KNSTRN
Domain
The coiled coil regions mediate binding to kinetochores.
Function
Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase (PubMed:19667759). Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:19667759, PubMed:22110139). The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule-kinetochore attachments (PubMed:21402792). Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division (PubMed:23035123). May be involved in UV-induced apoptosis via its interaction with PRPF19; however, these results need additional evidences (PubMed:24718257).
Involvement in disease
Roifman-Chitayat syndrome
ROCHIS
An autosomal recessive digenic disorder characterized by global developmental delay, variable neurologic features such as seizures and ataxia, optic atrophy, dysmorphic facial features, distal skeletal anomalies, and recurrent invasive infections due to combined immunodeficiency.
None
The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Caused by the simultaneous occurrence of homozygous mutations in PIK3CD and KNSTRN.
Cutaneous squamous cell carcinomas (SCC): A malignancy of the skin. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Disease susceptibility is associated with variants affecting the gene represented in this entry. Variant Phe-24 appears specific for UV-associated malignancies (PubMed:25194279).
Tissue Specificity
Widely expressed, including in skin.
Cellular localization
- Nucleus
- Chromosome
- Centromere
- Kinetochore
- Cytoplasm
- Cytoskeleton
- Spindle pole
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Colocalizes with microtubules around centrosomes in prophase and with the mitotic spindle at prometaphase and metaphase. From late prometaphase to anaphase, is highly concentrated on kinetochores. Located at the kinetochore-microtubule interface. The astrin (SPAG5)-kinastrin (SKAP) complex localizes to the microtubule plus ends (PubMed:23035123).
Alternative names
C15orf23, SKAP, TRAF4AF1, HSD11, KNSTRN, Small kinetochore-associated protein, Kinetochore-localized astrin-binding protein, Kinetochore-localized astrin/SPAG5-binding protein, TRAF4-associated factor 1, Kinastrin