RAD21 (SCC1, hHR21, NXP-1) is the alpha-kleisin subunit of the human cohesin complex. Its N-terminal domain binds the ATPase head of SMC3 and its C-terminal winged-helix domain binds the ATPase head of SMC1A, so that RAD21 bridges the two SMC heads and closes the tripartite SMC1A-SMC3-RAD21 ring; its central region is the docking platform for the HEAT-repeat subunit STAG1 or STAG2 and, through STAG, for the regulators PDS5A/PDS5B, WAPL and the loader NIPBL-MAU2. RAD21 has no catalytic activity; ATP binding and hydrolysis are performed by the SMC heads. RAD21-containing cohesin is loaded onto chromatin by NIPBL-MAU2 in telophase/G1, is converted during DNA replication (ESCO1/2 acetylation of SMC3, sororin binding) into a stably bound, cohesive form, and topologically entraps the two sister chromatids so that they remain paired from S phase until anaphase, which is required for chromosome biorientation and accurate mitotic segregation. In prophase most arm cohesin is released without cleavage by the WAPL pathway, promoted by PLK1 phosphorylation of STAG2 and CDK1 phosphorylation of sororin, whereas centromeric cohesin is protected by SGO1-PP2A. At anaphase onset separase (ESPL1) cleaves RAD21 after Arg172 and Arg450, opening the ring and triggering sister chromatid separation; RAD21 cleavage is essential for anaphase and for completion of cytokinesis, and PLK1-dependent phosphorylation of RAD21 enhances its cleavability. The cleaved fragments are cleared from recycled cohesin after HDAC8 deacetylation of SMC3. In interphase, RAD21-containing cohesin also extrudes chromatin loops that are anchored at convergent CTCF sites, building topologically associating domains and enhancer-promoter contacts; through this it acts as a transcriptional insulator and regulator (for example at H19/IGF2 and MYC), and cohesin-STAG2 additionally mediates CTCF-independent enhancer-promoter contacts. Cohesin accumulates at DNA double-strand breaks, facilitates recombinational repair using the sister chromatid, is SUMOylated during repair, and is required for the DNA damage-induced intra-S and G2/M checkpoints. RAD21 is hyperphosphorylated in mitosis and is cleaved after Asp279 by caspase-3/-7 early in apoptosis, generating a 64-kDa C-terminal fragment that relocates to the cytoplasm and amplifies the death signal. It is nuclear throughout interphase, lies along chromosome arms and is enriched at centromeres of metaphase chromosomes, is recovered in nuclear-matrix fractions and, as soluble mitotic cohesin, has been reported at spindle poles in association with NuMA. Heterozygous loss-of-function RAD21 variants cause Cornelia de Lange syndrome type 4 and biallelic variants cause Mungan syndrome (visceral neuromyopathy); altered RAD21 dosage reshapes three-dimensional genome organisation and transcription in cancer.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000120 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. Reason: Centromeric localisation is directly demonstrated for human RAD21 by chromosome spreads and is the site of the SGO1-protected, separase-cleaved cohesin pool; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11073952 hRad21 at the metaphase centromeres appears to be present at the inner pairing domain where the two sister chromatids are supposed to be in intimate contact |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of PLK1 phosphorylation of centromeric cohesin. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of PP2A-B56 dephosphorylation of centromeric cohesin. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of separase cleavage of centromeric cohesin. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of separation of sister chromatids after RAD21 cleavage. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of CDK1 phosphorylation of sororin on centromeric cohesin. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-2473151 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of sororin-enabled cohesion of sister centromeres. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000775 chromosome, centromeric region | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: RAD21 remains at centromeres of metaphase chromosomes after most arm cohesin has been released by the prophase pathway, located at the inner pairing domain between sister chromatids; this centromeric pool is what separase cleaves at anaphase onset. This Reactome row places RAD21-containing cohesin at the centromere in the context of kinetochore assembly on centromeres carrying cohesin. Reason: Reactome's centromeric cohesin entity is consistent with direct localisation of human RAD21 to metaphase centromeres; core location. Supporting Evidence: PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes PMID:11509732 Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres |
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: RAD21-containing cohesin is loaded onto chromatin by NIPBL-MAU2, binds chromatin dynamically in G1 and is stabilised on chromatin by DNA replication; ChIP-seq maps RAD21 to CTCF sites, enhancers and promoters. Reason: Chromatin is the site of every RAD21 function (cohesion, loop extrusion, repair); the mouse-derived transfer is corroborated by human loading and ChIP data. Supporting Evidence: PMID:22628566 Replication of cohesin-loaded DNA, both in vitro and in vivo, markedly increased the stability of cohesin associated with DNA. PMID:19468298 Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of a boundary/insulator interacting protein |
| GO:0000794 condensed nuclear chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: Human RAD21 remains associated along the entire length of condensing prometaphase-like chromosomes and persists at centromeres of metaphase chromosomes. Reason: Direct chromosome-spread evidence places human RAD21 on condensed mitotic chromosomes, matching the mouse-derived inference. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cohesin released from chromosomes in mitosis was reported at spindle poles in association with NuMA, and cohesin depletion impaired aster assembly in vitro. This is a minor, proposed localisation of the soluble mitotic pool rather than where RAD21 performs its cohesion, looping or repair functions. Reason: The observation is published (immunolocalisation, NuMA co-IP) and mirrored in UniProt, but it is a single-study proposal that has not become part of the accepted picture of cohesin function; retained as non-core. Supporting Evidence: PMID:11590136 we found that cohesin localizes to the spindle poles during mitosis and interacts with NuMA PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Cohesin is recruited to cis-regulatory elements (CTCF sites, enhancers, promoters), but RAD21 has no DNA-binding domain that recognises a specific sequence: enrichment at specific sites depends on CTCF, and STAG2 mediates the CTCF-independent enhancer contacts. Occupancy in ChIP does not demonstrate sequence-specific binding by RAD21. Reason: The essence (cohesin associates with regulatory chromatin) is sound but the term overstates the mechanism; cohesin's DNA interaction is topological/non-sequence-specific and site selection is conferred by CTCF and other factors. Chromatin binding (GO:0003682, already an IBA) is the accurate molecular function. Proposed replacements: chromatin binding Supporting Evidence: PMID:18235444 CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. PMID:29867216 cohesin-SA2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer; a response-to-hypoxia phenotype (presumably an expression change or knockdown effect in a hypoxia model) is not a process that the cohesin kleisin executes. Reason: Over-propagated electronic inference from a rat phenotypic study: RAD21 has no role in sensing or responding to oxygen and any effect is an indirect consequence of altered chromatin organisation or proliferation. Not supported by human or mouse cohesin biology. |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places chromatin binding at the Scc1/Rad21 kleisin node (seeded by budding-yeast Mcd1/Scc1). Human RAD21-cohesin binds chromatin after NIPBL-dependent loading and is mapped genome-wide by ChIP. Reason: Sound phylogenetic inference, fully consistent with human loading, residence-time and ChIP-seq data; appropriate molecular function for a chromatin-bound structural subunit. Supporting Evidence: PMID:22628566 Replication of cohesin-loaded DNA, both in vitro and in vivo, markedly increased the stability of cohesin associated with DNA. PMID:17113138 Wapl depletion also increases the residence time of cohesin on chromatin in interphase. PMID:19468298 Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of a boundary/insulator interacting protein |
| GO:0005515 protein binding | IPI PMID:12672959 Processing, localization, and requirement of human separase ... | REMOVE | Summary: IPI with separase (ESPL1). RAD21 is the separase substrate: it is cleaved after Arg172 and Arg450 at anaphase onset, with docking motifs (LPE, NHLEYE) and phosphorylation near the C-terminal site tuning cleavage. Substrate binding is not a molecular function of RAD21; the informative activity is separase's endopeptidase activity with RAD21 as its input. Reason: Generic protein binding is uninformative and GO does not annotate a substrate for being bound by its protease. The biology is captured on the ESPL1 side (cysteine-type endopeptidase activity with RAD21 as input) and, for RAD21, by the sister chromatid cohesion/segregation annotations that its cleavage terminates. Removal does not dispute the interaction. Supporting Evidence: PMID:12672959 Previous work has established that human separase can cleave the Scc1 subunit of human cohesin PMID:12672959 noncleavable mammalian Scc1 interferes with sister separation |
| GO:0005515 protein binding | IPI PMID:12930902 The alternative Ctf18-Dcc1-Ctf8-replication factor C complex... | REMOVE | Summary: IPI with CHTF18, the large subunit of the alternative Ctf18-RFC clamp loader implicated in cohesion establishment. The cached abstract describes PCNA loading by Ctf18-RFC and does not expose the RAD21 assay. Reason: Generic protein binding is uninformative; the interaction (cohesin co-purifying with Ctf18-RFC) is plausible but no RAD21-specific molecular function follows from it. Removal does not dispute the interaction. Supporting Evidence: PMID:12930902 These results support a model in which sister chromatid cohesion is linked to DNA replication. |
| GO:0005515 protein binding | IPI PMID:15737063 Dissociation of cohesin from chromosome arms and loss of arm... | REMOVE | Summary: IPI with separase (ESPL1). RAD21 is the separase substrate: it is cleaved after Arg172 and Arg450 at anaphase onset, with docking motifs (LPE, NHLEYE) and phosphorylation near the C-terminal site tuning cleavage. Substrate binding is not a molecular function of RAD21; the informative activity is separase's endopeptidase activity with RAD21 as its input. Reason: Generic protein binding is uninformative and GO does not annotate a substrate for being bound by its protease. The biology is captured on the ESPL1 side (cysteine-type endopeptidase activity with RAD21 as input) and, for RAD21, by the sister chromatid cohesion/segregation annotations that its cleavage terminates. Removal does not dispute the interaction. Supporting Evidence: PMID:15737063 Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis, but enhances the cleavability |
| GO:0005515 protein binding | IPI PMID:15837422 Sororin, a substrate of the anaphase-promoting complex, is r... | REMOVE | Summary: IPI with mouse sororin (Cdca5), the vertebrate cohesion-maintenance factor that binds chromatin-bound cohesin via PDS5 and antagonises WAPL. Reason: Generic protein binding is uninformative; sororin's contact is with PDS5 on the cohesin complex rather than a defined RAD21 function, and the cohesion role is already captured by the cohesion process annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:15837422 interacts with the cohesin complex PMID:21111234 Sororin displaces Wapl from its binding partner Pds5 |
| GO:0005515 protein binding | IPI PMID:15855230 Functional contribution of Pds5 to cohesin-mediated cohesion... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:15855230 Pds5 proteins physically interact with cohesin and associate with chromatin in a cohesin-dependent manner. PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:15855230 Functional contribution of Pds5 to cohesin-mediated cohesion... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:15855230 Pds5 proteins physically interact with cohesin and associate with chromatin in a cohesin-dependent manner. PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:15855230 Functional contribution of Pds5 to cohesin-mediated cohesion... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:15855230 Pds5 proteins physically interact with cohesin and associate with chromatin in a cohesin-dependent manner. PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:16802858 Metazoan Scc4 homologs link sister chromatid cohesion to cel... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17105772 The DNA helicase ChlR1 is required for sister chromatid cohe... | REMOVE | Summary: IPI with the DDX11/ChlR1 helicase, which co-purifies with Scc1, Smc1 and Smc3 and is required for cohesion establishment in mammalian cells. Reason: Generic protein binding is uninformative; the functional content (a cohesion-establishment helicase associating with the cohesin complex) belongs to DDX11's own annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:17105772 biochemical studies show that ChlR1 is in complex with cohesin factors Scc1, Smc1 and Smc3 |
| GO:0005515 protein binding | IPI PMID:17112726 Human Wapl is a cohesin-binding protein that promotes sister... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17112726 Anti-Smc1 precipitated cohesin subunits (Smc1, SA2 and Scc1) as well as Pds5A and Pds5B PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17112726 Human Wapl is a cohesin-binding protein that promotes sister... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17112726 Anti-Smc1 precipitated cohesin subunits (Smc1, SA2 and Scc1) as well as Pds5A and Pds5B PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:17112726 Human Wapl is a cohesin-binding protein that promotes sister... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17112726 reconstitution experiments using recombinant subunits demonstrate that Wapl binds to the two regulatory subunits of cohesin (Scc1 and SA1) and forms a stoichiometric, ternary complex PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:17112726 Human Wapl is a cohesin-binding protein that promotes sister... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17112726 Anti-Smc1 precipitated cohesin subunits (Smc1, SA2 and Scc1) as well as Pds5A and Pds5B PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:17112726 Human Wapl is a cohesin-binding protein that promotes sister... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17112726 Anti-Smc1 precipitated cohesin subunits (Smc1, SA2 and Scc1) as well as Pds5A and Pds5B PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:17113138 Wapl controls the dynamic association of cohesin with chroma... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17113138 Wapl is associated with cohesin throughout the cell cycle PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17349791 Sororin is required for stable binding of cohesin to chromat... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17349791 sororin interacts with chromatin-bound cohesin PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:17962804 Protein requirements for sister telomere association in huma... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17962804 Cohesin consists of a heterodimer of Smc1 and Smc3 bound to Scc1 and Scc3 PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:18235444 Cohesin mediates transcriptional insulation by CCCTC-binding... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:18235444 CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:19629043 The cohesin complex is required for the DNA damage-induced G... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19629043 Cohesin also becomes enriched at DNA double-strand break sites and facilitates recombinational DNA repair. PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:19696148 Releasing cohesin from chromosome arms in early mitosis: opp... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 in the absence of hRad21, virtually no interaction was detectable between hWapl and hSA1 |
| GO:0005515 protein binding | IPI PMID:20360068 Systematic analysis of human protein complexes identifies ch... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:20360068 Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:20818333 The hsSsu72 phosphatase is a cohesin-binding protein that re... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:20818333 Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:20818333 The hsSsu72 phosphatase is a cohesin-binding protein that re... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:20818333 Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:20818333 The hsSsu72 phosphatase is a cohesin-binding protein that re... | REMOVE | Summary: IPI with the SSU72 phosphatase, identified by two-hybrid as a Rad21-binding protein that also binds SA2 and counteracts SA2 phosphorylation to protect arm cohesion. Reason: Generic protein binding is uninformative; the regulatory activity is SSU72's phosphatase activity acting on cohesin, not a function of RAD21. Removal does not dispute the interaction. Supporting Evidence: PMID:20818333 Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells |
| GO:0005515 protein binding | IPI PMID:20818333 The hsSsu72 phosphatase is a cohesin-binding protein that re... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:20818333 Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:22293751 APRIN is a cell cycle specific BRCA2-interacting protein req... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:22293751 APRIN appears to play a major role in regulating the interaction between BRCA2 and proteins such as CDC45, PCNA and RAD21 PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:22885700 HDAC8 mutations in Cornelia de Lange syndrome affect the coh... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:22885700 In HDAC8 mutant cells, RAD21-N co-immunoprecipitates with SMC1A, SMC3, STAG1, and STAG2 PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:22885700 HDAC8 mutations in Cornelia de Lange syndrome affect the coh... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:22885700 In HDAC8 mutant cells, RAD21-N co-immunoprecipitates with SMC1A, SMC3, STAG1, and STAG2 PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:22885700 HDAC8 mutations in Cornelia de Lange syndrome affect the coh... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:22885700 In HDAC8 mutant cells, RAD21-N co-immunoprecipitates with SMC1A, SMC3, STAG1, and STAG2 PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:23242214 Phosphorylation-enabled binding of SGO1-PP2A to cohesin prot... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:23242214 Depletion of Scc1 or SA2 greatly reduced binding of Sgo1 to Smc1 PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:24981860 we report a high-confidence (85% precision) network involving 11,464 protein-protein interactions among 1,738 different human proteins PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:25173175 Structure of cohesin subcomplex pinpoints direct shugoshin-W... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Sgo1 and Wapl compete for binding to a conserved site on SA2-Scc1. PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:25173175 Structure of cohesin subcomplex pinpoints direct shugoshin-W... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI with the LIM-domain protein FHL3 from proteome-scale yeast two-hybrid screening; there is no known cohesin biology for this pair. Reason: Generic protein binding from a high-throughput binary screen with no functional follow-up is uninformative. Removal does not assert the interaction is false. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:29263825 Familial STAG2 germline mutation defines a new human cohesin... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:29263825 In human somatic cells, cohesin consists of four core subunits: SMC1, SMC3, SCC1, and one of two related helical repeat proteins STAG1 or STAG2 PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:29867216 Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromoso... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:29867216 Two variant cohesin complexes containing SMC1, SMC3, RAD21 and either SA1 (also known as STAG1) or SA2 (also known as STAG2) are present in all cell types. PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: IPI with the LIM-domain protein FHL3 from proteome-scale yeast two-hybrid screening; there is no known cohesin biology for this pair. Reason: Generic protein binding from a high-throughput binary screen with no functional follow-up is uninformative. Removal does not assert the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the cohesin regulator PDS5A. PDS5 binds the central region of RAD21, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with PDS5A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:34290405 Structural basis of human separase regulation by securin and... | REMOVE | Summary: IPI with separase (ESPL1). RAD21 is the separase substrate: it is cleaved after Arg172 and Arg450 at anaphase onset, with docking motifs (LPE, NHLEYE) and phosphorylation near the C-terminal site tuning cleavage. Substrate binding is not a molecular function of RAD21; the informative activity is separase's endopeptidase activity with RAD21 as its input. Reason: Generic protein binding is uninformative and GO does not annotate a substrate for being bound by its protease. The biology is captured on the ESPL1 side (cysteine-type endopeptidase activity with RAD21 as input) and, for RAD21, by the sister chromatid cohesion/segregation annotations that its cleavage terminates. Removal does not dispute the interaction. Supporting Evidence: PMID:34290405 Deletion of these linkers, or replacement with a random sequence, abolished Scc1 cleavage in vitro PMID:34290405 the Scc1 NHLEYE motif promotes Scc1 binding to separase |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI with the SMC1A ATPase-head subunit. RAD21's C-terminal winged-helix domain binds the SMC1A ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC1A is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI with the cohesin release factor WAPL. WAPL binds the STAG-RAD21 subcomplex (no WAPL-STAG interaction is detectable without RAD21) to gate DNA exit from the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with WAPL is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 the N-terminal half (amino acids 1–500) of hWapl was responsible primarily for interacting with Pds5 and a pair of SA1 and Rad21 (the non-SMC subunits of cohesin) |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI with the HEAT-repeat subunit STAG2 (SA2). the central region of RAD21 (residues ~287-449, with the conserved 372-392 block) is the docking site for STAG2/SA2, resolved crystallographically as the SA2-Scc1 subcomplex. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with STAG2 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:25173175 Scc1 makes extensive contacts with SA2, with one binding hotspot. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI with the cohesin regulator PDS5B (APRIN). PDS5B binds the central region of RAD21 directly, in a manner stimulated by STAG1/2, docking the PDS5-WAPL/sororin regulatory module onto the ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with PDS5B is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19696148 hWapl and hPds5B bound to the same region in the presence of hSA1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: IPI with the SMC3 ATPase-head subunit. RAD21's N-terminal domain binds the SMC3 ATPase head, one of the two head contacts through which the kleisin closes the cohesin ring. Bare protein binding does not convey this: the informative molecular function is RAD21's role as the kleisin adaptor that brings the SMC heads and the HEAT-repeat subunits together to assemble a functional cohesin ring. This row derives from a proteome-scale interaction screen; the interaction it reports is the constitutive cohesin complex interaction that is independently established by structural and biochemical work. Reason: Generic protein binding is uninformative. The interaction with SMC3 is genuine and structurally defined, and it reflects RAD21's adaptor/bridging role connecting the SMC1A-SMC3 heads with STAG1/2, PDS5 and WAPL, which GO captures as protein-macromolecule adaptor activity (the same resolution used for the fission-yeast Rad21 kleisin). Complex membership is separately annotated (GO:0008278/GO:0030892). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0005634 nucleus | EXP PMID:11073952 Human chromatid cohesin component hRad21 is phosphorylated i... | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. Reason: Direct biochemical/cytological evidence of nuclear localisation; core location. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. |
| GO:0005634 nucleus | EXP PMID:11509732 Cohesin cleavage by separase required for anaphase and cytok... | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. The cited paper studies separase cleavage of nuclear cohesin in HeLa cells. Reason: Nuclear localisation of human RAD21 is directly and repeatedly demonstrated; the curator annotation is retained. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:11509732 We have identified two separase cleavage sites in the human cohesin subunit SCC1 and have conditionally expressed noncleavable SCC1 mutants in human cells |
| GO:0005634 nucleus | EXP PMID:11875078 Caspase proteolysis of the cohesin component RAD21 promotes ... | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. Reason: The caspase-cleavage study confirms the nuclear localisation of intact RAD21 and its partial removal from chromatin on apoptosis. Supporting Evidence: PMID:11875078 the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal PMID:12417729 hRad21 is a nuclear protein; however, the cleaved 64-kDa carboxy-terminal product is translocated to the cytoplasm early in apoptosis before chromatin condensation and nuclear fragmentation |
| GO:0005634 nucleus | EXP PMID:12417729 Linking sister chromatid cohesion and apoptosis: role of Rad... | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. Reason: Direct evidence that intact hRad21 is nuclear while the apoptotic C-terminal fragment moves to the cytoplasm. Supporting Evidence: PMID:12417729 hRad21 is a nuclear protein; however, the cleaved 64-kDa carboxy-terminal product is translocated to the cytoplasm early in apoptosis before chromatin condensation and nuclear fragmentation |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. Reason: Consistent with direct human evidence; core location. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. |
| GO:0005634 nucleus | NAS PMID:32409525 Cryo-EM structure of the human cohesin-NIPBL-DNA complex. | ACCEPT | Summary: RAD21 is a nuclear phosphoprotein throughout interphase; only after apoptotic caspase cleavage does the 64-kDa C-terminal fragment relocate to the cytoplasm. ComplexPortal NAS row accompanying the cryo-EM cohesin-NIPBL-DNA structure. Reason: Nuclear localisation is directly demonstrated elsewhere; accepted. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. Reason: Human Protein Atlas immunofluorescence consistent with all other localisation data; core location. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2468039 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns ESCO1/2 acetylation of SMC3 in arm cohesin. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2468040 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns cohesin binding PDS5 and WAPL. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2468041 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns sororin-enabled arm cohesion. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2470935 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns NIPBL:MAU2-facilitated loading onto decondensed chromatin. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2473151 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns sororin-enabled centromeric cohesion. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2473152 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns ESCO1/2 acetylation of centromeric cohesin. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3108212 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns SMC5/6-NSMCE2 SUMOylation of RAD21 and STAG2. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9011997 | ACCEPT | Summary: RAD21 is nucleoplasmic (HPA immunofluorescence), where soluble cohesin, cohesin bound to decondensed chromatin and cohesin released from chromosome arms reside. This Reactome row concerns cohesin binding the distal MYC enhancer with ESR1 and JUND:FOSB. Reason: Nucleoplasm is the compartment of interphase cohesin; consistent with direct localisation evidence. Supporting Evidence: PMID:11073952 hRad21 is a nuclear phosphorylated protein. PMID:23242214 Although the cohesin complex consisting of Smc1, Smc3, Scc1, and SA1/2 is already loaded onto chromatin in G1 phase, it remains dynamic. |
| GO:0005694 chromosome | EXP PMID:11073952 Human chromatid cohesin component hRad21 is phosphorylated i... | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. Reason: Direct chromosome-spread evidence; core location. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths PMID:11073952 hRad21 remains specifically at the centromeres but disappears from the arm regions on metaphase-like chromosomes |
| GO:0005694 chromosome | EXP PMID:11590136 A potential role for human cohesin in mitotic spindle aster ... | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. Reason: The paper re-examines cohesin localisation in human cells and confirms chromosomal association in interphase; core location. Supporting Evidence: PMID:11590136 The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1 (Rad21) is required for sister chromatid cohesion in eukaryotes PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. Reason: UniProt subcellular-location mapping consistent with direct evidence. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005694 chromosome | TAS Reactome:R-HSA-2466068 | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. This Reactome row concerns PLK1 phosphorylation of arm cohesin. Reason: Chromosome-arm cohesin is directly observed for human RAD21; core location. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005694 chromosome | TAS Reactome:R-HSA-2467794 | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. This Reactome row concerns resolution of sister chromatid arms. Reason: Chromosome-arm cohesin is directly observed for human RAD21; core location. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005694 chromosome | TAS Reactome:R-HSA-2468041 | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. This Reactome row concerns sororin-enabled arm cohesion. Reason: Chromosome-arm cohesin is directly observed for human RAD21; core location. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005694 chromosome | TAS Reactome:R-HSA-2468293 | ACCEPT | Summary: RAD21 associates with chromosomes: scattered along arms before prophase, retained along prometaphase chromosomes and at metaphase centromeres, and mapped genome-wide by ChIP in interphase. This Reactome row concerns CDK1 phosphorylation of sororin on arm cohesin. Reason: Chromosome-arm cohesin is directly observed for human RAD21; core location. Supporting Evidence: PMID:11073952 hRad21 remains associated with prometaphase-like chromosomes along their entire lengths |
| GO:0005829 cytosol | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytosolic RAD21 corresponds to (i) cohesin released from chromosome arms in prophase, which resides in the mitotic cytoplasm after nuclear envelope breakdown, and (ii) the caspase-generated 64-kDa C-terminal fragment that translocates to the cytoplasm in apoptosis. Neither pool performs RAD21's chromatin functions. Reason: UniProt maps the cytosol to the apoptotic 64-kDa product; genuine but non-functional location for the kleisin. Supporting Evidence: PMID:12417729 hRad21 is a nuclear protein; however, the cleaved 64-kDa carboxy-terminal product is translocated to the cytoplasm early in apoptosis before chromatin condensation and nuclear fragmentation PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467794 | KEEP AS NON CORE | Summary: Cytosolic RAD21 corresponds to (i) cohesin released from chromosome arms in prophase, which resides in the mitotic cytoplasm after nuclear envelope breakdown, and (ii) the caspase-generated 64-kDa C-terminal fragment that translocates to the cytoplasm in apoptosis. Neither pool performs RAD21's chromatin functions. Reactome places released, cleaved or deacetylated cohesin in the mitotic cytosol. Reason: Soluble mitotic cohesin does reside in the cytoplasm after arm release and after separase cleavage, but this is where cohesin is recycled, not where RAD21 acts; non-core. Supporting Evidence: PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | KEEP AS NON CORE | Summary: Cytosolic RAD21 corresponds to (i) cohesin released from chromosome arms in prophase, which resides in the mitotic cytoplasm after nuclear envelope breakdown, and (ii) the caspase-generated 64-kDa C-terminal fragment that translocates to the cytoplasm in apoptosis. Neither pool performs RAD21's chromatin functions. Reactome places released, cleaved or deacetylated cohesin in the mitotic cytosol. Reason: Soluble mitotic cohesin does reside in the cytoplasm after arm release and after separase cleavage, but this is where cohesin is recycled, not where RAD21 acts; non-core. Supporting Evidence: PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2545203 | KEEP AS NON CORE | Summary: Cytosolic RAD21 corresponds to (i) cohesin released from chromosome arms in prophase, which resides in the mitotic cytoplasm after nuclear envelope breakdown, and (ii) the caspase-generated 64-kDa C-terminal fragment that translocates to the cytoplasm in apoptosis. Neither pool performs RAD21's chromatin functions. Reactome places released, cleaved or deacetylated cohesin in the mitotic cytosol. Reason: Soluble mitotic cohesin does reside in the cytoplasm after arm release and after separase cleavage, but this is where cohesin is recycled, not where RAD21 acts; non-core. Supporting Evidence: PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2545253 | KEEP AS NON CORE | Summary: Cytosolic RAD21 corresponds to (i) cohesin released from chromosome arms in prophase, which resides in the mitotic cytoplasm after nuclear envelope breakdown, and (ii) the caspase-generated 64-kDa C-terminal fragment that translocates to the cytoplasm in apoptosis. Neither pool performs RAD21's chromatin functions. Reactome places released, cleaved or deacetylated cohesin in the mitotic cytosol. Reason: Soluble mitotic cohesin does reside in the cytoplasm after arm release and after separase cleavage, but this is where cohesin is recycled, not where RAD21 acts; non-core. Supporting Evidence: PMID:11590136 the majority of cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis |
| GO:0006302 double-strand break repair | TAS PMID:8812457 Sequence conservation of the rad21 Schizosaccharomyces pombe... | ACCEPT | Summary: The cloning paper infers a repair role for hHR21 from conservation with the S. pombe DSB-repair gene rad21. In human cells cohesin (Scc1-containing) is enriched at DSBs, facilitates recombinational repair, and Scc1-depleted cells enter mitosis with highly fragmented, unrepaired chromosomes; RAD21 SUMOylation is required for sister-chromatid recombination. Reason: Although the original evidence is a sequence-conservation TAS, the function is directly confirmed for human RAD21/cohesin: cohesin supplies the sister-chromatid template proximity and break-site chromatin organisation that recombinational repair depends on (a structural contribution, comparable to the scaffold case), so the participation test is met. Supporting Evidence: PMID:8812457 The rad21 gene of Schizosaccharomyces pombe is involved in the repair of ionizing radiation-induced DNA double-strand breaks. PMID:19629043 Cohesin also becomes enriched at DNA double-strand break sites and facilitates recombinational DNA repair. PMID:19629043 almost all mitotic cells contained broken chromosomes, most of which were highly fragmented |
| GO:0006310 DNA recombination | TAS PMID:8812457 Sequence conservation of the rad21 Schizosaccharomyces pombe... | MODIFY | Summary: The TAS rests on a speculation in the cloning paper that testis/thymus expression might indicate roles in meiotic and V(D)J recombination. The recombination process cohesin genuinely supports is recombinational repair of DSBs using the sister chromatid. Reason: The general term is too broad and its original basis was expression-pattern speculation; the supported, specific process is replication-born DSB repair via sister chromatid exchange (also an IBA for this gene), with DSB repair (GO:0006302) already retained. Proposed replacements: replication-born double-strand break repair via sister chromatid exchange Supporting Evidence: PMID:8812457 Elevated expression of mHR21sp in testis and thymus supports a possible role for the rad21 mammalian homologs in V(D)J and meiotic recombination, respectively. PMID:19629043 Cohesin also becomes enriched at DNA double-strand break sites and facilitates recombinational DNA repair. |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:19468298 Transcriptional dysregulation in NIPBL and cohesin mutant hu... | KEEP AS NON CORE | Summary: RAD21/cohesin ChIP-chip in lymphoblastoid cells shows cohesin enriched at promoters of genes dysregulated in Cornelia de Lange syndrome, with binding reduced in NIPBL-mutant probands; cohesin also enables CTCF insulation at H19/IGF2 and supports estrogen-responsive MYC expression. These effects are mediated by cohesin's chromatin-looping/insulator function. Reason: Genuine, well-documented consequence of cohesin-mediated loop/insulator organisation, and the basis of CdLS transcriptional dysregulation; kept as non-core because RAD21 acts on transcription indirectly through chromatin architecture rather than as a transcription factor. Supporting Evidence: PMID:19468298 the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS proband PMID:18235444 Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. |
| GO:0007062 sister chromatid cohesion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT assigns sister chromatid cohesion at a kleisin node whose descendants include mitotic Scc1/Rad21 and meiotic Rec8-type kleisins across yeasts, plants, worms, flies and fish, hence the cell-cycle-neutral parent term. Human RAD21 depletion produces severe cohesion defects. Reason: Correct phylogenetic placement; the general term is right at a node that includes meiotic kleisins. For RAD21 the specific instance is mitotic sister chromatid cohesion, which is its core process. Supporting Evidence: PMID:15855230 Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly of chromosomes with severe cohesion defects. PMID:12417729 Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase, a caspase-like enzyme, allows chromosomal separation |
| GO:0007062 sister chromatid cohesion | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (Rad21/Rec8-like) assigns the general cohesion term; human RAD21 is the mitotic kleisin and its cohesion role is directly shown by RNAi (severe cohesion defects) and by noncleavable RAD21 blocking sister separation. Reason: Correct but less specific than the directly supported mitotic sister chromatid cohesion term. Proposed replacements: mitotic sister chromatid cohesion Supporting Evidence: PMID:15855230 Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly of chromosomes with severe cohesion defects. PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis |
| GO:0007131 reciprocal meiotic recombination | TAS PMID:8812457 Sequence conservation of the rad21 Schizosaccharomyces pombe... | REMOVE | Summary: Speculative TAS from testis expression in the cloning paper. Mammalian meiotic recombination and axis cohesion are executed by the meiosis-specific kleisins REC8 and RAD21L; a role for RAD21 itself in reciprocal (crossover) recombination has not been demonstrated. Reason: Not experimental and never substantiated: the abstract explicitly frames it as a possibility from expression data, and the meiotic kleisin paralogs (REC8, RAD21L) account for the meiotic functions. Over-annotation for RAD21. Supporting Evidence: PMID:8812457 Elevated expression of mHR21sp in testis and thymus supports a possible role for the rad21 mammalian homologs in V(D)J and meiotic recombination, respectively. |
| GO:0008278 cohesin complex | IDA PMID:11590136 A potential role for human cohesin in mitotic spindle aster ... | ACCEPT | Summary: RAD21 is the kleisin of the SMC1A-SMC3-RAD21-STAG1/2 cohesin complex; the paper re-examines the localisation and NuMA interaction of the human complex containing SMC1, SMC3, SA and Scc1/Rad21. Reason: Direct biochemical evidence of complex membership; core component. Supporting Evidence: PMID:11590136 The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1 (Rad21) is required for sister chromatid cohesion in eukaryotes |
| GO:0008278 cohesin complex | IDA PMID:22628566 In vitro loading of human cohesin on DNA by the human Scc2-S... | ACCEPT | Summary: RAD21 is the kleisin of the SMC1A-SMC3-RAD21-STAG1/2 cohesin complex; the paper purifies human cohesin and shows its loading onto pre-RC DNA by the human Scc2-Scc4 (NIPBL-MAU2) loader, with replication stabilising the loaded complex. Reason: Direct reconstitution with purified human cohesin; core component. Supporting Evidence: PMID:22628566 it interacts with h-cohesin and the heterodimeric Smc1-Smc3 complex but not with the Smc1 or Smc3 subunit alone PMID:22628566 Replication of cohesin-loaded DNA, both in vitro and in vivo, markedly increased the stability of cohesin associated with DNA. |
| GO:0008278 cohesin complex | IEA GO_REF:0000120 | ACCEPT | Summary: RAD21 is the kleisin of the SMC1A-SMC3-RAD21-STAG1/2 cohesin complex; the paper row is a combined IEA (ARBA/InterPro/Compara) inference. Reason: Consistent with direct human evidence; core component. Supporting Evidence: PMID:22885700 In humans, the multisubunit complex cohesin is made up of SMC1, SMC3, RAD21 and a STAG protein. |
| GO:0008278 cohesin complex | TAS PMID:19468298 Transcriptional dysregulation in NIPBL and cohesin mutant hu... | ACCEPT | Summary: RAD21 is the kleisin of the SMC1A-SMC3-RAD21-STAG1/2 cohesin complex; the paper introduction lists SCC1/RAD21 as a core non-SMC subunit. Reason: Complex membership is directly established elsewhere; core component. Supporting Evidence: PMID:19468298 Cohesin is an evolutionally conserved multisubunit protein complex consisting of an SMC1A and SMC3 heterodimer, and at least two non-SMC proteins SCC1 (also known as RAD21 or MCD1) and SCC3 (also known as SA or STAG). |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: Rat-derived Ensembl-Compara transfer of a generic gene-expression regulation term. Cohesin does modulate transcription, but through loop extrusion/insulation, and the direction-specific generic terms add nothing beyond the human IDA for regulation of transcription by RNA polymerase II. Reason: The essence (cohesin influences gene expression) is sound, but the generic bidirectional term should be replaced by the mechanism-level term already supported in human cells. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:18235444 Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: Rat-derived Ensembl-Compara transfer of a generic gene-expression regulation term. Cohesin does modulate transcription, but through loop extrusion/insulation, and the direction-specific generic terms add nothing beyond the human IDA for regulation of transcription by RNA polymerase II. Reason: The essence (cohesin influences gene expression) is sound, but the generic bidirectional term should be replaced by the mechanism-level term already supported in human cells. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:18235444 Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. |
| GO:0010972 negative regulation of G2/M transition of mitotic cell cycle | IEA GO_REF:0000107 | MODIFY | Summary: Mouse-derived transfer. In human cells cohesin (Scc1) is required for the DNA damage-induced G2/M checkpoint: Scc1-depleted cells fail to activate Chk2 properly, recruit 53BP1 poorly and enter mitosis with broken chromosomes; this checkpoint role is independent of cohesion. Cohesin does not otherwise restrain the unperturbed G2/M transition. Reason: The negative-regulation-of-G2/M term is too broad and implies a CDK-inhibitory signalling role; the supported process is the mitotic G2 DNA damage checkpoint, in which cohesin at break sites facilitates recruitment of checkpoint proteins (a scaffold-type contribution). Proposed replacements: mitotic G2 DNA damage checkpoint signaling Supporting Evidence: PMID:19629043 Here, we report that cohesin is essential for the DNA damage-induced G2/M checkpoint. PMID:19629043 In contrast to cohesin's role in DNA repair, the checkpoint function of cohesin is independent of its ability to mediate cohesion. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | REMOVE | Summary: High-throughput membrane proteome of the YTS NK-like cell line; the authors note that ~60% of identified proteins were not predicted membrane proteins and are likely transiently or non-specifically associated. RAD21 is a nuclear chromatin protein with no membrane function. Reason: Proteomic membrane-fraction identification of an abundant nuclear protein is a contaminant-level observation, and no membrane role for RAD21 exists; the annotation misleads. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. |
| GO:0016363 nuclear matrix | EXP PMID:10623634 NXP-1, a human protein related to Rad21/Scc1/Mcd1, is a comp... | KEEP AS NON CORE | Summary: A substantial fraction of RAD21 (NXP-1) and cohesin is recovered in nuclear-matrix preparations, with the N-terminal region (16-128) mediating matrix distribution. The nuclear matrix is an operationally defined biochemical fraction; the observation is consistent with cohesin being tightly chromatin/nuclear-scaffold associated rather than a distinct site of function. Reason: Directly observed by immunoblotting/immunofluorescence, but a fractionation-defined location that adds little to the chromatin/chromosome annotations; non-core. Supporting Evidence: PMID:10623634 Western blot analysis with anti-NXP-1 polyclonal antibody showed nuclear matrix localization of NXP-1 in HeLa cells PMID:10623634 Indirect immunofluorescence staining also showed nuclear and nuclear matrix localization of the NXP-1 |
| GO:0016363 nuclear matrix | IDA PMID:11590136 A potential role for human cohesin in mitotic spindle aster ... | KEEP AS NON CORE | Summary: A substantial fraction of RAD21 (NXP-1) and cohesin is recovered in nuclear-matrix preparations, with the N-terminal region (16-128) mediating matrix distribution. The nuclear matrix is an operationally defined biochemical fraction; the observation is consistent with cohesin being tightly chromatin/nuclear-scaffold associated rather than a distinct site of function. Reason: Directly observed (co-fractionation with NuMA), but a biochemically defined compartment rather than a functional site; non-core. Supporting Evidence: PMID:11590136 a significant amount of cohesin was found to associate with the nuclear matrix |
| GO:0016363 nuclear matrix | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A substantial fraction of RAD21 (NXP-1) and cohesin is recovered in nuclear-matrix preparations, with the N-terminal region (16-128) mediating matrix distribution. The nuclear matrix is an operationally defined biochemical fraction; the observation is consistent with cohesin being tightly chromatin/nuclear-scaffold associated rather than a distinct site of function. Reason: UniProt mapping of the two experimental nuclear-matrix reports; non-core. Supporting Evidence: PMID:10623634 Western blot analysis with anti-NXP-1 polyclonal antibody showed nuclear matrix localization of NXP-1 in HeLa cells PMID:11590136 a significant amount of cohesin was found to associate with the nuclear matrix |
| GO:0030892 mitotic cohesin complex | IPI PMID:23242214 Phosphorylation-enabled binding of SGO1-PP2A to cohesin prot... | ACCEPT | Summary: The mitotic cohesin complex (SMC1-SMC3-SCC1-SA1/2) is the binding partner of CDK1-phosphorylated SGO1-PP2A at centromeres; SGO1 binding is lost on Scc1 or SA2 depletion and is reconstituted with the Scc1-SA2 subcomplex. Reason: Direct evidence for RAD21 as a subunit of the mitotic cohesin complex that SGO1-PP2A protects; core component. Supporting Evidence: PMID:23242214 Depletion of Scc1 or SA2 greatly reduced binding of Sgo1 to Smc1 PMID:23242214 Cdk1-phosphorylated GST-Sgo1 bound efficiently to the Scc1–SA2 complex expressed in Sf9 insect cells |
| GO:0030893 meiotic cohesin complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT places meiotic-cohesin-complex membership at a vertebrate node (PTN000286934) seeded by mouse Rad21l, RAD21's meiosis-specific paralog. UniProt records human RAD21 in complexes with STAG3, the meiosis-specific SA subunit, and mammalian RAD21 does load on meiotic chromosome axes, but the principal meiotic kleisins are REC8 and RAD21L. Reason: Defensible phylogenetic inference (RAD21 is inside the vertebrate RAD21/RAD21L clade and forms STAG3-containing complexes), but a secondary, meiosis-restricted role relative to the mitotic cohesin complex; kept as non-core rather than challenged. Supporting Evidence: file:human/RAD21/RAD21-uniprot.txt Component of the cohesin complex, which consists of an SMC1A/B |
| GO:0030893 meiotic cohesin complex | NAS PMID:32409525 Cryo-EM structure of the human cohesin-NIPBL-DNA complex. | KEEP AS NON CORE | Summary: PAINT places meiotic-cohesin-complex membership at a vertebrate node (PTN000286934) seeded by mouse Rad21l, RAD21's meiosis-specific paralog. UniProt records human RAD21 in complexes with STAG3, the meiosis-specific SA subunit, and mammalian RAD21 does load on meiotic chromosome axes, but the principal meiotic kleisins are REC8 and RAD21L. This ComplexPortal NAS row defines the RAD21-STAG3 meiotic complex variant. Reason: Plausible complex variant recorded from complex definitions rather than direct human meiotic evidence; non-core. Supporting Evidence: file:human/RAD21/RAD21-uniprot.txt Component of the cohesin complex, which consists of an SMC1A/B |
| GO:0032691 negative regulation of interleukin-1 beta production | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer (negative regulation of interleukin-1 beta production). Cytokine output changes in a rat model are downstream, indirect consequences of perturbing a chromatin-architecture protein and are not a process the cohesin kleisin performs. Reason: Fails the participation test: RAD21 does none of the work of cytokine production or its signalling control; this is over-propagation of a pleiotropic phenotype from a single rat study to human. |
| GO:0032720 negative regulation of tumor necrosis factor production | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer (negative regulation of tumor necrosis factor production). Cytokine output changes in a rat model are downstream, indirect consequences of perturbing a chromatin-architecture protein and are not a process the cohesin kleisin performs. Reason: Fails the participation test: RAD21 does none of the work of cytokine production or its signalling control; this is over-propagation of a pleiotropic phenotype from a single rat study to human. |
| GO:0032733 positive regulation of interleukin-10 production | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer (positive regulation of interleukin-10 production). Cytokine output changes in a rat model are downstream, indirect consequences of perturbing a chromatin-architecture protein and are not a process the cohesin kleisin performs. Reason: Fails the participation test: RAD21 does none of the work of cytokine production or its signalling control; this is over-propagation of a pleiotropic phenotype from a single rat study to human. |
| GO:0034087 establishment of mitotic sister chromatid cohesion | NAS PMID:32409525 Cryo-EM structure of the human cohesin-NIPBL-DNA complex. | ACCEPT | Summary: Cohesive cohesin is generated during S phase: loaded human cohesin is stabilised on DNA by replication, and Scc1 depletion abolishes cohesion. RAD21 closes the ring that entraps the two sisters, so it is a direct structural participant in establishing mitotic cohesion. Reason: Although the row is a ComplexPortal NAS, establishment of mitotic sister chromatid cohesion is a core, directly supported process for the RAD21 kleisin. Supporting Evidence: PMID:22628566 Replication of cohesin-loaded DNA, both in vitro and in vivo, markedly increased the stability of cohesin associated with DNA. PMID:15855230 Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly of chromosomes with severe cohesion defects. PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0034089 establishment of meiotic sister chromatid cohesion | NAS PMID:32409525 Cryo-EM structure of the human cohesin-NIPBL-DNA complex. | KEEP AS NON CORE | Summary: ComplexPortal NAS row derived from the definition of a RAD21-STAG3 meiotic cohesin variant. Establishment of meiotic cohesion in mammals is carried out mainly by REC8- and RAD21L-containing cohesin; a contribution of RAD21 complexes is plausible but not experimentally established in human. Reason: Not contradicted, and consistent with RAD21 forming STAG3 complexes, but indirect evidence for a secondary meiotic role; non-core. Supporting Evidence: file:human/RAD21/RAD21-uniprot.txt Component of the cohesin complex, which consists of an SMC1A/B |
| GO:0034351 negative regulation of glial cell apoptotic process | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer (negative regulation of glial cell apoptotic process). Cell-survival phenotypes on manipulating a cohesin subunit in rat neural cells are indirect consequences of genome-organisation or proliferation defects. The only direct link between RAD21 and apoptosis in human cells is the opposite: caspase cleavage of RAD21 generates a pro-apoptotic fragment. Reason: Fails the participation test and is not corroborated in human; over-propagation of a pleiotropic rat phenotype. Supporting Evidence: PMID:11875078 the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived Ensembl-Compara transfer (negative regulation of neuron apoptotic process). Cell-survival phenotypes on manipulating a cohesin subunit in rat neural cells are indirect consequences of genome-organisation or proliferation defects. The only direct link between RAD21 and apoptosis in human cells is the opposite: caspase cleavage of RAD21 generates a pro-apoptotic fragment. Reason: Fails the participation test and is not corroborated in human; over-propagation of a pleiotropic rat phenotype. Supporting Evidence: PMID:11875078 the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal |
| GO:0045841 negative regulation of mitotic metaphase/anaphase transition | IEA GO_REF:0000107 | REMOVE | Summary: Mouse-derived transfer. RAD21 is the separase substrate whose cleavage executes sister separation; cells expressing noncleavable RAD21 fail to separate sisters and complete cytokinesis, but the metaphase/anaphase transition itself (APC/C activation, securin and cyclin B degradation) is not regulated by RAD21. Reason: Fails the participation test: being the substrate cleaved at anaphase onset is not regulating the transition, which is governed by the spindle checkpoint, APC/C-CDC20 and securin. The cohesion function is already captured by the cohesion/segregation terms. Supporting Evidence: PMID:11509732 cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis PMID:15737063 Cleavage of the Scc1 subunit of cohesin by the protease separase releases the complex from chromosomes and thereby enables the separation of sister chromatids in anaphase. |
| GO:0045876 positive regulation of sister chromatid cohesion | IMP PMID:18499658 Studies with the human cohesin establishment factor, ChlR1. ... | MODIFY | Summary: IMP from the ChlR1 cohesion-establishment study in which cohesin subunits were manipulated alongside ChlR1/Fen1. RAD21 is not a regulator of cohesion: it is the kleisin that physically mediates it, and its depletion causes complete loss of cohesion. Reason: The essence (RAD21 is required for cohesion) is sound but the regulation term is the wrong relation for a structural subunit that performs the process; the direct-participation term mitotic sister chromatid cohesion is appropriate. Proposed replacements: mitotic sister chromatid cohesion Supporting Evidence: PMID:18499658 Human ChlR1 (hChlR1), a member of the DEAD/DEAH subfamily of helicases, was shown to interact with components of the cohesin complex and play a role in sister chromatid cohesion. PMID:15855230 Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly of chromosomes with severe cohesion defects. |
| GO:0071168 protein localization to chromatin | IMP PMID:21111234 Sororin mediates sister chromatid cohesion by antagonizing W... | KEEP AS NON CORE | Summary: Sororin binds chromatin-bound cohesin through PDS5 and its chromatin association is cohesin-dependent; likewise PDS5, WAPL and phospho-SGO1 are recruited to chromatin via the cohesin (STAG-RAD21) platform. RAD21 therefore acts as the scaffold that localises these regulators to chromatin. Reason: Experimentally grounded scaffold-type contribution (the regulators dock on the STAG-RAD21 subcomplex), retained as a non-core process ancillary to cohesion itself. Supporting Evidence: PMID:21111234 Sororin displaces Wapl from its binding partner Pds5 PMID:15855230 Pds5 proteins physically interact with cohesin and associate with chromatin in a cohesin-dependent manner. PMID:17349791 sororin interacts with chromatin-bound cohesin |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | REMOVE | Summary: Rat-derived transfer of lncRNA binding. RAD21 has no RNA-binding domain; cohesin's nucleic-acid interaction is topological entrapment of DNA, and any lncRNA co-purification reflects chromatin-associated RNA rather than a RAD21 activity. Reason: Unsupported over-propagated electronic inference with no structural or human experimental basis; likely an indirect RIP/pull-down signal from chromatin-associated RNA. Supporting Evidence: PMID:32409525 As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Rat-derived transfer. Cohesin co-localises and co-purifies with DNA-binding transcription factors such as CTCF and ESR1, but the documented direct contact with CTCF is made by STAG2/SA2, not by RAD21, and functional cooperation with CTCF is a complex-level property. Reason: Not wrong at the complex level, but attributing transcription-factor binding to the RAD21 subunit over-reaches the evidence; the human data support chromatin binding and cohesin-CTCF cooperation, captured by GO:0003682 and GO:0006357. Supporting Evidence: PMID:18235444 CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. |
| GO:1990414 replication-born double-strand break repair via sister chromatid exchange | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT propagates from budding-yeast Mcd1/Scc1 the specific process of repairing replication-born DSBs by sister chromatid exchange. Human cohesin accumulates at DSBs and facilitates recombinational repair, sororin/cohesin are needed for efficient G2 DSB repair, and RAD21 SUMOylation is required for sister-chromatid recombination, so the inference is well founded although the exact sub-process is characterised mostly in yeast. Reason: Sound phylogenetic inference consistent with human cohesin repair data; retained as a non-core repair function alongside the DSB-repair TAS, following the treatment of the fission-yeast ortholog. Supporting Evidence: PMID:19629043 Cohesin also becomes enriched at DNA double-strand break sites and facilitates recombinational DNA repair. PMID:17349791 Like cohesin, sororin is also needed for efficient repair of DNA double-strand breaks in G2. |
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Download this section (compressed HTML)Q: No human cohesin subunit (RAD21, SMC1A, SMC3, STAG1, STAG2) currently carries GO:0140588 chromatin looping, although the GO definition names SMC complexes as the extrusion motor and fission-yeast rad21 carries it by IDA; should human RAD21 (and the other core subunits) receive this annotation from the RAD21-degron Hi-C and single-molecule loop-extrusion literature?
Q: Are cohesive (sister-entrapping) and loop-extruding cohesin populations in human cells distinguished by RAD21 post-translational state (phosphorylation, SUMOylation) or by STAG1 versus STAG2 partnership, and does the RAD21 central region gate the switch between them?
Q: Human RAD21 is SUMOylated during DNA damage repair and is required for the G2/M checkpoint independently of cohesion; which RAD21 contacts (PDS5, NIPBL, STAG) mediate recruitment of 53BP1/CHK2 at break sites, and is this a scaffold function that should be modelled with a defined molecular activity?
Q: Do RAD21-STAG3 complexes contribute to meiotic cohesion in human germ cells, or are the meiotic-cohesin-complex and establishment-of-meiotic-cohesion annotations better restricted to REC8 and RAD21L?
Experiment: Auxin-inducible degradation of endogenous RAD21 in synchronised human cells combined with Micro-C/Hi-C and sister-chromatid-resolved (e.g. scsHi-C) mapping to separate the contributions of RAD21-cohesin to loop extrusion versus sister chromatid cohesion within the same cell cycle.
Experiment: Structure-guided mutagenesis of the RAD21 central region (residues 287-449, including the conserved 372-392 block) to uncouple STAG binding from PDS5/WAPL docking, followed by chromosome-spread cohesion assays, FRAP residence-time measurements and ChIP-seq, to define which contacts are required for cohesion establishment, prophase release and loop anchoring.
Experiment: Knock-in of separase-noncleavable (R172E/R450E) and caspase-noncleavable (D279A) RAD21 alleles with live imaging to quantify the contributions of the two cleavage events to anaphase timing, cytokinesis completion and apoptotic chromatin changes.
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