Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the search for candidate genes for the tuberous sclerosis (TSC1) disease locus on chromosome 9q34, we have isolated an overlapping series of 22 plasmid and phage cDNA clones covering nearly 7 kb and with an open reading frame of 5070 bp encoding a protein of 1690 amino acids. The putative protein product is a member of the kinesin superfamily and is homologous to the mouse KIF1A and the Caenorhabditas elegans unc-104 genes. Both KIF1A and unc-104 function in the anterograde axonal transport of synaptic vesicles. The human homolog is therefore termed H-ATSV (axonal transporter of synaptic vesicles, HGMW-approved nomenclature ATSV) Screening of DNA from 107 tuberous sclerosis patients and 80 unaffected individuals with H-ATSV cDNA probes by pulsed-field gel electrophoresis/Southern blotting following digestion by rare-cutting methylation-sensitive restriction enzymes showed variant banding patterns in three patients with tuberous sclerosis. However, further analysis indicated that these variant fragments represent a rare polymorphism probably associated with methylation of clustered restriction sites. There is no evidence to support H-ATSV as a candidate gene for TSC1.
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PMID:Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9Q34. 866 Oct 1

Caenorhabditis elegans dynamin is expressed at high levels in neurons and at lower levels in other cell types, consistent with the important role that dynamin plays in the recycling of synaptic vesicles. Indirect immunofluorescence showed that dynamin is concentrated along the dorsal and ventral nerve cords and in the synapse-rich nerve ring. Green fluorescent protein (GFP) fused to the N terminus of dynamin is localized to synapse-rich regions. Furthermore, this chimera was detected along the apical membrane of intestinal cells, in spermathecae, and in coelomocytes. Dynamin localization was not affected by disrupting axonal transport of synaptic vesicles in the unc-104 (kinesin) mutant. To investigate the alternative mechanisms that dynamin might use for translocation to the synapse, we systematically tested the localization of different protein domains by fusion to GFP. Localization of each chimera was measured in one specific neuron, the ALM. The GTPase, a middle domain, and the putative coiled coil each contribute to synaptic localization. Surprisingly, the pleckstrin homology domain and the proline-rich domain, which are known to bind to coated-pit constituents, did not contribute to synaptic localization. The GFP-GTPase chimera was most strongly localized, although the GTPase domain has no known interactions with proteins other than with dynamin itself. Our results suggest that different dynamin domains contribute to axonal transport and the sequestration of a pool of dynamin molecules in synaptic cytosol.
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PMID:Contribution of the GTPase domain to the subcellular localization of dynamin in the nematode Caenorhabditis elegans. 980 8

By sequence analysis we show that the U104 domain found in the UNC104 subfamily of kinesins is a forkhead homology-associated domain (FHA). A combination of limited proteolysis, mass spectroscopy, and physicochemical analysis define this domain as a genuine autonomously folding domain. Our data show that the FHA domain is shorter than previously reported since the C-terminal alpha-helix is not part of its minimum core. Key amino acids postulated to recognize phosphorylated residues are conserved. These data suggest that the kinesin FHA domains are functional domains involved in protein-protein interactions regulated by phosphorylation.
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PMID:Kinesin subfamily UNC104 contains a FHA domain: boundaries and physicochemical characterization. 1111 20

KIF1A, a member of kinesin-3 motors, plays a pivotal role in anterograde axonal transport of synaptic vesicles (SVs). We have shown that the CC1-FHA tandem of KIF1A forms a stable dimer that is crucial for both the dimerization and activation of the motor. However, it remains to be determined whether the CC1-FHA dimer is essential for KIF1A-mediated axonal transport in vivo. Here, we use Caenorhabditis elegans as the model organism to probe the in vivo function of the CC1-FHA dimer. Disruption of the CC1-FHA dimer severely impairs the KIF1A-mediated regulation of the locomotion and pumping behavior of C. elegans and exerts a significant impact on KIF1A-mediated axonal SV transport. Thus, together with previous structural and biochemical studies, the in vivo data presented in this study firmly establish the essential role of the CC1-FHA dimer for KIF1A-mediated neuronal transport.
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PMID:The CC1-FHA dimer is essential for KIF1A-mediated axonal transport of synaptic vesicles in C. elegans. 2366 38