Description: Homo sapiens RAD21 homolog (S. pombe) (RAD21), mRNA. RefSeq Summary (NM_006265): The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr8:117,858,173-117,887,105 Size: 28,933 Total Exon Count: 14 Strand: - Coding Region Position: hg19 chr8:117,859,739-117,878,968 Size: 19,230 Coding Exon Count: 13
ID:RAD21_HUMAN DESCRIPTION: RecName: Full=Double-strand-break repair protein rad21 homolog; Short=hHR21; AltName: Full=Nuclear matrix protein 1; Short=NXP-1; AltName: Full=SCC1 homolog; 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. 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. Interacts with PDS5B and WAPAL; the interaction is direct. INTERACTION: Q29RF7:PDS5A; NbExp=3; IntAct=EBI-80739, EBI-1175454; Q9NTI5:PDS5B; NbExp=3; IntAct=EBI-80739, EBI-1175604; Q9UQE7:SMC3; NbExp=8; IntAct=EBI-80739, EBI-80718; Q7Z5K2:WAPAL; NbExp=11; IntAct=EBI-80739, EBI-1022242; SUBCELLULAR LOCATION: Nucleus. Chromosome. Chromosome, centromere. Note=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. DOMAIN: The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3 (By similarity). 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. 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. DISEASE: Defects in RAD21 are the cause of Cornelia de Lange syndrome type 4 (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. SIMILARITY: Belongs to the rad21 family. SEQUENCE CAUTION: Sequence=BAA07554.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rad21/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF04824 - Conserved region of Rad21 / Rec8 like protein PF04825 - N terminus of Rad21 / Rec8 like protein
ModBase Predicted Comparative 3D Structure on O60216
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0005515 protein binding GO:0044877 macromolecular complex binding
Biological Process: GO:0006281 DNA repair GO:0006302 double-strand break repair GO:0006310 DNA recombination GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006915 apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0007049 cell cycle GO:0007059 chromosome segregation GO:0007131 reciprocal meiotic recombination GO:0010972 negative regulation of G2/M transition of mitotic cell cycle GO:0045841 negative regulation of mitotic metaphase/anaphase transition GO:0045876 positive regulation of sister chromatid cohesion GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051301 cell division GO:0071168 protein localization to chromatin
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