KIF15

Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.^[5]

KIF15
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4BN2
Identifiers
Aliases	KIF15, HKLP2, KNSL7, NY-BR-62, kinesin family member 15, KLP2
External IDs	OMIM: 617569; MGI: 1098258; HomoloGene: 23210; GeneCards: KIF15; OMA:KIF15 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 44,761,721 bp[1] End 44,873,376 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F4 Start 122,780,111 bp[2] End 122,847,798 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence left testis right testis testicle gonad bone marrow mucosa of transverse colon bone marrow cells endometrium Top expressed in tail of embryo genital tubercle spermatocyte ventricular zone spermatid embryo yolk sac embryo blastocyst morula More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding microtubule motor activity nucleotide binding microtubule binding ATPase activity cytoskeletal motor activity ATP binding protein binding Cellular component cytoplasm cytosol centrosome membrane spindle plus-end kinesin complex microtubule cytoskeleton kinesin complex Biological process antigen processing and presentation of exogenous peptide antigen via MHC class II microtubule-based movement cell population proliferation retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56992 209737 Ensembl ENSG00000280610 ENSG00000163808 ENSMUSG00000036768 UniProt Q9NS87 Q6P9L6 RefSeq (mRNA) NM_020242 NM_010620 RefSeq (protein) NP_064627 NP_034750 Location (UCSC) Chr 3: 44.76 – 44.87 Mb Chr 9: 122.78 – 122.85 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a motor protein that is part of the kinesin superfamily. KIF15 maintains half spindle separation by opposing forces generated by other motor proteins. KIF15 co-localizes with microtubules and actin filaments in both dividing cells and in postmitotic neurons.^[5]

Function

KIF15 (also known as Kinesin-12 and HKLP2) is a motor protein expressed in all cells during mitosis and in postmitotic neurons undergoing axon growth.^[6] KIF15 maintains bipolar microtubule spindle apparatus in dividing cells and shares redundant functions with KIF11.^[7] KIF15 is thought to promote spindle assembly by cross-linking and sliding along microtubules creating a separation between centrosomes. The microtubule localization of Kif15 is being regulated by Kinesin binding protein (KBP).^[8] HeLa cells depleted of KIF11, with reduced microtubule dynamics, are able to form bipolar spindles from acentrosomal asters in a KIF15 dependent manner.^[9][10] Hence, inhibition of KIF15 function will be a vital therapeutic approach in cancer chemotherapy.^[11] Since KIF11 and KIF15 are functionally redundant, drugs targeting both the proteins will be more potent.^[8]

Function in neurons

KIF15 restricts the movement of short microtubules into growing axons by generating forces on microtubules which counteract those generated by cytoplasmic dynein.^[12][13] KIF15, together with KIF23 become enriched in dendrites as neurons mature to promote the transport of minus-end distal microtubules into nascent dendrites.^[12]

Interactions

KIF15 has been shown to interact with TPX2. Both these dimers cooperate to slide along microtubules and maintain bipolar spindles.^[14][15]

References

1. ENSG00000163808 GRCh38: Ensembl release 89: ENSG00000280610, ENSG00000163808 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036768 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Kinesin family member 15".
6. Buster DW, Baird DH, Yu W, Solowska JM, Chauvière M, Mazurek A, et al. (January 2003). "Expression of the mitotic kinesin Kif15 in postmitotic neurons: implications for neuronal migration and development". Journal of Neurocytology. 32 (1): 79–96. doi:10.1023/a:1027332432740. PMID 14618103. S2CID 6734564.
7. Vanneste D, Takagi M, Imamoto N, Vernos I (November 2009). "The role of Hklp2 in the stabilization and maintenance of spindle bipolarity". Current Biology. 19 (20): 1712–7. Bibcode:2009CBio...19.1712V. doi:10.1016/j.cub.2009.09.019. PMID 19818619.
8. Sebastian J, Rathinasamy K (July 2019). "Benserazide Perturbs Kif15-kinesin Binding Protein Interaction with Prolonged Metaphase and Defects in Chromosomal Congression: A Study Based on in silico Modeling and Cell Culture". Molecular Informatics. 39 (3): minf.201900035. doi:10.1002/minf.201900035. PMID 31347789. S2CID 198911009.
9. Florian S, Mayer TU (October 2011). "Modulated microtubule dynamics enable Hklp2/Kif15 to assemble bipolar spindles". Cell Cycle. 10 (20): 3533–44. doi:10.4161/cc.10.20.17817. PMID 22024925.
10. Dumont J (January 2012). "Bipolar disorder: kinesin-12 to the rescue". Cell Cycle. 11 (2): 212–3. doi:10.4161/cc.11.2.18785. PMID 22214669.
11. Sebastian J (June 2017). "Dihydropyrazole and dihydropyrrole structures based design of Kif15 inhibitors as novel therapeutic agents for cancer". Computational Biology and Chemistry. 68: 164–174. doi:10.1016/j.compbiolchem.2017.03.006. PMID 28355588.
12. Lin S, Liu M, Mozgova OI, Yu W, Baas PW (October 2012). "Mitotic motors coregulate microtubule patterns in axons and dendrites". The Journal of Neuroscience. 32 (40): 14033–49. doi:10.1523/JNEUROSCI.3070-12.2012. PMC 3482493. PMID 23035110.
13. Liu M, Nadar VC, Kozielski F, Kozlowska M, Yu W, Baas PW (November 2010). "Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching". The Journal of Neuroscience. 30 (44): 14896–906. doi:10.1523/JNEUROSCI.3739-10.2010. PMC 3064264. PMID 21048148.
14. Tanenbaum ME, Macůrek L, Janssen A, Geers EF, Alvarez-Fernández M, Medema RH (November 2009). "Kif15 cooperates with eg5 to promote bipolar spindle assembly". Current Biology. 19 (20): 1703–11. Bibcode:2009CBio...19.1703T. doi:10.1016/j.cub.2009.08.027. PMID 19818618. S2CID 15875832.
15. Vanneste D, Ferreira V, Vernos I (October 2011). "Chromokinesins: localization-dependent functions and regulation during cell division". Biochemical Society Transactions. 39 (5): 1154–60. doi:10.1042/BST0391154. PMID 21936781.

Further reading

• Courtois A, Schuh M, Ellenberg J, Hiiragi T (August 2012). "The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development". The Journal of Cell Biology. 198 (3): 357–70. doi:10.1083/jcb.201202135. PMC 3413348. PMID 22851319.
• Oh SA, Allen T, Kim GJ, Sidorova A, Borg M, Park SK, et al. (October 2012). "Arabidopsis Fused kinase and the Kinesin-12 subfamily constitute a signalling module required for phragmoplast expansion". The Plant Journal. 72 (2): 308–19. doi:10.1111/j.1365-313X.2012.05077.x. PMID 22709276.
• Dumont J (January 2012). "Bipolar disorder: kinesin-12 to the rescue". Cell Cycle. 11 (2): 212–3. doi:10.4161/cc.11.2.18785. PMID 22214669.
• Goshima G (2011). "Identification of a TPX2-like microtubule-associated protein in Drosophila". PLOS ONE. 6 (11): e28120. Bibcode:2011PLoSO...628120G. doi:10.1371/journal.pone.0028120. PMC 3227607. PMID 22140519.
• Ho CM, Hotta T, Guo F, Roberson RW, Lee YR, Liu B (August 2011). "Interaction of antiparallel microtubules in the phragmoplast is mediated by the microtubule-associated protein MAP65-3 in Arabidopsis". The Plant Cell. 23 (8): 2909–23. doi:10.1105/tpc.110.078204. PMC 3180800. PMID 21873565.
• Liu M, Nadar VC, Kozielski F, Kozlowska M, Yu W, Baas PW (November 2010). "Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching". The Journal of Neuroscience. 30 (44): 14896–906. doi:10.1523/JNEUROSCI.3739-10.2010. PMC 3064264. PMID 21048148.
• Gong Y, Ma Z, Patel V, Fischer E, Hiesberger T, Pontoglio M, et al. (January 2009). "HNF-1beta regulates transcription of the PKD modifier gene Kif12". Journal of the American Society of Nephrology. 20 (1): 41–7. doi:10.1681/ASN.2008020238. PMC 2615735. PMID 19005009.
• Lee YR, Li Y, Liu B (August 2007). "Two Arabidopsis phragmoplast-associated kinesins play a critical role in cytokinesis during male gametogenesis". The Plant Cell. 19 (8): 2595–605. doi:10.1105/tpc.107.050716. PMC 2002617. PMID 17720869.
• Müller S, Han S, Smith LG (May 2006). "Two kinesins are involved in the spatial control of cytokinesis in Arabidopsis thaliana". Current Biology. 16 (9): 888–94. Bibcode:2006CBio...16..888M. doi:10.1016/j.cub.2006.03.034. PMID 16682350.

External links

• "Research of Thomas Mayer". University of Konstanz. Archived from the original on 2013-02-03. Retrieved 2012-12-30.