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General Information
Symbol
Dmel\Khc
Species
D. melanogaster
Name
Kinesin heavy chain
Annotation Symbol
CG7765
Feature Type
FlyBase ID
FBgn0001308
Gene Model Status
Stock Availability
Enzyme Name (EC)
Adenosinetriphosphatase (3.6.1.3)
Gene Snapshot
Kinesin heavy chain (Khc) encodes the force generating subunit of kinesin-1, a microtubule motor protein. It functions in the long-distance transport of cytoplasmic "cargoes" such as mRNAs, protein complexes, and organelles. [Date last reviewed: 2019-03-14]
Also Known As
kinesin, kinesin-1, DmKHC, Kin, kinesin-1 heavy chain
Key Links
Genomic Location
Cytogenetic map
Sequence location
2R:16,266,960..16,271,971 [-]
Recombination map
2-79
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily. (P17210)
Catalytic Activity (EC)
Experimental Evidence
-
Predictions / Assertions
ATP + H(2)O = ADP + phosphate (3.6.1.3)
Summaries
Gene Group (FlyBase)
KINESINS -
Kinesin superfamily proteins (KIFs) are microtubule motor proteins which use the hydrolysis of ATP to drive directional movement along microtubules. KIFs possess a well-conserved 360 residue globular head domain which binds and hydrolyses ATP and interacts with microtubules. Many KIFs homodimerize via coiled-coil interactions in the stalk region. KIFs bind cargo through their variable tail regions and are involved in transporting organelles, protein complexes, mRNAs and the movement of spindles and chromosomes during cell division. (Adapted from FBrf0219884).
Protein Function (UniProtKB)
Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. Milt and Miro form an essential protein complex that links Khc to mitochondria for light chain-independent, anterograde transport of mitochondria.
(UniProt, P17210)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
Kin: Kinesin
Encodes a protein from Drosophila that behaves similarly in its effect on movement of microtubules and is antigenically similar to the heavy chain kinesin of squid and sea urchin (Saxton et al., 1988). The Drosophila kinesin is found in embryos, larvae, adults, and tissue culture cells. Flies deficient for Kin survive through early embryogenesis (Saxton).
Summary (Interactive Fly)
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
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\Khc or the JBrowse view of Dmel\Khc for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.50
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0087184
3718
975
Additional Transcript Data and Comments
Reported size (kB)
4.0 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0086328
110.4
975
5.51
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
34 (kD observed)
975 (aa); 110 (kD predicted)
Comments
External Data
Subunit Structure (UniProtKB)
Oligomer composed of two heavy chains and two light chains.
(UniProt, P17210)
Domain
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.
(UniProt, P17210)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

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.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (42 terms)
Molecular Function (7 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR001752, InterPro:IPR019821
(assigned by InterPro )
inferred from biological aspect of ancestor with PANTHER:PTN000648414
(assigned by GO_Central )
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
non-traceable author statement
Biological Process (29 terms)
Terms Based on Experimental Evidence (27 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by BHF-UCL )
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000648417
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001189978
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000648417
(assigned by GO_Central )
Cellular Component (6 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000648413
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Khc transcripts are detected in RNA isolated from heads.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
distribution deduced from reporter (Gal4 UAS)
Stage
Tissue/Position (including subcellular localization)
Reference
enzyme assay or biochemical detection
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for plus ends of microtubules.
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.
Khc protein is diffusely distributed in the cytoplasm of all cells in embryos. Before cellularization, staining is most intense in the layer of cytoplasm adjacent to the cortex. After cellularization, staining is most intense in the apical cytoplasm of each somatic cell.
Marker for
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Khc in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 84 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 39 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Khc
Transgenic constructs containing regulatory region of Khc
Deletions and Duplications ( 8 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
adult cuticle & scutellar bristle | somatic clone
eye photoreceptor cell & endoplasmic reticulum | somatic clone
eye photoreceptor cell & multivesicular body | somatic clone
follicle cell & mitochondrion | germ-line clone
germline cyst & mitochondrion | germ-line clone
microtubule & oocyte | oogenesis stage S9 | germ-line clone
oocyte & nucleus | germ-line clone
posterior fascicle & axon
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (15)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
 
13 of 15
No
Yes
13 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (13)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
13 of 15
Yes
Yes
13 of 15
Yes
Yes
2 of 15
No
No
 
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (13)
12 of 13
Yes
Yes
9 of 13
No
Yes
9 of 13
No
Yes
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (5)
8 of 12
Yes
Yes
7 of 12
No
Yes
6 of 12
No
Yes
2 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (13)
13 of 15
Yes
Yes
11 of 15
No
Yes
10 of 15
No
Yes
9 of 15
No
Yes
8 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (8)
15 of 15
Yes
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (20)
4 of 9
Yes
Yes
1 of 9
No
Yes
1 of 9
No
Yes
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
Saccharomyces cerevisiae (Brewer's yeast) (2)
4 of 15
Yes
Yes
1 of 15
No
No
Schizosaccharomyces pombe (Fission yeast) (1)
6 of 12
Yes
Yes
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091901XZ )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG0915018V )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W012F )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X014G )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G02A2 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (26)
3 of 10
3 of 10
3 of 10
2 of 10
2 of 10
2 of 10
2 of 10
2 of 10
2 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Model Summary Ribbon
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 4 )
Potential Models Based on Orthology ( 2 )
Modifiers Based on Experimental Evidence ( 5 )
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
esyN Network Diagram
Show neighbor-neighbor interactions:
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Interactions Browser

Please see the Physical Interaction reports below for full details
protein-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Subunit Structure (UniProtKB)
Oligomer composed of two heavy chains and two light chains.
(UniProt, P17210 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Gene Group - Pathway Membership (FlyBase)
External Data
Linkouts
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
Genomic Location and Detailed Mapping Data
Chromosome (arm)
2R
Recombination map
2-79
Cytogenetic map
Sequence location
2R:16,266,960..16,271,971 [-]
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
53A3-53A4
Limits computationally determined from genome sequence between P{lacW}Lis-1k11702&P{EP}CG8443EP969 and P{lacW}l(2)k07824k07824&P{lacW}vegk03402
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
53A3-53A5
(determined by in situ hybridisation)
53A1-53A2
(determined by in situ hybridisation)
52F-52F
(determined by in situ hybridisation)
53A-53A
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Location
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (22)
Genomic Clones (14)
 

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (35)
 

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.

cDNA clones, fully sequences
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

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.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Laboratory Generated Antibodies
 
Commercially Available Antibodies
 
Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
Other Information
Relationship to Other Genes
Source for database identify of
Source for database merge of
Source for merge of: Khc l(2)k13314
Source for merge of: Khc l(2)W12
Source for merge of: Khc l(2)k13219
Additional comments
Other Comments
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.
Khc restricts pole plasm formation to the posterior by moving osk mRNA away from microtubule-rich lateral and anterior cortical regions.
Khc is required for all cytoplasmic movements in the oocyte and for the posterior localisation of Dhc64C. Klc is not required for any of the functions of kinesin in the oocyte.
Khc is required for posterior localisation of osk mRNA and stau.
Homologous genetic loci in D.subobscura and D.melanogaster tend to show a similar ultrastructure in the two species.
Analysis of Khc-ncd fusion proteins indicates that residues or regions contributing to motor polarity are present in the Khc motor core region.
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.
The reciprocal location of nod and Khc fusion proteins indicates microtubule polarity in the oocyte, epithelium, neuron and muscle.
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.
Medium-resolution three-dimensional structure of microtubules interacting with two functional dimeric motors with opposite directionality (Khc and ncd) is determined.
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.
Khc protein is able to induce microtubule movement in vitro.
Antibodies to Drosophila Khc cross-react with mammalian kinesin protein, and antibodies to bovine brain kinesin cross-react with Drosophila Khc protein.
Flies deficient for Khc survive through early embryogenesis (Saxton).
Origin and Etymology
Discoverer
Etymology
The gene is named "partagas", after a brand of Cuban cigars, due to the mutant eggshell phenotype.
Identification
External Crossreferences and Linkouts ( 46 )
Sequence Crossreferences
NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
Other crossreferences
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
KEGG Genes - Molecular building blocks of life in the genomic space.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
modMine - A data warehouse for the modENCODE project
Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
Linkouts
ApoDroso - Functional genomic database for photoreceptor development, survival and function
BioGRID - A database of protein and genetic interactions.
DPiM - Drosophila Protein interaction map
DroID - A comprehensive database of gene and protein interactions.
DRSC - Results frm RNAi screens
Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyMine - An integrated database for Drosophila genomics
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
Synonyms and Secondary IDs (42)
Reported As
Symbol Synonym
Khc
(Métivier et al., 2019, Auld et al., 2018, Kwon et al., 2018, Russell et al., 2018, Zhang et al., 2018, Collins et al., 2017, Kreko-Pierce and Eaton, 2017, Lim et al., 2017, Lou et al., 2017, Tay and Pek, 2017, Transgenic RNAi Project members, 2017-, Arora et al., 2016, Ding et al., 2016, Monteith et al., 2016, Sarov et al., 2016, Vagnoni et al., 2016, Winding et al., 2016, Burn et al., 2015, Copf, 2015, Pek et al., 2015, Van Bortle et al., 2015, Winkler et al., 2015, Zirin et al., 2015, Zwarts et al., 2015, Ehaideb et al., 2014, Gallaud et al., 2014, Gaspar et al., 2014, Vazquez-Pianzola et al., 2014, Williams et al., 2014, Beckett et al., 2013, Duncan et al., 2013, Gassman et al., 2013, Johnson et al., 2013, Lin and Katanaev, 2013, Lu et al., 2013, Weaver et al., 2013, Bridon et al., 2012, Djagaeva et al., 2012, Füger et al., 2012, Gonsalvez and Long, 2012, Liu et al., 2012, Lloyd et al., 2012, Metzger et al., 2012, Ruggiero et al., 2012, Sanghavi et al., 2012, Saxton and Hollenbeck, 2012, Schmidt et al., 2012, Friedman et al., 2011, Lerit and Gavis, 2011, Moua et al., 2011, Bianco et al., 2010, Bitan et al., 2010, Cook and Cook, 2010.10.13, Gonsalvez et al., 2010, Li et al., 2010, Loiseau et al., 2010, Wasbrough et al., 2010, Dworkin et al., 2009, Johnson et al., 2009, Krauss et al., 2009, Krauss et al., 2009, Venken et al., 2009, Barkus et al., 2008, Christensen et al., 2008.9.3, Fisher et al., 2008, Gervais et al., 2008, Kucherenko et al., 2008, Shaklee et al., 2008, Shubeita et al., 2008, Toda et al., 2008, Wang and Riechmann, 2008, Zimyanin et al., 2008, Anne et al., 2007, Christensen and Cook, 2007.5.8, Goold and Davis, 2007, Januschke et al., 2007, Kaltenbach et al., 2007, Mische et al., 2007, Moua et al., 2007, Serbus and Sullivan, 2007, Tran and Welte, 2007, Vendra et al., 2007, Zimyanin et al., 2007, Cook and Estes, 2006.12.4, Cox and Spradling, 2006, Januschke et al., 2006, Kraft et al., 2006, Lin et al., 2006, Pilling et al., 2006, Shapiro and Anderson, 2006, Ferree et al., 2005, Martin et al., 2005, Navarro et al., 2004, Brendza, 2000.3.2, Brendza et al., 1999)
l(2)k13219
Name Synonyms
Kin-1 heavy chain
Kinesin-1 heavy chain
conventional kinesin
heavy chain of kinesin
kinesin heavy chain I
kinesin α-chain
Secondary FlyBase IDs
  • FBgn0021886
  • FBgn0021889
  • FBgn0028613
Datasets (0)
Study focus (0)
Experimental Role
Project
Project Type
Title
References (589)