KNL1

KNL1 (kinetochore scaffold 1, aka CASC5) is a protein that is encoded by the KNL1 gene in humans.{{cite web | title = Entrez Gene: CASC5 cancer susceptibility candidate 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57082}}{{cite journal | vauthors = Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R | title = AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14) | journal = Oncogene | volume = 19 | issue = 38 | pages = 4446–50 | date = September 2000 | pmid = 10980622 | doi = 10.1038/sj.onc.1203789 | s2cid = 8540747 | doi-access = }}{{cite journal | vauthors = Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N | title = Chromosomal assignment of a novel human gene D40 | journal = Nucleic Acids Symposium Series | issue = 42 | pages = 71–2 | date = Jun 2000 | volume = 42 | doi = 10.1093/nass/42.1.71 | pmid = 10780384 | doi-access = free }}{{cite journal | vauthors = Cheeseman IM, Hori T, Fukagawa T, Desai A | title = KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates | journal = Molecular Biology of the Cell | volume = 19 | issue = 2 | pages = 587–94 | date = February 2008 | pmid = 18045986 | pmc = 2230600 | doi = 10.1091/mbc.E07-10-1051 }}

Function

KNL1 is part of the outer kinetochore. It is a part of KMN network of proteins together with MIS12, and NDC80.{{cite journal | vauthors = D'Archivio S, Wickstead B | title = Trypanosome outer kinetochore proteins suggest conservation of chromosome segregation machinery across eukaryotes | journal = The Journal of Cell Biology | volume = 216 | issue = 2 | pages = 379–391 | date = February 2017 | pmid = 28034897 | pmc = 5294786 | doi = 10.1083/jcb.201608043 }}

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.{{cite journal | vauthors = 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 | title = Kinetochore KMN network gene CASC5 mutated in primary microcephaly | journal = Human Molecular Genetics | volume = 21 | issue = 24 | pages = 5306–17 | date = December 2012 | pmid = 22983954 | doi = 10.1093/hmg/dds386 | doi-access = free }}

Interactions

CASC5 has been shown to interact with MIS12,{{cite journal | vauthors = Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR, Oegema K, Desai A | title = A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension | journal = Genes & Development | volume = 18 | issue = 18 | pages = 2255–68 | date = September 2004 | pmid = 15371340 | pmc = 517519 | doi = 10.1101/gad.1234104 }}{{cite journal | vauthors = Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M | title = A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1 | journal = Nature Cell Biology | volume = 6 | issue = 11 | pages = 1135–41 | date = November 2004 | pmid = 15502821 | doi = 10.1038/ncb1187 | s2cid = 39408000 }} BUB1, BUBR1 and ZWINT-1.

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.

References

External links

{{UCSC gene info|CASC5}}

{{cite journal | vauthors = Ray ME, Su YA, Meltzer PS, Trent JM | title = Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma | journal = Oncogene | volume = 12 | issue = 12 | pages = 2527–33 | date = June 1996 | pmid = 8700511 }}
{{cite journal | vauthors = Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O | title = 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 | journal = DNA Research | volume = 7 | issue = 4 | pages = 273–81 | date = August 2000 | pmid = 10997877 | doi = 10.1093/dnares/7.4.271 | doi-access = free }}
{{cite journal | vauthors = 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 | title = Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers | journal = British Journal of Cancer | volume = 86 | issue = 11 | pages = 1757–62 | date = June 2002 | pmid = 12087463 | pmc = 2375411 | doi = 10.1038/sj.bjc.6600328 }}
{{cite journal | vauthors = Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD | title = A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15 | journal = Oncogene | volume = 22 | issue = 9 | pages = 1400–10 | date = March 2003 | pmid = 12618766 | doi = 10.1038/sj.onc.1206273 | doi-access = free | hdl = 10171/19622 | hdl-access = free }}
{{cite journal | vauthors = Kuefer MU, Chinwalla V, Zeleznik-Le NJ, Behm FG, Naeve CW, Rakestraw KM, Mukatira ST, Raimondi SC, Morris SW | title = Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14) | journal = Oncogene | volume = 22 | issue = 9 | pages = 1418–24 | date = March 2003 | pmid = 12618768 | doi = 10.1038/sj.onc.1206272 | doi-access = free }}
{{cite journal | vauthors = Cheeseman IM, Niessen S, Anderson S, Hyndman F, Yates JR, Oegema K, Desai A | title = A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension | journal = Genes & Development | volume = 18 | issue = 18 | pages = 2255–68 | date = September 2004 | pmid = 15371340 | pmc = 517519 | doi = 10.1101/gad.1234104 }}
{{cite journal | vauthors = Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M | title = A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1 | journal = Nature Cell Biology | volume = 6 | issue = 11 | pages = 1135–41 | date = November 2004 | pmid = 15502821 | doi = 10.1038/ncb1187 | s2cid = 39408000 }}
{{cite journal | vauthors = Sasao T, Itoh N, Takano H, Watanabe S, Wei G, Tsukamoto T, Kuzumaki N, Takimoto M | title = The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa | journal = Reproduction | volume = 128 | issue = 6 | pages = 709–16 | date = December 2004 | pmid = 15579588 | doi = 10.1530/rep.1.00312 | doi-access = free }}
{{cite journal | vauthors = Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R | title = Phosphoproteome analysis of the human mitotic spindle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 14 | pages = 5391–6 | date = April 2006 | pmid = 16565220 | pmc = 1459365 | doi = 10.1073/pnas.0507066103 | bibcode = 2006PNAS..103.5391N | doi-access = free }}
{{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | doi-access = free }}