Affinage

NCAPD2

Condensin complex subunit 1 · UniProt Q15021

Round 2 corrected
Length
1401 aa
Mass
157.2 kDa
Annotated
2026-04-29
61 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCAPD2 is a non-SMC subunit of the condensin I complex that is essential for mitotic chromosome condensation, sister chromatid resolution, and faithful chromosome segregation. Its C-terminal domain directly binds histones H1 and H3 to target condensin I to mitotic chromosomes independently of other subunits, while AKAP95 serves as an additional chromatin-recruitment receptor; cdc2-cyclin B phosphorylation of the condensin I complex activates its ATP-dependent positive supercoiling activity required for chromosome compaction (PMID:11136719, PMID:12138188, PMID:10791967). RNAi depletion of NCAPD2 destabilizes hCAP-H association with chromosomes, disorganizes chromatid axes, impairs kinetochore–microtubule attachment, and delays anaphase entry, establishing it as critical for both condensin I integrity and mitotic progression (PMID:15632074, PMID:14532007). NCAPD2 transcription is directly regulated by E2F factors, and accumulating cancer-cell studies have implicated NCAPD2 overexpression in PI3K/AKT signaling, autophagy suppression via mTOR, and Wnt/β-catenin pathway activation, although these non-canonical signaling links have not been biochemically reconstituted (PMID:16144839, PMID:34229059, PMID:38726276).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2000 High

    The existence of a human condensin I complex containing NCAPD2 was demonstrated, resolving whether the Xenopus condensin architecture was conserved in mammals and revealing cell-cycle-dependent chromosome association.

    Evidence Co-immunoprecipitation from HeLa extracts with immunofluorescence across cell-cycle stages

    PMID:10958694

    Open questions at the time
    • Biochemical activity of the purified complex was not yet tested
    • Whether NCAPD2 contacts chromatin directly or through other subunits was unknown
  2. 2000 High

    AKAP95 was identified as a chromatin-targeting receptor that recruits NCAPD2 (Eg7) to mitotic chromosomes, establishing an upstream mechanism for condensin I chromatin loading.

    Evidence GST pulldown and recombinant AKAP95 complementation of mitotic HeLa extract with dose-response condensation assay

    PMID:10791967

    Open questions at the time
    • Whether NCAPD2 also contacts chromatin independently of AKAP95 was unresolved
    • The relative contributions of AKAP95-dependent versus AKAP95-independent targeting were unclear
  3. 2001 High

    Purified human condensin I containing NCAPD2 was shown to require cdc2-cyclin B phosphorylation for ATP-dependent positive supercoiling activity, directly linking mitotic kinase signaling to condensin enzymatic function.

    Evidence In vitro supercoiling assay with purified complex and cdc2-cyclin B, complementation of Xenopus egg extract immunodepleted of condensin

    PMID:11136719

    Open questions at the time
    • Which subunit(s) must be phosphorylated for activation was not mapped
    • Structural basis of the supercoiling activity was unknown
  4. 2002 High

    The C-terminal domain of NCAPD2 was mapped as an autonomous mitotic chromosome-targeting module that directly binds histones H1 and H3 (via the H3 tail), answering how NCAPD2 contacts chromatin independently of other condensin subunits.

    Evidence Deletion mutagenesis, GST pulldown with purified histones, transfection of truncation constructs with immunofluorescence

    PMID:12138188

    Open questions at the time
    • Whether histone modifications regulate the interaction was not tested
    • Structural detail of the NCAPD2–histone interface was lacking
  5. 2003 High

    Condensin I and condensin II were shown to make mechanistically distinct contributions to chromosome architecture, placing NCAPD2-containing condensin I in a non-redundant pathway for lateral chromatid compaction.

    Evidence siRNA depletion of condensin I- versus condensin II-specific subunits in HeLa cells and Xenopus egg extracts with chromosome morphology analysis

    PMID:14532007

    Open questions at the time
    • How the two complexes are spatially coordinated on the same chromosome was unclear
    • Whether condensin I and II act sequentially or simultaneously was unresolved
  6. 2005 High

    NCAPD2 depletion revealed that it is required for hCAP-H chromosome loading, chromatid axis integrity, sister chromatid resolution, and correct kinetochore–microtubule attachment, extending its role beyond compaction to mitotic fidelity.

    Evidence RNAi in HeLa cells with immunofluorescence for chromatid axes, chromosome alignment, and anaphase timing assays

    PMID:15632074

    Open questions at the time
    • Whether kinetochore attachment defects are direct or secondary to axis disorganization was not distinguished
    • The mechanism by which NCAPD2 stabilizes hCAP-H on chromatin was not structurally defined
  7. 2005 Medium

    NCAPD2 was identified as a direct E2F transcriptional target, linking condensin I expression to the cell-cycle transcription program and explaining its mitotic upregulation.

    Evidence Promoter-reporter assays with E2F-site mutagenesis in pocket-protein knockout cells

    PMID:16144839

    Open questions at the time
    • Whether E2F regulation is rate-limiting for condensin I assembly was not tested
    • Post-transcriptional regulation of NCAPD2 levels was not addressed
  8. 2021 Medium

    A non-canonical role for NCAPD2 in suppressing autophagy was reported, linking it to Ca²⁺/CAMKK2/AMPK/mTORC1 signaling and colorectal cancer development, broadening its functional scope beyond mitosis.

    Evidence NCAPD2 knockout in colorectal cancer cells with autophagy flux assays and AOM/DSS mouse model

    PMID:34229059

    Open questions at the time
    • No biochemical reconstitution of NCAPD2 acting directly on Ca²⁺/CAMKK2 signaling components
    • Whether this reflects a condensin-independent function or an indirect consequence of mitotic errors was not resolved
  9. 2022 Medium

    An NCAPD2/E2F1/CDK1 positive-feedback axis was described in breast cancer, where NCAPD2 interacts with E2F1 to transcriptionally activate CDK1, suggesting NCAPD2 can function as a transcriptional co-regulator.

    Evidence Co-immunoprecipitation of NCAPD2–E2F1, CDK1 overexpression rescue of NCAPD2-knockdown phenotype, xenograft models

    PMID:35348268

    Open questions at the time
    • Single lab finding; NCAPD2–E2F1 interaction not validated by reciprocal IP or structural data
    • Whether this interaction occurs on chromatin or is condensin-complex-dependent was not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether the reported oncogenic signaling roles of NCAPD2 (PI3K/AKT, Wnt/β-catenin, mTOR) reflect direct biochemical activities distinct from its condensin I function or are indirect consequences of condensin-dependent genome organization and cell-cycle perturbation.
  • No separation-of-function mutant distinguishing condensin-dependent from condensin-independent roles exists
  • No structural model of full-length NCAPD2 has been reported
  • Whether NCAPD2 has catalytic activity independent of the condensin complex is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0042393 histone binding 1
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-4839726 Chromatin organization 3
Partners
AKAP95E2F1NCAPGNCAPHSMC2SMC4
Complex memberships
Condensin I

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CNAP1 (hCAP-D2/Eg7, the human ortholog of Xenopus XCAP-D2) was identified as a 155-kDa protein that co-immunoprecipitates with the hCAP-C–hCAP-E SMC heterodimer from HeLa extracts, demonstrating the existence of a condensin I complex in human cells. The complex associates with mitotic chromosomes in a cell-cycle-specific manner, with the majority sequestered in the cytoplasm during interphase, while a subpopulation remains on interphase chromosomes as foci. Coimmunoprecipitation from HeLa extracts, immunofluorescence, subcellular fractionation Molecular and cellular biology High 10958694
2001 Human condensin purified from HeLa nuclear extracts contains hCAP-D2/CNAP1 as one of three non-SMC subunits. The complex fails to supercoil DNA in vitro unless phosphorylated by purified cdc2-cyclin B, whereupon it gains ATP-dependent positive supercoiling activity and can rescue chromosome condensation in Xenopus egg extracts immunodepleted of endogenous condensin. Protein purification, in vitro supercoiling assay, Xenopus egg extract complementation, cdc2-cyclin B kinase assay The Journal of biological chemistry High 11136719
2000 AKAP95 acts as a chromatin-targeting receptor for hCAP-D2/Eg7 (NCAPD2). In HeLa cell mitotic extract, preventing AKAP95 association with chromatin blocks chromosome condensation; recombinant AKAP95 recruits Eg7 to chromosomes in a concentration-dependent manner, and the extent of Eg7 recruitment correlates with the degree of chromosome condensation. GST pulldown, recombinant protein complementation of mitotic extract, immunofluorescence co-localization, quantitative condensation assay The Journal of cell biology High 10791967
2002 The C-terminal region of CNAP1/hCAP-D2 contains a mitotic chromosome-targeting domain that functions independently of other condensin subunits. This domain directly binds histones H1 and H3 in vitro (mediated through the H3 tail), contains a bipartite nuclear localization signal, and is required for chromosome association; a deletion mutant lacking this domain remains in condensin but cannot associate with mitotic chromosomes. Deletion mutagenesis, GST pulldown with histones, in vivo co-immunoprecipitation, transfection of deletion constructs, immunofluorescence Molecular and cellular biology High 12138188
2003 Condensin I (containing hCAP-D2/NCAPD2) and condensin II share the same SMC subunits but differ in their non-SMC subunits; siRNA-mediated depletion of condensin I-specific subunits in HeLa cells produces a distinct chromosome morphology defect different from condensin II depletion, and simultaneous depletion causes the most severe defect, establishing that the two complexes make distinct mechanistic contributions to mitotic chromosome architecture. siRNA knockdown, immunofluorescence, chromosome morphology analysis in HeLa and Xenopus egg extracts Cell High 14532007
2005 RNAi-mediated depletion of hCAP-D2 in HeLa cells shows that hCAP-H (another non-SMC subunit of condensin I) requires hCAP-D2 for its association with mitotic chromosomes; chromatid axes (marked by topoisomerase II and hCAP-E) are disorganized, and sister chromatid resolution/segregation is impaired. hCAP-D2 depletion also disrupts chromosome alignment in metaphase and delays anaphase entry, implicating condensin I in correct kinetochore–microtubule attachment. RNA interference, immunofluorescence, chromosome morphology analysis, mitotic timing assays Molecular and cellular biology High 15632074
2005 In Drosophila, CAP-D2 (ortholog of NCAPD2) is nuclear throughout interphase and localizes on chromosome axes during mitosis. dsRNA-mediated loss of CAP-D2 demonstrates that it is essential for chromosome arm and centromere resolution; its loss destabilizes CAP-H levels, disrupts topoisomerase II localization, and causes chromosome segregation defects, establishing CAP-D2 as critical for condensin complex stability. dsRNAi, immunofluorescence, Western blot, live imaging in Drosophila embryos Journal of cell science High 15923665
2005 CNAP1/hCAP-D2 (NCAPD2) was identified as a bona fide E2F transcriptional target gene. Transfection and site-directed mutagenesis of E2F binding sites in the Cnap1 promoter confirmed direct E2F-dependent regulation; repression by 1,25(OH)2D3 required pocket proteins p107 and p130 but not pRb. cDNA microarray, promoter reporter transfection, site-directed mutagenesis of E2F sites, genetic knockout cell lines The Journal of biological chemistry Medium 16144839
2021 NCAPD2 inhibits autophagy in colorectal cancer cells by regulating the Ca²⁺/CAMKK2/AMPK/mTORC1 signaling pathway and the PARP-1/SIRT1 axis, thereby blocking autophagic flux. NCAPD2 knockout suppresses colorectal cancer development in an AOM/DSS mouse model. NCAPD2 knockout, autophagy flux assays, Western blot for pathway components, in vivo AOM/DSS mouse model Cancer letters Medium 34229059
2022 NCAPD2 promotes breast cancer progression through the ERK5 signaling pathway and transcriptionally activates CDK1 by interacting with E2F1 transcription factor in MDA-MB-231 cells; overexpression of CDK1 rescues the proliferation inhibition caused by NCAPD2 knockdown, establishing an NCAPD2/E2F1/CDK1 axis. Loss-of-function assays, co-immunoprecipitation (NCAPD2–E2F1 interaction), Western blot, in vivo xenograft, CDK1 overexpression rescue Cancer science Medium 35348268
2024 NCAPD2 activates the Wnt/β-catenin pathway to promote epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma under high-glucose conditions; NCAPD2 knockdown suppresses β-catenin pathway activity and inhibits HCC growth in vivo. Bioinformatics and functional data indicate NCAPD2 primarily interacts with NCAPG, SMC4, and NCAPH within condensin. In vitro functional assays, in vivo xenograft, Western blot for β-catenin pathway, bioinformatics interaction analysis American journal of cancer research Low 38726276
2025 NCAPD2 suppresses autophagy and promotes intestinal inflammation in Crohn's disease by stimulating mTOR phosphorylation and its effector S6K, downregulating autophagy proteins Beclin1, LC3II, and Atg5, while also activating the NF-κB signaling pathway to sustain inflammatory cytokine release. NCAPD2 knockdown in TNBS-induced mouse model, Western blot for mTOR/S6K/autophagy markers, immunofluorescence, qPCR Inflammatory bowel diseases Low 39340820
2025 NCAPD2 promotes lung adenocarcinoma progression through an AKT/MDM2/E2F1 positive feedback loop: NCAPD2 activates PI3K/AKT signaling, facilitating MDM2–E2F1 interaction and reducing E2F1 ubiquitination, increasing E2F1 protein levels; E2F1 in turn enhances NCAPD2 transcription. RNA sequencing, protein interaction experiments, Western blot, colony formation, Transwell, in vivo mouse models, NCAPD2 knockdown/overexpression Cancer biology & therapy Low 41319185
2025 NCAPD2 downregulates MHC-I surface expression in gastric cancer cells through the PI3K/AKT signaling pathway, facilitating immune evasion; treatment with the PI3K inhibitor LY294002 partially rescues MHC-I surface levels in NCAPD2-expressing cells. Transcriptome sequencing of NCAPD2-silenced cells, Western blot, flow cytometry, PI3K inhibitor rescue experiment Digestive diseases and sciences Low 41004034
2025 NCAPD2 promotes esophageal cancer metastasis by upregulating Wnt5A, which activates the Notch signaling pathway to enhance glycolytic flux (increased ECAR, lactate production, glucose consumption); knockdown of NCAPD2 or Wnt5A reverses these metabolic and metastatic phenotypes. Transcriptome sequencing, ECAR/OCR metabolic assays, Western blot, scratch/Transwell invasion assays, subcutaneous xenograft, immunohistochemistry Cellular signalling Low 40946944

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 1362 16751776
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 460 14532007
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1998 C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. The Journal of cell biology 377 9647649
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2006 Phosphoproteome analysis of the human mitotic spindle. Proceedings of the National Academy of Sciences of the United States of America 281 16565220
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2000 The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion. The Journal of cell biology 187 11076968
2017 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs. Nature communications 176 28685749
2001 Chromosome condensation by a human condensin complex in Xenopus egg extracts. The Journal of biological chemistry 163 11136719
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2020 AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System. Molecular cell 152 31995728
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2005 Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells. Molecular biology of the cell 130 16339073
2000 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. Molecular and cellular biology 102 10958694
2002 The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles. Journal of cell science 94 12140259
2005 Drosophila CAP-D2 is required for condensin complex stability and resolution of sister chromatids. Journal of cell science 71 15923665
2021 NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. Cancer letters 69 34229059
2000 A kinase-anchoring protein (AKAP)95 recruits human chromosome-associated protein (hCAP)-D2/Eg7 for chromosome condensation in mitotic extract. The Journal of cell biology 63 10791967
2008 A novel function of CEP135 as a platform protein of C-NAP1 for its centriolar localization. Experimental cell research 54 18851962
2018 STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles. Proceedings of the National Academy of Sciences of the United States of America 53 29463719
2014 Centlein mediates an interaction between C-Nap1 and Cep68 to maintain centrosome cohesion. Journal of cell science 53 24554434
2014 Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction. Journal of cell science 53 24695856
2002 Identification of a chromosome-targeting domain in the human condensin subunit CNAP1/hCAP-D2/Eg7. Molecular and cellular biology 51 12138188
2005 Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3. The Journal of biological chemistry 40 16144839
2005 Contribution of hCAP-D2, a non-SMC subunit of condensin I, to chromosome and chromosomal protein dynamics during mitosis. Molecular and cellular biology 38 15632074
2015 C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle. Nature communications 35 25902731
2012 C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis. Cell cycle (Georgetown, Tex.) 35 23070519
2022 NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1. Cancer science 30 35348268
2017 Centriole splitting caused by loss of the centrosomal linker protein C-NAP1 reduces centriolar satellite density and impedes centrosome amplification. Molecular biology of the cell 26 28100636
2022 cNap1 bridges centriole contact sites to maintain centrosome cohesion. PLoS biology 9 36282799
2024 High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/β-catenin signaling pathway in HCC. American journal of cancer research 8 38726276
2022 Centrosome linker protein C-Nap1 maintains stem cells in mouse testes. EMBO reports 8 35599622
2015 The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly. Biochemical and biophysical research communications 8 25660448
2024 NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K‑Akt‑mTOR signaling pathway. International journal of molecular medicine 7 39092569
2024 NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/β-catenin pathway. Cell cycle (Georgetown, Tex.) 6 38743408
2019 A novel homozygous splice-site variant of NCAPD2 gene identified in two siblings with primary microcephaly: The second case report. Clinical genetics 4 31056748
2026 CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1. Molecular cancer 1 41668133
2025 Targeting NCAPD2 as a Therapeutic Strategy for Crohn's Disease: Implications for Autophagy and Inflammation. Inflammatory bowel diseases 0 39340820
2025 NCAPD2 stimulates glycolysis and esophageal cancer metastasis through Wnt5A-dependent Notch activation. Cellular signalling 0 40946944
2025 NCAPD2 Modulates MHC-I Antigen Presentation via the PI3K/AKT Axis to Drive Metastatic Progression in Gastric Cancer. Digestive diseases and sciences 0 41004034
2025 NCAPD2 promotes the progression of lung adenocarcinoma through an AKT/MDM2/E2F1 positive feedback loop. Cancer biology & therapy 0 41319185