BABAM1 (BRISC and BRCA1-A complex member 1; MERIT40/NBA1) is a scaffold subunit, with a von Willebrand factor A-like fold (InterPro vWFA superfamily), of two BRCC3/BRCC36-containing K63-linked deubiquitinase complexes. In the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3, BABAM2/BRE, BABAM1), it binds BABAM2 directly and maintains complex stability, BRCC3 deubiquitinase activity, and targeting of BRCA1 to ubiquitinated chromatin at DNA double-strand breaks. It is required for the G2/M DNA damage checkpoint and for resistance to ionizing radiation. In the cytoplasmic and nuclear BRISC complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, regulated by SHMT2), it likewise stabilizes the complex, which deubiquitinates substrates such as IFNAR1 to sustain interferon signalling and NUMA1 for spindle assembly. BABAM1 also binds tankyrases through an RXXPEG motif, recruiting tankyrase to DSBs and regulating TNKS1 at the spindle. It is recruited early to DNA interstrand cross-links with RAP80, and it is phosphorylated by Akt and, at Ser29, downstream of mTORC2 after DNA damage.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | REMOVE | Summary: Protein binding (IPI) with ABRAXAS1. ABRAXAS1 is a BRCA1-A subunit, captured by GO:0070531. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | REMOVE | Summary: Protein binding (IPI) with TERF2IP. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:22153077 Structural basis and sequence rules for substrate recognitio... | REMOVE | Summary: Protein binding (IPI) with TNKS2. MERIT40 binds tankyrases through an RXXPEG motif and recruits tankyrase to DSBs; BRISC regulates TNKS1 during spindle assembly. No specific MF term fits this partner-recruitment role at row level. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:30571846 Here we demonstrated that MERIT40, a core component of BRISC complex, directly interacts with the RXXPEG motif in the ARC-V domain of Tankyrase1(TNKS1). PMID:30533199 We found that tankyrase is localized to DSBs through its interaction with MERIT40, and pharmacological inhibition of tankyrase sensitized human lung cancer cells to DNA-damaging anticancer agents. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with TRIM27. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding (IPI) with TNKS2. MERIT40 binds tankyrases through an RXXPEG motif and recruits tankyrase to DSBs; BRISC regulates TNKS1 during spindle assembly. No specific MF term fits this partner-recruitment role at row level. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:30571846 Here we demonstrated that MERIT40, a core component of BRISC complex, directly interacts with the RXXPEG motif in the ARC-V domain of Tankyrase1(TNKS1). PMID:30533199 We found that tankyrase is localized to DSBs through its interaction with MERIT40, and pharmacological inhibition of tankyrase sensitized human lung cancer cells to DNA-damaging anticancer agents. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding (IPI) with TRIM27. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TRIM27. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with TNKS2. MERIT40 binds tankyrases through an RXXPEG motif and recruits tankyrase to DSBs; BRISC regulates TNKS1 during spindle assembly. No specific MF term fits this partner-recruitment role at row level. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:30571846 Here we demonstrated that MERIT40, a core component of BRISC complex, directly interacts with the RXXPEG motif in the ARC-V domain of Tankyrase1(TNKS1). PMID:30533199 We found that tankyrase is localized to DSBs through its interaction with MERIT40, and pharmacological inhibition of tankyrase sensitized human lung cancer cells to DNA-damaging anticancer agents. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: Protein binding (IPI) with PMF1. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: Protein binding (IPI) with BABAM2. BABAM2 (BRE) is BABAM1's direct partner in both BRCA1-A and BRISC; that relationship is captured by the complex rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. PMID:21282113 Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: Protein binding (IPI) with LAMTOR2. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005634 nucleus | EXP PMID:21282113 NBA1/MERIT40 and BRE interaction is required for the integri... | ACCEPT | Summary: Nucleus (EXP). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:21282113 "Both BRCC36-containing complexes contain common components including BRE and NBA1/MERIT40."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:21282113 Both BRCC36-containing complexes contain common components including BRE and NBA1/MERIT40. |
| GO:0005634 nucleus | EXP PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: Nucleus (EXP). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:24075985 "The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:24075985 The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis. |
| GO:0005634 nucleus | IDA PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: Nucleus (IDA). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:19261746 "Here, we identify MERIT40 (Mediator of Rap80 Interactions and Targeting 40 kD)/(C19orf62) as a Rap80-associated protein that is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:19261746 Here, we identify MERIT40 (Mediator of Rap80 Interactions and Targeting 40 kD)/(C19orf62) as a Rap80-associated protein that is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting. |
| GO:0005634 nucleus | IDA PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Nucleus (IDA). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:19261748 "Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:19261748 Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage. |
| GO:0005634 nucleus | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Nucleus (IDA). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:19261749 "The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:19261749 The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus (IEA). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005634 nucleus | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: Nucleus (NAS). BABAM1 is nuclear and accumulates at sites of DNA damage, where it acts in the BRCA1-A complex. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] [PMID:20656689 "Finally, BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double strand breaks."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). PMID:20656689 Finally, BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double strand breaks. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm (IDA). Human Protein Atlas immunofluorescence. BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683385 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'Formation of BRCA1-A complex at DNA DSBs'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'CHEK2 is recruited to DNA DSBs'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'CHEK2 phosphorylates BRCA1'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684052 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'PIAS4 SUMOylates MDC1'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684071 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'RNF4 ubiquitinates MDC1'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686685 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'RIF1 and PAX1IP bind TP53BP1 at DNA DSBs'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5691411 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'BRCA1-A complex deubiquitinates K63polyUb-histone H2A'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693551 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'Phosphorylation of BRCA1-A complex at multiple sites by ATM'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: Nucleoplasm (TAS). BABAM1 is a nucleoplasmic DNA-damage-response protein. Accepted. Reactome event: 'Phosphorylation and activation of CHEK2 by ATM'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, file:human/BABAM1/BABAM1-uniprot.txt CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005737 cytoplasm | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Cytoplasm (IDA). As a BRISC subunit, BABAM1 is also cytoplasmic, where BRISC deubiquitinates IFNAR1, NLRP3 and other cytoplasmic substrates. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [PMID:19261749 "The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that PMID:19261749 The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. |
| GO:0005737 cytoplasm | IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: Cytoplasm (IDA). As a BRISC subunit, BABAM1 is also cytoplasmic, where BRISC deubiquitinates IFNAR1, NLRP3 and other cytoplasmic substrates. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [PMID:24075985 "The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that PMID:24075985 The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (IEA). As a BRISC subunit, BABAM1 is also cytoplasmic, where BRISC deubiquitinates IFNAR1, NLRP3 and other cytoplasmic substrates. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that |
| GO:0005737 cytoplasm | IPI PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: Cytoplasm (IPI). As a BRISC subunit, BABAM1 is also cytoplasmic, where BRISC deubiquitinates IFNAR1, NLRP3 and other cytoplasmic substrates. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [PMID:31253574 "While BRCA1-A is predominantly confined to the nucleus, BRISC localizes to the nucleus and the cytoplasm, where its wide range of reported substrates includes ATF4, THAP5, NLRP3, and the cytosolic domain of IFNAR1, an interferon receptor (Ambivero et al., 2012, Cilenti et al., 2011, Py et al., 2013, Zheng et al., 2013)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that PMID:31253574 While BRCA1-A is predominantly confined to the nucleus, BRISC localizes to the nucleus and the cytoplasm, where its wide range of reported substrates includes ATF4, THAP5, NLRP3, and the cytosolic domain of IFNAR1, an interferon receptor (Ambivero et al., 2012, Cilenti et al., 2011, Py et al., 2013, Zheng et al., 2013). |
| GO:0005737 cytoplasm | NAS PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: Cytoplasm (NAS). As a BRISC subunit, BABAM1 is also cytoplasmic, where BRISC deubiquitinates IFNAR1, NLRP3 and other cytoplasmic substrates. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [PMID:31253574 "While BRCA1-A is predominantly confined to the nucleus, BRISC localizes to the nucleus and the cytoplasm, where its wide range of reported substrates includes ATF4, THAP5, NLRP3, and the cytosolic domain of IFNAR1, an interferon receptor (Ambivero et al., 2012, Cilenti et al., 2011, Py et al., 2013, Zheng et al., 2013)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that PMID:31253574 While BRCA1-A is predominantly confined to the nucleus, BRISC localizes to the nucleus and the cytoplasm, where its wide range of reported substrates includes ATF4, THAP5, NLRP3, and the cytosolic domain of IFNAR1, an interferon receptor (Ambivero et al., 2012, Cilenti et al., 2011, Py et al., 2013, Zheng et al., 2013). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5691439 | ACCEPT | Summary: Cytosol (TAS). Cytosolic pool, as part of BRISC. Accepted. Reactome event: 'BRISC complex deubiquitinates NLRP3'. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749,"] [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261749, file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that |
| GO:0006282 regulation of DNA repair | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: Regulation of DNA repair (NAS). A correct parent of the positive-regulation rows. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:20656689 "Finally, BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double strand breaks."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:20656689 Finally, BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double strand breaks. |
| GO:0006302 double-strand break repair | IBA GO_REF:0000033 | ACCEPT | Summary: Double-strand break repair (IBA). BABAM1 is required for BRCA1 recruitment and retention at DNA double-strand breaks and for ionizing-radiation resistance. It acts by keeping the BRCA1-A complex intact. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001437420 SUPPORTS TRANSFER MERIT40 family node for the DNA-damage terms (DSB repair, G2 checkpoint, nuclear body). Human BABAM1's own IMP/IDA annotations are the descendant evidence. UniProtKB:Q9NWV8 SUPPORTS TRANSFER The target itself, with IDA/IMP support for this term. Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it |
| GO:0006302 double-strand break repair | IMP PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: Double-strand break repair (IMP). BABAM1 is required for BRCA1 recruitment and retention at DNA double-strand breaks and for ionizing-radiation resistance. It acts by keeping the BRCA1-A complex intact. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261746 "Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261746 Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation. |
| GO:0006302 double-strand break repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Double-strand break repair (IMP). BABAM1 is required for BRCA1 recruitment and retention at DNA double-strand breaks and for ionizing-radiation resistance. It acts by keeping the BRCA1-A complex intact. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261748 "Together, our study reveals that a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261748 Together, our study reveals that a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization. |
| GO:0006302 double-strand break repair | IMP PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Double-strand break repair (IMP). BABAM1 is required for BRCA1 recruitment and retention at DNA double-strand breaks and for ionizing-radiation resistance. It acts by keeping the BRCA1-A complex intact. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261749 "The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261749 The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Mitotic G2 DNA damage checkpoint signaling (IBA). BABAM1 depletion impairs the BRCA1-dependent G2/M checkpoint after DNA damage. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001437420 SUPPORTS TRANSFER MERIT40 family node for the DNA-damage terms (DSB repair, G2 checkpoint, nuclear body). Human BABAM1's own IMP/IDA annotations are the descendant evidence. UniProtKB:Q9NWV8 SUPPORTS TRANSFER The target itself, with IDA/IMP support for this term. Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: Mitotic G2 DNA damage checkpoint signaling (IMP). BABAM1 depletion impairs the BRCA1-dependent G2/M checkpoint after DNA damage. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261746 "Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261746 Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Mitotic G2 DNA damage checkpoint signaling (IMP). BABAM1 depletion impairs the BRCA1-dependent G2/M checkpoint after DNA damage. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261748 "Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261748 Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Mitotic G2 DNA damage checkpoint signaling (IMP). BABAM1 depletion impairs the BRCA1-dependent G2/M checkpoint after DNA damage. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261749 "The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261749 The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. |
| GO:0010212 response to ionizing radiation | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Response to ionizing radiation (IMP). BABAM1 (NBA1) was identified in a screen for ionizing-radiation resistance, and its loss sensitizes cells to IR. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261748 "Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261748 Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage. |
| GO:0010212 response to ionizing radiation | IMP PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Response to ionizing radiation (IMP). BABAM1 (NBA1) was identified in a screen for ionizing-radiation resistance, and its loss sensitizes cells to IR. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261749 "In this study, we employed a genetic screen to identify a gene, NBA1 (new component of the BRCA1 A complex), that is required for resistance to ionizing radiation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261749 In this study, we employed a genetic screen to identify a gene, NBA1 (new component of the BRCA1 A complex), that is required for resistance to ionizing radiation. |
| GO:0016604 nuclear body | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear body (IBA). Nuclear bodies. The basis is HPA's steady-state nuclear-body staining (IDA) and the inherited IBA. Damage-induced DSB foci are a separate, transient structure. A minor location; kept as non-core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001437420 SUPPORTS TRANSFER MERIT40 family node for the DNA-damage terms (DSB repair, G2 checkpoint, nuclear body). Human BABAM1's own IMP/IDA annotations are the descendant evidence. UniProtKB:Q9NWV8 SUPPORTS TRANSFER The target itself, with IDA/IMP support for this term. Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear body (IDA). Human Protein Atlas immunofluorescence. Nuclear bodies. The basis is HPA's steady-state nuclear-body staining (IDA) and the inherited IBA. Damage-induced DSB foci are a separate, transient structure. A minor location; kept as non-core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746,"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:19261746, |
| GO:0034516 response to vitamin B6 | NAS PMID:31142841 Metabolic control of BRISC-SHMT2 assembly regulates immune s... | MARK AS OVER ANNOTATED | Summary: Response to vitamin B6 (NAS). The source shows that intracellular pyridoxal-5'-phosphate controls whether the metabolic enzyme SHMT2 binds and inhibits BRISC: only PLP-free SHMT2 dimers bind. The vitamin B6 sensing is done by SHMT2, and BABAM1 is a structural BRISC subunit downstream of it. Over-annotation. Reason: [PMID:31142841 "Only the inactive SHMT2 dimer-and not the active PLP-bound tetramer-binds and inhibits BRISC."] [PMID:31142841 "Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses."] Supporting Evidence: PMID:31142841 Only the inactive SHMT2 dimer-and not the active PLP-bound tetramer-binds and inhibits BRISC. PMID:31142841 Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. |
| GO:0042802 identical protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | KEEP AS NON CORE | Summary: Identical protein binding (IPI). Purified MERIT40 forms a dimer, and the BRCA1-A and BRISC architectures each contain two copies. This reflects complex stoichiometry rather than a distinct function. Kept as non-core. Reason: [PMID:24125081 "Our findings suggest that MERIT40 forms a dimer in a concentration-independent manner."] [PMID:31253574 "Analogous to BRCA1-A, the BRISC structure comprises two copies each of proteins BRCC36, ABRO1, BRE, MERIT40, and SHMT2Ξ±."] Supporting Evidence: PMID:24125081 Our findings suggest that MERIT40 forms a dimer in a concentration-independent manner. PMID:31253574 Analogous to BRCA1-A, the BRISC structure comprises two copies each of proteins BRCC36, ABRO1, BRE, MERIT40, and SHMT2Ξ±. |
| GO:0044818 mitotic G2/M transition checkpoint | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: Mitotic G2/M transition checkpoint (NAS). A parent of the accepted core term GO:0007095 (mitotic G2 DNA damage checkpoint signaling), so it is accepted at the same altitude. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:22369660 "Interestingly knocking down any components of the A complex such as Rap80, Abraxas, NBA1, BRE, BRCC36 or the C complex component CtIP, the phenotype of G2-M checkpoint deficiency is much milder compared to cells depleted of BRCA1 indicating that only partial function of BRCA1 in G2-M checkpoint control is defective when individual complex was deficient [32,35,36,38,40,69,70,76]."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:22369660 Interestingly knocking down any components of the A complex such as Rap80, Abraxas, NBA1, BRE, BRCC36 or the C complex component CtIP, the phenotype of G2-M checkpoint deficiency is much milder compared to cells depleted of BRCA1 indicating that only partial function of BRCA1 in G2-M checkpoint control is defective when individual complex was deficient [32,35,36,38,40,69,70,76]. |
| GO:0045739 positive regulation of DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: Positive regulation of DNA repair (IEA). BABAM1 promotes BRCA1-A complex integrity and BRCA1 localization at DSBs, supporting repair. BRCA1-A also restrains end resection, so the net effect on repair pathway choice is complex. The IMP data show reduced repair-linked responses on depletion. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: Positive regulation of DNA repair (IMP). BABAM1 promotes BRCA1-A complex integrity and BRCA1 localization at DSBs, supporting repair. BRCA1-A also restrains end resection, so the net effect on repair pathway choice is complex. The IMP data show reduced repair-linked responses on depletion. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261746 "Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261746 Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation. |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Positive regulation of DNA repair (IMP). BABAM1 promotes BRCA1-A complex integrity and BRCA1 localization at DSBs, supporting repair. BRCA1-A also restrains end resection, so the net effect on repair pathway choice is complex. The IMP data show reduced repair-linked responses on depletion. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261748 "Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261748 Importantly, MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily via a role in maintaining the stability of BRE and this five-subunit protein complex at sites of DNA damage. |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Positive regulation of DNA repair (IMP). BABAM1 promotes BRCA1-A complex integrity and BRCA1 localization at DSBs, supporting repair. BRCA1-A also restrains end resection, so the net effect on repair pathway choice is complex. The IMP data show reduced repair-linked responses on depletion. Accepted. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261749 "The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261749 The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. |
| GO:0070531 BRCA1-A complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1-A complex (IBA). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001038203 SUPPORTS TRANSFER MERIT40 family node for the complex-membership terms (BRCA1-A, BRISC). Human BABAM1's IDA membership annotations are the descendant evidence. UniProtKB:Q9NWV8 SUPPORTS TRANSFER The target itself, with IDA/IMP support for this term. Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it |
| GO:0070531 BRCA1-A complex | IDA PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: BRCA1-A complex (IDA). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261746 "Here, we identify MERIT40 (Mediator of Rap80 Interactions and Targeting 40 kD)/(C19orf62) as a Rap80-associated protein that is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261746 Here, we identify MERIT40 (Mediator of Rap80 Interactions and Targeting 40 kD)/(C19orf62) as a Rap80-associated protein that is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1-A complex (IDA). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261748 "MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: BRCA1-A complex (IDA). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:19261749 "Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. |
| GO:0070531 BRCA1-A complex | IEA GO_REF:0000002 | ACCEPT | Summary: BRCA1-A complex (IEA). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it |
| GO:0070531 BRCA1-A complex | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: BRCA1-A complex (NAS). BABAM1 (MERIT40/NBA1) is a core subunit of the nuclear BRCA1-A complex (RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2/BRE, BABAM1). It binds BRE directly and keeps the complex stable and targeted to DSBs. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [file:human/BABAM1/BABAM1-uniprot.txt "CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it"] [PMID:20656689 "BRCC36 is a JAMM (JAB1/MPN/Mov34 metalloenzyme) domain, lysine 63-ubiquitin (K63-Ub)-specific deubiquitinating enzyme (DUB) and a member of two protein complexes: the DNA damage-responsive BRCA1-RAP80 complex, and the cytoplasmic BRCC36 isopeptidase complex (BRISC)."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically file:human/BABAM1/BABAM1-uniprot.txt CC linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it PMID:20656689 BRCC36 is a JAMM (JAB1/MPN/Mov34 metalloenzyme) domain, lysine 63-ubiquitin (K63-Ub)-specific deubiquitinating enzyme (DUB) and a member of two protein complexes: the DNA damage-responsive BRCA1-RAP80 complex, and the cytoplasmic BRCC36 isopeptidase complex (BRISC). |
| GO:0070552 BRISC complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRISC complex (IBA). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001038203 SUPPORTS TRANSFER MERIT40 family node for the complex-membership terms (BRCA1-A, BRISC). Human BABAM1's IDA membership annotations are the descendant evidence. UniProtKB:Q9NWV8 SUPPORTS TRANSFER The target itself, with IDA/IMP support for this term. Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is |
| GO:0070552 BRISC complex | IDA PMID:19214193 K63-specific deubiquitination by two JAMM/MPN+ complexes: BR... | ACCEPT | Summary: BRISC complex (IDA). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] [PMID:19214193 "When we analysed the individual complexes, we found that the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC), but that the CSN-associated activity was due entirely to an interaction with Brcc36."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is PMID:19214193 When we analysed the individual complexes, we found that the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC), but that the CSN-associated activity was due entirely to an interaction with Brcc36. |
| GO:0070552 BRISC complex | IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: BRISC complex (IDA). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] [PMID:24075985 "BRISC-SHMT2 complexes localize to and deubiquitinate actively engaged IFNAR1, thus limiting its K63-Ub-mediated internalization and lysosomal degradation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is PMID:24075985 BRISC-SHMT2 complexes localize to and deubiquitinate actively engaged IFNAR1, thus limiting its K63-Ub-mediated internalization and lysosomal degradation. |
| GO:0070552 BRISC complex | IEA GO_REF:0000002 | ACCEPT | Summary: BRISC complex (IEA). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is |
| GO:0070552 BRISC complex | IPI PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: BRISC complex (IPI). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] [PMID:31253574 "BRCA1-A and BRISC also contain proteins MERIT40 (Feng et al., 2009, Shao et al., 2009, Wang et al., 2009) and BRE (Feng et al., 2009, Hu et al., 2011a) as core components."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is PMID:31253574 BRCA1-A and BRISC also contain proteins MERIT40 (Feng et al., 2009, Shao et al., 2009, Wang et al., 2009) and BRE (Feng et al., 2009, Hu et al., 2011a) as core components. |
| GO:0070552 BRISC complex | NAS PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: BRISC complex (NAS). BABAM1 is a core subunit of the BRISC deubiquitinase complex (ABRAXAS2, BRCC3, BABAM2, BABAM1, with SHMT2), which cleaves K63-linked ubiquitin in the cytoplasm and nucleus. Core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC Component of the BRISC complex, a multiprotein complex that"] [file:human/BABAM1/BABAM1-uniprot.txt "CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is"] [PMID:31253574 "BRCA1-A and BRISC also contain proteins MERIT40 (Feng et al., 2009, Shao et al., 2009, Wang et al., 2009) and BRE (Feng et al., 2009, Hu et al., 2011a) as core components."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC Component of the BRISC complex, a multiprotein complex that file:human/BABAM1/BABAM1-uniprot.txt CC (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is PMID:31253574 BRCA1-A and BRISC also contain proteins MERIT40 (Feng et al., 2009, Shao et al., 2009, Wang et al., 2009) and BRE (Feng et al., 2009, Hu et al., 2011a) as core components. |
| GO:0140861 DNA repair-dependent chromatin remodeling | IMP PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | KEEP AS NON CORE | Summary: DNA repair-dependent chromatin remodeling (IMP). BABAM1 is needed for the BRCA1-A complex's K63-ubiquitin DUB activity, which edits ubiquitin chains on damaged chromatin (H2A/H2AX). An output of the complex; kept as non-core. Reason: [file:human/BABAM1/BABAM1-uniprot.txt "CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically"] [PMID:19261746 "Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation."] Supporting Evidence: file:human/BABAM1/BABAM1-uniprot.txt CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically PMID:19261746 Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:30533199 MERIT40-dependent recruitment of tankyrase to damaged DNA an... | NEW | Summary: Protein-macromolecule adaptor activity (NEW, IDA). MERIT40 binds BRE (BABAM2) directly to assemble the BRCA1-A and BRISC complexes. Through its RXXPEG motif it also binds tankyrase and brings it to DNA double-strand breaks, which depends on the MERIT40 interaction. Bringing tankyrase into contact with the damage-site complex is an adaptor activity. Affinage's deep research also frames MERIT40 as a scaffold/adaptor. Reason: [PMID:30533199 "We found that tankyrase is localized to DSBs through its interaction with MERIT40, and pharmacological inhibition of tankyrase sensitized human lung cancer cells to DNA-damaging anticancer agents."] [PMID:30571846 "Here we demonstrated that MERIT40, a core component of BRISC complex, directly interacts with the RXXPEG motif in the ARC-V domain of Tankyrase1(TNKS1)."] [PMID:19261748 "MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45."] Supporting Evidence: PMID:30533199 We found that tankyrase is localized to DSBs through its interaction with MERIT40, and pharmacological inhibition of tankyrase sensitized human lung cancer cells to DNA-damaging anticancer agents. PMID:30571846 Here we demonstrated that MERIT40, a core component of BRISC complex, directly interacts with the RXXPEG motif in the ARC-V domain of Tankyrase1(TNKS1). PMID:19261748 MERIT40 is assembled into this RAP80/CCDC98-containing complex via its direct interaction with BRE/BRCC45. |
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Download this section (compressed HTML)Q: MERIT40 localizes to psoralen ICLs in HeLa cells, its knockdown reduces BRCA1/RAD51/RPA recruitment there, and Merit40-null MEFs are MMC-sensitive but not IR-sensitive. Should BABAM1 (and the BRCA1-A complex) carry interstrand cross-link repair (GO:0036297)? BRCA1, RAP80 and ABRAXAS1 currently have no such GOA annotation, so it is not asserted here.
Q: Is MERIT40's tankyrase-recruiting RXXPEG motif a distinct, separable adaptor function from its structural role in BRCA1-A and BRISC, and is it regulated by Akt/mTORC2 phosphorylation?
Q: Does BABAM1 have any activity beyond scaffolding (for example ubiquitin or chromatin binding through its VWA domain), and how does it partition between the BRCA1-A and BRISC complexes?
Experiment: Use structure-guided BABAM1 mutants that disrupt BRE binding versus other VWA surfaces to separate complex-integrity functions from any direct substrate engagement, in both BRCA1-A foci formation and BRISC-IFNAR1 assays.
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