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KIF23

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KIF23
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKIF23, CHO1, KNSL5, MKLP-1, MKLP1, kinesin family member 23, CDAN3A
External IDsOMIM: 605064; MGI: 1919069; HomoloGene: 11491; GeneCards: KIF23; OMA:KIF23 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9493

71819

Ensembl

ENSG00000137807

ENSMUSG00000032254

UniProt

Q02241

E9Q5G3

RefSeq (mRNA)

NM_001281301
NM_004856
NM_138555
NM_001367804
NM_001367805

NM_024245

RefSeq (protein)

NP_001268230
NP_004847
NP_612565
NP_001354733
NP_001354734

NP_077207
NP_001391984
NP_001391985
NP_001391986

Location (UCSC)Chr 15: 69.41 – 69.45 MbChr 9: 61.82 – 61.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.[5][6]

Gene

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The human KIF23 gene is located on chromosome 15 at band q23 and spans 25 exons.[6] It encodes a member of the kinesin family of motor proteins, which are essential for processes such as cytokinesis. The KIF23 gene undergoes alternative splicing, resulting in at least two transcript variants that produce different protein isoforms, most notably the larger CHO1 and the smaller MKLP1.[6]

Structure

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KIF23 is a member of the kinesin superfamily of microtubule-dependent motor proteins. Structurally, KIF23 consists of several distinct domains: a conserved N-terminal kinesin motor domain responsible for ATP hydrolysis and microtubule binding, a central coiled-coil region that mediates dimerization and interaction with partner proteins, and a C-terminal tail domain, which includes the Arf6-interacting domain important for regulatory functions.[7] The protein exists as part of a heterotetrameric complex called centralspindlin, composed of two KIF23 molecules and two RACGAP1 molecules.[8][9] This complex localizes to the central spindle during anaphase and the midbody during cytokinesis, where it orchestrates the assembly of the contractile ring and abscission machinery necessary for cell division.[10] KIF23 is subject to alternative splicing, resulting in at least two isoforms: the larger CHO1 and the smaller MKLP1. The protein’s structure enables it to cross-bridge antiparallel microtubules and facilitate their movement, a function essential for both mitotic spindle organization and successful cytokinesis.[7]

Function

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Model for co-regulation of microtubule polarity in axons and dendrites by different mitotic kinesins. During axonal differentiation, forces generated by cytoplasmic dynein drive plus-end-distal microtubules into the axon and nascent dendrites (not shown). (A) Forces generated by kinesin-6 at the cell body oppose the forces generated by cytoplasmic dynein, restricting the transport of plus-end-distal microtubules into the axon. As the neuron matures, kinesin-6 fuels the transport of short microtubules with their minus-end distal into all of the processes except the one designated to remain the axon, thus causing the other processes to differentiate into dendrites. (B) Forces generated by kinesin-12 behave similarly to kinesin-6 with regard to introducing minus-end-distal microtubules into the dendrite, but kinesin-12 is also present in the axon and growth cone, pushing plus-end-distal microtubules back toward the cell body. As a result, kinesin-12 behaves like kinesin-6 with regard to dendrites but produces effects more like kinesin-5 with regard to the axon.

In cell division

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KIF23 (also known as Kinesin-6, CHO1/MKLP1, C. elegans ZEN-4 and Drosophila Pavarotti) is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in two transcript variants encoding two different isoforms, better known as CHO1, the larger isoform and MKLP1, the smaller isoform.[6] KIF23 is a plus-end directed motor protein expressed in mitosis, involved in the formation of the cleavage furrow in late anaphase and in cytokinesis.[5][11][12] KIF23 is part of the centralspindlin complex that includes PRC1, Aurora B and 14-3-3 which cluster together at the spindle midzone to enable anaphase in dividing cells.[13][14][15]

In neurons

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In neuronal development KIF23 is involved in the transport of minus-end distal microtubules into dendrites and is expressed exclusively in cell bodies and dendrites.[16][17][18][19][20] Knockdown of KIF23 by antisense oligonucleotides and by siRNA both cause a significant increase in axon length and a decrease in dendritic phenotype in neuroblastoma cells and in rat neurons.[18][19][21] In differentiating neurons, KIF23 restricts the movement of short microtubules into axons by acting as a "brake" against the driving forces of cytoplasmic dynein. As neurons mature, KIF23 drives minus-end distal microtubules into nascent dendrites contributing to the multi-polar orientation of dendritic microtubules and the formation of their short, fat, tapering morphology.[21]

Clinical significance

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Mutations in KIF23 have been associated with Congenital dyserythropoietic anemia type III, highlighting its importance in normal cell function and development.[22][23]

KIF23 has also been implicated in the formation and proliferation of GL261 gliomas in mouse.[24]

Interactions

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KIF23 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000137807 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032254 – 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. ^ a b Nislow C, Lombillo VA, Kuriyama R, McIntosh JR (Nov 1992). "A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles". Nature. 359 (6395): 543–547. Bibcode:1992Natur.359..543N. doi:10.1038/359543a0. PMID 1406973. S2CID 4361579.
  6. ^ a b c d "Entrez Gene: KIF23 kinesin family member 23".
  7. ^ a b "Kinesin family member 23". Zebrafish Information Network (ZFIN).
  8. ^ Vikberg AL (2021). Mitotic Kinesin-Like Protein 1 (MKLP1/KIF23) in hereditary congenital dyserythropoietic anemia type III and in cancer (PDF) (PhD. thesis). Umeå Universitet.
  9. ^ "KIF23". GeneCards.
  10. ^ "KIF23_HUMAN". UniProt. Q02241.
  11. ^ Hutterer A, Glotzer M, Mishima M (December 2009). "Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody". Current Biology. 19 (23): 2043–2049. Bibcode:2009CBio...19.2043H. doi:10.1016/j.cub.2009.10.050. PMC 3349232. PMID 19962307.
  12. ^ Hornick JE, Karanjeet K, Collins ES, Hinchcliffe EH (May 2010). "Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone". Seminars in Cell & Developmental Biology. 21 (3): 290–299. doi:10.1016/j.semcdb.2010.01.017. PMC 3951275. PMID 20109573.
  13. ^ Neef R, Klein UR, Kopajtich R, Barr FA (February 2006). "Cooperation between mitotic kinesins controls the late stages of cytokinesis". Current Biology. 16 (3): 301–307. Bibcode:2006CBio...16..301N. doi:10.1016/j.cub.2005.12.030. PMID 16461284.
  14. ^ a b Douglas ME, Davies T, Joseph N, Mishima M (May 2010). "Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis". Current Biology. 20 (10): 927–933. Bibcode:2010CBio...20..927D. doi:10.1016/j.cub.2010.03.055. PMC 3348768. PMID 20451386.
  15. ^ Glotzer M (January 2009). "The 3Ms of central spindle assembly: microtubules, motors and MAPs". Nature Reviews. Molecular Cell Biology. 10 (1): 9–20. doi:10.1038/nrm2609. PMC 2789570. PMID 19197328.
  16. ^ Sharp DJ, Kuriyama R, Essner R, Baas PW (October 1997). "Expression of a minus-end-directed motor protein induces Sf9 cells to form axon-like processes with uniform microtubule polarity orientation". Journal of Cell Science. 110 (19): 2373–2380. doi:10.1242/jcs.110.19.2373. PMID 9410876.
  17. ^ Sharp DJ, Yu W, Ferhat L, Kuriyama R, Rueger DC, Baas PW (August 1997). "Identification of a microtubule-associated motor protein essential for dendritic differentiation". The Journal of Cell Biology. 138 (4): 833–843. doi:10.1083/jcb.138.4.833. PMC 2138050. PMID 9265650.
  18. ^ a b Yu W, Sharp DJ, Kuriyama R, Mallik P, Baas PW (February 1997). "Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells". The Journal of Cell Biology. 136 (3): 659–668. doi:10.1083/jcb.136.3.659. PMC 2134303. PMID 9024695.
  19. ^ a b Yu W, Cook C, Sauter C, Kuriyama R, Kaplan PL, Baas PW (August 2000). "Depletion of a microtubule-associated motor protein induces the loss of dendritic identity". The Journal of Neuroscience. 20 (15): 5782–5791. doi:10.1523/JNEUROSCI.20-15-05782.2000. PMC 6772545. PMID 10908619.
  20. ^ Xu X, He C, Zhang Z, Chen Y (February 2006). "MKLP1 requires specific domains for its dendritic targeting". Journal of Cell Science. 119 (Pt 3): 452–458. doi:10.1242/jcs.02750. PMID 16418225. S2CID 29919060.
  21. ^ a b 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): 14033–14049. doi:10.1523/JNEUROSCI.3070-12.2012. PMC 3482493. PMID 23035110.
  22. ^ Matuliene J, Kuriyama R (June 2002). "Kinesin-like protein CHO1 is required for the formation of midbody matrix and the completion of cytokinesis in mammalian cells". Molecular Biology of the Cell. 13 (6): 1832–45. doi:10.1091/mbc.01-10-0504. PMC 117607. PMID 12058052.
  23. ^ Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, et al. (January 2006). "KIF14 and citron kinase act together to promote efficient cytokinesis". The Journal of Cell Biology. 172 (3): 363–72. doi:10.1083/jcb.200511061. PMC 2063646. PMID 16431929.
  24. ^ Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K, et al. (February 2012). "Downregulation of KIF23 suppresses glioma proliferation". Journal of Neuro-Oncology. 106 (3): 519–529. doi:10.1007/s11060-011-0706-2. PMID 21904957. S2CID 33089132.
  25. ^ Boman AL, Kuai J, Zhu X, Chen J, Kuriyama R, Kahn RA (October 1999). "Arf proteins bind to mitotic kinesin-like protein 1 (MKLP1) in a GTP-dependent fashion". Cell Motility and the Cytoskeleton. 44 (2): 119–132. doi:10.1002/(SICI)1097-0169(199910)44:2<119::AID-CM4>3.0.CO;2-C. PMID 10506747.
  26. ^ Guse A, Mishima M, Glotzer M (April 2005). "Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis". Current Biology. 15 (8): 778–786. Bibcode:2005CBio...15..778G. doi:10.1016/j.cub.2005.03.041. PMID 15854913.
  27. ^ Li J, Wang J, Jiao H, Liao J, Xu X (March 2010). "Cytokinesis and cancer: Polo loves ROCK'n' Rho(A)". Journal of Genetics and Genomics = Yi Chuan Xue Bao. 37 (3): 159–172. doi:10.1016/S1673-8527(09)60034-5. PMID 20347825.
  28. ^ Pohl C, Jentsch S (March 2008). "Final stages of cytokinesis and midbody ring formation are controlled by BRUCE". Cell. 132 (5): 832–845. doi:10.1016/j.cell.2008.01.012. PMID 18329369.
  29. ^ Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N, Todokoro K (August 2004). "Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation". The EMBO Journal. 23 (16): 3237–3248. doi:10.1038/sj.emboj.7600347. PMC 514520. PMID 15297875.

Further reading

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Further reading

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