{"gene":"NCAPG2","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2014,"finding":"NCAPG2, as a component of the condensin II complex, directly interacts with the polo-box domain (PBD) of PLK1 via its highly conserved C-terminal region (residues 1007VLS-pT-L1011), recruits PLK1 to prometaphase kinetochores, and promotes phosphorylation of the kinetochore substrate BubR1. Loss of NCAPG2 in humans and C. elegans loosens and misaligns spindle-kinetochore attachment. The crystal structure of PBD-NCAPG2 C-terminal peptide complex was solved, confirming phosphorylation-dependent interaction.","method":"Co-immunoprecipitation, crystal structure determination, siRNA knockdown in human cells and C. elegans RNAi, immunofluorescence, kinase substrate phosphorylation assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure solved, direct binding reconstituted, mutagenesis of phosphopeptide, orthologous functional validation in C. elegans, multiple orthogonal methods in single rigorous study","pmids":["25109385"],"is_preprint":false},{"year":2006,"finding":"The murine NCAPG2 ortholog MTB/mCAP-G2 was identified in a yeast two-hybrid screen as interacting with the hematopoietic bHLH transcription factor SCL; it also interacts with E12. MTB is recruited to the nucleus by SCL and E12, and represses SCL/E12-mediated transcriptional activation. Overexpression of MTB promotes terminal erythroid differentiation of murine erythroleukemia cells.","method":"Yeast two-hybrid screen, co-immunoprecipitation, nuclear localization assay, luciferase transcriptional reporter assay, overexpression in MEL cells with differentiation readout","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and reporter assay in single lab, multiple orthogonal methods, mouse ortholog","pmids":["16673016"],"is_preprint":false},{"year":2019,"finding":"NCAPG2 overexpression activates STAT3 and NF-κB signaling pathways in hepatocellular carcinoma cells to promote proliferation, migration, and invasion. A positive feedback loop exists between NCAPG2 and p-STAT3. Additionally, miR-188-3p directly targets NCAPG2 (negative feedback loop), and NCAPG2 is a direct target of miR-188-3p as shown by luciferase reporter assay.","method":"Co-immunoprecipitation, luciferase reporter assay, immunocytochemistry, ELISA, in vitro and in vivo functional assays, western blotting","journal":"EBioMedicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP and luciferase reporter in single lab, multiple orthogonal methods, functional rescue experiments","pmids":["31176678"],"is_preprint":false},{"year":2019,"finding":"Recessive loss-of-function mutations in NCAPG2 cause abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells of patient fibroblasts. In zebrafish, ncapg2 morphant and CRISPR-F0 mutants display microcephaly, renal anomalies, increased apoptosis, and altered mitotic progression; these phenotypes are rescued by wild-type but not mutant human NCAPG2 mRNA, establishing causality. Co-suppression of nphp1 and ncapg2 in zebrafish results in significantly more dysplastic renal tubules.","method":"Patient fibroblast cytogenetics, zebrafish morpholino knockdown, CRISPR-Cas9 F0 mutagenesis, mRNA rescue experiments, genetic epistasis (ncapg2 + nphp1 co-suppression)","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — orthogonal methods (fibroblast phenotyping, morpholino, CRISPR, mRNA rescue, epistasis), replicated across two model systems","pmids":["30609410"],"is_preprint":false},{"year":2012,"finding":"An anilinoquinazoline derivative (Q15) was identified as directly binding hCAP-G2 (NCAPG2), a subunit of the condensin II complex, using mRNA display technology. Q15 treatment compromises normal chromosome segregation, as shown by immunofluorescence, consistent with hCAP-G2 being a therapeutic target for mitotic disruption.","method":"mRNA display (in vitro binding selection), immunofluorescence, cell proliferation assays, in vivo xenograft","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding assay (mRNA display) plus functional immunofluorescence readout, single lab","pmids":["23028663"],"is_preprint":false},{"year":2020,"finding":"In glioblastoma cells, NCAPG2 promotes HBO1 phosphorylation and consequent H4 histone acetyltransferase activation, modulates Wnt/β-catenin pathway activation, and regulates MCM protein binding to chromatin. Knockdown of HBO1 reverses the proliferative and invasive effects of NCAPG2 overexpression, placing NCAPG2 upstream of HBO1 in this pathway.","method":"Knockdown/overexpression with functional assays (proliferation, migration, invasion, cell cycle), western blotting for phospho-HBO1 and H4 acetylation, chromatin binding assay for MCM, epistasis via HBO1 knockdown rescue","journal":"Cell and tissue research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis experiment (HBO1 KD rescues NCAPG2 OE) and mechanistic phosphorylation assay, single lab","pmids":["32897418"],"is_preprint":false},{"year":2024,"finding":"NCAPG2 directly binds STAT3 (shown by co-IP) and induces STAT3 occupancy on the MYC promoter (shown by ChIP assay), thereby transcriptionally activating c-MYC expression to promote prostate cancer malignancy and cancer stem cell self-renewal. TMT quantitative proteomics confirmed c-MYC activity is strongly correlated with NCAPG2 expression.","method":"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), TMT quantitative proteomics, knockdown/overexpression functional assays, xenograft models","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding by Co-IP, ChIP for promoter occupancy, proteomics, single lab with multiple orthogonal methods","pmids":["38166947"],"is_preprint":false},{"year":2022,"finding":"Brachyury transcription factor directly regulates NCAPG2 transcription in hepatocellular carcinoma, as demonstrated by ChIP-sequencing data showing brachyury occupancy at the NCAPG2 locus. Knockdown of brachyury reduces NCAPG2 levels and suppresses HCC proliferation and migration in vitro and in vivo; NCAPG2 knockdown similarly inhibits HCC progression and attenuates brachyury-induced tumorigenesis.","method":"ChIP-sequencing, knockdown functional assays (proliferation, migration), in vivo tumor models, epistasis (NCAPG2 KD reverses brachyury overexpression effects)","journal":"American journal of cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq for direct transcriptional regulation, epistasis experiment, single lab","pmids":["36119840"],"is_preprint":false},{"year":2023,"finding":"The RNA-binding protein PCBP2 directly binds NCAPG2 mRNA and protects it from degradation. PCBP2 knockdown reduces the mRNA half-life of NCAPG2 from approximately 8 hours to 5 hours, establishing PCBP2 as a post-transcriptional regulator (mRNA stability factor) of NCAPG2.","method":"RNA binding assay (direct binding shown), mRNA stability/half-life assay upon PCBP2 knockdown, label-free proteomics, functional assays in MCF-7 and T-47D cells","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA binding and half-life measurement, single lab, two cell lines","pmids":["37544634"],"is_preprint":false},{"year":2026,"finding":"USP52 deubiquitinates and stabilizes RBM5 protein in prostate cancer cells (shown by co-IP ubiquitination assay). RBM5 in turn interacts with the 3'UTR of NCAPG2 mRNA (shown by dual-luciferase reporter assay) to suppress NCAPG2 expression. This USP52–RBM5–NCAPG2 axis suppresses prostate cancer cell proliferation, migration, invasion, and stemness.","method":"Co-immunoprecipitation, ubiquitination assay, dual-luciferase reporter assay, knockdown/overexpression functional assays, xenograft tumor model","journal":"Molecular and cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP ubiquitination and luciferase reporter for 3'UTR interaction, single lab, multiple orthogonal methods","pmids":["41894088"],"is_preprint":false},{"year":2021,"finding":"miR-375 directly targets the 3'UTR of NCAPG2 mRNA, as confirmed by luciferase reporter assay, suppressing NCAPG2 protein expression. Overexpression of miR-375 represses HCC cell proliferation and migration; these effects are rescued by NCAPG2 overexpression, placing NCAPG2 downstream of miR-375.","method":"Luciferase reporter assay, western blotting, qRT-PCR, epistasis (NCAPG2 OE rescues miR-375 OE phenotype)","journal":"Neoplasma","confidence":"Low","confidence_rationale":"Tier 3 / Weak — luciferase reporter and rescue epistasis, single lab, single method for binding","pmids":["34818025"],"is_preprint":false},{"year":2025,"finding":"RPL35A regulates NCAPG2 expression in HCC; RPL35A overexpression increases NCAPG2 levels and promotes tumor progression, while RPL35A knockdown reduces NCAPG2 and reverses oncogenic effects. Gene expression analysis identified NCAPG2 as a key downstream target of RPL35A.","method":"shRNA knockdown, overexpression, gene expression analysis, xenograft model, functional assays (proliferation, migration, invasion, apoptosis)","journal":"Cancer medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — gene expression analysis and epistasis by knockdown, no direct binding shown, single lab","pmids":["40552444"],"is_preprint":false}],"current_model":"NCAPG2 is a non-SMC subunit of the condensin II complex that promotes chromosome condensation and segregation by recruiting PLK1 to prometaphase kinetochores via a direct phosphorylation-dependent interaction with PLK1's polo-box domain, thereby facilitating BubR1 phosphorylation and proper microtubule-kinetochore attachment; it also interacts with hematopoietic transcription factors SCL/E12 to repress transcription and promote erythroid differentiation, directly binds STAT3 to drive c-MYC transcription in cancer contexts, activates HBO1 phosphorylation and Wnt/β-catenin signaling, and is post-transcriptionally regulated by PCBP2-mediated mRNA stabilization and by miR-188-3p/miR-375/miR-638-mediated suppression."},"narrative":{"mechanistic_narrative":"NCAPG2 is a non-SMC subunit of the condensin II complex that ensures proper chromosome condensation and segregation during mitosis [PMID:25109385, PMID:30609410]. Its highly conserved C-terminal region, when phosphorylated (residues 1007VLS-pT-L1011), directly binds the polo-box domain of PLK1 and recruits PLK1 to prometaphase kinetochores, promoting phosphorylation of the kinetochore substrate BubR1; loss of NCAPG2 loosens and misaligns spindle-kinetochore attachments in both human cells and C. elegans [PMID:25109385]. Recessive loss-of-function mutations in NCAPG2 cause abnormal chromosome condensation, anaphase chromatin bridges, and micronuclei, and produce a human and zebrafish phenotype of microcephaly and renal anomalies that is rescued by wild-type but not mutant NCAPG2, establishing NCAPG2 as a causative disease gene [PMID:30609410]. Beyond its mitotic role, NCAPG2 functions in transcriptional and signaling contexts: in hematopoietic cells it is recruited to the nucleus by the bHLH factors SCL and E12 and represses SCL/E12-mediated transcription to promote erythroid differentiation [PMID:16673016], and in cancer cells it directly binds STAT3 and drives STAT3 occupancy of the MYC promoter to activate c-MYC [PMID:38166947], activates HBO1 phosphorylation and Wnt/β-catenin signaling [PMID:32897418], and engages STAT3/NF-κB signaling [PMID:31176678]. NCAPG2 expression is set post-transcriptionally, being stabilized by PCBP2 binding to its mRNA [PMID:37544634] and suppressed through 3'UTR-targeting regulators [PMID:41894088].","teleology":[{"year":2006,"claim":"The first mechanistic role for the NCAPG2 ortholog placed it outside mitosis, asking whether a condensin subunit could modulate hematopoietic transcription.","evidence":"Yeast two-hybrid, reciprocal Co-IP, luciferase reporter and MEL cell differentiation assays with the murine ortholog MTB/mCAP-G2","pmids":["16673016"],"confidence":"Medium","gaps":["Mechanism by which nuclear recruitment by SCL/E12 represses transcription not defined","Mouse ortholog; human relevance not directly tested","No link to the condensin function established here"]},{"year":2012,"claim":"Established that NCAPG2 is a druggable mitotic target by showing a small molecule can bind it and disrupt chromosome segregation.","evidence":"mRNA display in vitro binding selection of Q15 to hCAP-G2 plus immunofluorescence and xenograft readouts","pmids":["23028663"],"confidence":"Medium","gaps":["Binding site on NCAPG2 not mapped","Direct mechanistic link between compound binding and segregation defect not resolved"]},{"year":2014,"claim":"Resolved how NCAPG2 contributes mechanistically to mitosis, defining a direct phosphorylation-dependent interaction that recruits PLK1 to kinetochores.","evidence":"Co-IP, crystal structure of the PBD–NCAPG2 C-terminal phosphopeptide complex, phosphopeptide mutagenesis, kinase substrate assay, and siRNA/RNAi in human cells and C. elegans","pmids":["25109385"],"confidence":"High","gaps":["Kinase responsible for the priming phosphorylation of NCAPG2 not identified","Whether condensin assembly is required for PLK1 recruitment not tested"]},{"year":2019,"claim":"Connected NCAPG2 to oncogenic signaling, asking how its overexpression drives tumor phenotypes.","evidence":"Co-IP, luciferase reporter, ELISA and in vitro/in vivo functional assays in hepatocellular carcinoma linking NCAPG2 to STAT3/NF-κB and miR-188-3p","pmids":["31176678"],"confidence":"Medium","gaps":["Direct versus indirect activation of STAT3/NF-κB not distinguished","Single tumor type"]},{"year":2019,"claim":"Established NCAPG2 as a human disease gene by demonstrating causality of recessive loss-of-function alleles for chromosome instability and a microcephaly/renal phenotype.","evidence":"Patient fibroblast cytogenetics, zebrafish morpholino and CRISPR-F0 mutagenesis, mRNA rescue, and nphp1 epistasis","pmids":["30609410"],"confidence":"High","gaps":["Tissue-specific basis of microcephaly versus renal phenotype not resolved","Relationship of condensation defect to the PLK1 recruitment role not directly connected"]},{"year":2020,"claim":"Extended NCAPG2's signaling repertoire by placing it upstream of HBO1 acetyltransferase activation and Wnt/β-catenin signaling in glioblastoma.","evidence":"Knockdown/overexpression functional assays, phospho-HBO1 and H4 acetylation western blots, MCM chromatin-binding assay, HBO1 knockdown rescue","pmids":["32897418"],"confidence":"Medium","gaps":["How NCAPG2 promotes HBO1 phosphorylation mechanistically unknown","Direct binding to HBO1 not shown"]},{"year":2022,"claim":"Identified an upstream transcriptional regulator, showing brachyury directly drives NCAPG2 expression in HCC.","evidence":"ChIP-sequencing for brachyury occupancy plus knockdown functional assays and NCAPG2-brachyury epistasis in vitro and in vivo","pmids":["36119840"],"confidence":"Medium","gaps":["Direct binding of brachyury to the NCAPG2 promoter not validated beyond ChIP-seq","Single tumor type"]},{"year":2023,"claim":"Defined post-transcriptional control of NCAPG2 abundance by identifying PCBP2 as an mRNA-stabilizing factor.","evidence":"Direct RNA binding assay and mRNA half-life measurement (8 h to 5 h) upon PCBP2 knockdown in MCF-7 and T-47D cells","pmids":["37544634"],"confidence":"Medium","gaps":["Binding element on NCAPG2 mRNA not mapped","Single lab"]},{"year":2024,"claim":"Provided a direct transcriptional mechanism for NCAPG2 oncogenic activity by showing it binds STAT3 and induces STAT3 occupancy of the MYC promoter.","evidence":"Co-IP, ChIP, TMT proteomics and knockdown/overexpression with xenografts in prostate cancer","pmids":["38166947"],"confidence":"Medium","gaps":["Whether NCAPG2 acts as a coactivator or alters STAT3 phosphorylation not resolved","Single lab"]},{"year":2025,"claim":"Added regulators acting through the NCAPG2 3'UTR, defining a USP52–RBM5–NCAPG2 suppressive axis and RPL35A as a positive upstream factor.","evidence":"Co-IP ubiquitination and dual-luciferase 3'UTR reporter assays (RBM5/USP52) and shRNA/overexpression with gene expression analysis (RPL35A), in prostate cancer and HCC","pmids":["41894088","40552444"],"confidence":"Low","gaps":["RPL35A regulation of NCAPG2 shown only by expression analysis without direct binding","Mechanism of RBM5 3'UTR-mediated suppression not detailed"]},{"year":null,"claim":"How NCAPG2's mitotic condensin function mechanistically relates to its diverse transcriptional and signaling roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking kinetochore PLK1 recruitment to STAT3/HBO1/SCL transcriptional functions","The priming kinase for NCAPG2 phosphorylation is unidentified","Whether signaling roles require the condensin complex is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,6]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,3]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,5,6]}],"complexes":["condensin II"],"partners":["PLK1","BUBR1","SCL","E12","STAT3","HBO1","PCBP2","RBM5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86XI2","full_name":"Condensin-2 complex subunit G2","aliases":["Chromosome-associated protein G2","CAP-G2","hCAP-G2","Leucine zipper protein 5","Non-SMC condensin II complex subunit G2"],"length_aa":1143,"mass_kda":131.0,"function":"Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q86XI2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NCAPG2","classification":"Common Essential","n_dependent_lines":1064,"n_total_lines":1208,"dependency_fraction":0.8807947019867549},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FKBP5","stoichiometry":0.2},{"gene":"PTGES3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NCAPG2","total_profiled":1310},"omim":[{"mim_id":"618460","title":"KHAN-KHAN-KATSANIS SYNDROME; 3KS","url":"https://www.omim.org/entry/618460"},{"mim_id":"611230","title":"NON-SMC CONDENSIN II COMPLEX SUBUNIT H2; NCAPH2","url":"https://www.omim.org/entry/611230"},{"mim_id":"609276","title":"NON-SMC CONDENSIN II COMPLEX SUBUNIT D3; NCAPD3","url":"https://www.omim.org/entry/609276"},{"mim_id":"608532","title":"NON-SMC CONDENSIN II COMPLEX SUBUNIT G2; NCAPG2","url":"https://www.omim.org/entry/608532"},{"mim_id":"602822","title":"H4 CLUSTERED HISTONE 1; H4C1","url":"https://www.omim.org/entry/602822"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear speckles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":23.0},{"tissue":"lymphoid tissue","ntpm":26.0}],"url":"https://www.proteinatlas.org/search/NCAPG2"},"hgnc":{"alias_symbol":["FLJ20311","MTB","CAP-G2","hCAP-G2"],"prev_symbol":["LUZP5"]},"alphafold":{"accession":"Q86XI2","domains":[{"cath_id":"-","chopping":"500-587_609-679","consensus_level":"medium","plddt":93.0529,"start":500,"end":679},{"cath_id":"-","chopping":"899-999","consensus_level":"medium","plddt":84.8636,"start":899,"end":999},{"cath_id":"1.25.40","chopping":"1008-1143","consensus_level":"medium","plddt":86.5936,"start":1008,"end":1143},{"cath_id":"1.20.870","chopping":"2-159","consensus_level":"medium","plddt":83.5535,"start":2,"end":159},{"cath_id":"1.20.930","chopping":"382-495","consensus_level":"medium","plddt":96.8711,"start":382,"end":495}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86XI2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86XI2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86XI2-F1-predicted_aligned_error_v6.png","plddt_mean":87.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NCAPG2","jax_strain_url":"https://www.jax.org/strain/search?query=NCAPG2"},"sequence":{"accession":"Q86XI2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86XI2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86XI2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86XI2"}},"corpus_meta":[{"pmid":"31176678","id":"PMC_31176678","title":"NCAPG2 overexpression promotes hepatocellular carcinoma proliferation and metastasis through activating the STAT3 and NF-κB/miR-188-3p pathways.","date":"2019","source":"EBioMedicine","url":"https://pubmed.ncbi.nlm.nih.gov/31176678","citation_count":54,"is_preprint":false},{"pmid":"25109385","id":"PMC_25109385","title":"The condensin component NCAPG2 regulates microtubule-kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25109385","citation_count":47,"is_preprint":false},{"pmid":"16673016","id":"PMC_16673016","title":"MTB, the murine homolog of condensin II subunit CAP-G2, represses transcription and promotes erythroid cell differentiation.","date":"2006","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/16673016","citation_count":43,"is_preprint":false},{"pmid":"30609410","id":"PMC_30609410","title":"Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies.","date":"2019","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30609410","citation_count":34,"is_preprint":false},{"pmid":"32897418","id":"PMC_32897418","title":"NCAPG2 facilitates glioblastoma cells' malignancy and xenograft tumor growth via HBO1 activation by phosphorylation.","date":"2020","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/32897418","citation_count":29,"is_preprint":false},{"pmid":"24013099","id":"PMC_24013099","title":"Combined deletion of two Condensin II system genes (NCAPG2 and MCPH1) in a case of severe microcephaly and mental deficiency.","date":"2013","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24013099","citation_count":25,"is_preprint":false},{"pmid":"38166947","id":"PMC_38166947","title":"NCAPG2 promotes prostate cancer malignancy and stemness via STAT3/c-MYC signaling.","date":"2024","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38166947","citation_count":14,"is_preprint":false},{"pmid":"37248471","id":"PMC_37248471","title":"Circular RNA circ0001955 promotes cervical cancer tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis.","date":"2023","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37248471","citation_count":13,"is_preprint":false},{"pmid":"36139554","id":"PMC_36139554","title":"NCAPG2 Maintains Cancer Stemness and Promotes Erlotinib Resistance in Lung Adenocarcinoma.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36139554","citation_count":13,"is_preprint":false},{"pmid":"23028663","id":"PMC_23028663","title":"An anilinoquinazoline derivative inhibits tumor growth through interaction with hCAP-G2, a subunit of condensin II.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23028663","citation_count":12,"is_preprint":false},{"pmid":"37544634","id":"PMC_37544634","title":"The mRNA stability of NCAPG2, a novel contributor to breast invasive carcinoma, is enhanced by the RNA-binding protein PCBP2.","date":"2023","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/37544634","citation_count":11,"is_preprint":false},{"pmid":"36265182","id":"PMC_36265182","title":"NCAPG2 contributes to the progression of malignant melanoma through regulating proliferation and metastasis.","date":"2022","source":"Biochemistry and cell biology = Biochimie et biologie cellulaire","url":"https://pubmed.ncbi.nlm.nih.gov/36265182","citation_count":10,"is_preprint":false},{"pmid":"34818025","id":"PMC_34818025","title":"microRNA-375 inhibits the malignant behaviors of hepatic carcinoma cells by targeting NCAPG2.","date":"2021","source":"Neoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/34818025","citation_count":8,"is_preprint":false},{"pmid":"36119840","id":"PMC_36119840","title":"Brachyury promotes proliferation and migration of hepatocellular carcinoma via facilitating the transcription of NCAPG2.","date":"2022","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/36119840","citation_count":7,"is_preprint":false},{"pmid":"40552444","id":"PMC_40552444","title":"RPL35A Downregulation Suppresses Hepatocellular Carcinoma Cell Proliferation via NCAPG2 Inactivation.","date":"2025","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40552444","citation_count":3,"is_preprint":false},{"pmid":"38701261","id":"PMC_38701261","title":"MYC and NCAPG2 as molecular targets of colorectal cancer and gastric cancer in nursing.","date":"2024","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38701261","citation_count":2,"is_preprint":false},{"pmid":"37702425","id":"PMC_37702425","title":"miR-638 suppresses cervical cancer progression by inhibiting NCAPG2 under the treatment of Tetrandrine.","date":"2023","source":"Histology and histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/37702425","citation_count":0,"is_preprint":false},{"pmid":"40375564","id":"PMC_40375564","title":"NCAPG2 promotes the proliferation, metastasis and resistance to nab-paclitaxel in gastric adenocarcinoma cells.","date":"2025","source":"Journal of chemotherapy (Florence, Italy)","url":"https://pubmed.ncbi.nlm.nih.gov/40375564","citation_count":0,"is_preprint":false},{"pmid":"41894088","id":"PMC_41894088","title":"USP52 impedes malignant progression and cell stemness in prostate cancer by deubiquitinating RBM5 to down-regulate NCAPG2.","date":"2026","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41894088","citation_count":0,"is_preprint":false},{"pmid":"41907601","id":"PMC_41907601","title":"Bioinformatics and experimental analysis revealed the cancer-promoting role of NCAPG2 in epithelial ovarian cancer.","date":"2026","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41907601","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12242,"output_tokens":3429,"usd":0.044081,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10952,"output_tokens":3485,"usd":0.070943,"stage2_stop_reason":"end_turn"},"total_usd":0.115024,"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\": 2014,\n      \"finding\": \"NCAPG2, as a component of the condensin II complex, directly interacts with the polo-box domain (PBD) of PLK1 via its highly conserved C-terminal region (residues 1007VLS-pT-L1011), recruits PLK1 to prometaphase kinetochores, and promotes phosphorylation of the kinetochore substrate BubR1. Loss of NCAPG2 in humans and C. elegans loosens and misaligns spindle-kinetochore attachment. The crystal structure of PBD-NCAPG2 C-terminal peptide complex was solved, confirming phosphorylation-dependent interaction.\",\n      \"method\": \"Co-immunoprecipitation, crystal structure determination, siRNA knockdown in human cells and C. elegans RNAi, immunofluorescence, kinase substrate phosphorylation assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure solved, direct binding reconstituted, mutagenesis of phosphopeptide, orthologous functional validation in C. elegans, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"25109385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The murine NCAPG2 ortholog MTB/mCAP-G2 was identified in a yeast two-hybrid screen as interacting with the hematopoietic bHLH transcription factor SCL; it also interacts with E12. MTB is recruited to the nucleus by SCL and E12, and represses SCL/E12-mediated transcriptional activation. Overexpression of MTB promotes terminal erythroid differentiation of murine erythroleukemia cells.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, nuclear localization assay, luciferase transcriptional reporter assay, overexpression in MEL cells with differentiation readout\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and reporter assay in single lab, multiple orthogonal methods, mouse ortholog\",\n      \"pmids\": [\"16673016\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"NCAPG2 overexpression activates STAT3 and NF-κB signaling pathways in hepatocellular carcinoma cells to promote proliferation, migration, and invasion. A positive feedback loop exists between NCAPG2 and p-STAT3. Additionally, miR-188-3p directly targets NCAPG2 (negative feedback loop), and NCAPG2 is a direct target of miR-188-3p as shown by luciferase reporter assay.\",\n      \"method\": \"Co-immunoprecipitation, luciferase reporter assay, immunocytochemistry, ELISA, in vitro and in vivo functional assays, western blotting\",\n      \"journal\": \"EBioMedicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP and luciferase reporter in single lab, multiple orthogonal methods, functional rescue experiments\",\n      \"pmids\": [\"31176678\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Recessive loss-of-function mutations in NCAPG2 cause abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells of patient fibroblasts. In zebrafish, ncapg2 morphant and CRISPR-F0 mutants display microcephaly, renal anomalies, increased apoptosis, and altered mitotic progression; these phenotypes are rescued by wild-type but not mutant human NCAPG2 mRNA, establishing causality. Co-suppression of nphp1 and ncapg2 in zebrafish results in significantly more dysplastic renal tubules.\",\n      \"method\": \"Patient fibroblast cytogenetics, zebrafish morpholino knockdown, CRISPR-Cas9 F0 mutagenesis, mRNA rescue experiments, genetic epistasis (ncapg2 + nphp1 co-suppression)\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — orthogonal methods (fibroblast phenotyping, morpholino, CRISPR, mRNA rescue, epistasis), replicated across two model systems\",\n      \"pmids\": [\"30609410\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"An anilinoquinazoline derivative (Q15) was identified as directly binding hCAP-G2 (NCAPG2), a subunit of the condensin II complex, using mRNA display technology. Q15 treatment compromises normal chromosome segregation, as shown by immunofluorescence, consistent with hCAP-G2 being a therapeutic target for mitotic disruption.\",\n      \"method\": \"mRNA display (in vitro binding selection), immunofluorescence, cell proliferation assays, in vivo xenograft\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding assay (mRNA display) plus functional immunofluorescence readout, single lab\",\n      \"pmids\": [\"23028663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In glioblastoma cells, NCAPG2 promotes HBO1 phosphorylation and consequent H4 histone acetyltransferase activation, modulates Wnt/β-catenin pathway activation, and regulates MCM protein binding to chromatin. Knockdown of HBO1 reverses the proliferative and invasive effects of NCAPG2 overexpression, placing NCAPG2 upstream of HBO1 in this pathway.\",\n      \"method\": \"Knockdown/overexpression with functional assays (proliferation, migration, invasion, cell cycle), western blotting for phospho-HBO1 and H4 acetylation, chromatin binding assay for MCM, epistasis via HBO1 knockdown rescue\",\n      \"journal\": \"Cell and tissue research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis experiment (HBO1 KD rescues NCAPG2 OE) and mechanistic phosphorylation assay, single lab\",\n      \"pmids\": [\"32897418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NCAPG2 directly binds STAT3 (shown by co-IP) and induces STAT3 occupancy on the MYC promoter (shown by ChIP assay), thereby transcriptionally activating c-MYC expression to promote prostate cancer malignancy and cancer stem cell self-renewal. TMT quantitative proteomics confirmed c-MYC activity is strongly correlated with NCAPG2 expression.\",\n      \"method\": \"Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), TMT quantitative proteomics, knockdown/overexpression functional assays, xenograft models\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding by Co-IP, ChIP for promoter occupancy, proteomics, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"38166947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Brachyury transcription factor directly regulates NCAPG2 transcription in hepatocellular carcinoma, as demonstrated by ChIP-sequencing data showing brachyury occupancy at the NCAPG2 locus. Knockdown of brachyury reduces NCAPG2 levels and suppresses HCC proliferation and migration in vitro and in vivo; NCAPG2 knockdown similarly inhibits HCC progression and attenuates brachyury-induced tumorigenesis.\",\n      \"method\": \"ChIP-sequencing, knockdown functional assays (proliferation, migration), in vivo tumor models, epistasis (NCAPG2 KD reverses brachyury overexpression effects)\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq for direct transcriptional regulation, epistasis experiment, single lab\",\n      \"pmids\": [\"36119840\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The RNA-binding protein PCBP2 directly binds NCAPG2 mRNA and protects it from degradation. PCBP2 knockdown reduces the mRNA half-life of NCAPG2 from approximately 8 hours to 5 hours, establishing PCBP2 as a post-transcriptional regulator (mRNA stability factor) of NCAPG2.\",\n      \"method\": \"RNA binding assay (direct binding shown), mRNA stability/half-life assay upon PCBP2 knockdown, label-free proteomics, functional assays in MCF-7 and T-47D cells\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA binding and half-life measurement, single lab, two cell lines\",\n      \"pmids\": [\"37544634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"USP52 deubiquitinates and stabilizes RBM5 protein in prostate cancer cells (shown by co-IP ubiquitination assay). RBM5 in turn interacts with the 3'UTR of NCAPG2 mRNA (shown by dual-luciferase reporter assay) to suppress NCAPG2 expression. This USP52–RBM5–NCAPG2 axis suppresses prostate cancer cell proliferation, migration, invasion, and stemness.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, dual-luciferase reporter assay, knockdown/overexpression functional assays, xenograft tumor model\",\n      \"journal\": \"Molecular and cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP ubiquitination and luciferase reporter for 3'UTR interaction, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41894088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"miR-375 directly targets the 3'UTR of NCAPG2 mRNA, as confirmed by luciferase reporter assay, suppressing NCAPG2 protein expression. Overexpression of miR-375 represses HCC cell proliferation and migration; these effects are rescued by NCAPG2 overexpression, placing NCAPG2 downstream of miR-375.\",\n      \"method\": \"Luciferase reporter assay, western blotting, qRT-PCR, epistasis (NCAPG2 OE rescues miR-375 OE phenotype)\",\n      \"journal\": \"Neoplasma\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — luciferase reporter and rescue epistasis, single lab, single method for binding\",\n      \"pmids\": [\"34818025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPL35A regulates NCAPG2 expression in HCC; RPL35A overexpression increases NCAPG2 levels and promotes tumor progression, while RPL35A knockdown reduces NCAPG2 and reverses oncogenic effects. Gene expression analysis identified NCAPG2 as a key downstream target of RPL35A.\",\n      \"method\": \"shRNA knockdown, overexpression, gene expression analysis, xenograft model, functional assays (proliferation, migration, invasion, apoptosis)\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — gene expression analysis and epistasis by knockdown, no direct binding shown, single lab\",\n      \"pmids\": [\"40552444\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NCAPG2 is a non-SMC subunit of the condensin II complex that promotes chromosome condensation and segregation by recruiting PLK1 to prometaphase kinetochores via a direct phosphorylation-dependent interaction with PLK1's polo-box domain, thereby facilitating BubR1 phosphorylation and proper microtubule-kinetochore attachment; it also interacts with hematopoietic transcription factors SCL/E12 to repress transcription and promote erythroid differentiation, directly binds STAT3 to drive c-MYC transcription in cancer contexts, activates HBO1 phosphorylation and Wnt/β-catenin signaling, and is post-transcriptionally regulated by PCBP2-mediated mRNA stabilization and by miR-188-3p/miR-375/miR-638-mediated suppression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NCAPG2 is a non-SMC subunit of the condensin II complex that ensures proper chromosome condensation and segregation during mitosis [#0, #3]. Its highly conserved C-terminal region, when phosphorylated (residues 1007VLS-pT-L1011), directly binds the polo-box domain of PLK1 and recruits PLK1 to prometaphase kinetochores, promoting phosphorylation of the kinetochore substrate BubR1; loss of NCAPG2 loosens and misaligns spindle-kinetochore attachments in both human cells and C. elegans [#0]. Recessive loss-of-function mutations in NCAPG2 cause abnormal chromosome condensation, anaphase chromatin bridges, and micronuclei, and produce a human and zebrafish phenotype of microcephaly and renal anomalies that is rescued by wild-type but not mutant NCAPG2, establishing NCAPG2 as a causative disease gene [#3]. Beyond its mitotic role, NCAPG2 functions in transcriptional and signaling contexts: in hematopoietic cells it is recruited to the nucleus by the bHLH factors SCL and E12 and represses SCL/E12-mediated transcription to promote erythroid differentiation [#1], and in cancer cells it directly binds STAT3 and drives STAT3 occupancy of the MYC promoter to activate c-MYC [#6], activates HBO1 phosphorylation and Wnt/\\u03b2-catenin signaling [#5], and engages STAT3/NF-\\u03baB signaling [#2]. NCAPG2 expression is set post-transcriptionally, being stabilized by PCBP2 binding to its mRNA [#8] and suppressed through 3'UTR-targeting regulators [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"The first mechanistic role for the NCAPG2 ortholog placed it outside mitosis, asking whether a condensin subunit could modulate hematopoietic transcription.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP, luciferase reporter and MEL cell differentiation assays with the murine ortholog MTB/mCAP-G2\",\n      \"pmids\": [\"16673016\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which nuclear recruitment by SCL/E12 represses transcription not defined\", \"Mouse ortholog; human relevance not directly tested\", \"No link to the condensin function established here\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that NCAPG2 is a druggable mitotic target by showing a small molecule can bind it and disrupt chromosome segregation.\",\n      \"evidence\": \"mRNA display in vitro binding selection of Q15 to hCAP-G2 plus immunofluorescence and xenograft readouts\",\n      \"pmids\": [\"23028663\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding site on NCAPG2 not mapped\", \"Direct mechanistic link between compound binding and segregation defect not resolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolved how NCAPG2 contributes mechanistically to mitosis, defining a direct phosphorylation-dependent interaction that recruits PLK1 to kinetochores.\",\n      \"evidence\": \"Co-IP, crystal structure of the PBD\\u2013NCAPG2 C-terminal phosphopeptide complex, phosphopeptide mutagenesis, kinase substrate assay, and siRNA/RNAi in human cells and C. elegans\",\n      \"pmids\": [\"25109385\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for the priming phosphorylation of NCAPG2 not identified\", \"Whether condensin assembly is required for PLK1 recruitment not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected NCAPG2 to oncogenic signaling, asking how its overexpression drives tumor phenotypes.\",\n      \"evidence\": \"Co-IP, luciferase reporter, ELISA and in vitro/in vivo functional assays in hepatocellular carcinoma linking NCAPG2 to STAT3/NF-\\u03baB and miR-188-3p\",\n      \"pmids\": [\"31176678\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect activation of STAT3/NF-\\u03baB not distinguished\", \"Single tumor type\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Established NCAPG2 as a human disease gene by demonstrating causality of recessive loss-of-function alleles for chromosome instability and a microcephaly/renal phenotype.\",\n      \"evidence\": \"Patient fibroblast cytogenetics, zebrafish morpholino and CRISPR-F0 mutagenesis, mRNA rescue, and nphp1 epistasis\",\n      \"pmids\": [\"30609410\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-specific basis of microcephaly versus renal phenotype not resolved\", \"Relationship of condensation defect to the PLK1 recruitment role not directly connected\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended NCAPG2's signaling repertoire by placing it upstream of HBO1 acetyltransferase activation and Wnt/\\u03b2-catenin signaling in glioblastoma.\",\n      \"evidence\": \"Knockdown/overexpression functional assays, phospho-HBO1 and H4 acetylation western blots, MCM chromatin-binding assay, HBO1 knockdown rescue\",\n      \"pmids\": [\"32897418\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How NCAPG2 promotes HBO1 phosphorylation mechanistically unknown\", \"Direct binding to HBO1 not shown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified an upstream transcriptional regulator, showing brachyury directly drives NCAPG2 expression in HCC.\",\n      \"evidence\": \"ChIP-sequencing for brachyury occupancy plus knockdown functional assays and NCAPG2-brachyury epistasis in vitro and in vivo\",\n      \"pmids\": [\"36119840\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of brachyury to the NCAPG2 promoter not validated beyond ChIP-seq\", \"Single tumor type\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined post-transcriptional control of NCAPG2 abundance by identifying PCBP2 as an mRNA-stabilizing factor.\",\n      \"evidence\": \"Direct RNA binding assay and mRNA half-life measurement (8 h to 5 h) upon PCBP2 knockdown in MCF-7 and T-47D cells\",\n      \"pmids\": [\"37544634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding element on NCAPG2 mRNA not mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided a direct transcriptional mechanism for NCAPG2 oncogenic activity by showing it binds STAT3 and induces STAT3 occupancy of the MYC promoter.\",\n      \"evidence\": \"Co-IP, ChIP, TMT proteomics and knockdown/overexpression with xenografts in prostate cancer\",\n      \"pmids\": [\"38166947\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NCAPG2 acts as a coactivator or alters STAT3 phosphorylation not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Added regulators acting through the NCAPG2 3'UTR, defining a USP52\\u2013RBM5\\u2013NCAPG2 suppressive axis and RPL35A as a positive upstream factor.\",\n      \"evidence\": \"Co-IP ubiquitination and dual-luciferase 3'UTR reporter assays (RBM5/USP52) and shRNA/overexpression with gene expression analysis (RPL35A), in prostate cancer and HCC\",\n      \"pmids\": [\"41894088\", \"40552444\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"RPL35A regulation of NCAPG2 shown only by expression analysis without direct binding\", \"Mechanism of RBM5 3'UTR-mediated suppression not detailed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NCAPG2's mitotic condensin function mechanistically relates to its diverse transcriptional and signaling roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking kinetochore PLK1 recruitment to STAT3/HBO1/SCL transcriptional functions\", \"The priming kinase for NCAPG2 phosphorylation is unidentified\", \"Whether signaling roles require the condensin complex is untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 5, 6]}\n    ],\n    \"complexes\": [\"condensin II\"],\n    \"partners\": [\"PLK1\", \"BubR1\", \"SCL\", \"E12\", \"STAT3\", \"HBO1\", \"PCBP2\", \"RBM5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}