Alternative titles; symbols
HGNC Approved Gene Symbol: KLC1
Cytogenetic location: 14q32.33 Genomic coordinates (GRCh38): 14:103,629,211-103,701,544 (from NCBI)
Kinesins are tubulin (see 191130) molecular motors that transport organelles within cells and move chromosomes along microtubules during cell division. In sea urchin and mammalian cells, kinesins have been characterized as tetrameric proteins containing 2 heavy (alpha) chains of approximately 120 kD and 2 light (beta) chains of approximately 70 kD. The alpha chains provide the tubulin binding site and the ATPase domains, whereas the beta chains are responsible for the specific attachment of the organelle to be moved by the kinesin tetramer. Kinesins transport their bound organelle to the plus end of the microtubule (summary by Chernajovsky et al., 1996).
Chernajovsky et al. (1996) noted that differential splicing occurs for the kinesin beta (light chain) cDNA sequences at the 3-prime end of the rat kinesin mRNA, producing kinesins having different C-terminal ends that seem to confer the kinesin specificity for organelle binding. Cabeza-Arvelaiz et al. (1993) isolated and sequenced a cDNA encoding the human kinesin light chain protein (KLC). The cDNA encodes a deduced polypeptide of 569 amino acids with a predicted molecular mass of 64,789 Da. The predicted secondary internal structure of the KLC molecule consists of about 27 contiguous repeats, each of approximately 21 amino acids, and could be divided into 3 domains.
Rahman et al. (1998) cloned mouse Klc1. The deduced 581-amino acid protein has an N-terminal coiled-coil region of about 100 amino acids and 6 imperfect tetratricopeptide repeats of about 34 amino acids each. Northern and Western blot analyses detected Klc1 predominantly in mouse central and peripheral neuronal tissues. Immunofluorescence analysis of cultured rat hippocampal precursor cells showed that Klc1 levels increased with differentiation. In situ hybridization of mouse brain showed that both Klc1 and Klc2 (611729) were enriched in olfactory bulb, hippocampus, dentate gyrus, and the granular layer of cerebellum. Klc1 was expressed in a subset of cells in the sciatic nerve and showed diffuse axonal staining. Fractionation of whole mouse brain extracts revealed Klc1 and Klc2 in the cytosolic fraction and Klc2 in the microsomal fraction.
Chernajovsky et al. (1996) characterized the human KNS2 gene product of a differentially spliced, T-cell-derived mRNA and cloned its promoter region. The promoter region transcribes constitutively. In permanently transfected human HeLa and NB100 neuroblastoma cells, a reporter gene containing the promoter and part of the first exon of beta kinesin was 75-fold more active than the HSV-tk promoter. The first exon contains a 5-prime untranslated sequence capable of forming a stable double-hairpin loop, which functions as a translational enhancer. Its deletion decreases the efficiency of in vitro translation of beta kinesin mRNA.
Kamal et al. (2000) demonstrated that the axonal transport of APP (104760) in neurons is mediated by the direct binding of APP to the light chain subunit of kinesin-1.
Using anti-mouse Klc1 antibodies to immunoprecipitate proteins from mouse brain lysates, Rahman et al. (1998) showed that Klc1 associated with Nkhc (KIF5A; 602821) and Ukhc (KIF5B; 602809), but not with Klc2. In the presence of a nonhydrolyzable ATP analog, both Klc1 and Klc2 cosedimented with taxol-stabilized mouse brain microtubules.
Using a yeast 2-hybrid screen of a rat brain cDNA library with rat Arms (KIDINS220; 615759) as bait, Bracale et al. (2007) identified Klc1 as a binding partner, and they confirmed the interaction by pull-down and immunoprecipitation experiments. Confocal microscopy demonstrated colocalization of Arms and Klc1 in Ngf (162030)-differentiated rat PC12 cells. Mutation analysis showed that binding occurred through a KLC-interacting motif spanning residues 1361 through 1395 of Arms and a region of Klc1 spanning both the tetratricopeptide repeats and heptad repeats (amino acids 83 to 296). Further studies in PC12 cells revealed that formation of a complex with Klc1 was necessary for transport and intracellular localization of Arms.
By analyzing the virus capsid uncoating process during adenovirus infection in HeLa cells, Strunze et al. (2011) found that the incoming virus particle moved toward the nucleus via microtubules and docked to the nuclear pore complex (NPC) by interacting with Nup214 (114350). Adenovirus subsequently recruited kinesin-1 using viral capsid protein IX, which interacted with kinesin-1 light chain KLC1/KLC2. Kinesin-1 then bound to NUP358 (601181), which was attached to the NUP214/NUP88 (602552) complex, through its heavy chain KIF5C (604593) and disrupted the viral capsid and dislocated NUP214, NUP358, and NUP62 (605815) from the central NPC to the periphery. Disruption of the NPC increased permeability of the nuclear envelope and facilitated entry of viral DNA into the nucleus.
Chernajovsky et al. (1996) determined that the entire KNS2 gene spans 90 kb and encodes a 70-kD protein.
Cabeza-Arvelaiz et al. (1993) assigned the KLC gene to chromosome 14 by screening of a human/hamster somatic cell hybrid panel. Goedert et al. (1996) mapped the KNS2 gene to 14q32.3 by fluorescence in situ hybridization.
Bracale, A., Cesca, F., Neubrand, V. E., Newsome, T. P., Way, M., Schiavo, G. Kidins220/ARMS is transported by a kinesin-1-based mechanism likely to be involved in neuronal differentiation. Molec. Biol. Cell 18: 142-152, 2007. [PubMed: 17079733] [Full Text: https://doi.org/10.1091/mbc.e06-05-0453]
Cabeza-Arvelaiz, Y., Shih, L.-C. N., Hardman, N., Asselbergs, F., Bilbe, G., Schmitz, A., White, B., Siciliano, M. J., Lachman, L. B. Cloning and genetic organization of the human kinesin light-chain (KLC) gene. DNA Cell Biol. 12: 881-892, 1993. [PubMed: 8274221] [Full Text: https://doi.org/10.1089/dna.1993.12.881]
Chernajovsky, Y., Brown, A., Clark, J. Human kinesin light (beta) chain gene: DNA sequence and functional characterization of its promoter and first exon. DNA Cell Biol. 15: 965-974, 1996. [PubMed: 8945637] [Full Text: https://doi.org/10.1089/dna.1996.15.965]
Goedert, M., Marsh, S., Carter, N. Localization of the human kinesin light chain gene (KNS2) to chromosome 14q32.3 by fluorescence in situ hybridization. Genomics 32: 173-175, 1996. [PubMed: 8786116] [Full Text: https://doi.org/10.1006/geno.1996.0102]
Kamal, A., Stokin, G. B., Yang, Z., Xia, C., Goldstein, L. S. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28: 449-459, 2000. [PubMed: 11144355] [Full Text: https://doi.org/10.1016/s0896-6273(00)00124-0]
Rahman, A., Friedman, D. S., Goldstein, L. S. B. Two kinesin light chain genes in mice: identification and characterization of the encoded proteins. J. Biol. Chem. 273: 15395-15403, 1998. Note: Erratum: J. Biol. Chem. 273: 24280 only, 1998. [PubMed: 9624122] [Full Text: https://doi.org/10.1074/jbc.273.25.15395]
Strunze, S., Engelke, M. F., Wang, I-H., Puntener, D., Boucke, K., Schleich, S., Way, M., Schoenenberger, P., Burckhardt, C. J., Greber, U. F. Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection. Cell Host Microbe 10: 210-223, 2011. [PubMed: 21925109] [Full Text: https://doi.org/10.1016/j.chom.2011.08.010]