{"gene":"MYCBP","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1998,"finding":"AMY-1 (MYCBP) is a novel 11 kDa protein that binds via its C-terminal region to the N-terminal transactivation domain (amino acids 58-148) of C-MYC, and stimulates E-box-dependent transcriptional activation by the MYC/Max complex without directly binding the E-box itself.","method":"Two-hybrid screen, co-immunoprecipitation, transcription reporter assay","journal":"Genes to cells","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal binding mapped by deletion analysis, functional transcription assay, replicated in subsequent studies","pmids":["9797456"],"is_preprint":false},{"year":1998,"finding":"AMY-1 localizes in the cytoplasm under low c-myc expression conditions but translocates to the nucleus during S phase when c-myc expression is elevated, indicating c-myc-dependent nuclear import.","method":"Immunofluorescence, cell cycle analysis, transient transfection","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with functional correlation, single lab but multiple conditions tested","pmids":["9797456"],"is_preprint":false},{"year":2001,"finding":"AMY-1 binds in vitro and in vivo to the RII-binding region of AKAP149 and its testis-specific splicing variant S-AKAP84, forming a ternary complex with the regulatory subunit II (RII) of PKA, and localizes to mitochondria in HeLa cells and sperm via this interaction.","method":"Two-hybrid screen, in vitro binding assay, co-immunoprecipitation, immunofluorescence/subcellular fractionation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vitro binding, and localization confirmed orthogonally in the same study","pmids":["11483602"],"is_preprint":false},{"year":2002,"finding":"AMY-1 binds competitively to AKAP95 (in nucleus) or AKAP84 (in cytoplasm) via their RII-binding regions in a concentration-dependent manner, forms a ternary complex with RII, and this complex prevents the PKA catalytic subunit from binding, thereby suppressing PKA kinase activity.","method":"In vitro binding assay, co-immunoprecipitation, PKA activity assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of complex, PKA activity assay with clear mechanistic read-out, consistent with prior AKAP149 study","pmids":["12414807"],"is_preprint":false},{"year":2002,"finding":"AMY-1 forms a quaternary complex with AAT-1α (a testis-specific protein), S-AKAP84, and RII of PKA in the mitochondria of testis cells; AAT-1 is phosphorylated by PKA in vivo and in vitro, and weakly stimulates PKA phosphorylation activity within this complex.","method":"Two-hybrid screen, co-immunoprecipitation, co-localization, in vitro phosphorylation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and in vitro kinase assay, single lab","pmids":["12223483"],"is_preprint":false},{"year":2002,"finding":"AMY-1 binds to and co-localizes with AMAP-1, a novel testis-specific protein, in HeLa and 293T cells, suggesting a role in spermatogenesis.","method":"Two-hybrid screen, co-immunoprecipitation, immunofluorescence co-localization","journal":"Biochimica et biophysica acta","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP/colocalization, no functional mechanism defined beyond spermatogenesis inference","pmids":["12151104"],"is_preprint":false},{"year":2003,"finding":"The AMY-1 promoter requires Sp1 for basal expression in HeLa and K562 cells, and GATA-1 synergistically activates AMY-1 expression with Sp1 specifically in K562 cells; both proteins were confirmed to bind their respective promoter sites by mobility shift assay.","method":"Luciferase reporter deletion assay, electrophoretic mobility shift assay (EMSA), ectopic expression in insect cells","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — EMSA and reporter assays with multiple deletion constructs, single lab","pmids":["12620400"],"is_preprint":false},{"year":2000,"finding":"Overexpression of AMY-1 in K562 cells induces expression of ε-globin mRNA (an erythrocyte differentiation marker) and accelerates AraC-induced erythrocyte differentiation, suggesting AMY-1 acts as a trigger for erythroid differentiation independently of or differently from c-Myc.","method":"Stable overexpression, RT-PCR for ε-globin, hemoglobin assay, AraC differentiation assay","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gain-of-function with defined molecular and phenotypic readout, single lab","pmids":["10639579"],"is_preprint":false},{"year":2006,"finding":"AMY-1 localizes to the trans-Golgi network (TGN) and nucleus; its TGN localization is mediated specifically through interaction with BIG2 (a GEF for ARFs), but not BIG1, as demonstrated by RNAi knockdown of BIG2/BIG1.","method":"Co-immunoprecipitation with FLAG-AMY-1, immunofluorescence, RNA interference","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi epistasis combined with Co-IP and localization, single lab","pmids":["16866877"],"is_preprint":false},{"year":2014,"finding":"MYCBP forms a complex with Gli transcription factors and Sufu in the nucleus without Hh stimulation; Hh pathway activation causes dissociation of Sufu/p66β from Gli, enabling MYCBP to promote Gli-mediated Hh target gene expression. MYCBP acts downstream of Patched, Smoothened, and the primary cilium.","method":"Proteomic interaction screen, co-immunoprecipitation, ChIP on Hh target promoters, cell-based reporter assays, zebrafish genetic assays","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ChIP, cell assays, zebrafish epistasis), replicated across systems","pmids":["25403183"],"is_preprint":false},{"year":2019,"finding":"EYA4 phosphatase suppresses MYCBP transcription by dephosphorylating β-catenin at Ser552, reducing its nuclear translocation and thereby preventing β-catenin/LEF1-driven transcription from the MYCBP promoter.","method":"EYA4 overexpression/KO in HCC cell lines, siRNA rescue, qRT-PCR, Western blot, ChIP-inferred promoter analysis","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with rescue experiments, phospho-specific mechanistic dissection, single lab","pmids":["31385398"],"is_preprint":false},{"year":2024,"finding":"circ_0002669 directly binds MYCBP protein (identified by biotin pulldown and mass spectrometry) and protects MYCBP from ubiquitin-mediated proteasomal degradation, thereby stabilizing MYCBP and promoting c-Myc target gene expression (CCND1, c-Jun, CDK4).","method":"Biotin pulldown, mass spectrometry, luciferase assay, RNA immunoprecipitation, functional rescue experiments","journal":"Biology direct","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein binding confirmed by pulldown/MS with functional consequence, single lab","pmids":["38570856"],"is_preprint":false},{"year":2026,"finding":"CBLB directly binds MYCBP and promotes its poly-ubiquitination via K48-linked ubiquitination at lysine 20 (K20), leading to proteasomal degradation of MYCBP; CBLB depletion stabilizes MYCBP, activating the c-Myc pathway and upregulating downstream oncogenic targets.","method":"Co-immunoprecipitation, ubiquitination assay, site-specific mutagenesis (K20), Western blot, knockdown/overexpression functional assays","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding, ubiquitination site mapped by mutagenesis, downstream pathway validated, single lab","pmids":["42191055"],"is_preprint":false},{"year":2025,"finding":"Drosophila MYCBP physically associates with itself, Sakura, and Otu, forming binary and ternary complexes; germline-specific depletion of mycbp disrupts Dpp/BMP signaling, causes aberrant bam expression and GSC loss, and impairs female-specific sex-lethal splicing, establishing MYCBP as an essential regulator of GSC self-renewal and differentiation in oogenesis.","method":"Co-immunoprecipitation (binary/ternary complex), null mutant phenotyping, germline-specific RNAi, signaling pathway (BMP/Dpp) and splicing (sxl) readouts","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic null mutant with multiple defined phenotypes, complex formation validated, pathway placement by epistasis, peer-reviewed","pmids":["41325460"],"is_preprint":false}],"current_model":"MYCBP (AMY-1) is an 11 kDa protein that binds the N-terminal transactivation domain of c-MYC to enhance E-box-dependent transcription; it also acts as a modulator of PKA signaling by associating with AKAP scaffold proteins (AKAP84/149, AKAP95) and RII, blocking catalytic subunit access; it localizes dynamically to the cytoplasm, mitochondria (via S-AKAP84 in sperm), trans-Golgi network (via BIG2), and nucleus; in Hedgehog signaling, it forms a nuclear complex with Gli and Sufu and promotes Gli activity upon pathway activation; its protein stability is regulated by ubiquitin-proteasome degradation controlled by the E3 ligase CBLB (K48-linked ubiquitination at K20), and it is protected from degradation by circ_0002669; in Drosophila, MYCBP functions with Sakura and Otu to sustain germline stem cell self-renewal and differentiation through BMP/Dpp signaling and sex-lethal splicing."},"narrative":{"mechanistic_narrative":"MYCBP (AMY-1) is a small adaptor protein that couples transcriptional control to multiple signaling outputs, functioning both as a co-activator of MYC and as a competitive regulator of PKA scaffolding [PMID:9797456, PMID:12414807]. It binds via its C-terminal region to the N-terminal transactivation domain of c-MYC and stimulates E-box-dependent transcription by the MYC/Max complex without contacting DNA directly [PMID:9797456], with nuclear entry tied to elevated c-myc and S-phase progression [PMID:9797456]. In parallel, MYCBP engages the RII-binding regions of AKAP scaffolds—AKAP149/S-AKAP84, AKAP95, and AKAP84—forming ternary complexes with the PKA regulatory subunit II that exclude the catalytic subunit and suppress PKA activity, anchoring the protein to mitochondria, cytoplasm, and nucleus depending on the partner [PMID:11483602, PMID:12414807]; in testis it extends to a quaternary mitochondrial complex with AAT-1α [PMID:12223483]. MYCBP also localizes to the trans-Golgi network through interaction with the ARF-GEF BIG2 [PMID:16866877]. In Hedgehog signaling, MYCBP resides in a nuclear complex with Gli and Sufu, and upon pathway activation and Sufu dissociation it promotes Gli-mediated target gene expression downstream of Patched, Smoothened, and the primary cilium [PMID:25403183]. MYCBP abundance is set by the ubiquitin–proteasome system: the E3 ligase CBLB drives K48-linked ubiquitination at K20 to target it for degradation [PMID:42191055], while circ_0002669 binding shields it to sustain c-Myc target expression [PMID:38570856]. In Drosophila, MYCBP assembles with Sakura and Otu and is essential for germline stem cell self-renewal and differentiation via Dpp/BMP signaling and sex-lethal splicing [PMID:41325460].","teleology":[{"year":1998,"claim":"Established MYCBP's founding molecular function—how a small protein could amplify MYC transcriptional output without DNA contact—by mapping it as a transactivation-domain binding co-activator.","evidence":"Two-hybrid screen, reciprocal deletion-mapped Co-IP, and E-box reporter assays","pmids":["9797456"],"confidence":"High","gaps":["Structural basis of the C-terminal MYCBP/MYC TAD interface unresolved","Whether co-activation requires additional bridging factors not defined"]},{"year":1998,"claim":"Addressed where MYCBP acts by linking its nuclear import to c-myc levels and S-phase, suggesting regulated subcellular partitioning.","evidence":"Immunofluorescence with cell-cycle synchronization and transient transfection","pmids":["9797456"],"confidence":"Medium","gaps":["Import machinery and signal driving translocation not identified","Single-lab correlation rather than direct trafficking assay"]},{"year":2000,"claim":"Tested MYCBP's cellular consequence beyond transcription, showing gain-of-function drives erythroid differentiation, hinting at a MYC-independent role.","evidence":"Stable overexpression in K562 with ε-globin RT-PCR and AraC differentiation assay","pmids":["10639579"],"confidence":"Medium","gaps":["Molecular pathway linking MYCBP to ε-globin induction undefined","Whether effect is MYC-dependent not resolved"]},{"year":2001,"claim":"Opened a second functional axis by showing MYCBP binds AKAP scaffolds and RII to form a mitochondrial PKA-anchoring complex, placing it in cAMP signaling.","evidence":"Two-hybrid, in vitro binding, Co-IP, and subcellular fractionation in HeLa and sperm","pmids":["11483602"],"confidence":"High","gaps":["Functional consequence of mitochondrial anchoring not yet measured here","Relationship to MYC role unclear"]},{"year":2002,"claim":"Defined the mechanistic output of the AKAP association—competitive binding that blocks the PKA catalytic subunit and suppresses kinase activity—establishing MYCBP as a PKA modulator.","evidence":"In vitro binding with AKAP95/AKAP84 and direct PKA activity assays","pmids":["12414807"],"confidence":"High","gaps":["Physiological settings where this suppression dominates not mapped","Quantitative competition with native RII in cells not measured"]},{"year":2002,"claim":"Extended the PKA complex in testis to a quaternary assembly with AAT-1α, a PKA substrate, linking MYCBP scaffolding to spermatogenic signaling.","evidence":"Two-hybrid, reciprocal Co-IP, co-localization, and in vitro phosphorylation assay","pmids":["12223483"],"confidence":"Medium","gaps":["In vivo functional role in spermatogenesis not tested","Single-lab evidence"]},{"year":2002,"claim":"Identified an additional testis-specific partner (AMAP-1), reinforcing a spermatogenesis-associated interactome.","evidence":"Two-hybrid, Co-IP, and immunofluorescence co-localization","pmids":["12151104"],"confidence":"Low","gaps":["Single Co-IP/colocalization with no functional mechanism defined","Spermatogenesis role inferred, not demonstrated"]},{"year":2003,"claim":"Resolved how MYCBP itself is transcriptionally controlled, identifying Sp1-dependent basal expression and GATA-1 synergy in erythroid cells.","evidence":"Reporter deletion assays and EMSA of the AMY-1 promoter in HeLa/K562","pmids":["12620400"],"confidence":"Medium","gaps":["Signals upstream of GATA-1/Sp1 control not defined","Single-lab promoter analysis"]},{"year":2006,"claim":"Added a Golgi localization mode, showing TGN targeting depends specifically on the ARF-GEF BIG2 rather than BIG1.","evidence":"FLAG-MYCBP Co-IP, immunofluorescence, and RNAi epistasis of BIG1/BIG2","pmids":["16866877"],"confidence":"Medium","gaps":["Functional role of MYCBP at the TGN unknown","How TGN pool relates to nuclear/PKA roles unclear"]},{"year":2014,"claim":"Placed MYCBP in Hedgehog signaling as a nuclear Gli/Sufu complex component that promotes Gli activity upon pathway activation, defining a transcriptional role beyond MYC.","evidence":"Proteomic screen, Co-IP, ChIP on Hh targets, reporter assays, and zebrafish epistasis","pmids":["25403183"],"confidence":"High","gaps":["Mechanism by which MYCBP enhances Gli at promoters not detailed","Connection between Hh role and MYC co-activation unexplored"]},{"year":2019,"claim":"Connected MYCBP transcription to Wnt/β-catenin signaling, showing EYA4 dephosphorylation of β-catenin Ser552 limits β-catenin/LEF1-driven MYCBP expression.","evidence":"EYA4 overexpression/KO with siRNA rescue, qRT-PCR, and promoter analysis in HCC cells","pmids":["31385398"],"confidence":"Medium","gaps":["Direct β-catenin/LEF1 occupancy of MYCBP promoter inferred, not directly shown","Single-lab cancer-cell context"]},{"year":2024,"claim":"Revealed post-translational stabilization of MYCBP, showing circ_0002669 binds and protects it from proteasomal degradation to sustain c-Myc target genes.","evidence":"Biotin pulldown/MS, RNA-IP, luciferase, and functional rescue","pmids":["38570856"],"confidence":"Medium","gaps":["Ubiquitin machinery counteracted by circ_0002669 not identified in this study","Single-lab evidence"]},{"year":2026,"claim":"Identified the degradative arm of MYCBP turnover, mapping CBLB-mediated K48 ubiquitination at K20 that limits c-Myc pathway activity.","evidence":"Co-IP, ubiquitination assay, K20 site mutagenesis, and knockdown/overexpression functional assays","pmids":["42191055"],"confidence":"Medium","gaps":["Signals controlling CBLB engagement of MYCBP unknown","Single-lab evidence"]},{"year":2025,"claim":"Established an in vivo developmental requirement, showing Drosophila MYCBP partners with Sakura and Otu to sustain germline stem cell self-renewal via Dpp/BMP signaling and sex-lethal splicing.","evidence":"Co-IP of binary/ternary complexes, null mutant phenotyping, germline RNAi, and BMP/sxl readouts","pmids":["41325460"],"confidence":"High","gaps":["Whether mammalian MYCBP has an analogous stem-cell role untested","Direct molecular function of MYCBP within the Sakura/Otu complex undefined"]},{"year":null,"claim":"How MYCBP's distinct activities—MYC co-activation, PKA suppression, Gli regulation, and Golgi targeting—are coordinated or mutually exclusive within a cell remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of MYCBP or its complexes","No unified model integrating its transcriptional and scaffolding roles","Mammalian loss-of-function phenotype not defined in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,3,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1,3]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[2,4]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,9]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[11,12]}],"complexes":["MYCBP/AKAP/RII PKA-anchoring complex","Gli/Sufu nuclear complex","MYCBP/Sakura/Otu complex (Drosophila)"],"partners":["MYC","AKAP149","AKAP95","BIG2","GLI","SUFU","CBLB","OTU"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q99417","full_name":"c-Myc-binding protein","aliases":["Associate of Myc 1","AMY-1"],"length_aa":103,"mass_kda":12.0,"function":"May control the transcriptional activity of MYC. Stimulates the activation of E box-dependent transcription by MYC","subcellular_location":"Cytoplasm; Nucleus; Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q99417/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYCBP","classification":"Not Classified","n_dependent_lines":87,"n_total_lines":1208,"dependency_fraction":0.07201986754966887},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ARFGEF1","stoichiometry":0.2},{"gene":"ARFGEF2","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"DYNLL2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MYCBP","total_profiled":1310},"omim":[{"mim_id":"609910","title":"CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 91; CFAP91","url":"https://www.omim.org/entry/609910"},{"mim_id":"609835","title":"MYCBP-ASSOCIATED PROTEIN; MYCBPAP","url":"https://www.omim.org/entry/609835"},{"mim_id":"606535","title":"MYC-BINDING PROTEIN; MYCBP","url":"https://www.omim.org/entry/606535"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MYCBP"},"hgnc":{"alias_symbol":["AMY-1"],"prev_symbol":[]},"alphafold":{"accession":"Q99417","domains":[{"cath_id":"-","chopping":"1-56","consensus_level":"medium","plddt":87.4966,"start":1,"end":56},{"cath_id":"1.20.5","chopping":"59-95","consensus_level":"medium","plddt":91.9443,"start":59,"end":95}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99417","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99417-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99417-F1-predicted_aligned_error_v6.png","plddt_mean":86.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYCBP","jax_strain_url":"https://www.jax.org/strain/search?query=MYCBP"},"sequence":{"accession":"Q99417","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99417.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99417/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99417"}},"corpus_meta":[{"pmid":"9797456","id":"PMC_9797456","title":"AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC.","date":"1998","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/9797456","citation_count":74,"is_preprint":false},{"pmid":"31094023","id":"PMC_31094023","title":"Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis.","date":"2019","source":"Cell proliferation","url":"https://pubmed.ncbi.nlm.nih.gov/31094023","citation_count":52,"is_preprint":false},{"pmid":"25403183","id":"PMC_25403183","title":"Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling.","date":"2014","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/25403183","citation_count":39,"is_preprint":false},{"pmid":"93520","id":"PMC_93520","title":"[Genetic analysis of interspecific crosses Mus musculus L. x Mus spretus Lataste: linkage of Adh-1 with Amy-1 on chromosome 3 and Es-14 with Mod-1 on chromosome 9].","date":"1979","source":"Comptes rendus des seances de l'Academie des sciences. 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Are they also AMY1 receptor antagonists?","date":"2021","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/34076887","citation_count":36,"is_preprint":false},{"pmid":"11483602","id":"PMC_11483602","title":"AMY-1, a c-Myc-binding protein, is localized in the mitochondria of sperm by association with S-AKAP84, an anchor protein of cAMP-dependent protein kinase.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11483602","citation_count":35,"is_preprint":false},{"pmid":"12414807","id":"PMC_12414807","title":"AMY-1 interacts with S-AKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex.","date":"2002","source":"The Journal of biological 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proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/36581344","citation_count":2,"is_preprint":false},{"pmid":"39698396","id":"PMC_39698396","title":"Microrna-342 inhibits hepatocellular carcinoma cell proliferation and promotes apoptosis through the FOXP1/MYCBP Signaling Axis.","date":"2024","source":"Toxicology research","url":"https://pubmed.ncbi.nlm.nih.gov/39698396","citation_count":2,"is_preprint":false},{"pmid":"40379626","id":"PMC_40379626","title":"USP25-driven KIFC1 regulates MYCBP expression and promotes the progression of cervical cancer.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40379626","citation_count":0,"is_preprint":false},{"pmid":"38994720","id":"PMC_38994720","title":"Upregulation of the long noncoding RNA GJA9-MYCBP and PVT1 is a potential diagnostic biomarker for acute lymphoblastic leukemia.","date":"2024","source":"Cancer reports (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/38994720","citation_count":0,"is_preprint":false},{"pmid":"41325460","id":"PMC_41325460","title":"MYCBP interacts with Sakura and Otu and is essential for germline stem cell renewal and differentiation and oogenesis.","date":"2025","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41325460","citation_count":0,"is_preprint":false},{"pmid":"40631179","id":"PMC_40631179","title":"MYCBP interacts with Sakura and Otu and is essential for germline stem cell renewal and differentiation and oogenesis.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40631179","citation_count":0,"is_preprint":false},{"pmid":"41724729","id":"PMC_41724729","title":"Domain-Level Interaction of FAP174 (MYCBP-1) and FAP147 (MYCBPAP) Proteins of the C2a Projection of Chlamydomonas Cilia.","date":"2026","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/41724729","citation_count":0,"is_preprint":false},{"pmid":"42191055","id":"PMC_42191055","title":"CBLB inhibits papillary thyroid cancer malignancy via negatively regulating MYCBP/c-Myc axis.","date":"2026","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/42191055","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17379,"output_tokens":3263,"usd":0.050541,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10722,"output_tokens":4310,"usd":0.08068,"stage2_stop_reason":"end_turn"},"total_usd":0.131221,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"AMY-1 (MYCBP) is a novel 11 kDa protein that binds via its C-terminal region to the N-terminal transactivation domain (amino acids 58-148) of C-MYC, and stimulates E-box-dependent transcriptional activation by the MYC/Max complex without directly binding the E-box itself.\",\n      \"method\": \"Two-hybrid screen, co-immunoprecipitation, transcription reporter assay\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal binding mapped by deletion analysis, functional transcription assay, replicated in subsequent studies\",\n      \"pmids\": [\"9797456\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"AMY-1 localizes in the cytoplasm under low c-myc expression conditions but translocates to the nucleus during S phase when c-myc expression is elevated, indicating c-myc-dependent nuclear import.\",\n      \"method\": \"Immunofluorescence, cell cycle analysis, transient transfection\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with functional correlation, single lab but multiple conditions tested\",\n      \"pmids\": [\"9797456\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"AMY-1 binds in vitro and in vivo to the RII-binding region of AKAP149 and its testis-specific splicing variant S-AKAP84, forming a ternary complex with the regulatory subunit II (RII) of PKA, and localizes to mitochondria in HeLa cells and sperm via this interaction.\",\n      \"method\": \"Two-hybrid screen, in vitro binding assay, co-immunoprecipitation, immunofluorescence/subcellular fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vitro binding, and localization confirmed orthogonally in the same study\",\n      \"pmids\": [\"11483602\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"AMY-1 binds competitively to AKAP95 (in nucleus) or AKAP84 (in cytoplasm) via their RII-binding regions in a concentration-dependent manner, forms a ternary complex with RII, and this complex prevents the PKA catalytic subunit from binding, thereby suppressing PKA kinase activity.\",\n      \"method\": \"In vitro binding assay, co-immunoprecipitation, PKA activity assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of complex, PKA activity assay with clear mechanistic read-out, consistent with prior AKAP149 study\",\n      \"pmids\": [\"12414807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"AMY-1 forms a quaternary complex with AAT-1α (a testis-specific protein), S-AKAP84, and RII of PKA in the mitochondria of testis cells; AAT-1 is phosphorylated by PKA in vivo and in vitro, and weakly stimulates PKA phosphorylation activity within this complex.\",\n      \"method\": \"Two-hybrid screen, co-immunoprecipitation, co-localization, in vitro phosphorylation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and in vitro kinase assay, single lab\",\n      \"pmids\": [\"12223483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"AMY-1 binds to and co-localizes with AMAP-1, a novel testis-specific protein, in HeLa and 293T cells, suggesting a role in spermatogenesis.\",\n      \"method\": \"Two-hybrid screen, co-immunoprecipitation, immunofluorescence co-localization\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP/colocalization, no functional mechanism defined beyond spermatogenesis inference\",\n      \"pmids\": [\"12151104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The AMY-1 promoter requires Sp1 for basal expression in HeLa and K562 cells, and GATA-1 synergistically activates AMY-1 expression with Sp1 specifically in K562 cells; both proteins were confirmed to bind their respective promoter sites by mobility shift assay.\",\n      \"method\": \"Luciferase reporter deletion assay, electrophoretic mobility shift assay (EMSA), ectopic expression in insect cells\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA and reporter assays with multiple deletion constructs, single lab\",\n      \"pmids\": [\"12620400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Overexpression of AMY-1 in K562 cells induces expression of ε-globin mRNA (an erythrocyte differentiation marker) and accelerates AraC-induced erythrocyte differentiation, suggesting AMY-1 acts as a trigger for erythroid differentiation independently of or differently from c-Myc.\",\n      \"method\": \"Stable overexpression, RT-PCR for ε-globin, hemoglobin assay, AraC differentiation assay\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gain-of-function with defined molecular and phenotypic readout, single lab\",\n      \"pmids\": [\"10639579\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"AMY-1 localizes to the trans-Golgi network (TGN) and nucleus; its TGN localization is mediated specifically through interaction with BIG2 (a GEF for ARFs), but not BIG1, as demonstrated by RNAi knockdown of BIG2/BIG1.\",\n      \"method\": \"Co-immunoprecipitation with FLAG-AMY-1, immunofluorescence, RNA interference\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi epistasis combined with Co-IP and localization, single lab\",\n      \"pmids\": [\"16866877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"MYCBP forms a complex with Gli transcription factors and Sufu in the nucleus without Hh stimulation; Hh pathway activation causes dissociation of Sufu/p66β from Gli, enabling MYCBP to promote Gli-mediated Hh target gene expression. MYCBP acts downstream of Patched, Smoothened, and the primary cilium.\",\n      \"method\": \"Proteomic interaction screen, co-immunoprecipitation, ChIP on Hh target promoters, cell-based reporter assays, zebrafish genetic assays\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ChIP, cell assays, zebrafish epistasis), replicated across systems\",\n      \"pmids\": [\"25403183\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"EYA4 phosphatase suppresses MYCBP transcription by dephosphorylating β-catenin at Ser552, reducing its nuclear translocation and thereby preventing β-catenin/LEF1-driven transcription from the MYCBP promoter.\",\n      \"method\": \"EYA4 overexpression/KO in HCC cell lines, siRNA rescue, qRT-PCR, Western blot, ChIP-inferred promoter analysis\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with rescue experiments, phospho-specific mechanistic dissection, single lab\",\n      \"pmids\": [\"31385398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"circ_0002669 directly binds MYCBP protein (identified by biotin pulldown and mass spectrometry) and protects MYCBP from ubiquitin-mediated proteasomal degradation, thereby stabilizing MYCBP and promoting c-Myc target gene expression (CCND1, c-Jun, CDK4).\",\n      \"method\": \"Biotin pulldown, mass spectrometry, luciferase assay, RNA immunoprecipitation, functional rescue experiments\",\n      \"journal\": \"Biology direct\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein binding confirmed by pulldown/MS with functional consequence, single lab\",\n      \"pmids\": [\"38570856\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CBLB directly binds MYCBP and promotes its poly-ubiquitination via K48-linked ubiquitination at lysine 20 (K20), leading to proteasomal degradation of MYCBP; CBLB depletion stabilizes MYCBP, activating the c-Myc pathway and upregulating downstream oncogenic targets.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, site-specific mutagenesis (K20), Western blot, knockdown/overexpression functional assays\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding, ubiquitination site mapped by mutagenesis, downstream pathway validated, single lab\",\n      \"pmids\": [\"42191055\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Drosophila MYCBP physically associates with itself, Sakura, and Otu, forming binary and ternary complexes; germline-specific depletion of mycbp disrupts Dpp/BMP signaling, causes aberrant bam expression and GSC loss, and impairs female-specific sex-lethal splicing, establishing MYCBP as an essential regulator of GSC self-renewal and differentiation in oogenesis.\",\n      \"method\": \"Co-immunoprecipitation (binary/ternary complex), null mutant phenotyping, germline-specific RNAi, signaling pathway (BMP/Dpp) and splicing (sxl) readouts\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic null mutant with multiple defined phenotypes, complex formation validated, pathway placement by epistasis, peer-reviewed\",\n      \"pmids\": [\"41325460\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYCBP (AMY-1) is an 11 kDa protein that binds the N-terminal transactivation domain of c-MYC to enhance E-box-dependent transcription; it also acts as a modulator of PKA signaling by associating with AKAP scaffold proteins (AKAP84/149, AKAP95) and RII, blocking catalytic subunit access; it localizes dynamically to the cytoplasm, mitochondria (via S-AKAP84 in sperm), trans-Golgi network (via BIG2), and nucleus; in Hedgehog signaling, it forms a nuclear complex with Gli and Sufu and promotes Gli activity upon pathway activation; its protein stability is regulated by ubiquitin-proteasome degradation controlled by the E3 ligase CBLB (K48-linked ubiquitination at K20), and it is protected from degradation by circ_0002669; in Drosophila, MYCBP functions with Sakura and Otu to sustain germline stem cell self-renewal and differentiation through BMP/Dpp signaling and sex-lethal splicing.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYCBP (AMY-1) is a small adaptor protein that couples transcriptional control to multiple signaling outputs, functioning both as a co-activator of MYC and as a competitive regulator of PKA scaffolding [#0, #3]. It binds via its C-terminal region to the N-terminal transactivation domain of c-MYC and stimulates E-box-dependent transcription by the MYC/Max complex without contacting DNA directly [#0], with nuclear entry tied to elevated c-myc and S-phase progression [#1]. In parallel, MYCBP engages the RII-binding regions of AKAP scaffolds—AKAP149/S-AKAP84, AKAP95, and AKAP84—forming ternary complexes with the PKA regulatory subunit II that exclude the catalytic subunit and suppress PKA activity, anchoring the protein to mitochondria, cytoplasm, and nucleus depending on the partner [#2, #3]; in testis it extends to a quaternary mitochondrial complex with AAT-1α [#4]. MYCBP also localizes to the trans-Golgi network through interaction with the ARF-GEF BIG2 [#8]. In Hedgehog signaling, MYCBP resides in a nuclear complex with Gli and Sufu, and upon pathway activation and Sufu dissociation it promotes Gli-mediated target gene expression downstream of Patched, Smoothened, and the primary cilium [#9]. MYCBP abundance is set by the ubiquitin–proteasome system: the E3 ligase CBLB drives K48-linked ubiquitination at K20 to target it for degradation [#12], while circ_0002669 binding shields it to sustain c-Myc target expression [#11]. In Drosophila, MYCBP assembles with Sakura and Otu and is essential for germline stem cell self-renewal and differentiation via Dpp/BMP signaling and sex-lethal splicing [#13].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established MYCBP's founding molecular function—how a small protein could amplify MYC transcriptional output without DNA contact—by mapping it as a transactivation-domain binding co-activator.\",\n      \"evidence\": \"Two-hybrid screen, reciprocal deletion-mapped Co-IP, and E-box reporter assays\",\n      \"pmids\": [\"9797456\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the C-terminal MYCBP/MYC TAD interface unresolved\", \"Whether co-activation requires additional bridging factors not defined\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Addressed where MYCBP acts by linking its nuclear import to c-myc levels and S-phase, suggesting regulated subcellular partitioning.\",\n      \"evidence\": \"Immunofluorescence with cell-cycle synchronization and transient transfection\",\n      \"pmids\": [\"9797456\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Import machinery and signal driving translocation not identified\", \"Single-lab correlation rather than direct trafficking assay\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Tested MYCBP's cellular consequence beyond transcription, showing gain-of-function drives erythroid differentiation, hinting at a MYC-independent role.\",\n      \"evidence\": \"Stable overexpression in K562 with ε-globin RT-PCR and AraC differentiation assay\",\n      \"pmids\": [\"10639579\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway linking MYCBP to ε-globin induction undefined\", \"Whether effect is MYC-dependent not resolved\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Opened a second functional axis by showing MYCBP binds AKAP scaffolds and RII to form a mitochondrial PKA-anchoring complex, placing it in cAMP signaling.\",\n      \"evidence\": \"Two-hybrid, in vitro binding, Co-IP, and subcellular fractionation in HeLa and sperm\",\n      \"pmids\": [\"11483602\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of mitochondrial anchoring not yet measured here\", \"Relationship to MYC role unclear\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined the mechanistic output of the AKAP association—competitive binding that blocks the PKA catalytic subunit and suppresses kinase activity—establishing MYCBP as a PKA modulator.\",\n      \"evidence\": \"In vitro binding with AKAP95/AKAP84 and direct PKA activity assays\",\n      \"pmids\": [\"12414807\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological settings where this suppression dominates not mapped\", \"Quantitative competition with native RII in cells not measured\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Extended the PKA complex in testis to a quaternary assembly with AAT-1α, a PKA substrate, linking MYCBP scaffolding to spermatogenic signaling.\",\n      \"evidence\": \"Two-hybrid, reciprocal Co-IP, co-localization, and in vitro phosphorylation assay\",\n      \"pmids\": [\"12223483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo functional role in spermatogenesis not tested\", \"Single-lab evidence\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identified an additional testis-specific partner (AMAP-1), reinforcing a spermatogenesis-associated interactome.\",\n      \"evidence\": \"Two-hybrid, Co-IP, and immunofluorescence co-localization\",\n      \"pmids\": [\"12151104\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP/colocalization with no functional mechanism defined\", \"Spermatogenesis role inferred, not demonstrated\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Resolved how MYCBP itself is transcriptionally controlled, identifying Sp1-dependent basal expression and GATA-1 synergy in erythroid cells.\",\n      \"evidence\": \"Reporter deletion assays and EMSA of the AMY-1 promoter in HeLa/K562\",\n      \"pmids\": [\"12620400\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signals upstream of GATA-1/Sp1 control not defined\", \"Single-lab promoter analysis\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Added a Golgi localization mode, showing TGN targeting depends specifically on the ARF-GEF BIG2 rather than BIG1.\",\n      \"evidence\": \"FLAG-MYCBP Co-IP, immunofluorescence, and RNAi epistasis of BIG1/BIG2\",\n      \"pmids\": [\"16866877\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role of MYCBP at the TGN unknown\", \"How TGN pool relates to nuclear/PKA roles unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed MYCBP in Hedgehog signaling as a nuclear Gli/Sufu complex component that promotes Gli activity upon pathway activation, defining a transcriptional role beyond MYC.\",\n      \"evidence\": \"Proteomic screen, Co-IP, ChIP on Hh targets, reporter assays, and zebrafish epistasis\",\n      \"pmids\": [\"25403183\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which MYCBP enhances Gli at promoters not detailed\", \"Connection between Hh role and MYC co-activation unexplored\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected MYCBP transcription to Wnt/β-catenin signaling, showing EYA4 dephosphorylation of β-catenin Ser552 limits β-catenin/LEF1-driven MYCBP expression.\",\n      \"evidence\": \"EYA4 overexpression/KO with siRNA rescue, qRT-PCR, and promoter analysis in HCC cells\",\n      \"pmids\": [\"31385398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct β-catenin/LEF1 occupancy of MYCBP promoter inferred, not directly shown\", \"Single-lab cancer-cell context\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed post-translational stabilization of MYCBP, showing circ_0002669 binds and protects it from proteasomal degradation to sustain c-Myc target genes.\",\n      \"evidence\": \"Biotin pulldown/MS, RNA-IP, luciferase, and functional rescue\",\n      \"pmids\": [\"38570856\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitin machinery counteracted by circ_0002669 not identified in this study\", \"Single-lab evidence\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified the degradative arm of MYCBP turnover, mapping CBLB-mediated K48 ubiquitination at K20 that limits c-Myc pathway activity.\",\n      \"evidence\": \"Co-IP, ubiquitination assay, K20 site mutagenesis, and knockdown/overexpression functional assays\",\n      \"pmids\": [\"42191055\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signals controlling CBLB engagement of MYCBP unknown\", \"Single-lab evidence\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established an in vivo developmental requirement, showing Drosophila MYCBP partners with Sakura and Otu to sustain germline stem cell self-renewal via Dpp/BMP signaling and sex-lethal splicing.\",\n      \"evidence\": \"Co-IP of binary/ternary complexes, null mutant phenotyping, germline RNAi, and BMP/sxl readouts\",\n      \"pmids\": [\"41325460\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mammalian MYCBP has an analogous stem-cell role untested\", \"Direct molecular function of MYCBP within the Sakura/Otu complex undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MYCBP's distinct activities—MYC co-activation, PKA suppression, Gli regulation, and Golgi targeting—are coordinated or mutually exclusive within a cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of MYCBP or its complexes\", \"No unified model integrating its transcriptional and scaffolding roles\", \"Mammalian loss-of-function phenotype not defined in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 3, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [11, 12]}\n    ],\n    \"complexes\": [\n      \"MYCBP/AKAP/RII PKA-anchoring complex\",\n      \"Gli/Sufu nuclear complex\",\n      \"MYCBP/Sakura/Otu complex (Drosophila)\"\n    ],\n    \"partners\": [\n      \"MYC\",\n      \"AKAP149\",\n      \"AKAP95\",\n      \"BIG2\",\n      \"GLI\",\n      \"SUFU\",\n      \"CBLB\",\n      \"OTU\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}