The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis.

The motor may also play a role in the proper development of mammalian neuronal processes, including growth cone navigation and elongation.

[14][15] In most eukaryotic cells, Kinesin-5 is thought to form cross-bridges between pairs of oppositely oriented microtubules in prophase and prometaphase and drives apart duplicated centrosomes during the formation of the mitotic spindle.

[23] The discovery of small chemical inhibitors of human Kinesin-5 through a pioneering in vitro phenotypic screening on cancer cell lines has led to both the development of new anticancer therapeutic agents, and to novel tools to probe the mechanism of microtubule motor proteins.

[22][24] This toolkit of allosteric inhibitors has been used to probe the specific role of Kinesin-5 in mitotic spindle assembly [25] as well as fine dissection of motor domain function.

[26][27][28][29][30] Through this work it was found that, in mammalian cells, Kinesin-5 is required for the initial assembly of the mitotic spindle during prophase and prometaphase, but is dispensable to traverse subsequent anaphase during a round of mitosis.

[33] The process of self-assembly of the mitotic spindle remains a major unsolved question in cell biology, and a robust model awaits further details of the regulation and behavior of various microtubule motors and structural elements that compose this machinery.

[15] KIF11, like KIF15 and KIF23, is thought to act as a restrictor of short microtubules moving bi-directionally along the axon, exerting forces antagonistically to cytoplasmic dynein.

[48][49] Kinesin-5 has been shown to interact with the dynactin subunit p150Glued[50] as well as many other cell cycle related proteins in vivo and in vitro,[51][52][53] however, additional experimentation is needed to confirm that their association is necessary for Kinesin-5 to function normally.

[54][55] X-ray crystallography, cryo-electron microscopy, and real-time infrared spectroscopy have been used to measure the structure of Kinesin-5 in the different catalytic intermediate states.

A two-water catalytic model was proposed and confirmed by an alternate method to track Kinesin-5 catalysis in real-time[59] and in a kinesin protein in a different subfamily.

[60] Two-water catalytic models also are proposed in a divergent motor protein, myosin, and observed experimentally in one of its crystal structures.

[61][62] Mechanical Properties The antiparallel tetrameric organization of the Kinesin-5 family is fundamentally different from the majority of other kinesins that are dimers, such as the well-characterized conventional Kinesin-1 (KIF5B).

Conventional kinesin dimerizes in such a manner that the catalytic (head) domains are together on one end of the complex to facilitate hand-over-hand movement along a microtubule that enables long-range, directed transport of cellular cargoes.

These obstacles have been overcome by either adapting the original experiments to analyze the tetrameric organization of Kinesin-5, or by working with shorter Kinesin-5 proteins that form dimers like conventional kinesin.

The most striking outcomes of the analysis of Kinesin-5 motility is that it is slow – about 10 times slower than conventional Kinesin-1 – with a velocity in the range of 50 nanometers per second and that it could generate very high levels of mechanical force (7-9 picoNewtons per molecule).

Since the motors are attached to the glass, their motile behavior translates into movement of the microtubule across the anchored kinesins, akin to someone crowd surfing.

This experiment showed that Kinesin-5 was indeed capable of carrying out the role that had been proposed for it in mitosis – sliding oppositely oriented microtubules in the mitotic spindle.

Since the bead is being held in place by the trap laser, it acts like a spring and exerts a force that resists the forward movement of the kinesin.

[22][69] Since then, over 100 different chemical classes of allosteric inhibitors have been identified in the scientific literature and they have a wide range in potency against human Kinesin-5.

[83] With these promising preclinical studies, ispinesib (SB-715992; Cytokinetics/GSK), SB-743921 from Cytokinetics/GSK,[84] MK-0731 from Merck,[85] filanesib (ARRY-520) (Array BioPharma), and litronesib (LY2523355) (Eli Lilly) have entered into clinical trials.

[28] In this manner, the L5 loop may be able to directly control nucleotide binding and beta-sheet twist can manipulate the adjacent microtubule-binding site.