What is KIF superfamily?
Genes in the Kinesins Gene Family (KIF) superfamily code proteins called kinesins. There are 46 different kinesins in humans and other mammals being identified according to HGNC database. These proteins are classified into 14 subfamilies based on differences in their structure. The activity of kinesins supports several cellular functions such as meiosis, mitosis and transport of cellular cargo. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the microtubules' minus end.
Kinesins, which are similar to dynein and myosin in function, are remarkable enzymes and they catalyze the movement of specific cargos in a spatially and temporally regulated manner. Cells expend enormous amounts of energy organizing themselves in order to counter the thermodynamic effects of entropy, and molecular motors such as kinesin are essential for establishing and maintaining many of the aspects of this cellular order. Kinesins utilize the chemical energy stored in ATP to spatially organize specific macromolecular cargos, organelles, and cytoskeletal components on a timescale that is much shorter than purely stochastic means such as diffusion. A critical aspect of kinesin biology that enables these molecular motors to be integrated into such a variety of cellular processes is the tight regulatory control of kinesin activity by both intermolecular and intramolecular cues.
Kinesins Gene Family proteins generally consist of three domains termed the motor or head, stalk, and tail or cargo-binding domain. The motor domain functions to hydrolyze ATP to produce directed motion along a microtubule substrate. The structural and biophysical details of this process have been studied in great detail. The majority of functional kinesins exist in multimeric form, and these complexes are generally assembled by the formation of coiledcoils in the stalk domains. The known sites for post-translational modifications and ligand binding locate in tail domains.
Kinesin superfamily proteins (KIF) subfamily and classification
Kinesin superfamily proteins (KIF) can be classified into 14 groups in total including 2 groups of C-kinesins (C-1 kinesin and C-2 kinesin), 1 group of M-kinesins, 11 groups of N-kinesins, comprising 16 families. As usual, one group consists of one family, excepting N-3, N-4, and N-8 groups. N-3 kinesins includes KIF1, KIF13, and KIF16 families. N-4 kinesins includes KIF3 family and KIF17 family. N-8 kinesins includes the KIF18 family and KIF22 family.
Most KIFs of other species also can be categorized into these 14 groups. Below, we present a brief summary of the characterization of each kinesin group.
N-1 Kinesins: N-1 kinesins consists of the kinesin heavy chain (KHC) family which was the first KIF reported. KHC forms a heterotetramer by two KHCs and two kinesin light chains. This highly related family includes KIF5A, KIF5B and KIF5C.
N-2 Kinesins: N-2 kinesins consists of the KIF11 family. This family contains KIF11, a homotetrameric KIF which functions in bipolar spindle formation.
N-3 Kinesins: N-3 kinesins includes KIF1, KIF13, and KIF16 families. KIF1 family consists of KIF1A, KIF1B, and KIF1C. The KIF13 family consists of KIF13A and KIF13B. The KIF16 family includes KIF14, KIF16A, and KIF16B
N-4 Kinesins: N-4 kinesins consists of KIF3 and KIF17 families. The KIF3 family includes KIF3A, KIF3B, and KIF3C in mice. KIF17 family includes Osm3 in C. elegans which is necessary for sensory cilia growth.
N-5 Kinesins: N-5 kinesins is composed of the KIF4 family with an only member KIF4A, a microtubule plus end-directed anterograde motor.
N-6 Kinesins: N-6 Kkinesins includes KIF20 and KIF23 families. KIF20A functions in Golgi-derived vesicle transport and cell division.
N-7 Kinesins: N-7 kinesins is composed of KIF10 family, which plays a role in chromosome segregation.
N-8 Kinesins: N-8 kinesins contains KIF18 and KIF22 families.
N-9 Kinesins: N-9 kinesins is composed of KIF12 family which may be important in kidney.
N-10 Kinesins: The KIF15 family consists of this group. Human KIF15 expressed in spleen and testis, involves a cell proliferation marker protein (91).
N-11 Kinesins: N-11 kinesins includes KIF26 family which is related to DmCos2 and CeVab-8. These group proteins are KIF25, KIF24, KIF26A, and KIF26B.
M-Kinesins: M-kinesins contains KIF2 family with a motor domain in the center of the molecule. KIF2A carries a b-subunit of the insulin-like growth factor-1 receptor,βgc. KIF2C is a mitotic-centromere-associated kinesin. In addition, KIF2B is a novel member in this family.
C-1 Kinesins: This group contains the KIFC1 family which functions in meiosis, mitosis, and karyogamy.
C-2 Kinesins: C-2 kinesins contains KIFC2 and KIFC3 family. These proteins play roles in the dendritic transportation of multivesicular body-like membranous organelles.
Kinesins are one type of motor proteins that transport intracellular cargo with microtubule tracks and this process is derived from ATP hydrolysis. The functions of kinesins include active transport of vesicles, proteins and organelles in cell cytoplasm, axons, cilia and flagella. In addition, during cell division, kinesins help in the maintenance of mitotic spindles, in separation the chromosomes and depolymerizing the microtubules.
Microtubules are polymers composed of the protein tubulin, which contains alpha and beta-tubulin subunits. A microtubule protofilament has tubulin monomers arranged in a head to tail style and 12-16 protofilaments join later to form a hollow cylindrical microtubule with a diameter of 25 nm. The microtubules have a structural polarity with a fast polymerizing plus-end towards the beta-tubulin and a slow growing minus-end towards the alpha-subunit. In cells, the microtubules are marked by dynamic instability, the growth of microtubules occurs through a cycle of polymerization, followed by transition to catastrophe or the depolymerizing phase, and then is rescued back to the growing phase. Microtubules emanate from the centrosome near the nucleus, dynamically grow, and are stabilized at the cell wall. Microtubules act as tracks for transport by motors. They help keep the integrity of cellular structure and form the intricate spindle during cell division as well.
Structurally, active kinesin have two heavy chains and two light chains. The heavy chains consist of a well conserved catalytic motor domain and the microtubule binding site, followed by a neck linker and a long coiled-coil stalk and finally the tail domain. The light chains function to bind cargos and interact with the tail of the heavy chains. In the kinesin superfamily, the structure and sequence of tail is highly variable depending on the cargo they transport.
Kinesin superfamily proteins (KIF) reference
1. Miki H, Setou M, Kaneshiro K, et al. All kinesin superfamily protein, KIF, genes in mouse and human[J]. Proceedings of the National Academy of Sciences, 2001, 98(13): 7004-7011.
2. Sharp D J, Rogers G C, Scholey J M. Microtubule motors in mitosis[J]. Nature, 2000, 407(6800): 41-47.
3. Sato-Yoshitake R, Shiomura Y, Miyasaka H, et al. Microtubule-associated protein 1B: molecular structure, localization, and phosphorylation-dependent ex
4. Kirschner M, Mitchison T. Beyond self-assembly: from microtubules to morphogenesis[J]. Cell, 1986, 45(3): 329-342.