Anticorpi Shugoshin

Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity. Involved in centromeric enrichment of AUKRB in prometaphase.

The protein encoded by this gene is a member of the shugoshin family of proteins. This protein is thought to protect centromeric cohesin from cleavage during mitotic prophase by preventing phosphorylation of a cohesin subunit. Reduced expression of this gene leads to the premature loss of centromeric cohesion, mis-segregation of sister chromatids, and mitotic arrest. Evidence suggests that this protein also protects a small subset of cohesin found along the length of the chromosome arms during mitotic prophase. An isoform lacking exon 6 has been shown to play a role in the cohesion of centrioles (PMID: 16582621 and PMID:18331714). Mutations in this gene have been associated with Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome, characterized by the co-occurrence of Sick Sinus Syndrome (SSS) and Chronic Intestinal Pseudo-obstruction (CIPO) within the first four decades of life (PMID:25282101). Fibroblast cells from CAID patients exhibited both increased cell proliferation and higher rates of senescence. Pseudogenes of this gene have been found on chromosomes 1 and 7. Alternative splicing results in multiple transcript variants.

Widely expressed. Highly expressed in testis. Expressed in lung, small intestine, breast, liver and placenta. Strongly overexpressed in 90% of breast cancers tested.

Chronic atrial and intestinal dysrhythmia: A disease characterized by dysregulation of the cardiac sinus node resulting in sick sinus syndrome, in association with chronic intestinal pseudo-obstruction, a disorder of gastrointestinal motility in which intestinal obstruction occurs in the absence of a mechanical obstacle.

Belongs to the shugoshin family.

Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.

Nucleus. Chromosome > Centromere. Chromosome > Centromere > Kinetochore. Cytoplasm > Cytoskeleton > Spindle pole. Cytoplasm > Cytoskeleton > Microtubule organizing center > Centrosome.

Localizes to the inner centromere throughout prophase until metaphase and disappears at anaphase (PubMed:16541025). Centromeric localization requires the presence of BUB1 and the interaction with PPP2R1A (PubMed:16580887)(PubMed:16541025)(PubMed:15604152). Colocalizes with NEK2 at the kinetochore (PubMed:17621308). Colocalizes with and SS18L1 at the kinetochore (PubMed:16582621). Phosphorylation by AUKRB and the presence of BUB1 are required for localization to the kinetochore (PubMed:17617734). Isoform 1 primarily localizes to kinetochores during G2 phase and mitotic prophase, metaphase, and anaphase and does not appear to be associated with kinetochores during late mitosis (PubMed:16582621). Isoform 3 is found at the centrosome in interphase and at spindle poles in mitosis and its spindle pole localization is PLK1 dependent (PubMed:16582621). Isoform 3 does not localize to kinetochores during any stages of the cell cycle (PubMed:16582621).