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| | Schematic representation of the KIF14 protein (not to scale). KIF14 contains two major effector domains. The first is a highly conserved 274 aa kinesin motor domain containing an ATP-binding site (aa 447-454) which is involved in microtubule-dependent ATPase activity, and a microtubule binding site (aa 455-628) involved in ATP-dependent protein transport. The second is a 67 aa forkhead-associated (FHA) domain (aa 825-891) which has similarity to the SMAD Mad Homology 2 (MH2) domain, and is involved in mediating protein-protein interactions with phosphoproteins, although no such interactions have been documented for KIF14. In addition to the highly conserved N-type neck region (N) adjacent to the motor domain, KIF14 also contains 4 other C-terminal regions predicted to form coiled-coil structures (1-4). Phosphorylation sites have been identified on Tyr-196, Ser-1200 and Ser-1292 (P), and a ubiquitination site identified on Lys-275 (U). The kinesin motor and FHA domains are flanked by a 354 aa N-terminal extension, and a 758 aa C-terminal stalk and tail region. The N-terminal extension is involved in the binding of PRC1 (protein-regulating cytokinesis 1), a protein crucial for the proper formation of the central spindle structure during cytokinesis. Citron kinase has been shown to interact with the C-terminal stalk and tail of KIF14, and this interaction is required for proper localization of KIF14 to the mitotic spindle. |
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| Description | KIF14 is a 186 kDa, 1648 aa protein, containing kinesin motor and forkhead-associated (FHA) domains. It is a member of the N-3 family of kinesins. High-throughput studies have identified phosphorylations on Tyr-196; Ser-1200 and Ser-1292, and ubiquitination on Lys-275. |
| Expression | KIF14 was cloned from an immature myeloid cell line, KG-1. By qRT-PCR, KIF14 is expressed at low levels in normal adult tissues and at higher levels in placenta and fetal tissues; highest expression is in fetal thymus and liver. KIF14 expression varies with the cell cycle, with highest expression at G2-M. |
| Localisation | In HeLa cells, KIF14 is localized to the cytoplasm during interphase, and becomes tightly localized to the midbody and central spindle during cytokinesis. |
| Function | KIF14 is a mitotic kinesin motor protein with ATPase activity. It interacts with protein regulator of cytokinesis 1 (PRC1) and is essential for localizing citron kinase to the mitotic spindle. KIF14 knockdown results in failure of cytokinesis, leading to multinucleation and/or apoptosis, but no chromosome segregation defects. |
| Homology | There are KIF14 orthologs in several mammalian species. The closest Drosophila melanogaster gene, with 40% amino acid identity, is nebbish/tiovivo, encoding Klp38B (kinesin-like protein 38B). Klp38B is a mitotic kinesin that binds to chromatin and microtubules in the formation of the bipolar spindle and attachment of chromosomes to the spindle, and/or acts in cytokinesis. |
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| Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to failure of cytokinesis. |
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| The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms. |
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| The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms. |
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| PMID 11106755 |
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| KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers. |
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| Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. |
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| PMID 15843429 |
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| RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure. |
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| Molecular and cellular biology. 2006 ; 26 (10) : 3853-3863. |
| PMID 16648480 |
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| KIF14 mRNA expression is a predictor of grade and outcome in breast cancer. |
| Corson TW, Gallie BL |
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| PMID 16570270 |
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| KIF14 and citron kinase act together to promote efficient cytokinesis. |
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| The Journal of cell biology. 2006 ; 172 (3) : 363-372. |
| PMID 16431929 |
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| Profiling genomic copy number changes in retinoblastoma beyond loss of RB1. |
| Bowles E, Corson TW, Bayani J, Squire JA, Wong N, Lai PB, Gallie BL |
| Genes, chromosomes & cancer. 2007 ; 46 (2) : 118-129. |
| PMID 17099872 |
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| KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer. |
| Corson TW, Zhu CQ, Lau SK, Shepherd FA, Tsao MS, Gallie BL |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 ; 13 (11) : 3229-3234. |
| PMID 17545527 |
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| High expression of KIF14 in retinoblastoma: association with older age at diagnosis. |
| Madhavan J, Coral K, Mallikarjuna K, Corson TW, Amit N, Khetan V, George R, Biswas J, Gallie BL, Kumaramanickavel G |
| Investigative ophthalmology & visual science. 2007 ; 48 (11) : 4901-4906. |
| PMID 17962437 |
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