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- Table of Contents
Facts about Kinesin-like protein KIF2A.
Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate.
Human | |
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Gene Name: | KIF2A |
Uniprot: | O00139 |
Entrez: | 3796 |
Belongs to: |
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TRAFAC class myosin-kinesin ATPase superfamily |
HK2; KIF2kinesin-2; kinesin heavy chain member 2; kinesin heavy chain member 2A; Kinesin, heavy chain, 2; Kinesin-2; kinesin-like protein KIF2A; KNS2
Mass (kDA):
79.955 kDA
Human | |
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Location: | 5q12.1 |
Sequence: | 5; NC_000005.10 (62306162..62391025) |
Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Cytoplasm, cytoskeleton, spindle. Localized to the spindle microtubules and spindle poles from prophase to metaphase. Efficient targeting to spindle microtubules and spindle poles requires the kinase activity of PLK1. Recruited to mitotic spindles by interaction with PSRC1.
KIF2A is a member the Kinesin superfamily. This article explains its functions and clinical applications. We'll also look at how to price the KIF2A gene as a biomarker. Here's a quick overview of this gene. For more information, please read our Bio: Best Uses of the KIF2A marker article.
The kinesin proteins superfamily includes proteins involved in intracellular circulation, cell division, basic cell functions, and cell division. These proteins are directly associated with neurodegenerative conditions and many types of cancer. Breast cancer is also associated to Kinesin superfamily members. For example, Wang et al. Wang et al. have shown that KIF2A downregulation inhibits the proliferation and migration of breast cancer cells. This suggests that this marker could be an independent prognostic marker.
This gene is found in many types and forms of cancer. The presence of the kinesin 20A family member is associated with prognosis, oncogenesis, and progression. Recent bioinformatics analysis of LUAD tumors revealed that KIF20A was overexpressed in the tumor tissues. This was confirmed by immunohistochemistry as well as TCGA analysis.
The human KIF7 Motor Domain structure allows for a better understanding of this key member of the kinesin suprafamily. Kif7 has been implicated not only in cancer but also in embryonic development. Kif7 is involved the formation of primary cells and the Hedgehog signalling pathway. It is also involved in the development and maintenance of the kidney. Kif7 as well as Kif27 are orthologues for the Costal-2 Protein from Drosophila.
Blocking the mitotic exit of cancer cells is another promising anticancer strategy. This therapy could overcome cancer cell resistance to chemotherapy. KIFs play a vital role in intracellular transport, as they are essential for mitosis. Many compounds targeting mitotic Kinsins have been proven effective in animal models. They don't appear to translate into human treatments. Some, however, increase the sensitivity of chemotherapy drugs.
KIF23 could be a therapeutic target for lung cancer. However we do not know the exact function of these kinase-proteins in the disease. More research is needed in order to determine the function of KIFs within HCC. This is a novel way to diagnose and treat cancer. The Kinesin superfamily markers are best
Functional studies on mice lacking the KIF2A genes have shown that mutant proteins exhibit abnormal axonal branching patterns, overextensions of collateral branches, and decreased microtubule depolymerizing ability. The researchers further noted that individual microtubules displayed abnormal behavior at the cell edge of Kif2a-/ mice. These findings suggest that KIF2A plays a critical role in microtubule dynamics at the growth cone edge.
To evaluate the functions of the KIF2A gene, the expression of the marker was measured using immunohistochemistry. The protein was stained by a monoclonal antibody that was specific for the protein. Its expression was then classified into four levels: moderate, high (and very high). The combination of the four parameters was used to determine the final score. A cell's KIF2A levels were considered low when more than 50% of cells were positive.
Additionally, tumor progression in human and glioma gliomas was linked to KIF2A overexpression. KIF2A was found to correlate with several clinical parameters of glioma patients. It was also associated tumor invasion or migration. KIF2A could be a therapeutic target. This gene can be found in many human glioma tissues.
KIF2A mutations in lymphoma cells can cause moderate inhibition of cell proliferation. SU-DHL-8 cells were transfected with shRNA plasmids to decrease pAKT. However, total AKT levels were not affected. KIF2A may be a key step in improving the treatment and prevention of tumors. This marker plays an important part in the prognosis human cancer.
Mutant KIF2A results in abnormal cellular organization and microtubule decoration. Wild-type KIF2A exhibits diffuse punctiform, cytoplasmic, and nuclear distribution. KIF2A is also known to function in a dimer. This results in the existence of two distinct units. Poirier et al. (2013) suggested that KIF2A may have a dominant-negative effect on chromosome movement.
KIF2A has been shown to be linked to a variety malignant tumors in human cells, including breast, colorectal, and DLBCL. It may also contribute to tumorigenesis by increasing PI3K/AKT signaling. Further research is needed in order to confirm this. We do know a lot more about how this protein works.
KIF2A could be used in clinical applications to treat brain malformations including lissencephaly. It is possible to detect mutations in KIF2A through targeted clinical diagnostic NextGen sequencing panels, designed to identify brain malformations and abnormalities of cortical development. The NINDS K12 NS049453 grant, and the R01 GM097376 grant by the NIH were supported by the authors.
Molecular studies show that the overexpression of mutant KIF2A results is monopolar spindles formation in human cancer cell cells. This mutant also causes cell block in Xenopus embryos and demonstrates KIF2A's crucial role in neuronal growth and assembly. Moreover, Kif2a depletion leads to neuronal migration delay. Studies have also shown KIF2A is necessary for neuronal fecundity in nonmitotic tissues. Further, Kif2A is established as a plus-end-directed microtubule-dependent motor that regulates the dynamics of microtubules during axonal growth.
In vitro studies show that knockdown KIF2A reduces the proliferation rate of ESCC cells. In vitro studies have also shown that knockdown KIF2A can inhibit the growth and proliferation of ESCC cells. Knockdown of KIF2A leads to significant decreases in Ki67 and PCNA expression. This results in a positive correlation between ESCC and KIF2A.
The KIF2A gene is involved in regulating cell growth, differentiation, and apoptosis. It is associated with poor prognosis for patients with ESCC. KIF2A is also known to inhibit apoptosis from tumor cells. KIF2A could be a biomarker for BLBC. It is in fact the most frequently used gene for cancer research.
Axons that had a KIF2A-related gene mutation were observed to be overextended by a mouse model. KIF2a/ mice had abnormal axonal branching. They also displayed overextensions of collateral branches in vitro. KIF2A mice also showed decreased microtubule polymerizing activity in growth conves. This indicates that KIF2A regulates microtubule dynamics near the growth cone edge.
KIF2A expression was identified by a marker AAV-shRNA. Molecular analyses were performed using this marker. The antibody was used to perform immunoprecipitation as well as Western blot, Immunocytochemistry and Immunofluorescence. The concentration of the antibody used for Western blots was between 10 and 15 uL using Lipofectamine 2000 transfection medium. The KIF2A protein was detected in the CaEs-17 cell and EC109 cell lines.
PMID: 9177777 by Debernardi S., et al. Identification of a novel human kinesin-related gene (HK2) by the cDNA differential display technique.
PMID: 15843429 by Zhu C., et al. Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference.