KIF15

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

KIF15
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKIF15, HKLP2, KNSL7, NY-BR-62, kinesin family member 15, KLP2
External IDsOMIM: 617569 MGI: 1098258 HomoloGene: 23210 GeneCards: KIF15
Gene location (Human)
Chr.Chromosome 3 (human)[1]
Band3p21.31Start44,761,721 bp[1]
End44,873,376 bp[1]
Orthologs
SpeciesHumanMouse
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 MbChr 9: 122.95 – 123.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

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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.
  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. 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: minf.201900035. doi:10.1002/minf.201900035. PMID 31347789.
  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. doi:10.1016/j.cub.2009.08.027. PMID 19818618.
  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


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