Affinage

AHCTF1

Protein ELYS · UniProt Q8WYP5

Length
2266 aa
Mass
252.5 kDa
Annotated
2026-06-09
29 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AHCTF1 (ELYS/MEL-28) is the seeding nucleoporin that initiates post-mitotic nuclear pore complex (NPC) assembly by linking chromatin to the Nup107-160 (Y-complex) scaffold (PMID:17098863, PMID:17235358). It is a multidomain protein comprising an N-terminal β-propeller, a central α-helical region that together mediate NPC anchorage, and a C-terminal disordered region responsible for chromatin engagement (PMID:23499022); this C-terminal region binds AT-rich chromatin through an AT-hook motif and directly contacts the nucleosome acidic patch via its RRK stretch, with point mutations in the AT-hook abolishing NPC assembly (PMID:17825564, PMID:18596237, PMID:31069272). Chromatin-bound ELYS recruits the Nup107-160 complex, which in turn brings in POM121- and NDC1-containing membrane vesicles to nucleate pores (PMID:17235358, PMID:18596237), integrating into the Y-complex at the Nup120/Nup37 interface (PMID:22955883). Beyond pore seeding, ELYS sets nuclear size by controlling NPC density and nuclear import capacity, an activity rescuable by importin α (PMID:31085625), and it organizes inner nuclear membrane proteins during NE reassembly: it recruits the lamin B receptor (LBR) to the chromosomal non-core region through a CDK/SRPK/PP1 phosphorylation network and via a phospho-FFAT–dependent interaction with VAPB (PMID:22555603, PMID:27802161, PMID:38605278). ELYS also associates with the Mcm2-7 replication-licensing machinery on chromatin, coupling pore assembly to replication competence (PMID:17825564, PMID:18974873), and localizes to kinetochores during mitosis where it ensures chromosome segregation (PMID:17098863, PMID:35609608). In colon cancer cells, AHCTF1 tethers active MYC alleles to nuclear pores through β-catenin at WNT-driven super-enhancers, accelerating MYC mRNA export (PMID:31784729).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established that ELYS is a physical and functional partner of the Nup107-160 complex required for nuclear pore assembly, defining its central role at the nuclear envelope.

    Evidence Co-IP/MS and RNAi in HeLa cells and Xenopus extracts, with kinetochore targeting at mitosis

    PMID:17098863

    Open questions at the time
    • Mechanism of chromatin engagement not yet defined
    • Direct vs scaffold-mediated kinetochore role unresolved
  2. 2007 High

    Showed ELYS acts upstream as the seeding point that recruits the Nup107-160 complex to chromatin, ordering the NPC assembly pathway.

    Evidence In vitro NE assembly assay with immunodepletion and Co-IP

    PMID:17235358

    Open questions at the time
    • Chromatin determinant of recruitment unknown
    • Membrane vesicle step not yet placed
  3. 2007 High

    Identified the AT-hook chromatin-binding domain and linked ELYS to the Mcm2-7 replication-licensing machinery, connecting pore assembly to replication.

    Evidence Xenopus egg extract, chromatin binding competition, Co-IP

    PMID:17825564

    Open questions at the time
    • Functional consequence of Mcm2-7 association for replication not established here
    • Whether interaction is direct unresolved
  4. 2008 High

    Demonstrated that AT-hook–mediated chromatin binding is essential for downstream recruitment of POM121/NDC1 membrane vesicles, completing the chromatin-to-membrane assembly chain.

    Evidence Point mutagenesis, DNA-binding antibiotic competition, Xenopus in vitro assembly, Co-IP

    PMID:18596237

    Open questions at the time
    • gp210 vesicle recruitment pathway distinct and unaddressed
    • Structural basis of POM121-Y-complex contact unknown
  5. 2008 Medium

    Provided in vivo genetic support that Elys promotes Mcm2-chromatin loading, implicating it in replication licensing in an intact organism.

    Evidence Zebrafish loss-of-function mutants, Co-IP with Xenopus extracts, immunohistochemistry

    PMID:18974873

    Open questions at the time
    • Selectivity for Mcm2 over Mcm3/4 mechanistically unexplained
    • Cross-species pulldown leaves directness uncertain
  6. 2012 High

    Resolved how ELYS integrates structurally into the Y-complex via the Nup120/Nup37 interface.

    Evidence X-ray crystallography (1.9 Å) of Nup37–Nup120 with reconstitution and binding assays in fission yeast ortholog

    PMID:22955883

    Open questions at the time
    • Human complex geometry inferred from ortholog
    • Stoichiometry within assembled NPC not addressed
  7. 2012 Medium

    Extended ELYS function to inner nuclear membrane organization by showing it recruits LBR and focuses A-type lamin-binding proteins during NE reassembly.

    Evidence RNAi in HeLa cells, phosphorylation-dependent Co-IP, immunofluorescence

    PMID:22555603

    Open questions at the time
    • Kinase/phosphatase identities not yet defined
    • Direct vs indirect LBR interaction unresolved at this stage
  8. 2013 High

    Defined the three-domain architecture, assigning chromatin binding to the disordered C-terminus and NPC anchorage to the β-propeller/α-helical regions.

    Evidence X-ray crystallography (1.9 Å) of β-propeller plus domain deletion analysis

    PMID:23499022

    Open questions at the time
    • Structure of central α-helical and C-terminal regions not solved
    • Nucleosome contact residues not yet mapped
  9. 2016 Medium

    Defined a CDK/SRPK1/2–PP1 phosphorylation network through which ELYS controls LBR localization at the inner nuclear membrane.

    Evidence RNAi, phosphorylation analysis, kinase inhibitors, PP1 depletion

    PMID:27802161

    Open questions at the time
    • Whether ELYS scaffolds the kinases/phosphatase directly is unclear
    • Single-lab evidence
  10. 2016 Medium

    Dissected separable ELYS domains for function, localization, chromatin binding, spindle matrix association, and segregation, and revealed an AT-hook checkpoint role.

    Evidence Systematic domain mutagenesis, RNAi, microscopy, genetic epistasis in C. elegans and human cells

    PMID:27341616

    Open questions at the time
    • Molecular basis of checkpoint delay not defined
    • Meiotic role mechanistically open
  11. 2017 Medium

    Revealed that RNA is required for proper ELYS chromatin recruitment and downstream import of S-phase kinases, adding an RNA-dependent layer to assembly.

    Evidence Xenopus egg extract with RNA depletion and rescue, fractionation

    PMID:29242643

    Open questions at the time
    • Identity of the required RNA(s) unknown
    • Whether ELYS binds RNA directly not established
  12. 2019 High

    Provided the structural mechanism of chromatin engagement: the C-terminal RRK stretch binds the nucleosome acidic patch.

    Evidence Cryo-EM, crosslinking MS, mutagenesis, binding assays

    PMID:31069272

    Open questions at the time
    • Relationship between AT-hook DNA binding and acidic-patch binding not integrated
    • In vivo requirement of RRK not tested in mammals here
  13. 2019 Medium

    Established ELYS as a determinant of nuclear size via control of NPC density and nuclear import capacity, rescuable by importin α.

    Evidence High-throughput RNAi, gain/loss-of-function, importin α rescue, nuclear import assay

    PMID:31085625

    Open questions at the time
    • Whether size control is separable from pore-seeding function unclear
    • Importin α as direct vs downstream effector unresolved
  14. 2019 Medium

    Connected AHCTF1 to oncogenic transcription by showing it tethers MYC alleles to nuclear pores via β-catenin to accelerate MYC mRNA export.

    Evidence ChIP, gene-gating assays, RNA export measurement, knockdown, β-catenin interaction assays in colon cancer cells

    PMID:31784729

    Open questions at the time
    • Directness of AHCTF1–β-catenin contact not fully resolved
    • Generality beyond MYC/colon cancer untested
  15. 2024 Medium

    Identified a mitotic phospho-FFAT motif in ELYS mediating interaction with VAPB at the forming non-core nuclear envelope, linking ELYS to ER membrane proteins during NE reassembly.

    Evidence Reciprocal Co-IP, recombinant binding, mass spectrometry, VAPB depletion phenotypes

    PMID:38605278

    Open questions at the time
    • Kinase generating the phospho-FFAT not identified
    • Functional separation from POM121/NDC1 pathway unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ELYS coordinates its multiple roles—chromatin seeding, replication licensing, kinetochore function, INM protein organization, and gene gating—into a single regulated program across the cell cycle remains unresolved.
  • No unified model integrating AT-hook DNA, acidic-patch, and RNA-dependent recruitment
  • Direct human structural data for full-length protein lacking
  • Whether disease-relevant mutations exist not addressed in corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0042393 histone binding 1
Localization
GO:0005635 nuclear envelope 4 GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
CTNNB1LBRMCM2NDC1NUP107NUP37POM121VAPB
Complex memberships
Nup107-160 (Y-complex)kinetochore

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 ELYS co-purifies with the Nup107-160 complex in Xenopus interphase extracts, mitotic extracts, and human cell extracts (co-immunoprecipitation/mass spectrometry), and is required for nuclear pore assembly; RNAi depletion of ELYS in HeLa cells severely disrupts nuclear pores in the nuclear envelope and leads to cytokinesis defects, while lamin, Ran, and tubulin staining appear normal. At mitosis, ELYS targets to kinetochores. Co-immunoprecipitation, mass spectrometry, RNAi knockdown, immunofluorescence in HeLa cells and Xenopus extracts Proceedings of the National Academy of Sciences of the United States of America High 17098863
2007 MEL-28/ELYS (vertebrate homologue) is essential for post-mitotic NPC assembly; it interacts with the Nup107-160 complex and is required for recruitment of the Nup107-160 complex to chromatin, acting as a seeding point for NPC assembly, as demonstrated in in vitro nuclear envelope assembly assays. In vitro nuclear envelope assembly assay, immunodepletion, co-immunoprecipitation EMBO reports High 17235358
2007 ELYS contains an AT-hook domain that binds chromatin with high affinity; this domain competes with full-length ELYS for chromatin association thereby blocking NPC assembly. ELYS also physically associates with the Mcm2-7 replication-licensing proteins on chromatin, and ELYS chromatin loading is delayed when Mcm2-7 is prevented from loading. Xenopus egg extract cell-free system, proteomics, chromatin binding competition assay, co-immunoprecipitation Current biology : CB High 17825564
2008 ELYS binds AT-rich chromatin via its AT-hook motif; point mutation of only two amino acids in the AT-hook blocks nuclear pore assembly. Chromatin-bound ELYS/Nup107-160 complex is required for recruitment of vesicles containing integral membrane pore proteins POM121 and NDC1 (but not gp210 vesicles). A direct interaction between the cytoplasmic domain of POM121 and the Nup107-160 complex was identified. Point mutagenesis, DNA-binding antibiotics competition assay, Xenopus in vitro nuclear assembly, co-immunoprecipitation Molecular biology of the cell High 18596237
2008 In zebrafish elys mutants, Elys binds Mcm2-7 complexes from Xenopus egg extracts, and loss of Elys reduces chromatin binding of Mcm2 (but not Mcm3 or Mcm4) in the intestine, indicating a role for Elys in Mcm2-chromatin interactions and replication licensing. Zebrafish genetics (loss-of-function mutation), co-immunoprecipitation with Xenopus extracts, immunofluorescence/immunohistochemistry PLoS genetics Medium 18974873
2012 Crystal structure of S. pombe Nup37 in complex with Nup120 (174-kDa subassembly) was determined; ELY5/ELYS (fission yeast ELYS ortholog) integrates into the Y-complex via Nup120/160 and binds near the Nup120-Nup37 interface, as shown by reconstitution assays and in vivo/in vitro biochemical data. X-ray crystallography (1.9 Å), reconstitution assays, in vivo and in vitro biochemical binding assays Proceedings of the National Academy of Sciences of the United States of America High 22955883
2012 ELYS/Mel28 is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region during NE reassembly; this depends on Nup107 but not Pom121. ELYS/Mel28 biochemically interacts with LBR in a phosphorylation-dependent manner. ELYS/Mel28 also focuses A-type lamin-binding proteins (emerin, Lap2α, BAF) at the chromosomal core region. RNAi knockdown in HeLa cells, co-immunoprecipitation, immunofluorescence Nucleus (Austin, Tex.) Medium 22555603
2013 ELYS contains three domains: an N-terminal β-propeller domain (crystal structure resolved at 1.9 Å), a central α-helical domain, and a C-terminal disordered region. The disordered C-terminal region is responsible for chromatin interactions, while the β-propeller and α-helical domains synergistically mediate tethering to the NPC. Surface analysis of the β-propeller identifies regions required for NPC anchorage. X-ray crystallography (1.9 Å resolution), domain mapping/deletion analysis, biochemical binding assays Structure (London, England : 1993) High 23499022
2016 ELYS depletion promotes LBR phosphorylation at CDK- and SRPK1/SRPK2-targeted residues; PP1 phosphatase normally counterbalances this phosphorylation; depletion of PP1 similarly mislocalizes LBR. These results define an ELYS-mediated phosphorylation network controlling LBR localization at the inner nuclear membrane. RNAi knockdown, phosphorylation analysis, kinase inhibitor experiments, PP1 depletion Journal of cell science Medium 27802161
2016 MEL-28/ELYS in C. elegans has distinct functional domains: an AT-hook domain required for function (but not localization) whose perturbation delays cell cycle progression in a DNA damage checkpoint-dependent manner; domains for nuclear envelope/kinetochore localization; chromatin binding; mitotic spindle matrix association; and chromosome segregation. A novel meiotic role was also identified. Systematic domain mutagenesis, RNAi, fluorescence microscopy, genetic epistasis in C. elegans and human cells PLoS genetics Medium 27341616
2017 RNAs are required for proper ELYS recruitment to chromatin during nuclear envelope assembly in Xenopus egg extracts; RNA-depleted extracts show defective ELYS recruitment, impaired NPC assembly, failure in chromatin relaxation, and inability to import/concentrate S-phase kinases needed for DNA replication activation. Xenopus egg extract with RNA depletion, immunofluorescence, biochemical fractionation Nature communications Medium 29242643
2019 ELYS knockdown in human cells results in small nuclei, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import capacity; overexpression of importin α rescues nuclear size and lamin B2 import; ELYS overexpression increases nuclear size, NPC density, and nuclear import. ELYS thus controls nuclear size through regulation of NPC number and nuclear import capacity. High-throughput RNAi screen, importin α overexpression rescue, ELYS overexpression, nuclear import assay, immunofluorescence in mammalian cells EMBO reports Medium 31085625
2019 The Arg-Arg-Lys (RRK) stretch of the C-terminal ELYS region is essential for nucleosome binding; cryo-EM structure and crosslinking mass spectrometry reveal that the ELYS C-terminal region directly binds the acidic patch of the nucleosome, providing a mechanism for how ELYS engages chromatin to initiate post-mitotic NPC assembly. Cryo-EM structure determination, crosslinking mass spectrometry, mutagenesis, binding assays Communications biology High 31069272
2019 AHCTF1/ELYS connects nucleoporins to the oncogenic MYC super-enhancer via β-catenin (WNT signaling effector), facilitating tethering of active MYC alleles to nuclear pores to increase transcript export rates, thereby reducing nuclear MYC mRNA degradation and increasing cytoplasmic MYC mRNA levels in colon cancer cells. ChIP, chromatin conformation/gene gating assays, RNA export measurements, AHCTF1 knockdown, β-catenin interaction assays Nature genetics Medium 31784729
2020 Drosophila ELYS (dElys) depletion leads to nuclear pore and nuclear lamina assembly defects; genetically, dElys depletion re-activates the Dorsal (NF-κB) pathway during late larval stages, causing ectopic expression of Dorsal target genes and up-regulation of pro-apoptotic genes reaper and hid leading to apoptosis. dElys contains a noncanonical AT-hook-like motif through which it strongly binds DNA. RNAi depletion, fluorescence and electron microscopy, genetic epistasis, quantitative PCR in Drosophila The Journal of biological chemistry Medium 31941789
2022 In C. elegans oocyte meiosis, MEL-28/ELYS (ortholog of human ELYS) acts in parallel with CENP-C to recruit outer kinetochore components to meiotic chromosomes. MEL-28 also independently links chromosomes to spindle microtubules together with the NDC-80 complex (part of the KMN network), and this function involves the Y-complex nucleoporins that associate with MEL-28. The PP1-docking function shared by MEL-28 and KNL-1 is not involved in microtubule linkage. Genetic epistasis, engineered separation-of-function mutants, RNAi, live imaging in C. elegans Current biology : CB Medium 35609608
2024 During mitosis, ELYS is phosphorylated at multiple sites including a predicted FFAT motif; this phosphorylation enables interaction with the MSP domain of membrane protein VAPB. In anaphase, ELYS and VAPB co-localize to the non-core region of the newly forming nuclear envelope. VAPB depletion results in prolonged mitosis, slow meta-to-anaphase progression, and chromosome segregation defects. Co-immunoprecipitation, recombinant protein binding assays, mass spectrometry, immunofluorescence, VAPB depletion EMBO reports Medium 38605278

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. Proceedings of the National Academy of Sciences of the United States of America 212 17098863
2007 MEL-28/ELYS is required for the recruitment of nucleoporins to chromatin and postmitotic nuclear pore complex assembly. EMBO reports 205 17235358
2008 Capture of AT-rich chromatin by ELYS recruits POM121 and NDC1 to initiate nuclear pore assembly. Molecular biology of the cell 134 18596237
2007 ELYS/MEL-28 chromatin association coordinates nuclear pore complex assembly and replication licensing. Current biology : CB 118 17825564
2019 WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating. Nature genetics 81 31784729
2012 Molecular basis for Nup37 and ELY5/ELYS recruitment to the nuclear pore complex. Proceedings of the National Academy of Sciences of the United States of America 62 22955883
2019 The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity. EMBO reports 52 31085625
2008 Mutation of the zebrafish nucleoporin elys sensitizes tissue progenitors to replication stress. PLoS genetics 50 18974873
2012 The nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation in HeLa cells. Nucleus (Austin, Tex.) 45 22555603
2016 Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation. PLoS genetics 41 27341616
2008 Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish. Gastroenterology 40 19073184
2013 Structural and functional studies of the 252 kDa nucleoporin ELYS reveal distinct roles for its three tethered domains. Structure (London, England : 1993) 36 23499022
2004 Targeted disruption of the mouse ELYS gene results in embryonic death at peri-implantation development. Genes to cells : devoted to molecular & cellular mechanisms 32 15507119
2002 Identification of a novel transcription factor, ELYS, expressed predominantly in mouse foetal haematopoietic tissues. Genes to cells : devoted to molecular & cellular mechanisms 32 11952839
2011 The nuclear pore complex protein Elys is required for genome stability in mouse intestinal epithelial progenitor cells. Gastroenterology 27 21315719
2016 ELYS regulates the localization of LBR by modulating its phosphorylation state. Journal of cell science 24 27802161
2019 Structural and biochemical analyses of the nuclear pore complex component ELYS identify residues responsible for nucleosome binding. Communications biology 16 31069272
2017 RNAs coordinate nuclear envelope assembly and DNA replication through ELYS recruitment to chromatin. Nature communications 10 29242643
2020 Drosophila ELYS regulates Dorsal dynamics during development. The Journal of biological chemistry 9 31941789
2024 Phosphorylation of ELYS promotes its interaction with VAPB at decondensing chromosomes during mitosis. EMBO reports 6 38605278
2003 Genomic organization and characterization of the mouse ELYS gene. Biochemical and biophysical research communications 6 12745078
2023 ahctf1 and kras mutations combine to amplify oncogenic stress and restrict liver overgrowth in a zebrafish model of hepatocellular carcinoma. eLife 5 36648336
2022 MEL-28/ELYS and CENP-C coordinately control outer kinetochore assembly and meiotic chromosome-microtubule interactions. Current biology : CB 5 35609608
2018 Genetic Analyses of Elys Mutations in Drosophila Show Maternal-Effect Lethality and Interactions with Nucleoporin Genes. G3 (Bethesda, Md.) 5 29773558
2020 Author Correction: WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating. Nature genetics 4 32948851
2025 AHCTF1 Functions as an Oncogenic Factor and Promotes Tumor Progression in Hepatocellular Carcinoma. Digestive diseases and sciences 1 40707755
2026 ELYS promotes hepatocellular carcinoma stemness by activating a FOXO6-NUP205 transcriptional module downstream of PI3K/AKT to drive Hedgehog signaling. Cell & bioscience 0 42231458
2025 The Drosophila nucleoporin ELYS is required for parental chromosome arrangement at fertilization. G3 (Bethesda, Md.) 0 40359232
2018 Author Correction: RNAs coordinate nuclear envelope assembly and DNA replication through ELYS recruitment to chromatin. Nature communications 0 29402910

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