KIF15

Last updated

KIF15
KIF15.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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

Contents

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. 1 2 3 ENSG00000163808 GRCh38: Ensembl release 89: ENSG00000280610, ENSG00000163808 Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 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. 1 2 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