UniProt functional annotation for Q5FBB7



	UniProt functional annotation for Q5FBB7

UniProt code: Q5FBB7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:15737064, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}.

Subunit: Interacts with PPP2CA (or PPP2CB), PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E, SET, LRRC59, RBM10 (or RBM5), RPL10A, RPL28, RPL7, RPL7A and RPLP1. Interaction with protein phosphatase 2A occurs most probably through direct binding to the regulatory B56 subunits: PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E. Interacts with PPP2R1A and NEK2. Isoform 3 interacts with PLK1. Interacts with CDCA8. {ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}.

Subcellular location: Nucleus {ECO:0000305|PubMed:16582621}. Chromosome, centromere {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:21346195}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:16582621, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:16582621, ECO:0000269|PubMed:18331714}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:18331714}. Note=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). {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:16582621, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308}.

Tissue specificity: Widely expressed. Highly expressed in testis. Expressed in lung, small intestine, breast, liver and placenta. Strongly overexpressed in 90% of breast cancers tested. {ECO:0000269|PubMed:12747765}.

Developmental stage: Appears in prophase cells and remains present until metaphase. Strongly decreases at the onset of anaphase and completely disappears at telophase. Not present in interphase cells (at protein level). {ECO:0000269|PubMed:15723797}.

Domain: The KEN box and D-box 3 are required for its ubiquitination and degradation. {ECO:0000269|PubMed:19015261}.

Ptm: Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1. {ECO:0000269|PubMed:19015261}.

Ptm: Phosphorylation by NEK2 is essential for chromosome congression in mitosis and for the proper attachment of spindle microtubule to the kinetochore. Phosphorylated by PLK1 and AUKRB. {ECO:0000269|PubMed:16582621, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308}.

Disease: Chronic atrial and intestinal dysrhythmia (CAID) [MIM:616201]: 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. {ECO:0000269|PubMed:25282101}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).

Similarity: Belongs to the shugoshin family. {ECO:0000305}.

Sequence caution: Sequence=AAH01339.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH32696.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000269\|PubMed:15604152, ECO:0000269\|PubMed:15723797, ECO:0000269\|PubMed:15737064, ECO:0000269\|PubMed:16580887, ECO:0000269\|PubMed:17617734, ECO:0000269\|PubMed:17621308, ECO:0000269\|PubMed:18331714, ECO:0000269\|PubMed:20739936}.


Subunit:		Interacts with PPP2CA (or PPP2CB), PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E, SET, LRRC59, RBM10 (or RBM5), RPL10A, RPL28, RPL7, RPL7A and RPLP1. Interaction with protein phosphatase 2A occurs most probably through direct binding to the regulatory B56 subunits: PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E. Interacts with PPP2R1A and NEK2. Isoform 3 interacts with PLK1. Interacts with CDCA8. {ECO:0000269\|PubMed:16541025, ECO:0000269\|PubMed:16580887, ECO:0000269\|PubMed:17621308, ECO:0000269\|PubMed:18331714, ECO:0000269\|PubMed:20739936}.
Subcellular location:		Nucleus {ECO:0000305\|PubMed:16582621}. Chromosome, centromere {ECO:0000269\|PubMed:15604152, ECO:0000269\|PubMed:15723797, ECO:0000269\|PubMed:16541025, ECO:0000269\|PubMed:16580887, ECO:0000269\|PubMed:21346195}. Chromosome, centromere, kinetochore {ECO:0000269\|PubMed:16582621, ECO:0000269\|PubMed:17617734, ECO:0000269\|PubMed:17621308}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:16582621, ECO:0000269\|PubMed:18331714}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:18331714}. Note=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). {ECO:0000269\|PubMed:15604152, ECO:0000269\|PubMed:16541025, ECO:0000269\|PubMed:16580887, ECO:0000269\|PubMed:16582621, ECO:0000269\|PubMed:17617734, ECO:0000269\|PubMed:17621308}.
Tissue specificity:		Widely expressed. Highly expressed in testis. Expressed in lung, small intestine, breast, liver and placenta. Strongly overexpressed in 90% of breast cancers tested. {ECO:0000269\|PubMed:12747765}.
Developmental stage:		Appears in prophase cells and remains present until metaphase. Strongly decreases at the onset of anaphase and completely disappears at telophase. Not present in interphase cells (at protein level). {ECO:0000269\|PubMed:15723797}.
Domain:		The KEN box and D-box 3 are required for its ubiquitination and degradation. {ECO:0000269\|PubMed:19015261}.
Ptm:		Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1. {ECO:0000269\|PubMed:19015261}.
Ptm:		Phosphorylation by NEK2 is essential for chromosome congression in mitosis and for the proper attachment of spindle microtubule to the kinetochore. Phosphorylated by PLK1 and AUKRB. {ECO:0000269\|PubMed:16582621, ECO:0000269\|PubMed:17617734, ECO:0000269\|PubMed:17621308}.
Disease:		Chronic atrial and intestinal dysrhythmia (CAID) [MIM:616201]: 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. {ECO:0000269\|PubMed:25282101}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).
Similarity:		Belongs to the shugoshin family. {ECO:0000305}.
Sequence caution:		Sequence=AAH01339.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH32696.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};