KNL1

KNL1
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Last updated December 02, 2023

KNL1 (kinetochore scaffold 1, aka CASC5) is a protein that is encoded by the KNL1 gene in humans.^[1]^[2]^[3]^[4]

Function

KNL1 is part of the outer kinetochore. It is a part of KMN network of proteins together with MIS12, and NDC80.^[5]

KNL1 is involved in microtubule attachment to chromosome centromeres and in the activation of the spindle checkpoint during mitosis. The CASC5 gene is upregulated in the areas of cell proliferation surrounding the ventricles during fetal brain development.^[6]

Interactions

CASC5 has been shown to interact with MIS12,^[7]^[8] BUB1, BUBR1 and ZWINT-1.^[6]

Polymorphisms

Homozygous polymorphisms in the CASC5 gene have been seen in patients with autosomal recessive primary microcephaly (MCPH). The mutation resulted in the skipping of exon 18 transcription, causing a frameshift and the production of a truncated protein. This truncation inhibits the binding ability of MIS12.^[6]

Related Research Articles

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.

Kinetochore protein NDC80 homolog is a protein that in humans is encoded by the NDC80 gene.

Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.

Centromere protein C 1 is a protein that in humans is encoded by the CENPC1 gene.

Kinetochore protein Nuf2 is a protein that in humans is encoded by the NUF2 gene.

Polyamine-modulated factor 1 is a protein that in humans is encoded by the PMF1 gene.

Centromere protein U is a protein that in humans is encoded by the CENPU gene.

Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase.

ZW10 interactor (Zwint-1) is a protein that in humans is encoded by the ZWINT gene.

Protein AF-9 is a protein that in humans is encoded by the MLLT3 gene.

Centromere protein H is a protein that in humans is encoded by the CENPH gene. It is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation.

Centromere protein I is a protein that in humans is encoded by the CENPI gene.

Protein ENL is a protein that in humans is encoded by the MLLT1 gene.

Kinetochore-associated protein NSL1 homolog is a protein that in humans is encoded by the NSL1 gene.

Protein MIS12 homolog is a protein that in humans is encoded by the MIS12 gene.

DSN1, MIND kinetochore complex component, homolog , also known as DSN1 or MIS13, is a protein which in humans encoded by the DSN1 gene.

Zinc finger FYVE domain-containing protein 19 is a protein that in humans is encoded by the ZFYVE19 gene.

Iain Cheeseman investigates the role of the kinetochore, a group of proteins required for cell division and chromosome segregation. This core network of proteins facilitates the attachment of chromosomes to microtubule polymers—the spindle structures that attach to the ends of cells, pulling and dividing them during cell division. The kinetochore is critical to ensuring duplication without loss or damage to the genetic material. Cheeseman is also investigating the activities of the individual molecular machines that make up this structure and how these proteins are controlled and regulated.

References

↑ "Entrez Gene: CASC5 cancer susceptibility candidate 5".
↑ Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R (September 2000). "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)". Oncogene. 19 (38): 4446–50. doi:10.1038/sj.onc.1203789. PMID 10980622. S2CID 8540747.
↑ Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N (Jun 2000). "Chromosomal assignment of a novel human gene D40". Nucleic Acids Symposium Series. 42 (42): 71–2. doi: 10.1093/nass/42.1.71 . PMID 10780384.
↑ Cheeseman IM, Hori T, Fukagawa T, Desai A (February 2008). "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates". Molecular Biology of the Cell. 19 (2): 587–94. doi:10.1091/mbc.E07-10-1051. PMC 2230600 . PMID 18045986.
↑ D'Archivio S, Wickstead B (February 2017). "Trypanosome outer kinetochore proteins suggest conservation of chromosome segregation machinery across eukaryotes". The Journal of Cell Biology. 216 (2): 379–391. doi:10.1083/jcb.201608043. PMC 5294786 . PMID 28034897.
1 2 3 Genin A, Desir J, Lambert N, Biervliet M, Van Der Aa N, Pierquin G, Killian A, Tosi M, Urbina M, Lefort A, Libert F, Pirson I, Abramowicz M (December 2012). "Kinetochore KMN network gene CASC5 mutated in primary microcephaly". Human Molecular Genetics. 21 (24): 5306–17. doi: 10.1093/hmg/dds386 . PMID 22983954.
↑ Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR, Oegema K, Desai A (September 2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes & Development. 18 (18): 2255–68. doi:10.1101/gad.1234104. PMC 517519 . PMID 15371340.
↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (November 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821. S2CID 39408000.

External links

Human CASC5 genome location and CASC5 gene details page in the UCSC Genome Browser .

Ray ME, Su YA, Meltzer PS, Trent JM (June 1996). "Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma". Oncogene. 12 (12): 2527–33. PMID 8700511.
Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O (August 2000). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (4): 273–81. doi: 10.1093/dnares/7.4.271 . PMID 10997877.
Takimoto M, Wei G, Dosaka-Akita H, Mao P, Kondo S, Sakuragi N, Chiba I, Miura T, Itoh N, Sasao T, Koya RC, Tsukamoto T, Fujimoto S, Katoh H, Kuzumaki N (June 2002). "Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers". British Journal of Cancer. 86 (11): 1757–62. doi:10.1038/sj.bjc.6600328. PMC 2375411 . PMID 12087463.
Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD (March 2003). "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15". Oncogene. 22 (9): 1400–10. doi: 10.1038/sj.onc.1206273 . hdl: 10171/19622 . PMID 12618766.
Kuefer MU, Chinwalla V, Zeleznik-Le NJ, Behm FG, Naeve CW, Rakestraw KM, Mukatira ST, Raimondi SC, Morris SW (March 2003). "Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14)". Oncogene. 22 (9): 1418–24. doi: 10.1038/sj.onc.1206272 . PMID 12618768.
Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR, Oegema K, Desai A (September 2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes & Development. 18 (18): 2255–68. doi:10.1101/gad.1234104. PMC 517519 . PMID 15371340.
Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (November 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821. S2CID 39408000.
Sasao T, Itoh N, Takano H, Watanabe S, Wei G, Tsukamoto T, Kuzumaki N, Takimoto M (December 2004). "The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa". Reproduction. 128 (6): 709–16. doi: 10.1530/rep.1.00312 . PMID 15579588.
Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–6. Bibcode:2006PNAS..103.5391N. doi: 10.1073/pnas.0507066103 . PMC 1459365 . PMID 16565220.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi: 10.1016/j.cell.2006.09.026 . PMID 17081983.

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[entrez-1] "Entrez Gene: CASC5 cancer susceptibility candidate 5".

[pmid10980622-2] Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R (September 2000). "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)". Oncogene. 19 (38): 4446–50. doi:10.1038/sj.onc.1203789. PMID 10980622. S2CID 8540747.

[pmid10780384-3] Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N (Jun 2000). "Chromosomal assignment of a novel human gene D40". Nucleic Acids Symposium Series. 42 (42): 71–2. doi: 10.1093/nass/42.1.71 . PMID 10780384.

[pmid18045986-4] Cheeseman IM, Hori T, Fukagawa T, Desai A (February 2008). "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates". Molecular Biology of the Cell. 19 (2): 587–94. doi:10.1091/mbc.E07-10-1051. PMC 2230600 . PMID 18045986.

[5] D'Archivio S, Wickstead B (February 2017). "Trypanosome outer kinetochore proteins suggest conservation of chromosome segregation machinery across eukaryotes". The Journal of Cell Biology. 216 (2): 379–391. doi:10.1083/jcb.201608043. PMC 5294786 . PMID 28034897.

[Genin_2012-6] 1 2 3 Genin A, Desir J, Lambert N, Biervliet M, Van Der Aa N, Pierquin G, Killian A, Tosi M, Urbina M, Lefort A, Libert F, Pirson I, Abramowicz M (December 2012). "Kinetochore KMN network gene CASC5 mutated in primary microcephaly". Human Molecular Genetics. 21 (24): 5306–17. doi: 10.1093/hmg/dds386 . PMID 22983954.

[pmid15371340-7] Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR, Oegema K, Desai A (September 2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes & Development. 18 (18): 2255–68. doi:10.1101/gad.1234104. PMC 517519 . PMID 15371340.

[pmid15502821-8] Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (November 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821. S2CID 39408000.

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