KNL1

KNL1

<div class="infobox infobox-gene">
<span class="infobox-title">KNL1</span>
<table>
<tr><th>Full Name</th><td>Kinetochore Scaffold 1 (Spc105)</td></tr>
<tr><th>Chromosomal Location</th><td>2p24.2</td></tr>
<tr><th>NCBI Gene ID</th><td>83707</td></tr>
<tr><th>OMIM</th><td>612186</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000137812</td></tr>
<tr><th>UniProt ID</th><td>Q8NG66</td></tr>
<tr><th>Protein</th><td>KNL1 protein (Spc105)</td></tr>
<tr><th>Associated Diseases</th><td>Cancer (multiple types), Mosaic Variegated Aneuploidy syndrome</td></tr>
</table>
</div>

Overview

KNL1

<div class="infobox infobox-gene">
<span class="infobox-title">KNL1</span>
<table>
<tr><th>Full Name</th><td>Kinetochore Scaffold 1 (Spc105)</td></tr>
<tr><th>Chromosomal Location</th><td>2p24.2</td></tr>
<tr><th>NCBI Gene ID</th><td>83707</td></tr>
<tr><th>OMIM</th><td>612186</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000137812</td></tr>
<tr><th>UniProt ID</th><td>Q8NG66</td></tr>
<tr><th>Protein</th><td>KNL1 protein (Spc105)</td></tr>
<tr><th>Associated Diseases</th><td>Cancer (multiple types), Mosaic Variegated Aneuploidy syndrome</td></tr>
</table>
</div>

Overview

BUB1 is a human gene whose product kNL1 (also known as Spc105 in yeast) is a fundamental kinetochore scaffold protein that links microtubules to centromeric chromatin and activates the spindle assembly checkpoint["@cheeseman2006"]. It serves as a platform for multiple signaling pathways essential for accurate chromosome segregation. Variants in BUB1 have been implicated in Cancer, Neurodegeneration. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

KNL1 (also known as Spc105 in yeast) is a fundamental kinetochore scaffold protein that links microtubules to centromeric chromatin and activates the spindle assembly checkpoint[@cheeseman2006]. It serves as a platform for multiple signaling pathways essential for accurate chromosome segregation.

Key Molecular Functions

• Microtubule attachment: KNL1 recruits the NDC80 and MIS12 complexes to form a functional kinetochore[@deluca2006]
• Spindle checkpoint activation: BUB1 and BUBR1 phosphorylate KNL1 to generate checkpoint signals[@london2012]
• Chromatin binding: Direct interaction with CENP-A nucleosomes at centromeres[@nishino2013]
• Spindly recruitment: Recruits the dynein/dynactin complex for checkpoint silencing[@barisic2014]

• N-terminal MELT motifs (BUB1/BUBR1 phosphorylation sites)[@yamagishi2012]
• C-terminal coiled-coil domains (protein interactions)
• Spindly and RZZ motifs (dynein recruitment)

Disease Associations

Cancer

• Multiple cancers: KNL1 overexpression in aggressive tumors[@singh2014]
• Chromosomal instability: KNL1 dysfunction leads to aneuploidy[@holland2014]
• Therapeutic target: Potential for anti-mitotic therapy[@bakhoum2009]

Neurodegeneration

• Alzheimer's disease: Kinetochore dysfunction contributes to neuronal aneuploidy[@yang2001]
• Aging: Age-related decline in kinetochore function[@baker2014]

Expression

KNL1 is expressed in proliferating cells:

• High expression: Bone marrow, testis, embryonic tissues
• Cell cycle-regulated: Peak in G2/M phase[@obrien2015]
• Low in non-dividing cells

• Neural progenitor cells
• Low in mature [neurons](/entities/neurons)

Therapeutic Implications

• Anti-mitotic therapy: Targeting KNL1 pathway[@khodjakov2004]
• Biomarker: Expression as prognostic indicator[@zhang2015]
• Combination therapy: With microtubule-targeting agents[@dumont2015]

See Also

• [BUB1](/genes/bub1) - Kinase that phosphorylates KNL1
• [BUBR1](/genes/bub1b) - Checkpoint partner
• [NDC80 Complex](/entities/kinetochore) - Kinetochore structure
• [Spindle Assembly](/mechanisms/mitosis) - Pathway

External Links

• [NCBI Gene: KNL1](https://www.ncbi.nlm.nih.gov/gene/83707)
• [UniProt: Q8NG66](https://www.uniprot.org/uniprot/Q8NG66)
• [OMIM: 612186](https://www.omim.org/entry/612186)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving KNL1 discovered through SciDEX knowledge graph analysis: