-4), creating a functional motor that can bind diverse cargoes[4].
KIF5A mediates anterograde transport of multiple cargoes essential for synaptic function:
KIF5A activity is regulated by:
KIF5A mutations cause autosomal dominant SPG10, characterized by:
KIF5A mutations have been identified in familial and sporadic ALS:
KIF5A polymorphisms and mutations are associated with PD risk:
KIF5A mutations cause CMT2A phenotype:
KIF5A represents a potential therapeutic target for neurodegenerative diseases:
KIF5A interacts with:
Hirokawa et al. Kinesin superfamily proteins (2010). 2010. ↩︎
Marti et al. Hereditary spastic paraplegia type 10 caused by KIF5A mutations (2003). 2003. ↩︎ ↩︎
Puls et al. Mutant KIF5A in Charcot-Marie-Tooth disease and ALS (2005). 2005. ↩︎ ↩︎
Hirokawa & Takemura, Kinesin superfamily proteins and their multiple functions (2003). 2003. ↩︎
Liu et al. KIF5A variants in Parkinson's disease (2020). 2020. ↩︎
Bennett et al. KIF5A mutations cause CMT2 (2020). 2020. ↩︎
Baas et al. Microtubule-based transport and neurodegenerative disease (2016). 2016. ↩︎