UniProt functional annotation for O60216



	UniProt functional annotation for O60216

UniProt code: O60216.

Organism: Homo sapiens (Human).

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

Function: [Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions (PubMed:11509732). The cohesin complex may also play a role in spindle pole assembly during mitosis (PubMed:11590136). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter (PubMed:25575569). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity). {ECO:0000250|UniProtKB:Q61550, ECO:0000250|UniProtKB:Q6TEL1, ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:25575569, ECO:0000305|PubMed:25575569}.

Function: [64-kDa C-terminal product]: May promote apoptosis. {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.

Subunit: Component of the cohesin complex, which consists of an SMC1A/B and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3 (PubMed:10931856, PubMed:11590136, PubMed:22628566, PubMed:25575569). The cohesin complex interacts with NUMA1 (PubMed:11590136). The cohesin complex also interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate the ability of the cohesin complex to mediate sister chromatid cohesion (PubMed:15837422). The interaction with PDS5B is direct and is stimulated by STAG1/SA1 (PubMed:19696148). The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4 (PubMed:22628566). The cohesin complex interacts with DDX11/ChIR1 (PubMed:17105772). Directly interacts with WAPL; this interaction is stimulated by STAG1/SA1 (PubMed:19696148). {ECO:0000269|PubMed:10931856, ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:15837422, ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:25575569}.

Subcellular location: [Double-strand-break repair protein rad21 homolog]: Nucleus {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:12417729}. Nucleus matrix {ECO:0000269|PubMed:10623634, ECO:0000269|PubMed:11590136}. Chromosome {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11590136}. Chromosome, centromere {ECO:0000269|PubMed:11073952}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11590136}. Note=Associates with chromatin (PubMed:11590136, PubMed:11073952). Before prophase, scattered along chromosome arms (PubMed:11073952). During prophase and prometaphase, most cohesins dissociate from the arms of condensing chromosome, possibly through PLK1-mediated phosphorylation (PubMed:11931760). A small amount of cohesin remains in centromeric regions and is removed from chromosomes only at the onset of anaphase. At anaphase, cleavage by separase/ESPL1 leads to the dissociation of cohesin from chromosomes and chromosome separation (PubMed:11073952, PubMed:11509732). {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:11931760}.

Subcellular location: [64-kDa C-terminal product]: Cytoplasm, cytosol {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}. Nucleus {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.

Tissue specificity: Expressed in the gut (at protein level). {ECO:0000269|PubMed:25575569}.

Developmental stage: Regulated in a cell cycle-dependent manner: expression increases in late S phase and reaches maximum in G2 at the nucleotide level (PubMed:8812457). Not regulated during the cell cycle (at protein level) (PubMed:11073952). {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:8812457}.

Domain: The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3. {ECO:0000250}.

Ptm: Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis (PubMed:11509732). Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the beginning of apoptosis (PubMed:12417729, PubMed:11875078). {ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.

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 PLK1. {ECO:0000269|PubMed:11073952}.

Disease: Cornelia de Lange syndrome 4 with or without midline brain defects (CDLS4) [MIM:614701]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22633399, ECO:0000269|PubMed:31334757}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Mungan syndrome (MGS) [MIM:611376]: An autosomal recessive disease characterized by visceral neuromyopathy, intestinal dysmotility and chronic intestinal pseudoobstruction, megaduodenum, long-segment Barrett esophagus, and a variety of cardiac valve or septal defects such as membranous ventricular septal defect, pulmonary and tricuspid valve regurgitation. {ECO:0000269|PubMed:25575569}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the rad21 family. {ECO:0000305}.

Sequence caution: Sequence=BAA07554.2; Type=Erroneous initiation; Note=Extended 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:		[Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions (PubMed:11509732). The cohesin complex may also play a role in spindle pole assembly during mitosis (PubMed:11590136). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter (PubMed:25575569). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity). {ECO:0000250\|UniProtKB:Q61550, ECO:0000250\|UniProtKB:Q6TEL1, ECO:0000269\|PubMed:11509732, ECO:0000269\|PubMed:11590136, ECO:0000269\|PubMed:25575569, ECO:0000305\|PubMed:25575569}.



Function:		[64-kDa C-terminal product]: May promote apoptosis. {ECO:0000269\|PubMed:11875078, ECO:0000269\|PubMed:12417729}.


Subunit:		Component of the cohesin complex, which consists of an SMC1A/B and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3 (PubMed:10931856, PubMed:11590136, PubMed:22628566, PubMed:25575569). The cohesin complex interacts with NUMA1 (PubMed:11590136). The cohesin complex also interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate the ability of the cohesin complex to mediate sister chromatid cohesion (PubMed:15837422). The interaction with PDS5B is direct and is stimulated by STAG1/SA1 (PubMed:19696148). The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4 (PubMed:22628566). The cohesin complex interacts with DDX11/ChIR1 (PubMed:17105772). Directly interacts with WAPL; this interaction is stimulated by STAG1/SA1 (PubMed:19696148). {ECO:0000269\|PubMed:10931856, ECO:0000269\|PubMed:11590136, ECO:0000269\|PubMed:15837422, ECO:0000269\|PubMed:17105772, ECO:0000269\|PubMed:19696148, ECO:0000269\|PubMed:22628566, ECO:0000269\|PubMed:25575569}.
Subcellular location:		[Double-strand-break repair protein rad21 homolog]: Nucleus {ECO:0000269\|PubMed:11073952, ECO:0000269\|PubMed:11509732, ECO:0000269\|PubMed:12417729}. Nucleus matrix {ECO:0000269\|PubMed:10623634, ECO:0000269\|PubMed:11590136}. Chromosome {ECO:0000269\|PubMed:11073952, ECO:0000269\|PubMed:11590136}. Chromosome, centromere {ECO:0000269\|PubMed:11073952}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:11073952, ECO:0000269\|PubMed:11590136}. Note=Associates with chromatin (PubMed:11590136, PubMed:11073952). Before prophase, scattered along chromosome arms (PubMed:11073952). During prophase and prometaphase, most cohesins dissociate from the arms of condensing chromosome, possibly through PLK1-mediated phosphorylation (PubMed:11931760). A small amount of cohesin remains in centromeric regions and is removed from chromosomes only at the onset of anaphase. At anaphase, cleavage by separase/ESPL1 leads to the dissociation of cohesin from chromosomes and chromosome separation (PubMed:11073952, PubMed:11509732). {ECO:0000269\|PubMed:11073952, ECO:0000269\|PubMed:11509732, ECO:0000269\|PubMed:11590136, ECO:0000269\|PubMed:11931760}.
Subcellular location:		[64-kDa C-terminal product]: Cytoplasm, cytosol {ECO:0000269\|PubMed:11875078, ECO:0000269\|PubMed:12417729}. Nucleus {ECO:0000269\|PubMed:11875078, ECO:0000269\|PubMed:12417729}.
Tissue specificity:		Expressed in the gut (at protein level). {ECO:0000269\|PubMed:25575569}.
Developmental stage:		Regulated in a cell cycle-dependent manner: expression increases in late S phase and reaches maximum in G2 at the nucleotide level (PubMed:8812457). Not regulated during the cell cycle (at protein level) (PubMed:11073952). {ECO:0000269\|PubMed:11073952, ECO:0000269\|PubMed:8812457}.
Domain:		The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3. {ECO:0000250}.
Ptm:		Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis (PubMed:11509732). Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the beginning of apoptosis (PubMed:12417729, PubMed:11875078). {ECO:0000269\|PubMed:11509732, ECO:0000269\|PubMed:11875078, ECO:0000269\|PubMed:12417729}.
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 PLK1. {ECO:0000269\|PubMed:11073952}.
Disease:		Cornelia de Lange syndrome 4 with or without midline brain defects (CDLS4) [MIM:614701]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269\|PubMed:22633399, ECO:0000269\|PubMed:31334757}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Mungan syndrome (MGS) [MIM:611376]: An autosomal recessive disease characterized by visceral neuromyopathy, intestinal dysmotility and chronic intestinal pseudoobstruction, megaduodenum, long-segment Barrett esophagus, and a variety of cardiac valve or septal defects such as membranous ventricular septal defect, pulmonary and tricuspid valve regurgitation. {ECO:0000269\|PubMed:25575569}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the rad21 family. {ECO:0000305}.
Sequence caution:		Sequence=BAA07554.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};