Domain:The C-terminal part associates with the head of SMC1A , while the N-terminal part binds to the head of SMC3. ,Function:Cleavable component of the cohesin complex , involved in chromosome cohesion during cell cycle , in DNA repair , and in apoptosis. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At metaphase-anaphase transition , this protein is cleaved by separase/ESPL1 and dissociates from chromatin , allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Also plays a role in apoptosis , via its cleavage by caspase-3/CASP3 or caspase-7/CASP7 during early steps of apoptosis: the C-terminal 64 kDa cleavage product may act as a nuclear signal to initiate cytoplasmic events involved in the apoptotic pathway. ,polymorphism:Some radiosensitive cancer patients seem to have Arg-481 instead of the conserved Gly-481. It may be that this mutation could contribute to radiosensitivity. ,PTM:Cleaved by separase/ESPL1 at the onset of anaphase. Cleaved by caspase-3 and caspase-7 at the beginning of apoptosis. The cleavage by ESPL1 and caspase-3 take place at different sites. ,PTM:Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK. ,similarity:Belongs to the rad21 family. ,subcellular location:Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase , most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK , except at centromeres , where cohesin complexes remain. At anaphase , it is cleaved by separase/ESPL1 , leading to the dissociation of the complex from chromosomes , allowing chromosome separation. Once cleaved by caspase-3 , the C-terminal 64 kDa cleavage product translocates to the cytoplasm , where it may trigger apoptosis. ,subunit:Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain , RAD21 which link them , and one STAG protein (STAG1 , STAG2 or STAG3) , which interacts with RAD21. Found in a complex with SMC1A , SMC3 , CDCA5 , PDS5A/APRIN and PDS5B/SCC-112. ,
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