{"gene":"NCAPD2","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2000,"finding":"CNAP1 (hCAP-D2/NCAPD2) was identified as a component of the human condensin complex by co-immunoprecipitation of endogenous hCAP-C–hCAP-E complex from HeLa extracts. CNAP1 is the human ortholog of Xenopus condensin component XCAP-D2. The complex associates with mitotic chromosomes in a cell cycle-specific manner, with the majority sequestered in the cytoplasm during interphase; a subpopulation remains on chromosomes as foci in the interphase nucleus. During late G2/early prophase, nuclear condensin foci colocalize with phosphorylated histone H3 on partially condensed chromosomes.","method":"Co-immunoprecipitation from HeLa cell extracts; immunofluorescence; subcellular fractionation; sequence homology","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP from endogenous proteins, multiple orthogonal methods (Co-IP, immunofluorescence, fractionation), replicated by subsequent studies","pmids":["10958694"],"is_preprint":false},{"year":2000,"finding":"AKAP95 recruits hCAP-D2 (CNAP1/NCAPD2) to chromosomes in mitotic extract and is required for chromosome condensation. Recombinant AKAP95 binds chromatin and elicits concentration-dependent recruitment of hCAP-D2; the amount of hCAP-D2 recruited correlates with extent of chromosome condensation. GST pulldown data suggest AKAP95 also recruits additional condensin subunits.","method":"Mitotic extract chromosome condensation assay; GST pulldown; immunofluorescence colocalization; recombinant AKAP95 rescue experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vitro condensation reconstitution with functional correlation, GST pulldown, rescue experiment, single lab but multiple orthogonal methods","pmids":["10791967"],"is_preprint":false},{"year":2002,"finding":"The C-terminal domain of CNAP1 (hCAP-D2/NCAPD2) contains a mitotic chromosome-targeting domain that functions independently of other condensin components. This domain also contains a functional bipartite nuclear localization signal. The chromosome-targeting domain directly binds histones H1 and H3 in vitro, with the H3 interaction mediated through the H3 histone tail; a subfragment interacts with histone H3 in vivo. A deletion mutant lacking this domain is incorporated into condensin but fails to associate with mitotic chromosomes.","method":"Deletion mutagenesis; in vitro histone binding assays; co-immunoprecipitation; immunofluorescence with GFP-tagged mutants; in vivo interaction assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis combined with in vitro reconstitution binding assays and in vivo validation, multiple orthogonal methods in single study","pmids":["12138188"],"is_preprint":false},{"year":2005,"finding":"RNAi depletion of hCAP-D2 (NCAPD2) in HeLa cells shows that the association of hCAP-H (another non-SMC condensin I subunit) with mitotic chromosomes depends on the presence of hCAP-D2. Loss of hCAP-D2 also disorganizes chromatid axes (as defined by topoisomerase II and hCAP-E localization), impairs sister chromatid resolution and segregation, causes chromosome misalignment in metaphase, and delays anaphase entry, indicating a role in kinetochore–microtubule attachment.","method":"RNA interference (RNAi) knockdown in HeLa cells; immunofluorescence; live-cell imaging; flow cytometry","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean RNAi knockdown with multiple defined cellular phenotype readouts, replicated findings consistent with Drosophila CAP-D2 work","pmids":["15632074"],"is_preprint":false},{"year":2005,"finding":"Drosophila CAP-D2 (ortholog of NCAPD2) is required for stability of the condensin complex; loss of CAP-D2 by dsRNAi destabilizes CAP-H, mislocalizes DNA topoisomerase II and other condensin subunits, and causes failure of chromosome arm and centromere resolution as well as chromosome segregation defects. CAP-D2 is nuclear throughout interphase, increases during S phase, and localizes to chromosome axes in mitosis persisting as chromosomes begin to decondense.","method":"dsRNA-mediated interference in Drosophila embryos; immunofluorescence; immunoprecipitation to demonstrate complex composition","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — ortholog study with clean loss-of-function, multiple orthogonal phenotypic readouts, consistent with mammalian condensin I data","pmids":["15923665"],"is_preprint":false},{"year":2005,"finding":"The CNAP1 (NCAPD2) gene was characterized as a bona fide E2F transcriptional target. Transfection studies and site-directed mutagenesis of E2F binding sites in the CNAP1 promoter confirmed E2F regulation. Repression by 1,25-dihydroxyvitamin D3 depends on pocket proteins p107 and p130 (not pRb), as the antiproliferative effect and repression of CNAP1 were lost in p107−/−;p130−/− cells but not in pRb−/− cells.","method":"Promoter-reporter transfection assays; site-directed mutagenesis of E2F binding sites; cDNA microarray; knockout cell lines (p107−/−;p130−/−; pRb−/−)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis of transcriptional regulatory element plus genetic epistasis using knockout cells, single lab","pmids":["16144839"],"is_preprint":false},{"year":2021,"finding":"NCAPD2 inhibits autophagy and blocks autophagic flux via the Ca2+/CAMKK2/AMPK/mTORC1 pathway and the PARP-1/SIRT1 axis in colorectal cancer cells. NCAPD2 knockout suppresses colorectal cancer development in an AOM/DSS-induced mouse model.","method":"Knockout cell lines; in vitro autophagic flux assays; in vivo AOM/DSS mouse model; western blotting for pathway components","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined pathway readouts (AMPK/mTORC1 phosphorylation, autophagic markers), in vivo validation, single lab","pmids":["34229059"],"is_preprint":false},{"year":2022,"finding":"NCAPD2 transcriptionally activates CDK1 by interacting with E2F transcription factor 1 (E2F1) in breast cancer cells (MDA-MB-231). NCAPD2 promotes breast cancer progression through the ERK5 signaling pathway, and overexpression of CDK1 rescues the inhibitory effects of NCAPD2 knockdown.","method":"Co-immunoprecipitation (NCAPD2–E2F1 interaction); knockdown/overexpression functional assays; CDK1 rescue experiment; western blotting","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP demonstrates interaction, rescue experiment supports epistasis, single lab with two orthogonal methods","pmids":["35348268"],"is_preprint":false},{"year":2025,"finding":"NCAPD2 promotes lung adenocarcinoma progression through a positive feedback loop: NCAPD2 activates the PI3K/AKT pathway, facilitating MDM2–E2F1 interaction, reducing E2F1 ubiquitination and increasing E2F1 protein levels; E2F1 in turn enhances NCAPD2 transcription.","method":"RNA sequencing; protein interaction experiments (co-IP/pulldown); knockdown/overexpression assays; in vivo mouse models; western blotting for pathway components","journal":"Cancer biology & therapy","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, abstract does not specify rigorous controls for the MDM2–E2F1–NCAPD2 feedback, protein interaction method details incomplete","pmids":["41319185"],"is_preprint":false},{"year":2025,"finding":"NCAPD2 knockdown in gastric cancer cells reduces surface MHC-I expression; treatment with PI3K inhibitor LY294002 partially rescues MHC-I levels, placing NCAPD2-mediated MHC-I downregulation downstream of the PI3K/AKT pathway.","method":"NCAPD2 siRNA knockdown; flow cytometry for MHC-I surface expression; pharmacological inhibition with LY294002; western blotting; transcriptome sequencing","journal":"Digestive diseases and sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, partial rescue only, pathway placement inferred from pharmacological inhibition without direct epistasis","pmids":["41004034"],"is_preprint":false},{"year":2025,"finding":"NCAPD2 overexpression in esophageal cancer cells upregulates Wnt5A, which activates the Notch pathway and promotes glycolysis (increased ECAR, lactate production, glucose consumption) and EMT-driven metastasis; knockdown reverses these effects in vitro and in vivo.","method":"Transcriptome sequencing; ECAR/OCR/lactate assays; western blotting; scratch and Transwell assays; subcutaneous xenograft mouse model; immunohistochemistry","journal":"Cellular signalling","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, pathway assignment based on transcriptomics and correlative western blot without direct epistasis experiments for NCAPD2–Wnt5A–Notch axis","pmids":["40946944"],"is_preprint":false},{"year":2025,"finding":"NCAPD2 suppresses autophagy in Crohn's disease context by promoting phosphorylation of mTOR and its effector S6K, and downregulating autophagy-related proteins Beclin1, LC3II, and Atg5. NCAPD2 also activates the NF-κB signaling pathway, sustaining inflammatory cytokine release; knockdown inhibits TNBS-induced intestinal inflammation in a mouse model.","method":"NCAPD2 knockdown in cell lines and TNBS mouse model; western blotting for mTOR/S6K/autophagy markers; immunofluorescence; qRT-PCR","journal":"Inflammatory bowel diseases","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, mechanistic pathway placement relies on correlative western blot readouts without direct reconstitution","pmids":["39340820"],"is_preprint":false}],"current_model":"NCAPD2 (also known as CNAP1/hCAP-D2) is a non-SMC subunit of the condensin I complex that is essential for mitotic chromosome condensation and sister chromatid resolution: its C-terminal domain directly binds histones H1 and H3 to target condensin to mitotic chromosomes, it stabilizes the association of other condensin I subunits (hCAP-H) with chromosomes, and it is recruited to chromatin via AKAP95; beyond its canonical chromosome condensation role, NCAPD2 has been shown to inhibit autophagy through the Ca2+/CAMKK2/AMPK/mTORC1 and PARP-1/SIRT1 axes, to transcriptionally activate CDK1 by interacting with E2F1, and to be itself transcriptionally regulated as an E2F target gene through a p107/p130-dependent mechanism."},"narrative":{"mechanistic_narrative":"NCAPD2 (CNAP1/hCAP-D2) is a non-SMC subunit of the human condensin complex that drives mitotic chromosome condensation and sister chromatid resolution [PMID:10958694, PMID:15632074]. It targets condensin to mitotic chromosomes through its C-terminal domain, which directly binds histones H1 and H3 via the H3 tail and carries a bipartite nuclear localization signal; a deletion mutant lacking this domain still assembles into condensin but fails to load onto mitotic chromosomes [PMID:12138188]. Chromatin recruitment is further promoted by AKAP95, whose dose-dependent loading of NCAPD2 correlates with the extent of chromosome condensation [PMID:10791967]. Within the complex, NCAPD2 is required for the chromosome association of the non-SMC subunit hCAP-H and for organizing chromatid axes; its depletion disorganizes topoisomerase II and SMC localization, impairs sister chromatid resolution and segregation, and delays anaphase [PMID:15632074], a role conserved in the Drosophila ortholog where loss destabilizes the complex [PMID:15923665]. NCAPD2 transcription is controlled as an E2F target gene through a p107/p130-dependent mechanism [PMID:16144839]. Beyond chromosome condensation, NCAPD2 has been linked in cancer and inflammation contexts to transcriptional activation of CDK1 via interaction with E2F1 [PMID:35348268] and to suppression of autophagy through the Ca2+/CAMKK2/AMPK/mTORC1 and PARP-1/SIRT1 axes [PMID:34229059].","teleology":[{"year":2000,"claim":"Establishing that NCAPD2 is a bona fide subunit of the human condensin complex defined its molecular context and linked it to mitotic chromosome architecture.","evidence":"Co-immunoprecipitation of the endogenous hCAP-C–hCAP-E complex from HeLa extracts with immunofluorescence and fractionation","pmids":["10958694"],"confidence":"High","gaps":["Did not define how NCAPD2 is targeted to chromosomes","Did not resolve the contribution of the interphase chromosome-bound subpopulation"]},{"year":2000,"claim":"Identifying AKAP95 as a chromatin factor that recruits NCAPD2 answered how condensin is loaded onto mitotic chromosomes and tied recruitment quantitatively to condensation.","evidence":"Mitotic extract condensation assay with recombinant AKAP95 rescue, GST pulldown, and colocalization","pmids":["10791967"],"confidence":"High","gaps":["Did not establish whether AKAP95 binding is direct to NCAPD2 versus other subunits","Did not define the binding interface"]},{"year":2002,"claim":"Mapping the C-terminal chromosome-targeting domain and its direct histone H1/H3 binding explained the molecular basis of NCAPD2-dependent chromosome loading independent of the rest of the complex.","evidence":"Deletion mutagenesis, in vitro histone binding assays, and GFP-mutant localization in cells","pmids":["12138188"],"confidence":"High","gaps":["No structure of the targeting domain–histone interaction","Regulation of the H3-tail interaction (e.g. by phosphorylation) not defined"]},{"year":2005,"claim":"Loss-of-function in human and Drosophila cells established that NCAPD2 is required for condensin complex stability, chromatid axis organization, and accurate segregation.","evidence":"RNAi/dsRNAi depletion with immunofluorescence, live imaging, and IP of complex composition in HeLa cells and Drosophila embryos","pmids":["15632074","15923665"],"confidence":"High","gaps":["Did not separate direct condensation roles from downstream kinetochore–microtubule effects","Mechanism stabilizing hCAP-H association not defined at molecular level"]},{"year":2005,"claim":"Demonstrating NCAPD2 is an E2F-regulated gene repressed via p107/p130 placed its expression under cell-cycle/proliferative transcriptional control.","evidence":"Promoter-reporter assays with E2F-site mutagenesis and epistasis in p107−/−;p130−/− versus pRb−/− knockout cells","pmids":["16144839"],"confidence":"Medium","gaps":["Which E2F family member drives expression in vivo not resolved","Link between transcriptional regulation and condensin function not tested"]},{"year":2021,"claim":"Identifying NCAPD2 as an autophagy suppressor extended its role beyond mitosis into cancer-relevant signaling.","evidence":"Knockout cell lines, autophagic flux assays, AOM/DSS mouse model, and pathway western blots in colorectal cancer","pmids":["34229059"],"confidence":"Medium","gaps":["Direct molecular target of NCAPD2 in the Ca2+/CAMKK2/AMPK/mTORC1 axis not identified","Whether this is condensin-dependent or a moonlighting function unclear"]},{"year":2022,"claim":"Showing NCAPD2 interacts with E2F1 to transactivate CDK1 proposed a feed-forward link between NCAPD2 and cell-cycle driver expression.","evidence":"Co-IP of NCAPD2–E2F1, knockdown/overexpression assays, and CDK1 rescue in MDA-MB-231 cells","pmids":["35348268"],"confidence":"Medium","gaps":["Reciprocal/endogenous validation of the NCAPD2–E2F1 interaction limited","Whether NCAPD2 acts directly at the CDK1 promoter not shown"]},{"year":2025,"claim":"Multiple tumor and inflammation studies positioned NCAPD2 in PI3K/AKT, MDM2–E2F1, Wnt5A/Notch, mTOR/NF-κB, and MHC-I regulatory circuits.","evidence":"Knockdown/overexpression with transcriptomics, pharmacological inhibition, and xenograft/TNBS mouse models across lung, gastric, esophageal cancers and Crohn's disease","pmids":["41319185","41004034","40946944","39340820"],"confidence":"Low","gaps":["Pathway placements rest on correlative western blots and partial pharmacological rescue without direct epistasis","Direct molecular partners in these axes not biochemically defined","Relationship to canonical condensin function not addressed"]},{"year":null,"claim":"How NCAPD2's mitotic condensin function mechanistically connects to its reported signaling and transcriptional roles in cancer remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of NCAPD2 within human condensin","Whether non-mitotic functions require condensin assembly is untested","Direct substrates/effectors of the signaling roles unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[2]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,3]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[7]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,2,3,4]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,4]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[6]}],"complexes":["condensin I complex"],"partners":["NCAPH","SMC2","SMC4","AKAP95","E2F1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15021","full_name":"Condensin complex subunit 1","aliases":["Chromosome condensation-related SMC-associated protein 1","Chromosome-associated protein D2","hCAP-D2","Non-SMC condensin I complex subunit D2","XCAP-D2 homolog"],"length_aa":1401,"mass_kda":157.2,"function":"Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain (PubMed:11136719). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of non-centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959)","subcellular_location":"Nucleus; Cytoplasm; Chromosome","url":"https://www.uniprot.org/uniprotkb/Q15021/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NCAPD2","classification":"Common Essential","n_dependent_lines":1196,"n_total_lines":1208,"dependency_fraction":0.9900662251655629},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NCAPH","stoichiometry":10.0},{"gene":"ATG4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NCAPD2","total_profiled":1310},"omim":[{"mim_id":"621147","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 102B; CCDC102B","url":"https://www.omim.org/entry/621147"},{"mim_id":"617983","title":"MICROCEPHALY 21, PRIMARY, AUTOSOMAL RECESSIVE; MCPH21","url":"https://www.omim.org/entry/617983"},{"mim_id":"615639","title":"SMALL CAJAL BODY-SPECIFIC RNA 10; SCARNA10","url":"https://www.omim.org/entry/615639"},{"mim_id":"615638","title":"NON-SMC CONDENSIN I COMPLEX SUBUNIT D2; NCAPD2","url":"https://www.omim.org/entry/615638"},{"mim_id":"609276","title":"NON-SMC CONDENSIN II COMPLEX SUBUNIT D3; NCAPD3","url":"https://www.omim.org/entry/609276"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":71.5}],"url":"https://www.proteinatlas.org/search/NCAPD2"},"hgnc":{"alias_symbol":["CNAP1","hCAP-D2","CAP-D2","KIAA0159"],"prev_symbol":[]},"alphafold":{"accession":"Q15021","domains":[{"cath_id":"-","chopping":"2-141_162-172","consensus_level":"medium","plddt":87.9408,"start":2,"end":172},{"cath_id":"1.25.10","chopping":"350-437","consensus_level":"medium","plddt":93.0552,"start":350,"end":437}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15021","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15021-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15021-F1-predicted_aligned_error_v6.png","plddt_mean":79.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NCAPD2","jax_strain_url":"https://www.jax.org/strain/search?query=NCAPD2"},"sequence":{"accession":"Q15021","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15021.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15021/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15021"}},"corpus_meta":[{"pmid":"9647649","id":"PMC_9647649","title":"C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2.","date":"1998","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9647649","citation_count":377,"is_preprint":false},{"pmid":"11076968","id":"PMC_11076968","title":"The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion.","date":"2000","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11076968","citation_count":187,"is_preprint":false},{"pmid":"16339073","id":"PMC_16339073","title":"Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells.","date":"2005","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/16339073","citation_count":130,"is_preprint":false},{"pmid":"10958694","id":"PMC_10958694","title":"A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation.","date":"2000","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10958694","citation_count":102,"is_preprint":false},{"pmid":"12140259","id":"PMC_12140259","title":"The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles.","date":"2002","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/12140259","citation_count":94,"is_preprint":false},{"pmid":"15923665","id":"PMC_15923665","title":"Drosophila CAP-D2 is required for condensin complex stability and resolution of sister chromatids.","date":"2005","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15923665","citation_count":71,"is_preprint":false},{"pmid":"34229059","id":"PMC_34229059","title":"NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer.","date":"2021","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/34229059","citation_count":70,"is_preprint":false},{"pmid":"10791967","id":"PMC_10791967","title":"A kinase-anchoring protein (AKAP)95 recruits human chromosome-associated protein (hCAP)-D2/Eg7 for chromosome condensation in mitotic extract.","date":"2000","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10791967","citation_count":63,"is_preprint":false},{"pmid":"24554434","id":"PMC_24554434","title":"Centlein mediates an interaction between C-Nap1 and Cep68 to maintain centrosome cohesion.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24554434","citation_count":55,"is_preprint":false},{"pmid":"18851962","id":"PMC_18851962","title":"A novel function of CEP135 as a platform protein of C-NAP1 for its centriolar localization.","date":"2008","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/18851962","citation_count":55,"is_preprint":false},{"pmid":"24695856","id":"PMC_24695856","title":"Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24695856","citation_count":53,"is_preprint":false},{"pmid":"29463719","id":"PMC_29463719","title":"STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles.","date":"2018","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/29463719","citation_count":53,"is_preprint":false},{"pmid":"12138188","id":"PMC_12138188","title":"Identification of a chromosome-targeting domain in the human condensin subunit CNAP1/hCAP-D2/Eg7.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12138188","citation_count":51,"is_preprint":false},{"pmid":"16144839","id":"PMC_16144839","title":"Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16144839","citation_count":40,"is_preprint":false},{"pmid":"15632074","id":"PMC_15632074","title":"Contribution of hCAP-D2, a non-SMC subunit of condensin I, to chromosome and chromosomal protein dynamics during mitosis.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15632074","citation_count":38,"is_preprint":false},{"pmid":"23070519","id":"PMC_23070519","title":"C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis.","date":"2012","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/23070519","citation_count":35,"is_preprint":false},{"pmid":"25902731","id":"PMC_25902731","title":"C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25902731","citation_count":35,"is_preprint":false},{"pmid":"35348268","id":"PMC_35348268","title":"NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1.","date":"2022","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/35348268","citation_count":33,"is_preprint":false},{"pmid":"28100636","id":"PMC_28100636","title":"Centriole splitting caused by loss of the centrosomal linker protein C-NAP1 reduces centriolar satellite density and impedes centrosome amplification.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/28100636","citation_count":26,"is_preprint":false},{"pmid":"36282799","id":"PMC_36282799","title":"cNap1 bridges centriole contact sites to maintain centrosome cohesion.","date":"2022","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/36282799","citation_count":11,"is_preprint":false},{"pmid":"38726276","id":"PMC_38726276","title":"High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/β-catenin signaling pathway in HCC.","date":"2024","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/38726276","citation_count":10,"is_preprint":false},{"pmid":"39092569","id":"PMC_39092569","title":"NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K‑Akt‑mTOR signaling pathway.","date":"2024","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39092569","citation_count":8,"is_preprint":false},{"pmid":"35599622","id":"PMC_35599622","title":"Centrosome linker protein C-Nap1 maintains stem cells in mouse testes.","date":"2022","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/35599622","citation_count":8,"is_preprint":false},{"pmid":"25660448","id":"PMC_25660448","title":"The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly.","date":"2015","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/25660448","citation_count":8,"is_preprint":false},{"pmid":"38743408","id":"PMC_38743408","title":"NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/β-catenin pathway.","date":"2024","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/38743408","citation_count":6,"is_preprint":false},{"pmid":"31056748","id":"PMC_31056748","title":"A novel homozygous splice-site variant of NCAPD2 gene identified in two siblings with primary microcephaly: The second case report.","date":"2019","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31056748","citation_count":4,"is_preprint":false},{"pmid":"40946944","id":"PMC_40946944","title":"NCAPD2 stimulates glycolysis and esophageal cancer metastasis through Wnt5A-dependent Notch activation.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/40946944","citation_count":1,"is_preprint":false},{"pmid":"41668133","id":"PMC_41668133","title":"CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1.","date":"2026","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/41668133","citation_count":1,"is_preprint":false},{"pmid":"41319185","id":"PMC_41319185","title":"NCAPD2 promotes the progression of lung adenocarcinoma through an AKT/MDM2/E2F1 positive feedback loop.","date":"2025","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/41319185","citation_count":0,"is_preprint":false},{"pmid":"39340820","id":"PMC_39340820","title":"Targeting NCAPD2 as a Therapeutic Strategy for Crohn's Disease: Implications for Autophagy and Inflammation.","date":"2025","source":"Inflammatory bowel diseases","url":"https://pubmed.ncbi.nlm.nih.gov/39340820","citation_count":0,"is_preprint":false},{"pmid":"41004034","id":"PMC_41004034","title":"NCAPD2 Modulates MHC-I Antigen Presentation via the PI3K/AKT Axis to Drive Metastatic Progression in Gastric Cancer.","date":"2025","source":"Digestive diseases and sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41004034","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16953,"output_tokens":3458,"usd":0.051365,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11040,"output_tokens":3054,"usd":0.065775,"stage2_stop_reason":"end_turn"},"total_usd":0.11714,"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\": 2000,\n      \"finding\": \"CNAP1 (hCAP-D2/NCAPD2) was identified as a component of the human condensin complex by co-immunoprecipitation of endogenous hCAP-C–hCAP-E complex from HeLa extracts. CNAP1 is the human ortholog of Xenopus condensin component XCAP-D2. The complex associates with mitotic chromosomes in a cell cycle-specific manner, with the majority sequestered in the cytoplasm during interphase; a subpopulation remains on chromosomes as foci in the interphase nucleus. During late G2/early prophase, nuclear condensin foci colocalize with phosphorylated histone H3 on partially condensed chromosomes.\",\n      \"method\": \"Co-immunoprecipitation from HeLa cell extracts; immunofluorescence; subcellular fractionation; sequence homology\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP from endogenous proteins, multiple orthogonal methods (Co-IP, immunofluorescence, fractionation), replicated by subsequent studies\",\n      \"pmids\": [\"10958694\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"AKAP95 recruits hCAP-D2 (CNAP1/NCAPD2) to chromosomes in mitotic extract and is required for chromosome condensation. Recombinant AKAP95 binds chromatin and elicits concentration-dependent recruitment of hCAP-D2; the amount of hCAP-D2 recruited correlates with extent of chromosome condensation. GST pulldown data suggest AKAP95 also recruits additional condensin subunits.\",\n      \"method\": \"Mitotic extract chromosome condensation assay; GST pulldown; immunofluorescence colocalization; recombinant AKAP95 rescue experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro condensation reconstitution with functional correlation, GST pulldown, rescue experiment, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"10791967\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The C-terminal domain of CNAP1 (hCAP-D2/NCAPD2) contains a mitotic chromosome-targeting domain that functions independently of other condensin components. This domain also contains a functional bipartite nuclear localization signal. The chromosome-targeting domain directly binds histones H1 and H3 in vitro, with the H3 interaction mediated through the H3 histone tail; a subfragment interacts with histone H3 in vivo. A deletion mutant lacking this domain is incorporated into condensin but fails to associate with mitotic chromosomes.\",\n      \"method\": \"Deletion mutagenesis; in vitro histone binding assays; co-immunoprecipitation; immunofluorescence with GFP-tagged mutants; in vivo interaction assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis combined with in vitro reconstitution binding assays and in vivo validation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"12138188\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"RNAi depletion of hCAP-D2 (NCAPD2) in HeLa cells shows that the association of hCAP-H (another non-SMC condensin I subunit) with mitotic chromosomes depends on the presence of hCAP-D2. Loss of hCAP-D2 also disorganizes chromatid axes (as defined by topoisomerase II and hCAP-E localization), impairs sister chromatid resolution and segregation, causes chromosome misalignment in metaphase, and delays anaphase entry, indicating a role in kinetochore–microtubule attachment.\",\n      \"method\": \"RNA interference (RNAi) knockdown in HeLa cells; immunofluorescence; live-cell imaging; flow cytometry\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean RNAi knockdown with multiple defined cellular phenotype readouts, replicated findings consistent with Drosophila CAP-D2 work\",\n      \"pmids\": [\"15632074\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Drosophila CAP-D2 (ortholog of NCAPD2) is required for stability of the condensin complex; loss of CAP-D2 by dsRNAi destabilizes CAP-H, mislocalizes DNA topoisomerase II and other condensin subunits, and causes failure of chromosome arm and centromere resolution as well as chromosome segregation defects. CAP-D2 is nuclear throughout interphase, increases during S phase, and localizes to chromosome axes in mitosis persisting as chromosomes begin to decondense.\",\n      \"method\": \"dsRNA-mediated interference in Drosophila embryos; immunofluorescence; immunoprecipitation to demonstrate complex composition\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ortholog study with clean loss-of-function, multiple orthogonal phenotypic readouts, consistent with mammalian condensin I data\",\n      \"pmids\": [\"15923665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The CNAP1 (NCAPD2) gene was characterized as a bona fide E2F transcriptional target. Transfection studies and site-directed mutagenesis of E2F binding sites in the CNAP1 promoter confirmed E2F regulation. Repression by 1,25-dihydroxyvitamin D3 depends on pocket proteins p107 and p130 (not pRb), as the antiproliferative effect and repression of CNAP1 were lost in p107−/−;p130−/− cells but not in pRb−/− cells.\",\n      \"method\": \"Promoter-reporter transfection assays; site-directed mutagenesis of E2F binding sites; cDNA microarray; knockout cell lines (p107−/−;p130−/−; pRb−/−)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis of transcriptional regulatory element plus genetic epistasis using knockout cells, single lab\",\n      \"pmids\": [\"16144839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NCAPD2 inhibits autophagy and blocks autophagic flux via the Ca2+/CAMKK2/AMPK/mTORC1 pathway and the PARP-1/SIRT1 axis in colorectal cancer cells. NCAPD2 knockout suppresses colorectal cancer development in an AOM/DSS-induced mouse model.\",\n      \"method\": \"Knockout cell lines; in vitro autophagic flux assays; in vivo AOM/DSS mouse model; western blotting for pathway components\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined pathway readouts (AMPK/mTORC1 phosphorylation, autophagic markers), in vivo validation, single lab\",\n      \"pmids\": [\"34229059\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NCAPD2 transcriptionally activates CDK1 by interacting with E2F transcription factor 1 (E2F1) in breast cancer cells (MDA-MB-231). NCAPD2 promotes breast cancer progression through the ERK5 signaling pathway, and overexpression of CDK1 rescues the inhibitory effects of NCAPD2 knockdown.\",\n      \"method\": \"Co-immunoprecipitation (NCAPD2–E2F1 interaction); knockdown/overexpression functional assays; CDK1 rescue experiment; western blotting\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP demonstrates interaction, rescue experiment supports epistasis, single lab with two orthogonal methods\",\n      \"pmids\": [\"35348268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NCAPD2 promotes lung adenocarcinoma progression through a positive feedback loop: NCAPD2 activates the PI3K/AKT pathway, facilitating MDM2–E2F1 interaction, reducing E2F1 ubiquitination and increasing E2F1 protein levels; E2F1 in turn enhances NCAPD2 transcription.\",\n      \"method\": \"RNA sequencing; protein interaction experiments (co-IP/pulldown); knockdown/overexpression assays; in vivo mouse models; western blotting for pathway components\",\n      \"journal\": \"Cancer biology & therapy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, abstract does not specify rigorous controls for the MDM2–E2F1–NCAPD2 feedback, protein interaction method details incomplete\",\n      \"pmids\": [\"41319185\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NCAPD2 knockdown in gastric cancer cells reduces surface MHC-I expression; treatment with PI3K inhibitor LY294002 partially rescues MHC-I levels, placing NCAPD2-mediated MHC-I downregulation downstream of the PI3K/AKT pathway.\",\n      \"method\": \"NCAPD2 siRNA knockdown; flow cytometry for MHC-I surface expression; pharmacological inhibition with LY294002; western blotting; transcriptome sequencing\",\n      \"journal\": \"Digestive diseases and sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, partial rescue only, pathway placement inferred from pharmacological inhibition without direct epistasis\",\n      \"pmids\": [\"41004034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NCAPD2 overexpression in esophageal cancer cells upregulates Wnt5A, which activates the Notch pathway and promotes glycolysis (increased ECAR, lactate production, glucose consumption) and EMT-driven metastasis; knockdown reverses these effects in vitro and in vivo.\",\n      \"method\": \"Transcriptome sequencing; ECAR/OCR/lactate assays; western blotting; scratch and Transwell assays; subcutaneous xenograft mouse model; immunohistochemistry\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, pathway assignment based on transcriptomics and correlative western blot without direct epistasis experiments for NCAPD2–Wnt5A–Notch axis\",\n      \"pmids\": [\"40946944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NCAPD2 suppresses autophagy in Crohn's disease context by promoting phosphorylation of mTOR and its effector S6K, and downregulating autophagy-related proteins Beclin1, LC3II, and Atg5. NCAPD2 also activates the NF-κB signaling pathway, sustaining inflammatory cytokine release; knockdown inhibits TNBS-induced intestinal inflammation in a mouse model.\",\n      \"method\": \"NCAPD2 knockdown in cell lines and TNBS mouse model; western blotting for mTOR/S6K/autophagy markers; immunofluorescence; qRT-PCR\",\n      \"journal\": \"Inflammatory bowel diseases\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, mechanistic pathway placement relies on correlative western blot readouts without direct reconstitution\",\n      \"pmids\": [\"39340820\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NCAPD2 (also known as CNAP1/hCAP-D2) is a non-SMC subunit of the condensin I complex that is essential for mitotic chromosome condensation and sister chromatid resolution: its C-terminal domain directly binds histones H1 and H3 to target condensin to mitotic chromosomes, it stabilizes the association of other condensin I subunits (hCAP-H) with chromosomes, and it is recruited to chromatin via AKAP95; beyond its canonical chromosome condensation role, NCAPD2 has been shown to inhibit autophagy through the Ca2+/CAMKK2/AMPK/mTORC1 and PARP-1/SIRT1 axes, to transcriptionally activate CDK1 by interacting with E2F1, and to be itself transcriptionally regulated as an E2F target gene through a p107/p130-dependent mechanism.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NCAPD2 (CNAP1/hCAP-D2) is a non-SMC subunit of the human condensin complex that drives mitotic chromosome condensation and sister chromatid resolution [#0, #3]. It targets condensin to mitotic chromosomes through its C-terminal domain, which directly binds histones H1 and H3 via the H3 tail and carries a bipartite nuclear localization signal; a deletion mutant lacking this domain still assembles into condensin but fails to load onto mitotic chromosomes [#2]. Chromatin recruitment is further promoted by AKAP95, whose dose-dependent loading of NCAPD2 correlates with the extent of chromosome condensation [#1]. Within the complex, NCAPD2 is required for the chromosome association of the non-SMC subunit hCAP-H and for organizing chromatid axes; its depletion disorganizes topoisomerase II and SMC localization, impairs sister chromatid resolution and segregation, and delays anaphase [#3], a role conserved in the Drosophila ortholog where loss destabilizes the complex [#4]. NCAPD2 transcription is controlled as an E2F target gene through a p107/p130-dependent mechanism [#5]. Beyond chromosome condensation, NCAPD2 has been linked in cancer and inflammation contexts to transcriptional activation of CDK1 via interaction with E2F1 [#7] and to suppression of autophagy through the Ca2+/CAMKK2/AMPK/mTORC1 and PARP-1/SIRT1 axes [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing that NCAPD2 is a bona fide subunit of the human condensin complex defined its molecular context and linked it to mitotic chromosome architecture.\",\n      \"evidence\": \"Co-immunoprecipitation of the endogenous hCAP-C–hCAP-E complex from HeLa extracts with immunofluorescence and fractionation\",\n      \"pmids\": [\"10958694\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how NCAPD2 is targeted to chromosomes\", \"Did not resolve the contribution of the interphase chromosome-bound subpopulation\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Identifying AKAP95 as a chromatin factor that recruits NCAPD2 answered how condensin is loaded onto mitotic chromosomes and tied recruitment quantitatively to condensation.\",\n      \"evidence\": \"Mitotic extract condensation assay with recombinant AKAP95 rescue, GST pulldown, and colocalization\",\n      \"pmids\": [\"10791967\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish whether AKAP95 binding is direct to NCAPD2 versus other subunits\", \"Did not define the binding interface\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Mapping the C-terminal chromosome-targeting domain and its direct histone H1/H3 binding explained the molecular basis of NCAPD2-dependent chromosome loading independent of the rest of the complex.\",\n      \"evidence\": \"Deletion mutagenesis, in vitro histone binding assays, and GFP-mutant localization in cells\",\n      \"pmids\": [\"12138188\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of the targeting domain–histone interaction\", \"Regulation of the H3-tail interaction (e.g. by phosphorylation) not defined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Loss-of-function in human and Drosophila cells established that NCAPD2 is required for condensin complex stability, chromatid axis organization, and accurate segregation.\",\n      \"evidence\": \"RNAi/dsRNAi depletion with immunofluorescence, live imaging, and IP of complex composition in HeLa cells and Drosophila embryos\",\n      \"pmids\": [\"15632074\", \"15923665\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not separate direct condensation roles from downstream kinetochore–microtubule effects\", \"Mechanism stabilizing hCAP-H association not defined at molecular level\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrating NCAPD2 is an E2F-regulated gene repressed via p107/p130 placed its expression under cell-cycle/proliferative transcriptional control.\",\n      \"evidence\": \"Promoter-reporter assays with E2F-site mutagenesis and epistasis in p107−/−;p130−/− versus pRb−/− knockout cells\",\n      \"pmids\": [\"16144839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Which E2F family member drives expression in vivo not resolved\", \"Link between transcriptional regulation and condensin function not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying NCAPD2 as an autophagy suppressor extended its role beyond mitosis into cancer-relevant signaling.\",\n      \"evidence\": \"Knockout cell lines, autophagic flux assays, AOM/DSS mouse model, and pathway western blots in colorectal cancer\",\n      \"pmids\": [\"34229059\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular target of NCAPD2 in the Ca2+/CAMKK2/AMPK/mTORC1 axis not identified\", \"Whether this is condensin-dependent or a moonlighting function unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showing NCAPD2 interacts with E2F1 to transactivate CDK1 proposed a feed-forward link between NCAPD2 and cell-cycle driver expression.\",\n      \"evidence\": \"Co-IP of NCAPD2–E2F1, knockdown/overexpression assays, and CDK1 rescue in MDA-MB-231 cells\",\n      \"pmids\": [\"35348268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reciprocal/endogenous validation of the NCAPD2–E2F1 interaction limited\", \"Whether NCAPD2 acts directly at the CDK1 promoter not shown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Multiple tumor and inflammation studies positioned NCAPD2 in PI3K/AKT, MDM2–E2F1, Wnt5A/Notch, mTOR/NF-κB, and MHC-I regulatory circuits.\",\n      \"evidence\": \"Knockdown/overexpression with transcriptomics, pharmacological inhibition, and xenograft/TNBS mouse models across lung, gastric, esophageal cancers and Crohn's disease\",\n      \"pmids\": [\"41319185\", \"41004034\", \"40946944\", \"39340820\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Pathway placements rest on correlative western blots and partial pharmacological rescue without direct epistasis\", \"Direct molecular partners in these axes not biochemically defined\", \"Relationship to canonical condensin function not addressed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NCAPD2's mitotic condensin function mechanistically connects to its reported signaling and transcriptional roles in cancer remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of NCAPD2 within human condensin\", \"Whether non-mitotic functions require condensin assembly is untested\", \"Direct substrates/effectors of the signaling roles unidentified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 2, 3, 4]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\"condensin I complex\"],\n    \"partners\": [\"NCAPH\", \"SMC2\", \"SMC4\", \"AKAP95\", \"E2F1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}