{"gene":"BABAM1","run_date":"2026-04-28T17:12:38","timeline":{"discoveries":[{"year":2009,"finding":"BABAM1 (NBA1/MERIT40) is a component of the BRCA1 A complex (containing BRCA1/BARD1, Abraxas, RAP80, BRCC36, and BRE), localizes to sites of DNA damage, and is required for BRE and Abraxas protein stability and for recruitment of BRCA1 to DNA damage sites.","method":"Genetic screen, proteomic analysis (mass spectrometry), co-immunoprecipitation, immunofluorescence at DNA damage foci, knockdown with functional readouts (IR resistance, G2/M checkpoint)","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP and proteomic analysis replicated across three independent labs in the same year","pmids":["19261749","19261748","19261746"],"is_preprint":false},{"year":2009,"finding":"MERIT40 (BABAM1) is assembled into the RAP80/Abraxas-containing complex via direct interaction with BRE/BRCC45, and is required for maintaining the stability of BRE and the five-subunit BRCA1-A complex at sites of DNA damage.","method":"Co-immunoprecipitation, siRNA knockdown, western blotting for protein stability, immunofluorescence at DNA damage foci","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP with functional knockdown, replicated across multiple labs","pmids":["19261748","19261746"],"is_preprint":false},{"year":2009,"finding":"MERIT40 (BABAM1) is required for Rap80-associated lysine-63 ubiquitin deubiquitinase (DUB) activity of BRCC36, linking complex integrity to ubiquitin chain hydrolysis at DNA double-strand breaks.","method":"Co-immunoprecipitation, DUB activity assay, siRNA knockdown, immunofluorescence","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro DUB activity assay combined with reciprocal Co-IP and knockdown","pmids":["19261746"],"is_preprint":false},{"year":2011,"finding":"BABAM1 (NBA1/MERIT40) exists in two distinct BRCC36-containing complexes: one nuclear (with Abraxas/BRCA1) and one cytoplasmic (with ABRO1, lacking BRCA1 interaction); both share BRE and NBA1, and NBA1 interacts with BRE via its C-terminal conserved motif engaging the C-terminal UEV domain of BRE.","method":"Co-immunoprecipitation, subcellular fractionation, domain-mapping mutagenesis, siRNA knockdown with protein stability and IR-resistance assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — domain mutagenesis combined with fractionation and functional rescue, single lab but multiple orthogonal methods","pmids":["21282113"],"is_preprint":false},{"year":2015,"finding":"MERIT40 (BABAM1) is phosphorylated by Akt at a specific site following doxorubicin treatment, and this phosphorylation facilitates assembly of the BRCA1-A complex in response to DNA damage, contributing to DNA repair and cell survival.","method":"In vitro Akt kinase assay, phosphosite identification, phospho-mimetic/phospho-dead mutants, co-immunoprecipitation, cell viability assays with PI3K/Akt inhibitors","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro kinase assay plus mutagenesis and functional complex assembly assays","pmids":["26027929"],"is_preprint":false},{"year":2015,"finding":"MERIT40 (BABAM1) is required for repair of DNA interstrand cross-links (ICLs): Merit40-null mice are hypersensitive to ICL agents but not IR; MERIT40 is recruited to ICL lesions prior to FANCD2, and loss of MERIT40 delays ICL unhooking, reduces end resection, and impairs homologous recombination at ICL damage.","method":"Merit40 knockout mice, ICL sensitivity assays, FANCD2 foci timing by immunofluorescence, end-resection and HR assays, genetic epistasis with Brca2 and Fancd2 double mutants","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 — knockout mouse model with multiple orthogonal repair assays and genetic epistasis","pmids":["26338419"],"is_preprint":false},{"year":2015,"finding":"MERIT40 (BABAM1)-containing DUB complexes attenuate hematopoietic stem cell (HSC) expansion by dampening thrombopoietin (Tpo)/Mpl receptor signaling; M40-deficient HSCs show hypersensitivity to Tpo and expanded HSC pools, with the phenotype abrogated by Mpl deletion.","method":"Merit40 knockout mice, HSC phenotyping by flow cytometry, serial transplantation assays, genetic epistasis (M40/Mpl double knockout)","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 — knockout mouse with genetic epistasis and functional HSC reconstitution assays","pmids":["25636339"],"is_preprint":false},{"year":2018,"finding":"MERIT40 (BABAM1) directly binds Tankyrase (a PARP family member) via a tankyrase-binding consensus motif, and recruits Tankyrase to DNA double-strand break sites; this interaction is required for MERIT40-mediated resistance to ionizing radiation.","method":"LC-MS/MS interactome, co-immunoprecipitation, site-directed mutagenesis of tankyrase-binding motif, immunofluorescence at DSBs, knockdown/rescue assays","journal":"Oncotarget","confidence":"High","confidence_rationale":"Tier 2 — MS identification confirmed by Co-IP, mutagenesis of binding motif, and functional rescue","pmids":["30533199"],"is_preprint":false},{"year":2019,"finding":"The RXXPEG motif of MERIT40 (BABAM1) mediates direct interaction with the ARC-V domain of Tankyrase1, and mutation of this motif (R28A) disrupts Tankyrase1 binding and causes mitotic defects including aberrant spindle assembly and chromosome misalignment.","method":"Site-directed mutagenesis of RXXPEG motif, co-immunoprecipitation, live-cell and fixed immunofluorescence of mitotic spindles","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 2 — mutagenesis with Co-IP and functional mitotic phenotype, single lab","pmids":["30571846"],"is_preprint":false},{"year":2013,"finding":"MERIT40 (BABAM1) forms a homodimer in a concentration-independent manner and interacts with Abraxas via its stable central domain, which has structural similarity to a vWA-like region; this interaction helps bridge and stabilize the BRCA1-A complex.","method":"Recombinant protein purification, spectroscopic and calorimetric unfolding analysis, molecular modeling, monomer-monomer docking, protease digestion mapping, protein-protein interaction assays","journal":"Journal of biomolecular structure & dynamics","confidence":"Medium","confidence_rationale":"Tier 1–3 — biophysical characterization combined with interaction assays, single lab","pmids":["24125081"],"is_preprint":false},{"year":2022,"finding":"BABAM1 is phosphorylated at Ser29 by mTORC2 signaling, and this phosphorylation is required for initiation of DNA damage response and DNA repair in glioblastoma cells; mTORC2 inhibition ablates pBABAM1(Ser29), reduces nuclear DNA repair activity, and promotes apoptosis.","method":"Quantitative phosphoproteomics, mTORC2 inhibitor treatment, phospho-site mutant constructs, γH2AX foci assay, apoptosis assay","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 — phosphoproteomics with functional validation using inhibitors and mutants, single lab","pmids":["36315652"],"is_preprint":false},{"year":2023,"finding":"WWOX interacts with MERIT40 (BABAM1) and inhibits excessive homologous recombination activity induced by MERIT40 overexpression; mechanistically, WWOX impairs the MERIT40-Tankyrase interaction, preventing Tankyrase recruitment to DSBs.","method":"Co-immunoprecipitation, HR reporter assays, MERIT40/WWOX overexpression and knockdown, immunofluorescence at DSBs","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP with functional HR assay, single lab","pmids":["37248434"],"is_preprint":false}],"current_model":"BABAM1 (MERIT40/NBA1) is a core structural component of two distinct BRCC36 deubiquitinase complexes — the nuclear BRCA1-A complex (with RAP80, Abraxas, BRCC36, BRE, and BRCA1/BARD1) and the cytoplasmic BRISC complex (with ABRO1) — where it interacts with BRE via its C-terminal motif to maintain complex integrity, facilitates BRCC36-dependent K63-ubiquitin chain deubiquitination at DNA double-strand breaks, recruits BRCA1 and Tankyrase to damage sites via an RXXPEG motif, and is post-translationally regulated by both Akt and mTORC2-mediated phosphorylation to promote DNA damage response and repair, including interstrand cross-link repair upstream of FANCD2 and homologous recombination."},"narrative":{"teleology":[{"year":2009,"claim":"The discovery that BABAM1 is an integral subunit of the BRCA1-A complex established its identity as a previously unrecognized scaffolding factor required for BRCA1 recruitment and G2/M checkpoint activation at DNA double-strand breaks.","evidence":"Genetic screens, mass spectrometry, reciprocal co-immunoprecipitation, and siRNA knockdown in human cells across three independent labs","pmids":["19261749","19261748","19261746"],"confidence":"High","gaps":["How BABAM1 is itself recruited to damage sites was not defined","Structure of the full pentameric BRCA1-A complex was unknown","Whether BABAM1 participates in complexes outside the BRCA1-A complex was not tested"]},{"year":2009,"claim":"Demonstrating that BABAM1 is required for BRCC36-dependent K63-ubiquitin deubiquitinase activity connected complex integrity to ubiquitin chain hydrolysis, establishing the enzymatic consequence of BABAM1 loss.","evidence":"In vitro DUB activity assays on K63-linked ubiquitin chains combined with siRNA knockdown in human cells","pmids":["19261746"],"confidence":"High","gaps":["Whether BABAM1 directly activates BRCC36 or acts indirectly via BRE/Abraxas stabilization was unclear","No structural basis for how complex assembly enables DUB activity"]},{"year":2011,"claim":"Identification of a second, cytoplasmic BRCC36 complex (BRISC, containing ABRO1) sharing BRE and BABAM1 revealed that BABAM1 serves as a common structural component of distinct DUB assemblies distinguished by nuclear versus cytoplasmic localization.","evidence":"Subcellular fractionation, co-immunoprecipitation, and C-terminal domain-mapping mutagenesis in human cells","pmids":["21282113"],"confidence":"High","gaps":["Cytoplasmic substrates of the BRISC complex were not identified","How BABAM1 partitioning between BRCA1-A and BRISC is regulated was unknown"]},{"year":2013,"claim":"Biophysical characterization showing BABAM1 forms a stable homodimer with a vWA-like central domain that bridges Abraxas provided the first structural insight into how BABAM1 organizes the BRCA1-A complex.","evidence":"Recombinant protein purification, spectroscopic/calorimetric unfolding, molecular modeling, and protein–protein interaction assays","pmids":["24125081"],"confidence":"Medium","gaps":["No high-resolution crystal or cryo-EM structure was determined","Dimerization was not validated by an independent lab","Functional consequence of disrupting dimerization in cells was not tested"]},{"year":2015,"claim":"Knockout mouse studies revealed that BABAM1 functions upstream of FANCD2 in interstrand cross-link repair — promoting unhooking, end resection, and homologous recombination — establishing a repair function distinct from its role at ionizing-radiation-induced breaks.","evidence":"Merit40-null mice, ICL sensitivity assays, FANCD2 foci timing, HR and end-resection assays, genetic epistasis with Brca2 and Fancd2","pmids":["26338419"],"confidence":"High","gaps":["The molecular mechanism by which BABAM1 facilitates ICL unhooking was not defined","Whether K63-DUB activity is specifically required for ICL repair was not tested"]},{"year":2015,"claim":"Akt-mediated phosphorylation of BABAM1 was shown to promote BRCA1-A complex assembly after DNA damage, linking PI3K/Akt signaling to the DSB repair machinery and explaining how survival signaling modulates repair competence.","evidence":"In vitro Akt kinase assay, phospho-mimetic/dead mutants, co-immunoprecipitation, and cell viability assays with PI3K/Akt inhibitors","pmids":["26027929"],"confidence":"High","gaps":["The precise phosphorylation site's effect on BABAM1 structure or BRE binding was not resolved","Whether Akt phosphorylation selectively affects the BRCA1-A versus BRISC complex was untested"]},{"year":2015,"claim":"BABAM1-containing DUB complexes were found to restrain thrombopoietin/Mpl receptor signaling and limit hematopoietic stem cell expansion, revealing a cytokine-regulatory function outside DNA repair.","evidence":"Merit40 knockout mice, HSC flow cytometry, serial transplantation, and genetic epistasis with Mpl deletion","pmids":["25636339"],"confidence":"High","gaps":["Whether this phenotype is mediated by BRISC, BRCA1-A, or both was not dissected","The ubiquitinated substrate on the Mpl pathway was not identified"]},{"year":2018,"claim":"Identification of Tankyrase as a direct BABAM1-binding partner recruited to DSBs via a tankyrase-binding motif added a PARP-family enzyme to the BABAM1-mediated repair network and showed this interaction is required for ionizing radiation resistance.","evidence":"LC-MS/MS interactome, co-immunoprecipitation, motif mutagenesis, and knockdown/rescue assays in human cells","pmids":["30533199"],"confidence":"High","gaps":["The enzymatic activity of Tankyrase at DSBs (PARylation substrates) was not characterized","Relationship between Tankyrase recruitment and BRCC36 DUB activity was not tested"]},{"year":2019,"claim":"Mapping the RXXPEG motif as the Tankyrase1 ARC-V binding interface and showing its mutation causes mitotic spindle defects extended BABAM1's functional roles beyond DNA repair to mitotic fidelity.","evidence":"Site-directed mutagenesis, co-immunoprecipitation, and live-cell/fixed immunofluorescence of mitotic spindles","pmids":["30571846"],"confidence":"Medium","gaps":["Whether mitotic defects are due to loss of Tankyrase PARylation at spindles or another mechanism was not determined","Single lab observation; independent replication lacking"]},{"year":2022,"claim":"Demonstrating that mTORC2 phosphorylates BABAM1 at Ser29 to initiate DNA damage response in glioblastoma cells identified a second kinase input regulating BABAM1 and established mTORC2 as an upstream activator of DNA repair.","evidence":"Quantitative phosphoproteomics, mTORC2 inhibitor treatment, phospho-site mutants, γH2AX foci and apoptosis assays in glioblastoma cells","pmids":["36315652"],"confidence":"Medium","gaps":["Single cell-type study; generalizability to non-glioblastoma contexts not shown","How Ser29 phosphorylation mechanistically alters BABAM1 interactions was not resolved","Relationship between Akt (Ser-specific) and mTORC2 (Ser29) phosphorylation events is unclear"]},{"year":2023,"claim":"WWOX was identified as a negative regulator that physically interacts with BABAM1 and antagonizes its Tankyrase-recruiting function, providing a mechanism to prevent excessive homologous recombination.","evidence":"Co-immunoprecipitation, HR reporter assays, and overexpression/knockdown of MERIT40 and WWOX in human cells","pmids":["37248434"],"confidence":"Medium","gaps":["Single lab; independent confirmation of the WWOX–BABAM1 interaction is lacking","Whether WWOX competes for the same RXXPEG motif used by Tankyrase was not tested","In vivo relevance (animal model) not demonstrated"]},{"year":null,"claim":"A high-resolution structure of full-length BABAM1 in complex with BRE and/or the complete BRCA1-A/BRISC assembly, and the identification of specific ubiquitinated substrates through which BABAM1-containing DUB complexes regulate ICL repair and Mpl signaling, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No atomic-resolution structure of BABAM1 or its complexes from the primary literature","Ubiquitinated substrates of the BABAM1-dependent DUB complexes in ICL repair and thrombopoietin signaling are unknown","How BABAM1 partitioning between nuclear BRCA1-A and cytoplasmic BRISC is regulated remains undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,3,9]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,6]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[3]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,5]}],"pathway":[{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[0,2,4,5,7,10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,6,10]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,8]}],"complexes":["BRCA1-A complex","BRISC complex"],"partners":["BRE","BRCC36","ABRAXAS1","RAP80","ABRO1","TNKS","WWOX"],"other_free_text":[]},"mechanistic_narrative":"BABAM1 (MERIT40/NBA1) is a scaffolding subunit of K63-linked ubiquitin deubiquitinase complexes that functions in DNA damage signaling, DNA repair, and cytokine receptor regulation. It assembles into two distinct BRCC36-containing complexes — the nuclear BRCA1-A complex (with RAP80, Abraxas, BRCC36, BRE, and BRCA1/BARD1) and the cytoplasmic BRISC complex (with ABRO1) — by binding BRE via its C-terminal motif; this interaction is essential for subunit stability, K63-ubiquitin deubiquitinase activity, and BRCA1 recruitment to DNA double-strand breaks [PMID:19261746, PMID:21282113]. BABAM1 functions upstream of FANCD2 in interstrand cross-link repair, where it promotes lesion unhooking, end resection, and homologous recombination, and it recruits Tankyrase to damage sites via an RXXPEG motif that is also required for proper mitotic spindle assembly [PMID:26338419, PMID:30533199, PMID:30571846]. Phosphorylation by Akt and mTORC2 at distinct sites regulates BRCA1-A complex assembly and DNA repair initiation, linking PI3K/mTOR signaling to the DNA damage response [PMID:26027929, PMID:36315652]."},"prefetch_data":{"uniprot":{"accession":"Q9NWV8","full_name":"BRISC and BRCA1-A complex member 1","aliases":["Mediator of RAP80 interactions and targeting subunit of 40 kDa","New component of the BRCA1-A complex"],"length_aa":329,"mass_kda":36.6,"function":"Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9NWV8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BABAM1","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/BABAM1","total_profiled":1310},"omim":[{"mim_id":"612766","title":"BRISC AND BRCA1 A COMPLEX, MEMBER 1; BABAM1","url":"https://www.omim.org/entry/612766"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear bodies","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BABAM1"},"hgnc":{"alias_symbol":["FLJ20571","HSPC142","NBA1","MERIT40"],"prev_symbol":["C19orf62"]},"alphafold":{"accession":"Q9NWV8","domains":[{"cath_id":"3.40.50.410","chopping":"98-301","consensus_level":"high","plddt":94.1739,"start":98,"end":301}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NWV8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NWV8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NWV8-F1-predicted_aligned_error_v6.png","plddt_mean":78.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BABAM1","jax_strain_url":"https://www.jax.org/strain/search?query=BABAM1"},"sequence":{"accession":"Q9NWV8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NWV8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NWV8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NWV8"}},"corpus_meta":[{"pmid":"19261749","id":"PMC_19261749","title":"NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261749","citation_count":143,"is_preprint":false},{"pmid":"19261748","id":"PMC_19261748","title":"MERIT40 facilitates BRCA1 localization and DNA damage repair.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261748","citation_count":132,"is_preprint":false},{"pmid":"19261746","id":"PMC_19261746","title":"MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261746","citation_count":124,"is_preprint":false},{"pmid":"21282113","id":"PMC_21282113","title":"NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21282113","citation_count":62,"is_preprint":false},{"pmid":"26027929","id":"PMC_26027929","title":"MERIT40 Is an Akt Substrate that Promotes Resolution of DNA Damage Induced by Chemotherapy.","date":"2015","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26027929","citation_count":39,"is_preprint":false},{"pmid":"26338419","id":"PMC_26338419","title":"MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links.","date":"2015","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/26338419","citation_count":23,"is_preprint":false},{"pmid":"30533199","id":"PMC_30533199","title":"MERIT40-dependent recruitment of tankyrase to damaged DNA and its implication for cell sensitivity to DNA-damaging anticancer drugs.","date":"2018","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/30533199","citation_count":17,"is_preprint":false},{"pmid":"19572197","id":"PMC_19572197","title":"Mutation screening of the MERIT40 gene encoding a novel BRCA1 and RAP80 interacting protein in breast cancer families.","date":"2009","source":"Breast cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/19572197","citation_count":11,"is_preprint":false},{"pmid":"36315652","id":"PMC_36315652","title":"Phosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells.","date":"2022","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/36315652","citation_count":9,"is_preprint":false},{"pmid":"25636339","id":"PMC_25636339","title":"MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling.","date":"2015","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/25636339","citation_count":8,"is_preprint":false},{"pmid":"24667604","id":"PMC_24667604","title":"Role of MERIT40 in stabilization of BRCA1 complex: a protein-protein interaction study.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/24667604","citation_count":7,"is_preprint":false},{"pmid":"37248434","id":"PMC_37248434","title":"WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer.","date":"2023","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/37248434","citation_count":5,"is_preprint":false},{"pmid":"24125081","id":"PMC_24125081","title":"Structural and functional characterization of the MERIT40 to understand its role in DNA repair.","date":"2013","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/24125081","citation_count":5,"is_preprint":false},{"pmid":"30571846","id":"PMC_30571846","title":"RXXPEG motif of MERIT40 is required to maintain spindle structure and function through its interaction with Tankyrase1.","date":"2019","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/30571846","citation_count":4,"is_preprint":false},{"pmid":"29383164","id":"PMC_29383164","title":"Regulation of macrophage migration in ischemic mouse hearts via an AKT2/NBA1/SPK1 pathway.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29383164","citation_count":1,"is_preprint":false},{"pmid":"21431873","id":"PMC_21431873","title":"Germline mutational analysis of the C19orf62 gene in African-American women with breast cancer.","date":"2011","source":"Breast cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/21431873","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.29.24316388","title":"Isoform-level analyses of 6 cancers uncover extensive genetic risk mechanisms undetected at the gene-level","date":"2024-10-30","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.29.24316388","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8412,"output_tokens":2902,"usd":0.034383},"stage2":{"model":"claude-opus-4-6","input_tokens":6271,"output_tokens":3266,"usd":0.169508},"total_usd":0.203891,"stage1_batch_id":"msgbatch_01TqNM6p6FsoMBT2jzQTwKBr","stage2_batch_id":"msgbatch_01Ya473eco8sTHbvRymQaU8o","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"BABAM1 (NBA1/MERIT40) is a component of the BRCA1 A complex (containing BRCA1/BARD1, Abraxas, RAP80, BRCC36, and BRE), localizes to sites of DNA damage, and is required for BRE and Abraxas protein stability and for recruitment of BRCA1 to DNA damage sites.\",\n      \"method\": \"Genetic screen, proteomic analysis (mass spectrometry), co-immunoprecipitation, immunofluorescence at DNA damage foci, knockdown with functional readouts (IR resistance, G2/M checkpoint)\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and proteomic analysis replicated across three independent labs in the same year\",\n      \"pmids\": [\"19261749\", \"19261748\", \"19261746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MERIT40 (BABAM1) is assembled into the RAP80/Abraxas-containing complex via direct interaction with BRE/BRCC45, and is required for maintaining the stability of BRE and the five-subunit BRCA1-A complex at sites of DNA damage.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, western blotting for protein stability, immunofluorescence at DNA damage foci\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with functional knockdown, replicated across multiple labs\",\n      \"pmids\": [\"19261748\", \"19261746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MERIT40 (BABAM1) is required for Rap80-associated lysine-63 ubiquitin deubiquitinase (DUB) activity of BRCC36, linking complex integrity to ubiquitin chain hydrolysis at DNA double-strand breaks.\",\n      \"method\": \"Co-immunoprecipitation, DUB activity assay, siRNA knockdown, immunofluorescence\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro DUB activity assay combined with reciprocal Co-IP and knockdown\",\n      \"pmids\": [\"19261746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"BABAM1 (NBA1/MERIT40) exists in two distinct BRCC36-containing complexes: one nuclear (with Abraxas/BRCA1) and one cytoplasmic (with ABRO1, lacking BRCA1 interaction); both share BRE and NBA1, and NBA1 interacts with BRE via its C-terminal conserved motif engaging the C-terminal UEV domain of BRE.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, domain-mapping mutagenesis, siRNA knockdown with protein stability and IR-resistance assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — domain mutagenesis combined with fractionation and functional rescue, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"21282113\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 (BABAM1) is phosphorylated by Akt at a specific site following doxorubicin treatment, and this phosphorylation facilitates assembly of the BRCA1-A complex in response to DNA damage, contributing to DNA repair and cell survival.\",\n      \"method\": \"In vitro Akt kinase assay, phosphosite identification, phospho-mimetic/phospho-dead mutants, co-immunoprecipitation, cell viability assays with PI3K/Akt inhibitors\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro kinase assay plus mutagenesis and functional complex assembly assays\",\n      \"pmids\": [\"26027929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 (BABAM1) is required for repair of DNA interstrand cross-links (ICLs): Merit40-null mice are hypersensitive to ICL agents but not IR; MERIT40 is recruited to ICL lesions prior to FANCD2, and loss of MERIT40 delays ICL unhooking, reduces end resection, and impairs homologous recombination at ICL damage.\",\n      \"method\": \"Merit40 knockout mice, ICL sensitivity assays, FANCD2 foci timing by immunofluorescence, end-resection and HR assays, genetic epistasis with Brca2 and Fancd2 double mutants\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — knockout mouse model with multiple orthogonal repair assays and genetic epistasis\",\n      \"pmids\": [\"26338419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 (BABAM1)-containing DUB complexes attenuate hematopoietic stem cell (HSC) expansion by dampening thrombopoietin (Tpo)/Mpl receptor signaling; M40-deficient HSCs show hypersensitivity to Tpo and expanded HSC pools, with the phenotype abrogated by Mpl deletion.\",\n      \"method\": \"Merit40 knockout mice, HSC phenotyping by flow cytometry, serial transplantation assays, genetic epistasis (M40/Mpl double knockout)\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — knockout mouse with genetic epistasis and functional HSC reconstitution assays\",\n      \"pmids\": [\"25636339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MERIT40 (BABAM1) directly binds Tankyrase (a PARP family member) via a tankyrase-binding consensus motif, and recruits Tankyrase to DNA double-strand break sites; this interaction is required for MERIT40-mediated resistance to ionizing radiation.\",\n      \"method\": \"LC-MS/MS interactome, co-immunoprecipitation, site-directed mutagenesis of tankyrase-binding motif, immunofluorescence at DSBs, knockdown/rescue assays\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — MS identification confirmed by Co-IP, mutagenesis of binding motif, and functional rescue\",\n      \"pmids\": [\"30533199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The RXXPEG motif of MERIT40 (BABAM1) mediates direct interaction with the ARC-V domain of Tankyrase1, and mutation of this motif (R28A) disrupts Tankyrase1 binding and causes mitotic defects including aberrant spindle assembly and chromosome misalignment.\",\n      \"method\": \"Site-directed mutagenesis of RXXPEG motif, co-immunoprecipitation, live-cell and fixed immunofluorescence of mitotic spindles\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — mutagenesis with Co-IP and functional mitotic phenotype, single lab\",\n      \"pmids\": [\"30571846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MERIT40 (BABAM1) forms a homodimer in a concentration-independent manner and interacts with Abraxas via its stable central domain, which has structural similarity to a vWA-like region; this interaction helps bridge and stabilize the BRCA1-A complex.\",\n      \"method\": \"Recombinant protein purification, spectroscopic and calorimetric unfolding analysis, molecular modeling, monomer-monomer docking, protease digestion mapping, protein-protein interaction assays\",\n      \"journal\": \"Journal of biomolecular structure & dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–3 — biophysical characterization combined with interaction assays, single lab\",\n      \"pmids\": [\"24125081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BABAM1 is phosphorylated at Ser29 by mTORC2 signaling, and this phosphorylation is required for initiation of DNA damage response and DNA repair in glioblastoma cells; mTORC2 inhibition ablates pBABAM1(Ser29), reduces nuclear DNA repair activity, and promotes apoptosis.\",\n      \"method\": \"Quantitative phosphoproteomics, mTORC2 inhibitor treatment, phospho-site mutant constructs, γH2AX foci assay, apoptosis assay\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — phosphoproteomics with functional validation using inhibitors and mutants, single lab\",\n      \"pmids\": [\"36315652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"WWOX interacts with MERIT40 (BABAM1) and inhibits excessive homologous recombination activity induced by MERIT40 overexpression; mechanistically, WWOX impairs the MERIT40-Tankyrase interaction, preventing Tankyrase recruitment to DSBs.\",\n      \"method\": \"Co-immunoprecipitation, HR reporter assays, MERIT40/WWOX overexpression and knockdown, immunofluorescence at DSBs\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP with functional HR assay, single lab\",\n      \"pmids\": [\"37248434\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BABAM1 (MERIT40/NBA1) is a core structural component of two distinct BRCC36 deubiquitinase complexes — the nuclear BRCA1-A complex (with RAP80, Abraxas, BRCC36, BRE, and BRCA1/BARD1) and the cytoplasmic BRISC complex (with ABRO1) — where it interacts with BRE via its C-terminal motif to maintain complex integrity, facilitates BRCC36-dependent K63-ubiquitin chain deubiquitination at DNA double-strand breaks, recruits BRCA1 and Tankyrase to damage sites via an RXXPEG motif, and is post-translationally regulated by both Akt and mTORC2-mediated phosphorylation to promote DNA damage response and repair, including interstrand cross-link repair upstream of FANCD2 and homologous recombination.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"BABAM1 (MERIT40/NBA1) is a scaffolding subunit of K63-linked ubiquitin deubiquitinase complexes that functions in DNA damage signaling, DNA repair, and cytokine receptor regulation. It assembles into two distinct BRCC36-containing complexes — the nuclear BRCA1-A complex (with RAP80, Abraxas, BRCC36, BRE, and BRCA1/BARD1) and the cytoplasmic BRISC complex (with ABRO1) — by binding BRE via its C-terminal motif; this interaction is essential for subunit stability, K63-ubiquitin deubiquitinase activity, and BRCA1 recruitment to DNA double-strand breaks [PMID:19261746, PMID:21282113]. BABAM1 functions upstream of FANCD2 in interstrand cross-link repair, where it promotes lesion unhooking, end resection, and homologous recombination, and it recruits Tankyrase to damage sites via an RXXPEG motif that is also required for proper mitotic spindle assembly [PMID:26338419, PMID:30533199, PMID:30571846]. Phosphorylation by Akt and mTORC2 at distinct sites regulates BRCA1-A complex assembly and DNA repair initiation, linking PI3K/mTOR signaling to the DNA damage response [PMID:26027929, PMID:36315652].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"The discovery that BABAM1 is an integral subunit of the BRCA1-A complex established its identity as a previously unrecognized scaffolding factor required for BRCA1 recruitment and G2/M checkpoint activation at DNA double-strand breaks.\",\n      \"evidence\": \"Genetic screens, mass spectrometry, reciprocal co-immunoprecipitation, and siRNA knockdown in human cells across three independent labs\",\n      \"pmids\": [\"19261749\", \"19261748\", \"19261746\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How BABAM1 is itself recruited to damage sites was not defined\",\n        \"Structure of the full pentameric BRCA1-A complex was unknown\",\n        \"Whether BABAM1 participates in complexes outside the BRCA1-A complex was not tested\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Demonstrating that BABAM1 is required for BRCC36-dependent K63-ubiquitin deubiquitinase activity connected complex integrity to ubiquitin chain hydrolysis, establishing the enzymatic consequence of BABAM1 loss.\",\n      \"evidence\": \"In vitro DUB activity assays on K63-linked ubiquitin chains combined with siRNA knockdown in human cells\",\n      \"pmids\": [\"19261746\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether BABAM1 directly activates BRCC36 or acts indirectly via BRE/Abraxas stabilization was unclear\",\n        \"No structural basis for how complex assembly enables DUB activity\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identification of a second, cytoplasmic BRCC36 complex (BRISC, containing ABRO1) sharing BRE and BABAM1 revealed that BABAM1 serves as a common structural component of distinct DUB assemblies distinguished by nuclear versus cytoplasmic localization.\",\n      \"evidence\": \"Subcellular fractionation, co-immunoprecipitation, and C-terminal domain-mapping mutagenesis in human cells\",\n      \"pmids\": [\"21282113\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Cytoplasmic substrates of the BRISC complex were not identified\",\n        \"How BABAM1 partitioning between BRCA1-A and BRISC is regulated was unknown\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Biophysical characterization showing BABAM1 forms a stable homodimer with a vWA-like central domain that bridges Abraxas provided the first structural insight into how BABAM1 organizes the BRCA1-A complex.\",\n      \"evidence\": \"Recombinant protein purification, spectroscopic/calorimetric unfolding, molecular modeling, and protein–protein interaction assays\",\n      \"pmids\": [\"24125081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No high-resolution crystal or cryo-EM structure was determined\",\n        \"Dimerization was not validated by an independent lab\",\n        \"Functional consequence of disrupting dimerization in cells was not tested\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Knockout mouse studies revealed that BABAM1 functions upstream of FANCD2 in interstrand cross-link repair — promoting unhooking, end resection, and homologous recombination — establishing a repair function distinct from its role at ionizing-radiation-induced breaks.\",\n      \"evidence\": \"Merit40-null mice, ICL sensitivity assays, FANCD2 foci timing, HR and end-resection assays, genetic epistasis with Brca2 and Fancd2\",\n      \"pmids\": [\"26338419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular mechanism by which BABAM1 facilitates ICL unhooking was not defined\",\n        \"Whether K63-DUB activity is specifically required for ICL repair was not tested\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Akt-mediated phosphorylation of BABAM1 was shown to promote BRCA1-A complex assembly after DNA damage, linking PI3K/Akt signaling to the DSB repair machinery and explaining how survival signaling modulates repair competence.\",\n      \"evidence\": \"In vitro Akt kinase assay, phospho-mimetic/dead mutants, co-immunoprecipitation, and cell viability assays with PI3K/Akt inhibitors\",\n      \"pmids\": [\"26027929\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The precise phosphorylation site's effect on BABAM1 structure or BRE binding was not resolved\",\n        \"Whether Akt phosphorylation selectively affects the BRCA1-A versus BRISC complex was untested\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"BABAM1-containing DUB complexes were found to restrain thrombopoietin/Mpl receptor signaling and limit hematopoietic stem cell expansion, revealing a cytokine-regulatory function outside DNA repair.\",\n      \"evidence\": \"Merit40 knockout mice, HSC flow cytometry, serial transplantation, and genetic epistasis with Mpl deletion\",\n      \"pmids\": [\"25636339\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether this phenotype is mediated by BRISC, BRCA1-A, or both was not dissected\",\n        \"The ubiquitinated substrate on the Mpl pathway was not identified\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identification of Tankyrase as a direct BABAM1-binding partner recruited to DSBs via a tankyrase-binding motif added a PARP-family enzyme to the BABAM1-mediated repair network and showed this interaction is required for ionizing radiation resistance.\",\n      \"evidence\": \"LC-MS/MS interactome, co-immunoprecipitation, motif mutagenesis, and knockdown/rescue assays in human cells\",\n      \"pmids\": [\"30533199\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The enzymatic activity of Tankyrase at DSBs (PARylation substrates) was not characterized\",\n        \"Relationship between Tankyrase recruitment and BRCC36 DUB activity was not tested\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Mapping the RXXPEG motif as the Tankyrase1 ARC-V binding interface and showing its mutation causes mitotic spindle defects extended BABAM1's functional roles beyond DNA repair to mitotic fidelity.\",\n      \"evidence\": \"Site-directed mutagenesis, co-immunoprecipitation, and live-cell/fixed immunofluorescence of mitotic spindles\",\n      \"pmids\": [\"30571846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether mitotic defects are due to loss of Tankyrase PARylation at spindles or another mechanism was not determined\",\n        \"Single lab observation; independent replication lacking\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrating that mTORC2 phosphorylates BABAM1 at Ser29 to initiate DNA damage response in glioblastoma cells identified a second kinase input regulating BABAM1 and established mTORC2 as an upstream activator of DNA repair.\",\n      \"evidence\": \"Quantitative phosphoproteomics, mTORC2 inhibitor treatment, phospho-site mutants, γH2AX foci and apoptosis assays in glioblastoma cells\",\n      \"pmids\": [\"36315652\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single cell-type study; generalizability to non-glioblastoma contexts not shown\",\n        \"How Ser29 phosphorylation mechanistically alters BABAM1 interactions was not resolved\",\n        \"Relationship between Akt (Ser-specific) and mTORC2 (Ser29) phosphorylation events is unclear\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"WWOX was identified as a negative regulator that physically interacts with BABAM1 and antagonizes its Tankyrase-recruiting function, providing a mechanism to prevent excessive homologous recombination.\",\n      \"evidence\": \"Co-immunoprecipitation, HR reporter assays, and overexpression/knockdown of MERIT40 and WWOX in human cells\",\n      \"pmids\": [\"37248434\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab; independent confirmation of the WWOX–BABAM1 interaction is lacking\",\n        \"Whether WWOX competes for the same RXXPEG motif used by Tankyrase was not tested\",\n        \"In vivo relevance (animal model) not demonstrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A high-resolution structure of full-length BABAM1 in complex with BRE and/or the complete BRCA1-A/BRISC assembly, and the identification of specific ubiquitinated substrates through which BABAM1-containing DUB complexes regulate ICL repair and Mpl signaling, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No atomic-resolution structure of BABAM1 or its complexes from the primary literature\",\n        \"Ubiquitinated substrates of the BABAM1-dependent DUB complexes in ICL repair and thrombopoietin signaling are unknown\",\n        \"How BABAM1 partitioning between nuclear BRCA1-A and cytoplasmic BRISC is regulated remains undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 3, 9]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [0, 2, 4, 5, 7, 10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 6, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"complexes\": [\n      \"BRCA1-A complex\",\n      \"BRISC complex\"\n    ],\n    \"partners\": [\n      \"BRE\",\n      \"BRCC36\",\n      \"ABRAXAS1\",\n      \"RAP80\",\n      \"ABRO1\",\n      \"TNKS\",\n      \"WWOX\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}