kinesin-1, kinesin, DmKHC, Kin, kinesin-1 heavy chain
plus end directed vesicular transport motor protein - microtubule-microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes - heterotrimeric kinesin-2, together with kinesin-1, steers vesicular acetylcholinesterase movements toward the synapse
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.50
There is only one protein coding transcript and one polypeptide associated with this gene
Oligomer composed of two heavy chains and two light chains.
Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Khc using the Feature Mapper tool.
Khc protein is evenly distributed in neurons and glial cells in the peripheral nerves.
Expression of Khc labels cross-sectioned lamina cartridges, but is both weak and diffuse. Using immunoelectron microscopy, immunosignals are seen to localized beneath the platform, and to the side of the pedestal, of the T-bar ribbon at photoreceptor tetrads.
An even distribution of protein was observed throughout the germline cells of the germarium and early egg chambers. Staining was usually more intense in the somatic follicle cells and particularly strong in polar follicle cells.From stage 8 to stage 10A oocytes protein was most concentrated in the posterior pole of the oocyte and a small concentration was also observed in the anterodorsal corner.
This construct is a marker for plus ends of microtubules, and localizes apically in developing facets.
Posterior localization within oocyte is not observed.
GBrowse - Visual display of RNA-Seq signalsView Dmel\Khc in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Host gene for maternally inherited stable intronic sequence RNA (sisRNA).
Candidate stable intronic sequence RNA (sisRNA) identified within CDS of this gene.
Both the tail and 701-849 region are required for positioning of the oocyte nucleus and establishment of the embryonic dorsal-ventral axis.
4 alleles of Khc have been isolated in a screen for mutants with defects in dorsoventral patterning of the eggshell.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
Posterior localisation of Dynein and dorsal-ventral axis formation in the oocyte is dependent on Khc.
Using crystallographic data an atomic resolution model of the motor domain dimer is built, this dimer can be successfully 'docked' into the three-dimensional framework of the maps from electron cryomicroscopy.
Chromophore-assisted light inactivation (CALI) can destroy kinesin activity in at least two ways: loss of motor activity or irreversible attachment of the kinesin enzyme to its microtubule substrate.
Studies of N-terminal Khc fragments reveals that more than one kinesin head is required for continuous movement at maximal velocity.
A study of Khc movement along microtubules suggests a fundamental enzymatic cycle for kinesin in which hydrolysis of a single ATP molecule is coupled to a step distance of the microtubule protofilament lattice spacing of 8.12nm.
Analysis of recombinant Khc fragments in which the neck domain is shortened or replaced by an artificial random coil suggests that the neck domain does not act as a rigid lever arm to magnify the structural change at the catalytic domain but instead it acts as a flexible joint to guarantee the mobility of the motor domain.
Khc mutations cause axonal swellings that are filled with the cargoes of fast axonal transport, including many membrane-bounded organelles and synaptic membrane proteins. Mutations also inhibit motor axon terminal development. Impaired kinesin function causes a general disruption of fast axonal transport that in turn leads to dystrophic neuron development, length-dependent defects in neurotransmission and progressive distal paralysis.
Mutations in Khc enhance the para and mel and suppress the Sh and eag mutant phenotypes. Khc activity is required for normal inward sodium currents during neuronal action potentials, but mutants do not affect the driving force on sodium ions. Loss of Khc function may inhibit the anterograde axonal transport of vesicles bearing sodium channels.
The crystal structure of the MgADP complex of the ncd motor domain is determined to 2.5A by X ray crystallography and compared to the Khc motor domain. The domains are similar in structure and locations of conserved surface amino acids suggest the motors share a common microtubule-binding site. Structural and functional comparisons indicate the NTPases may have a similar strategy of changing conformation between NTP and NDP states.
ncd and Khc differ in their initial, weak binding to microtubules which causes the proteins to move in opposite directions. The nature of a structural bias that may serve as a determinant of motor polarity is not clear, results suggest the microtubule binding site may determine direction.
Truncated Khc molecules having only a single motor domain do not show detectable processive movement along a microtubule in a gliding assay, which is consistent with a model in which Khc's two force-generating heads operate by a hand-over-hand mechanism.
Observations of truncated Khc derivatives with either two or one mechanochemical head suggest that the ability of single two-headed kinesin molecules to drive continuous movement results from a hand-over-hand mechanism in which one head remains bound to the microtubule while the other detaches and moves forwards.
Clonal analysis in the eye reveals that Khc mutant tissue has missing or disorganized facets, abnormal lens structure and bristle multiplications, as well as disorganization of the ommatidial array. Individual ommatidia may have abnormal numbers of photoreceptors.
Studies of the oligomeric states of truncated Khc proteins indicates that the region between amino acids 367 and 401 of Khc either contains a dimerisation domain or that dimerisation is strongly affected by the removal of this region.
Comparison of monomeric and dimeric Khc derivatives demonstrates that dimeric derivatives contain structures distinct from the rod domain that induce the formation of dimers with mechanochemical activities analogous to those of the native kinesin. The one-headed derivative displays microtubule-stimulated ATPase activity and is functional is a motility assay. Also the one headed enzyme fails to track microtubule protofilaments.
Rapid kinetic techniques are used to define a mechanism for the microtubule - kinesin ATPase using Khc motor domain.
Direct measurement of the kinetics of Khc dissociation from microtubules, the release of phosphate and ADP from kinesin and rebinding of kinesin to the microtubule have defined the mechanism for the kinase ATPase cycle and provides an explanation for the motility difference between skeletal myosin and kinesin.
Studies of a bacterially expressed head domain demonstrate it represents a biologically relevant and fully characterised protein preparation useful for mechanistic studies.
Mixtures of Khc motor domain protein treated with the zero-length cross linker EDC generates covalently cross linked products of Khc with βTub56D and Khc with αTub84B. These results indicate that the Khc motor domain interacts with both βTub56D and αTub84B.
Identified as a 120kD polypeptide in an ATP MAPs 1-24 hour embryonic fraction.
The pre-steady-state kinetics of the microtubule.kinesin ATPase pathway is studied using a mutant of Khc and chemical quench flow techniques to measure steps of ATP binding, ATP hydrolysis and ADP release during the first turnover of the enzyme.
The sequence of the Khc protein has been compared with the sequences of a variety of kinesin family proteins.
A truncated Khc protein consising of the N terminal 401 amino acids, containing both the ATP and microtubule binding sites, behaves as native kinesin with respect to steady state properties, having full catalytic activity with microtubules.
Drosphila kinesin heavy chain has been used in a study of the interaction of the kinesin motor domain with the microtubule surface: binding becomes saturated at one kinesin head per heterodimer.
A series of truncated kinesin heavy chain and ncd proteins were generated and assayed for movement along microtubules in vitro: conserved domain of both proteins has microtubule motor activity, and direction of movement is intrinsic to conserved motor domain.
Kinesin may be active in transport of ion channels and components of synaptic release machinery to appropriate cellular locations, but is not required for anterograde transport of synaptic vesicles/components.
Ultrastructural analysis of a Khc-α-Spec fusion protein suggests that the Khc stalk region forms a parallel dimer. Chemical-cross linking studies suggest that the two chains are in register. The stalk forms an α-helical coiled coil structure. Part of this α-helical structure may be less stable than the rest of the α-helical structure.
Immunocytochemical and genetic analysis of the kinesin heavy chain gene indicates that the heavy chain is an essential protein. Normal heavy chain function is important in the neuromuscular system, but probably not for the basic cell cycle.
Flies deficient for Khc survive through early embryogenesis (Saxton).
The gene is named "partagas", after a brand of Cuban cigars, due to the mutant eggshell phenotype.