KIF23

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

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
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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]