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Gene Review

KIF1A  -  kinesin family member 1A

Homo sapiens

Synonyms: ATSV, Axonal transporter of synaptic vesicles, C2orf20, HSN2C, Kinesin-like protein KIF1A, ...
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Psychiatry related information on KIF1A

  • To elucidate the function of this mechanism, we have cloned KIF1A, a novel neuron-specific kinesin superfamily motor that was discovered to be a monomeric, globular molecule and that had the fastest reported anterograde motor activity (1.2 microns/s) [1].

High impact information on KIF1A

  • However, we have recently demonstrated that a monomeric motor domain construct of KIF1A (C351), a kinesin superfamily protein, moves processively, taking about 700 steps before being detached from microtubules [2].
  • The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors [1].
  • Docking of the ADP-bound and ATP-like crystallographic models of KIF1A into the corresponding cryo-electron microscopy maps suggests a rationale for the plus-end directional bias associated with the kinesin catalytic core [3].
  • Recent evidence implies that KIF1A, a synaptic vesicle motor, moves processively [4].
  • This surprising behavior for a monomeric motor depends upon a lysine-rich loop in KIF1A that binds to the negatively charged carboxyl terminus of tubulin and, in the context of motor processivity, compensates for the lack of a second motor domain on the KIF1A holoenzyme [4].

Biological context of KIF1A

  • These results suggest that the intramolecular FHA-CC2 interaction negatively regulates KIF1A activity by inhibiting MT binding and dimerization of KIF1A, and point to a novel role of the FHA domain in the regulation of kinesin motors [5].
  • In addition, point mutations causing rigidity in the predicted flexible hinge disrupt the intramolecular FHA-CC2 interaction and increase MT binding and peripheral accumulation of KIF1A [5].
  • KIF1A is a kinesin motor known to transport synaptic vesicle precursors in neuronal axons, but little is known about whether KIF1A mediates fast and processive axonal transport in vivo [6].
  • In addition, single molecule biophysics and optical trapping have shown that the motility of monomeric KIF1A is caused by biased Brownian movement, and X-ray crystallography has shown how the conformational changes occur for KIF1A to move during ATP hydrolysis [7].
  • This Brownian movement will allow the small KIF1A motor domain to span the distance between the binding sites on microtubule and also will give the diffusive nature to the movement of single KIF1A molecules [8].

Anatomical context of KIF1A


Associations of KIF1A with chemical compounds

  • KIF1A colocalizes with liprin-alpha in various subcellular regions of neurons [9].

Other interactions of KIF1A

  • KIF1C represents a member of the Unc104 subfamily of kinesin-like proteins that are involved in the transport of mitochondria or synaptic vesicles in axons [11].
  • There is no evidence to support H-ATSV as a candidate gene for TSC1 [12].
  • During the search for the candidate tumor suppressor genes mapped within the region, we found the KIAA0591 gene which encoded a new human kinesin-related protein with a homology to human axonal transporter of synaptic vesicles (ATSV) [13].
  • Here we demonstrate the nucleotide-dependent binding between the lysine-rich, highly positively charged loop 12 of the KIF1A motor domain (K-loop) and the glutamate-rich, highly negatively charged C-terminal region of tubulin (E-hook) [8].
  • Despite considerable functional differences from the monomeric transporter kinesin KIF1A and the oppositely directed ncd kinesin, CENP-E appears to share many features of the intermolecular interactions, suggesting that differences in motor function are governed by small variations in the loops at the microtubule interface [14].

Analytical, diagnostic and therapeutic context of KIF1A

  • Analysis of a radiation hybrid panel indicated that ADIPOQ showed the most significant linkage to FOXL2 (LOD = 12.63, 12 cR) and ATSV (LOD = 7.53, 3 cR) both of which are located on chicken chromosome 9 [15].


  1. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Okada, Y., Yamazaki, H., Sekine-Aizawa, Y., Hirokawa, N. Cell (1995) [Pubmed]
  2. 15 A resolution model of the monomeric kinesin motor, KIF1A. Kikkawa, M., Okada, Y., Hirokawa, N. Cell (2000) [Pubmed]
  3. Switch-based mechanism of kinesin motors. Kikkawa, M., Sablin, E.P., Okada, Y., Yajima, H., Fletterick, R.J., Hirokawa, N. Nature (2001) [Pubmed]
  4. The UNC-104/KIF1 family of kinesins. Bloom, G.S. Curr. Opin. Cell Biol. (2001) [Pubmed]
  5. An intramolecular interaction between the FHA domain and a coiled coil negatively regulates the kinesin motor KIF1A. Lee, J.R., Shin, H., Choi, J., Ko, J., Kim, S., Lee, H.W., Kim, K., Rho, S.H., Lee, J.H., Song, H.E., Eom, S.H., Kim, E. EMBO J. (2004) [Pubmed]
  6. Characterization of the movement of the kinesin motor KIF1A in living cultured neurons. Lee, J.R., Shin, H., Ko, J., Choi, J., Lee, H., Kim, E. J. Biol. Chem. (2003) [Pubmed]
  7. Kinesin superfamily proteins and their various functions and dynamics. Hirokawa, N., Takemura, R. Exp. Cell Res. (2004) [Pubmed]
  8. Mechanism of the single-headed processivity: diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin. Okada, Y., Hirokawa, N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. Shin, H., Wyszynski, M., Huh, K.H., Valtschanoff, J.G., Lee, J.R., Ko, J., Streuli, M., Weinberg, R.J., Sheng, M., Kim, E. J. Biol. Chem. (2003) [Pubmed]
  10. Mapping of the kinesin-related gene ATSV to chromosome 2q37. Keller, M.P., Seifried, B.A., Rabin, B.A., Chance, P.F. Hum. Genet. (1999) [Pubmed]
  11. Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum. Dorner, C., Ciossek, T., Müller, S., Møller, P.H., Ullrich, A., Lammers, R. J. Biol. Chem. (1998) [Pubmed]
  12. Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9Q34. Furlong, R.A., Zhou, C.Y., Ferguson-Smith, M.A., Affara, N.A. Genomics (1996) [Pubmed]
  13. Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2. Nagai, M., Ichimiya, S., Ozaki, T., Seki, N., Mihara, M., Furuta, S., Ohira, M., Tomioka, N., Nomura, N., Sakiyama, S., Kubo, O., Takakura, K., Hori, T., Nakagawara, A. Int. J. Oncol. (2000) [Pubmed]
  14. Human Kinetochore-associated Kinesin CENP-E Visualized at 17 A Resolution Bound to Microtubules. Neumann, E., Garcia-Saez, I., Debonis, S., Wade, R.H., Kozielski, F., Conway, J.F. J. Mol. Biol. (2006) [Pubmed]
  15. cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken. Yuan, J., Liu, W., Liu, Z.L., Li, N. Cytogenet. Genome Res. (2006) [Pubmed]
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