G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
kinesin family member 5C
G00000779 (Mus musculus)

Databases (7)

ENSG00000168280 (Ensembl human gene)
3800 (Entrez Gene)
1191 (G2Cdb plasticity & disease)
KIF5C (GeneCards)
604593 (OMIM)
Marker Symbol
HGNC:6325 (HGNC)
Protein Sequence
O60282 (UniProt)

Literature (15)

Pubmed - other

  • The mechanism of Ca2+ -dependent regulation of kinesin-mediated mitochondrial motility.

    Wang X and Schwarz TL

    F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA.

    Mitochondria are mobile organelles and cells regulate mitochondrial movement in order to meet the changing energy needs of each cellular region. Ca(2+) signaling, which halts both anterograde and retrograde mitochondrial motion, serves as one regulatory input. Anterograde mitochondrial movement is generated by kinesin-1, which interacts with the mitochondrial protein Miro through an adaptor protein, milton. We show that kinesin is present on all axonal mitochondria, including those that are stationary or moving retrograde. We also show that the EF-hand motifs of Miro mediate Ca(2+)-dependent arrest of mitochondria and elucidate the regulatory mechanism. Rather than dissociating kinesin-1 from mitochondria, Ca(2+)-binding permits Miro to interact directly with the motor domain of kinesin-1, preventing motor/microtubule interactions. Thus, kinesin-1 switches from an active state in which it is bound to Miro only via milton, to an inactive state in which direct binding to Miro prevents its interaction with microtubules. Disrupting Ca(2+)-dependent regulation diminishes neuronal resistance to excitotoxicity.

    Funded by: NIGMS NIH HHS: R01 GM069808, R01 GM069808-01A1, R01 GM069808-02, R01 GM069808-03, R01 GM069808-04, R01GM069808

    Cell 2009;136;1;163-74

  • KIF5C: a new binding partner for protein kinase CK2 with a preference for the CK2alpha' subunit.

    Schäfer B, Götz C, Dudek J, Hessenauer A, Matti U and Montenarh M

    Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Gebäude 44, 66424, Homburg, Germany.

    Protein kinase CK2 is a highly conserved serine/threonine kinase that is ubiquitously expressed in eukaryotic cells. CK2 is a constitutively active tetrameric enzyme composed of two catalytic alpha and/or alpha'-subunits and two regulatory beta-subunits. There is increasing evidence that the individual subunits may have independent functions and that they are asymmetrically distributed inside the cell. To gain a better understanding of the functions of the individual subunits, we employed a yeast-two-hybrid screen with CK2alpha and CK2alpha'. We identified the motor neuron protein KIF5C as a new binding partner for CK2. The interaction found in the yeast-two-hybrid screen was confirmed by co-sedimentation analysis on a sucrose density gradient and by co-immunoprecipitation analysis. Pull-down experiments and surface plasmon resonance spectrometry revealed a direct binding of KIF5C to CK2alpha'. Co-localization studies with neuroblastoma cells, bone marrow and with primary neurons confirmed the biochemical analysis that KIF5C preferentially bound to CK2alpha'.

    Cellular and molecular life sciences : CMLS 2009;66;2;339-49

  • The kinesin I family member KIF5C is a novel substrate for protein kinase CK2.

    Schäfer B, Götz C and Montenarh M

    Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Gebäude 44, 66424 Homburg, Germany.

    Protein kinase CK2 is ubiquitously expressed. The holoenzyme is composed of two catalytic alpha- or alpha'-subunits and two regulatory beta-subunits but evidence is accumulating that the subunits can function independently. The composition of the holoenzyme as well as the expression of the individual subunits varies in different tissues, with high expression of CK2alpha' in testis and brain. CK2 phosphorylates a number of different substrates which are implicated in basal cellular processes such as proliferation and survival of cells. Here, we report a new substrate, KIF5C, which is a member of the kinesin 1 family of motor neuron proteins. Phosphorylation of KIF5C was demonstrated in vitro and in vivo. Using deletion mutants, a peptide library, and mutation analysis a phosphorylation site for CK2 was mapped to amino acid 338 which is located in the non-motor domain of KIF5C. Interestingly, KIF5C is phosphorylated by holoenzymes composed of CK2alpha/CK2beta and CK2alpha'/CK2beta as well as by CK2alpha' alone but not by CK2alpha alone.

    Biochemical and biophysical research communications 2008;375;2;179-83

  • Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function.

    Cho KI, Cai Y, Yi H, Yeh A, Aslanukov A and Ferreira PA

    Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA.

    The Ran-binding protein 2 (RanBP2) is a large mosaic protein with a pleiotropic role in cell function. Although the contribution of each partner and domain of RanBP2 to its biological functions are not understood, physiological deficits of RanBP2 downregulate glucose catabolism and energy homeostasis and lead to delocalization of mitochondria components in photosensory neurons. The kinesin-binding domain (KBD) of RanBP2 associates selectively in the central nervous system (CNS), and directly, with the ubiquitous and CNS-specific kinesins, KIF5B and KIF5C, respectively, but not with the highly homologous KIF5A. Here, we determine the molecular and biological bases of the selective interaction between RanBP2 and KIF5B/KIF5C. This interaction is conferred by a approximately 100-residue segment, comprising a portion of the coiled-coil and globular tail cargo-binding domains of KIF5B/KIF5C. A single residue conserved in KIF5B and KIF5C, but not KIF5A, confers KIF5-isotype-specific association with RanBP2. This interaction is also mediated by a conserved leucine-like heptad motif present in KIF5s and KBD of RanBP2. Selective inhibition of the interaction between KBD of RanBP2 and KIF5B/KIF5C in cell lines causes perinuclear clustering of mitochondria, but not of lysosomes, deficits in mitochondrial membrane potential and ultimately, cell shrinkage. Collectively, the data provide a rationale of the KIF5 subtype-specific interaction with RanBP2 and support a novel kinesin-dependent role of RanBP2 in mitochondria transport and function. The data also strengthen a model whereby the selection of a large array of cargoes for transport by a restricted number of motor proteins is mediated by adaptor proteins such as RanBP2.

    Funded by: NEI NIH HHS: 2P30-EY005722-21, EY11993, R01 EY011993

    Traffic (Copenhagen, Denmark) 2007;8;12;1722-35

  • Large-scale mapping of human protein-protein interactions by mass spectrometry.

    Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T and Figeys D

    Protana, Toronto, Ontario, Canada.

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

    Molecular systems biology 2007;3;89

  • Mapping the GRIF-1 binding domain of the kinesin, KIF5C, substantiates a role for GRIF-1 as an adaptor protein in the anterograde trafficking of cargoes.

    Smith MJ, Pozo K, Brickley K and Stephenson FA

    Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.

    Gamma-aminobutyric acid, type A (GABAA) receptor interacting factor-1 (GRIF-1) and N-acetylglucosamine transferase interacting protein (OIP) 106 are both members of a newly identified coiled-coil family of proteins. They are kinesin-associated proteins proposed to function as adaptors in the anterograde trafficking of organelles to synapses. Here we have studied in more detail the interaction between the prototypic kinesin heavy chain, KIF5C, kinesin light chain, and GRIF-1. The GRIF-1 binding site of KIF5C was mapped using truncation constructs in yeast two-hybrid interaction assays, co-immunoprecipitations, and co-localization studies following expression in mammalian cells. Using these approaches, it was shown that GRIF-1 and the KIF5C binding domain of GRIF-1, GRIF-1-(124-283), associated with the KIF5C non-motor domain. Refined studies using yeast two-hybrid interactions and co-immunoprecipitations showed that GRIF-1 and GRIF-1-(124-283) associated with the cargo binding region within the KIF5C non-motor domain. Substantiation that the GRIF-1-KIF5C interaction was direct was shown by fluorescence resonance energy transfer analyses using fluorescently tagged GRIF-1 and KIF5C constructs. A significant fluorescence resonance energy transfer value was found between the C-terminal EYFP-tagged KIF5C and ECFP-GRIF-1, the C-terminal EYFP-tagged KIF5C non-motor domain and ECFP-GRIF-1, but not between the N-terminal EYFP-tagged KIF5C nor the EYFP-KIF5C motor domain and ECFP-GRIF-1, thus confirming direct association between the two proteins at the KIF5C C-terminal and GRIF-1 N-terminal regions. Co-immunoprecipitation and confocal imaging strategies further showed that GRIF-1 can bind to the tetrameric kinesin light-chain/kinesin heavy-chain complex. These findings support a role for GRIF-1 as a kinesin adaptor molecule requisite for the anterograde delivery of defined cargoes such as mitochondria and/or vesicles incorporating beta2 subunit-containing GABAA receptors, in the brain.

    The Journal of biological chemistry 2006;281;37;27216-28

  • A human protein-protein interaction network: a resource for annotating the proteome.

    Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H and Wanker EE

    Max Delbrueck Center for Molecular Medicine, 13092 Berlin-Buch, Germany.

    Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and co-immunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.

    Cell 2005;122;6;957-68

  • GRIF-1 and OIP106, members of a novel gene family of coiled-coil domain proteins: association in vivo and in vitro with kinesin.

    Brickley K, Smith MJ, Beck M and Stephenson FA

    Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.

    Gamma-aminobutyric acid(A) receptor-interacting factor (GRIF-1) is a 913-amino acid protein proposed to function as a GABA(A) receptor beta(2) subunit-interacting, trafficking protein. GRIF-1 shares approximately 44% amino acid sequence identity with O-linked N-acetylglucosamine transferase interacting protein 106, OIP106. Both proteins contain predicted coiled-coil domains and probably constitute a novel gene family. The Drosophila orthologue of this family of proteins may be Milton. Milton shares approximately 44% amino acid homology with GRIF-1. Milton is proposed to function in kinesin-mediated transport of mitochondria to nerve terminals. We report here that GRIF-1 and OIP106 also associate with kinesin and mitochondria. Following expression in human embryonic kidney 293 cells, both GRIF-1 and OIP106 were shown by co-immunoprecipitation to be specifically associated with an endogenous kinesin heavy chain species of 115 kDa and exogenous KIF5C. Association of GRIF-1 with kinesin was also evident in native brain and heart tissue. In the brain, anti-GRIF-1-(8-633) antibodies specifically co-immunoprecipitated two kinesin-immunoreactive species with molecular masses of 118 and 115 kDa, and in the heart, one kinesin-immunoreactive species, 115 kDa, was immunoprecipitated. Further studies revealed that GRIF-1 was predominantly associated with KIF5A in the brain and with KIF5B in both the heart and in HEK 293 cells. Yeast two-hybrid interaction assays and immunoprecipitations showed that GRIF-1 associated directly with KIF5C with the GRIF-1/KIF5C interaction domain localized to GRIF-1-(124-283). These results further support a role for GRIF-1 and OIP106 in protein and/or organelle transport in excitable cells in a manner analogous to glutamate receptor-interacting-protein 1, in the motor-dependent transport of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate glutamate excitatory neurotransmitter receptors to dendrites.

    The Journal of biological chemistry 2005;280;15;14723-32

  • Kinesin light-chain KLC3 expression in testis is restricted to spermatids.

    Junco A, Bhullar B, Tarnasky HA and van der Hoorn FA

    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

    Kinesins are tetrameric motor molecules, consisting of two kinesin heavy chains (KHCs) and two kinesin light chains (KLCs) that are involved in transport of cargo along microtubules. The function of the light chain may be in cargo binding and regulation of kinesin activity. In the mouse, two KLC genes, KLC1 and KLC2, had been identified. KLC1 plays a role in neuronal transport, and KLC2 appears to be more widely expressed. We report the cloning from a testicular cDNA expression library of a mammalian light chain, KLC3. The KLC3 gene is located in close proximity to the ERCC2 gene. KLC3 can be classified as a genuine light chain: it interacts in vitro with the KHC, the interaction is mediated by a conserved heptad repeat sequence, and it associates in vitro with microtubules. In mouse and rat testis, KLC3 protein expression is restricted to round and elongating spermatids, and KLC3 is present in sperm tails. In contrast, KLC1 and KLC2 can only be detected before meiosis in testis. Interestingly, the expression profiles of the three known KHCs and KLC3 differ significantly: Kif5a and Kif5b are not expressed after meiosis, and Kif5c is expressed at an extremely low level in spermatids but is not detectable in sperm tails. Our characterization of the KLC3 gene suggests that it carries out a unique and specialized role in spermatids.

    Funded by: Canadian Institutes of Health Research: 11361, 13680

    Biology of reproduction 2001;64;5;1320-30

  • Chromosomal localization reveals three kinesin heavy chain genes in mouse.

    Xia Ch, Rahman A, Yang Z and Goldstein LS

    Division of Cellular and Molecular Medicine, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0683, USA.

    Kinesin-related proteins constitute a superfamily of microtubule-dependent motors that play important roles in organelle transport and cell division. These molecules share a conserved motor region of approximately 340 amino acids, which is attached to diverse "tail" or cargo-binding domains. The kinesin superfamily was first defined by kinesin heavy chain, which is the principal component of "true" kinesin. Invertebrates appear to possess only a single gene encoding kinesin heavy chain. Mammals appear to have two or more genes encoding kinesin heavy chain, although the precise situation has been unclear. Here we definitively demonstrate that mouse has three kinesin heavy chain genes, Kif5a, Kif5b, and Kif5c. Kif5a, Kif5b, and Kif5c map to mouse chromosomes 10, 18, and 2; Kif5a and Kif5c appear to be expressed only in neuronal tissues by Northern blot analysis while Kif5b appears to be ubiquitous in its expression.

    Genomics 1998;52;2;209-13

  • Two kinesin light chain genes in mice. Identification and characterization of the encoded proteins.

    Rahman A, Friedman DS and Goldstein LS

    Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, Program in Biomedical Sciences and Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0683, USA.

    Native kinesin consists of two light chains and two heavy chains in a 1:1 stoichiometric ratio. To date, only one gene for kinesin light chain has been characterized, while a second gene was identified in a genomic sequencing study but not analyzed biochemically. Here we describe new genes encoding kinesin light chains in mouse. One of these light chains is neuronally enriched, while another shows ubiquitous expression. The presence of multiple kinesin light chain genes in mice is especially interesting, since there are two kinesin heavy chain genes in humans (Niclas, J., Navone, F., Hom-Booher, N., and Vale, R. D. (1994) Neuron 12, 1059-1072). To assess the selectivity of kinesin light chain interaction with the heavy chains, we performed immunoprecipitation experiments. The data suggested that the light chains form homodimers with no specificity in their interaction with the two heavy chains. Immunofluorescence and biochemical subfractionation suggested differences in the subcellular localization of the two kinesin light chain gene products. Although both kinesin light chains are distributed throughout the central and peripheral nervous systems, there is enrichment of one in sciatic nerve axons, while the other shows elevated levels in olfactory bulb glomeruli. These results indicate that the mammalian nervous system contains multiple kinesin light chain gene products with potentially distinct functions.

    The Journal of biological chemistry 1998;273;25;15395-403

  • Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

    Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N and Ohara O

    Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.

    As an extension of a series of projects for sequencing human cDNA clones derived from relatively long transcripts, we herein report the entire sequences of 100 newly determined cDNA clones with the potential of coding for large proteins in vitro. The cDNA clones were isolated from size-fractionated human brain cDNA libraries with insert sizes between 4.5 and 8.3 kb. The sequencing of these clones revealed that the average size of the cDNA inserts and of their open reading frames was 5.3 kb and 2.8 kb (930 amino acid residues), respectively. Homology search against public databases indicated that the predicted coding sequences of 86 clones exhibited significant similarities to known genes; 51 of them (59%) were related to those for cell signaling/communication, nucleic acid management, and cell structure/motility. All the clones characterized in this study are accompanied by their expression profiles in 14 human tissues examined by reverse transcription-coupled polymerase chain reaction and the chromosomal mapping data.

    DNA research : an international journal for rapid publication of reports on genes and genomes 1998;5;1;31-9

  • Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin.

    Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL and Ross CA

    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.

    Funded by: NIGMS NIH HHS: GM48661; NIMH NIH HHS: MH01152; NINDS NIH HHS: NS16375

    Human molecular genetics 1997;6;13;2205-12

  • Cloning and localization of a conventional kinesin motor expressed exclusively in neurons.

    Niclas J, Navone F, Hom-Booher N and Vale RD

    Department of Pharmacology, University of California, San Francisco 94143.

    Kinesin is a microtubule-based motor protein involved in organelle transport in neuronal and nonneuronal cells. Although a single kinesin motor has been thought to serve all cell types, we document here that neurons express a second conventional kinesin heavy chain (nKHC) that is 65% identical in amino acid sequence to the ubiquitously expressed kinesin heavy chain (uKHC). By preparing antibodies which distinguish between the two KHCs, we demonstrate that nKHC is a nucleotide-dependent microtubule-binding protein which partially cofractionates with membrane organelles. Immunolocalization experiments show that nKHC is distributed throughout the CNS but is highly enriched in subsets of neurons. In hippocampal neurons in culture, uKHC is distributed uniformly throughout the neuron, whereas nKHC is selectively concentrated in the cell body. These results demonstrate that mammalian neuronal tissue contains two conventional kinesin motors which may serve distinct functions in microtubule-based transport.

    Funded by: NIGMS NIH HHS: GM38499

    Neuron 1994;12;5;1059-72

Gene lists (6)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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