KIF23

KIF23
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3VHX
Identifiers
Aliases	KIF23 , CHO1, KNSL5, MKLP-1, MKLP1, kinesin family member 23, CDAN3A
External IDs	OMIM: 605064; MGI: 1919069; HomoloGene: 11491; GeneCards: KIF23; OMA:KIF23 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q23 Start 69,414,246 bp [1] End 69,448,427 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 B Start 61,823,187 bp [2] End 61,854,056 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone secondary oocyte ganglionic eminence gonad testicle stromal cell of endometrium bone marrow mucosa of transverse colon trabecular bone left testis Top expressed in zygote secondary oocyte tail of embryo genital tubercle primary oocyte Ileal epithelium ventricular zone morula morula maxillary prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding microtubule binding ATPase activity protein binding ATP binding microtubule motor activity Cellular component cytoplasm cytosol centrosome centralspindlin complex kinesin complex focal adhesion spindle nucleoplasm intercellular bridge mitotic spindle microtubule cytoskeleton nucleus midbody Flemming body Biological process plus-end-directed vesicle transport along microtubule antigen processing and presentation of exogenous peptide antigen via MHC class II mitotic spindle midzone assembly mitotic cytokinesis cell division positive regulation of cytokinesis microtubule-based movement actomyosin contractile ring assembly cell cycle mitotic spindle elongation retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum cytokinesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 9: 61.82 – 61.85 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Gene

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

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

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

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

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

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

KIF23 has been shown to interact with:

• ARF3, ^[25]
• AURKB, ^{[14] [26] [27]}
• BIRC6, ^[28] and
• PRC1. ^[29]

References

1. GRCh38: Ensembl release 89: ENSG00000137807 – Ensembl, May 2017
2. 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. 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. "Entrez Gene: KIF23 kinesin family member 23".
7. "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. 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. 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. 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. 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

• Miki H, Setou M, Kaneshiro K, Hirokawa N (June 2001). "All kinesin superfamily protein, KIF, genes in mouse and human". Proceedings of the National Academy of Sciences of the United States of America. 98 (13): 7004–7011. Bibcode:2001PNAS...98.7004M. doi: 10.1073/pnas.111145398 . PMC   34614 . PMID   11416179.
• Lee KS, Yuan YL, Kuriyama R, Erikson RL (December 1995). "Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1". Molecular and Cellular Biology. 15 (12): 7143–7151. doi:10.1128/MCB.15.12.7143. PMC   230970 . PMID   8524282.
• Deavours BE, Walker RA (July 1999). "Nuclear localization of C-terminal domains of the kinesin-like protein MKLP-1". Biochemical and Biophysical Research Communications. 260 (3): 605–608. doi:10.1006/bbrc.1999.0952. PMID   10403813.
• Mishima M, Kaitna S, Glotzer M (January 2002). "Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity". Developmental Cell. 2 (1): 41–54. doi: 10.1016/S1534-5807(01)00110-1 . PMID   11782313.
• Kuriyama R, Gustus C, Terada Y, Uetake Y, Matuliene J (March 2002). "CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis". The Journal of Cell Biology. 156 (5): 783–790. doi:10.1083/jcb.200109090. PMC   2173305 . PMID   11877456.
• Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T (December 2001). "Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation". Cell Structure and Function. 26 (6): 645–651. doi: 10.1247/csf.26.645 . PMID   11942621.
• Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (February 2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes to Cells. 9 (2): 105–120. doi: 10.1111/j.1365-2443.2004.00705.x . PMID   15009096. S2CID   21813024.
• Matuliene J, Kuriyama R (July 2004). "Role of the midbody matrix in cytokinesis: RNAi and genetic rescue analysis of the mammalian motor protein CHO1". Molecular Biology of the Cell. 15 (7): 3083–3094. doi:10.1091/mbc.E03-12-0888. PMC   452566 . PMID   15075367.
• Liu X, Zhou T, Kuriyama R, Erikson RL (July 2004). "Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1". Journal of Cell Science. 117 (Pt 15): 3233–3246. doi:10.1242/jcs.01173. PMID   15199097. S2CID   3178600.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi: 10.1073/pnas.0404720101 . PMC   514446 . PMID   15302935.
• Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, et al. (August 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–1450. Bibcode:2004CBio...14.1436J. doi: 10.1016/j.cub.2004.07.051 . PMID   15324660. S2CID   2371325.
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, et al. (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID   15592455. S2CID   7200157.
• Benzinger A, Muster N, Koch HB, Yates JR, Hermeking H (June 2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Molecular & Cellular Proteomics. 4 (6): 785–795. doi: 10.1074/mcp.M500021-MCP200 . PMID   15778465.
• Zhu C, Bossy-Wetzel E, Jiang W (July 2005). "Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells". The Biochemical Journal. 389 (Pt 2): 373–381. doi:10.1042/BJ20050097. PMC   1175114 . PMID   15796717.
• Naher S, Iemura K (4 December 2024). "Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex". The EMBO Journal. 44 (2). European Molecular Biology Organization: 331–355. doi:10.1038/s44318-024-00327-7. PMC   11729872 . PMID   39632980.

Further reading

• Barr F (May 2005). "Francis Barr Lab". Current Biology. 15 (9): R314 –R315. Bibcode:2005CBio...15.R314B. doi: 10.1016/j.cub.2005.04.040 . PMID   15931723. S2CID   19619462.

External links

• Baas P. "Peter Baas Lab". Research Lab.
• Kuriyama R. "Ryoko Kuriyama Lab". Research Lab. Archived from the original on 2012-12-14. Retrieved 2012-12-31.
• Glotzer M. "Michael Glotzer Lab". Research Lab. Archived from the original on 2011-08-21. Retrieved 2012-12-31.
• Mishima M. "Masanori Mishima". Research Lab. Archived from the original on 2016-03-04. Retrieved 2012-12-31.