Affinage

NPAT

Protein NPAT · UniProt Q14207

Length
1427 aa
Mass
154.3 kDa
Annotated
2026-06-10
78 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPAT (p220) is a nuclear scaffold protein that couples the cell cycle to replication-dependent histone gene expression, acting as a substrate of cyclin E/CDK2 whose phosphorylation at the G1/S boundary accelerates S-phase entry (PMID:9472014). NPAT localizes to discrete nuclear foci—histone locus bodies coincident with Cajal bodies—that associate with the replication-dependent histone gene clusters on chromosomes 1 and 6, where it activates histone transcription in a cyclin E/CDK2-stimulated manner; CDK2 phosphorylation of NPAT is required for this transcriptional activation (PMID:10995386, PMID:10995387). Two functionally separable regions underlie its activities: an N-terminal LisH-like motif is required for histone gene activation but dispensable for S-phase induction, which is driven by the C-terminal half (PMID:12724424). NPAT activates histone genes by recruiting the TRRAP–Tip60 histone acetyltransferase complex to histone promoters, where it drives H4 acetylation, and by recruiting CDK9, thereby coupling transcription to histone mRNA 3′-end processing (PMID:17967892, PMID:20190802). NPAT is itself an E2F target gene whose induction at G1/S links E2F to histone gene transcription, and its loss impedes cell cycle progression and histone gene expression (PMID:12665581). Nuclear import, export, and condensation are tightly controlled: KPNA3 imports NPAT and sterically blocks premature cytoplasmic phase separation through its C-terminal self-interaction motif, while CRM1 binds a nuclear export signal within the LisH domain and competitively suppresses NPAT self-association and histone locus body assembly (PMID:39621428, PMID:41481226). NPAT is essential in vivo, with loss causing early embryonic arrest and tissue-specific proliferation defects, and its depletion in TP53-mutated AML triggers genome-wide histone loss and replication catastrophe (PMID:9199343, PMID:41160778).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Medium

    Established that NPAT is essential for development before any molecular function was known, by showing genetic loss arrests early embryogenesis.

    Evidence proviral disruption of mouse Npat with in vitro embryo culture, controlling for the linked Atm gene

    PMID:9199343

    Open questions at the time
    • did not identify the molecular activity responsible for the arrest
    • did not localize the protein or define partners
  2. 1998 High

    Identified NPAT as a cyclin E/CDK2 substrate that promotes S-phase entry, placing it directly downstream of a key G1/S kinase.

    Evidence in vivo Co-IP, in vitro kinase assay, and overexpression with flow cytometry

    PMID:9472014

    Open questions at the time
    • did not identify the downstream transcriptional targets
    • phosphosites not mapped
  3. 2000 High

    Defined NPAT's core function: it localizes to histone gene clusters within Cajal-body-associated foci and activates histone transcription, with CDK2 phosphorylation of specific sites required for activation.

    Evidence FISH, immunofluorescence co-localization, luciferase reporters, phospho-specific antibodies, and CDK2 phosphosite mutagenesis

    PMID:10995386 PMID:10995387

    Open questions at the time
    • did not identify the coactivator machinery recruited
    • did not separate S-phase from transcription functions
  4. 2002 Medium

    Mapped the determinants of NPAT nuclear localization, showing three C-terminal basic-residue clusters and a central hydrophobic sequence are required.

    Evidence GFP fusion deletion mutagenesis and fluorescence microscopy

    PMID:12473189

    Open questions at the time
    • did not identify the import receptor
    • single localization readout
  5. 2003 High

    Separated NPAT's two activities by domain and connected its transcription to E2F, establishing the LisH motif as required for histone activation and the C-terminus for S-phase induction.

    Evidence scanning mutagenesis with reporter/localization assays, plus ChIP, promoter reporters, and siRNA for E2F regulation

    PMID:12665581 PMID:12724424

    Open questions at the time
    • mechanism by which the C-terminus drives S phase independent of transcription unresolved
    • coactivators not yet identified
  6. 2007 High

    Revealed the activation mechanism: NPAT recruits the TRRAP–Tip60 acetyltransferase complex to histone promoters, driving H4 acetylation at G1/S.

    Evidence reciprocal Co-IP, NPAT-dependent ChIP, and siRNA knockdown with reporter assays

    PMID:17967892

    Open questions at the time
    • did not address coupling to mRNA processing
    • stoichiometry of the complex unresolved
  7. 2010 High

    Showed NPAT couples histone transcription to 3′-end processing by recruiting CDK9, and that this output is reduced upon p53-induced G1 arrest via E2F.

    Evidence siRNA knockdown, ChIP for CDK9, and 3′-end processing/polyadenylation assays

    PMID:20190802

    Open questions at the time
    • direct CDK9-NPAT contact not structurally defined
    • did not establish whether processing defect is cause or consequence
  8. 2010 Medium

    Extended the regulatory logic to stem cells, showing cyclin D2 rather than cyclin E drives NPAT phosphorylation in human ES cells to support self-renewal.

    Evidence siRNA knockdown of cyclin D2/NPAT with phospho-blotting, flow cytometry, and RT-PCR; complementary hES cell foci/phosphorylation analysis (idx 6)

    PMID:17520687 PMID:19890848

    Open questions at the time
    • did not map cyclin D2-specific phosphosites
    • context-specificity across cell types not generalized
  9. 2015 Medium

    Refined the cyclin partner specificity, identifying cyclin E2 as the preferential NPAT-associated cyclin correlating with histone expression in cancer cells; also identified Cpn10/HSPE as a partner required for NPAT focus and histone locus body integrity.

    Evidence co-localization and Co-IP for cyclin E2; Co-IP, siRNA, and DLFD-motif mutagenesis for Cpn10

    PMID:25741376 PMID:26429916

    Open questions at the time
    • functional consequence of cyclin E1 vs E2 specificity unresolved
    • how Cpn10, a chaperonin, mechanistically nucleates HLBs unclear
  10. 2020 Medium

    Provided structural and conserved-regulation insight: the NPAT C-terminal helix binds the FLASH/YARP SANT/Myb domain, and the yeast ortholog Spt21 is controlled by inhibitory DDR-kinase phosphorylation.

    Evidence multidimensional NMR of the FLASH/YARP–NPAT peptide complex; yeast genetics and phosphosite/epistasis analysis of Spt21

    PMID:32722282 PMID:32814778

    Open questions at the time
    • functional validation of the structural interface limited
    • conservation of Rad53-type DDR control in mammalian NPAT untested
  11. 2022 Medium

    Demonstrated in vivo tissue-specific requirements for NPAT-driven histone expression in Sertoli cell proliferation and thymocyte development, with the Drosophila ortholog Mxc required for neural stem cell maintenance.

    Evidence conditional knockouts (Sertoli, thymocyte) with histology/flow cytometry; Drosophila RNAi/mutants with γH2AX DSB assays

    PMID:31084574 PMID:35642004 PMID:35922064

    Open questions at the time
    • tissue-specific downstream effectors only partly defined
    • link between histone loss and DSB accumulation mechanistically incomplete
  12. 2024 High

    Identified KPNA3 as the NPAT importin and uncovered phase-separation control: KPNA3 binding to the NLS sterically blocks C-SIF-mediated self-association to prevent aberrant cytoplasmic condensation; NPAT stability is also regulated by proteasomal degradation.

    Evidence Co-IP, domain mapping, phase separation and nuclear import assays with NLS/C-SIF mutagenesis; proteasome inhibitor rescue in myoblasts

    PMID:38496008 PMID:39621428

    Open questions at the time
    • physiological signals triggering NPAT degradation beyond cigarette smoke unknown
    • regulation of import-to-condensation switch in cell cycle context incomplete
  13. 2026 High

    Completed the nuclear-condensation control circuit and disease relevance: CRM1 binds a LisH-domain NES to competitively suppress NPAT self-association and HLB formation, while in TP53-mutated AML XPO7 retains NPAT in the nucleus and its loss causes replication catastrophe.

    Evidence Co-IP, phase separation/export assays, CRM1 cancer-mutant mutagenesis, peptide competition; CRISPR dropout screens and PDX models for the XPO7-NPAT axis

    PMID:41160778 PMID:41481226

    Open questions at the time
    • how CRM1 vs XPO7 export functions are balanced unresolved
    • therapeutic window of targeting NPAT condensation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the import (KPNA3), export (CRM1, XPO7), phase-separation, and CDK-phosphorylation inputs are integrated to time histone locus body assembly across the cell cycle, and how this is rewired in specific cancers, remains to be unified.
  • no integrated quantitative model of HLB assembly dynamics
  • structural basis of the full NPAT scaffold undefined
  • in vivo phase-separation regulation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 1 R-HSA-8953854 Metabolism of RNA 1
Partners
CCNE1CDK2CDK9FLASHKAT5KPNA3TRRAPXPO1
Complex memberships
histone locus body

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NPAT associates with cyclin E-CDK2 in vivo and can be phosphorylated by this CDK complex. Overexpression of NPAT accelerates S-phase entry, and this effect is enhanced by coexpression of cyclin E-CDK2, establishing NPAT as a substrate of cyclin E-CDK2 that plays a role in S-phase entry. In vivo co-immunoprecipitation, in vitro kinase assay, overexpression with flow cytometry cell cycle analysis Genes & development High 9472014
2000 NPAT is associated with replication-dependent histone gene clusters on chromosomes 1 and 6 during S phase, activates histone gene transcription in a manner dependent on SSCS promoter elements, and cyclin E-Cdk2 stimulates NPAT-mediated histone gene transcription. Cyclin E is also co-localized at the histone gene loci. Fluorescence in situ hybridization, immunofluorescence co-localization, luciferase reporter transcription assays, co-immunoprecipitation Genes & development High 10995386
2000 p220(NPAT) localizes to discrete nuclear foci coincident with Cajal bodies that associate with histone gene clusters on chromosomes 1 and 6. Five cyclin E/Cdk2 phosphorylation sites were identified in p220; phosphorylation at two sites occurs within Cajal bodies in a cell cycle-specific manner at the G1/S boundary and is maintained until prophase. Mutation of Cdk2 phosphorylation sites to alanine abrogates p220's ability to activate the histone H2B promoter, demonstrating that phosphorylation is required for transcriptional activation. Immunofluorescence microscopy, phospho-specific antibodies, site-directed mutagenesis, luciferase reporter assays, mass spectrometry phosphosite identification Genes & development High 10995387
2003 A LisH-like motif at the N-terminus of p220(NPAT) is critical for activation of histone H4 and H2B transcription. Point mutations in conserved residues of the LisH motif block histone H4 transcriptional activity without affecting Cajal body localization or Cdk2 phosphorylation. The C-terminal half contains elements required for S-phase induction, demonstrating that the ability to promote S phase is independent of the ability to activate histone transcription. 'Lox-scanning' mutagenesis, luciferase reporter assays, immunofluorescence, flow cytometry Molecular and cellular biology High 12724424
2003 NPAT transcription is regulated by E2F proteins: E2F sites in the NPAT promoter are required for its activation at the G1/S boundary, endogenous E2F proteins bind the NPAT promoter in vivo, and induced E2F1 expression stimulates NPAT mRNA. Inhibition of NPAT by siRNA impedes cell cycle progression and histone gene expression, establishing NPAT as an E2F target linking E2F to S-phase histone gene transcription. Chromatin immunoprecipitation (ChIP), promoter reporter assays, siRNA knockdown, flow cytometry Molecular and cellular biology High 12665581
2007 NPAT interacts with components of the Tip60 histone acetyltransferase complex (TRRAP and Tip60) through a novel amino acid motif conserved in E2F and adenovirus E1A. TRRAP and Tip60 associate with histone gene promoters at the G1/S boundary in an NPAT-dependent manner. Histone H4 acetylation at histone gene promoters increases at G1/S in an NPAT-dependent manner, and knockdown of TRRAP or Tip60 inhibits histone gene activation. Co-immunoprecipitation, ChIP, siRNA knockdown, reporter assays Molecular and cellular biology High 17967892
2007 In human embryonic stem cells, p220(NPAT) is phosphorylated at CDK-dependent epitopes most prominently in S phase when cyclin E and A levels are elevated. The number of p220(NPAT) foci increases in G1 in ES cells, and the HiNF-P/p220(NPAT) pathway operates in a cell cycle-dependent manner to support histone gene expression and chromatin assembly for stem cell self-renewal. Immunofluorescence microscopy, BrdU incorporation, phospho-specific antibodies, cell cycle analysis Journal of cellular physiology Medium 17520687
2008 In mammalian cells, two distinct nuclear organelles exist: histone gene locus bodies (detectable with FLASH or NPAT as markers) and canonical Cajal bodies (marked by Coilin). Only FLASH/NPAT-positive histone gene locus bodies correlate with cell ploidy and are cell cycle-regulated; these two organelles completely co-localize during S phase. Immunofluorescence microscopy with antibodies against NPAT, FLASH, and Coilin; cell cycle analysis Cell cycle (Georgetown, Tex.) Medium 18677100
2010 NPAT is essential for histone mRNA 3' end processing: NPAT knockdown decreases CDK9 recruitment to replication-dependent histone genes, decreases histone gene transcription, and increases polyadenylation of remaining histone mRNAs. NPAT recruits CDK9 to histone gene promoters, providing a mechanism for coupling 3' end processing to transcription. p53-induced G1 arrest decreases NPAT expression via E2F-dependent transcription, thereby altering histone mRNA 3' end processing. siRNA knockdown, ChIP, RT-PCR, 3' end processing assays Oncogene High 20190802
2010 In human embryonic stem cells, cyclin D2 (rather than cyclin E) is the predominant cyclin that drives p220(NPAT) phosphorylation. Depletion of cyclin D2 or p220(NPAT) causes G1 cell cycle defect, diminished p220(NPAT) phosphorylation, decreased cell cycle-dependent histone H4 expression, and reduced S-phase progression, demonstrating that cyclin D2 and p220(NPAT) are principal regulators of hES cell self-renewal. siRNA knockdown, immunoblotting, flow cytometry, RT-PCR Journal of cellular physiology Medium 19890848
2002 Three clusters of basic residues at the carboxyl terminus of NPAT are all necessary for nuclear localization; deletion of any one of the three clusters results in distribution of the NPAT-GFP fusion throughout both nucleus and cytoplasm. Additionally, a short hydrophobic sequence near the central domain also contributes to nuclear localization. GFP fusion constructs, deletion mutagenesis, fluorescence microscopy Journal of biochemistry Medium 12473189
2004 p220(NPAT) interacts with CBP/p300 histone acetyltransferases in a cell cycle-dependent manner; their subnuclear foci partially overlap at the G1/S boundary. Co-overexpression of p220(NPAT) and CBP/p300 cooperatively promotes G1/S transition and DNA synthesis even in the absence of CDK2 phosphorylation sites on NPAT. Co-immunoprecipitation, immunofluorescence co-localization, overexpression, flow cytometry, BrdU incorporation Biochemical and biophysical research communications Medium 15555599
2006 Trastuzumab treatment inhibits CDK2 activity and, as a downstream consequence, decreases NPAT protein levels and histone H4 mRNA expression via the PI3K pathway. Blockade of PI3K with LY294002 reproduces the same effects on NPAT and histone H4, placing NPAT downstream of HER2/PI3K/CDK2 signaling. Kinase activity assays, immunoblotting, Northern blotting, real-time RT-PCR, pharmacological inhibition Cell cycle (Georgetown, Tex.) Medium 16861913
2015 Cyclin E2, but not cyclin E1, uniquely co-localizes with NPAT in breast cancer cells and is found in complex with NPAT. This preferential association of cyclin E2 with NPAT (compared to cyclin E1) correlates with higher expression of replication-dependent histones. Immunofluorescence co-localization, co-immunoprecipitation, gene expression analysis Cell division Medium 25741376
2015 Cpn10/HSPE (a 10 kDa heat shock protein) is a novel binding partner of NPAT. A pool of Cpn10 co-localizes with NPAT foci during G1 and S phases. Knockdown of Cpn10 disrupts NPAT focus formation and FLASH-positive histone locus bodies (without affecting Coilin-positive Cajal bodies), impairs histone transcription, and inhibits S-phase progression. A conserved DLFD motif within Cpn10 is critical for targeting NPAT. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, RT-PCR, flow cytometry, domain mutagenesis The Journal of biological chemistry Medium 26429916
1997 Proviral disruption of the mouse Npat gene results in early embryonic arrest at the uncompacted 8-cell stage in homozygous embryos, establishing that NPAT is essential for early embryonic development. The closely linked Atm gene expression was unaffected by the proviral insertion. Transgenic mouse genetics, in vitro embryo culture, molecular cloning of insertion site Molecular and cellular biology Medium 9199343
2019 Conditional deletion of Npat in Sertoli cells inhibits their programmed fetal proliferation, disrupts developing testis cord formation, and causes postnatal testicular hypoplasia. In Npat-deficient testes, gonocytes (normally quiescent) exit G0 and re-enter mitotic cell cycle prematurely, and some acquire meiotic signals, demonstrating that NPAT-dependent Sertoli cell proliferation is required to maintain germ cell quiescence. Conditional knockout mouse (AMH-Cre), histology, immunofluorescence, cell cycle analysis FASEB journal Medium 31084574
2022 Selective deletion of NPAT at the immature CD8 single-positive (ISP) thymocyte stage leads to reduced histone gene expression, impaired ISP cell proliferation, reduced thymus size, and significant loss of double-positive (DP) cells. NPAT deletion also increases IL-7R expression as a compensatory mechanism, but this in turn inhibits transcription factors TCF-1 and LEF-1, blocking the ISP-to-DP transition. Conditional knockout mouse, flow cytometry, RT-PCR, immunoblotting Journal of immunology Medium 35922064
2020 In yeast, the Rad53(CHK1/CHK2) DDR kinase regulates histone levels through inhibitory phosphorylation of the transcription factor Spt21(NPAT) on Ser276 under physiological conditions (without DNA damage), demonstrating a conserved mechanism by which the DDR kinase axis controls histone dosage and metabolic homeostasis. Yeast genetics, phospho-specific analysis, epistasis experiments, metabolic assays Nature communications Medium 32814778
2020 NMR structural analysis reveals that the C-terminal SANT/Myb domain of FLASH and YARP forms a triple α-helical bundle that binds the last 31 amino acids of NPAT. The NPAT C-terminal peptide contains a single α-helix making multiple contacts with α-helices I and III of the FLASH/YARP domain. Despite shared sequence similarity, FLASH and YARP likely bind NPAT via distinct interaction networks. The complexes are structurally compatible with DNA binding. Multidimensional NMR spectroscopy, in silico modeling International journal of molecular sciences Medium 32722282
2022 Mxc, the Drosophila ortholog of NPAT, is required for neural stem cell (neuroblast) fate maintenance and GMC differentiation. Knockdown of mxc causes loss of neurons, reduced histone gene transcription, and DNA double-strand breaks in larval brains, demonstrating that NPAT/Mxc function in histone gene regulation is essential for neural stem cell proliferation. Drosophila genetics (RNAi knockdown, mutants), immunofluorescence, RT-PCR, γH2AX assay for DSBs Cell & bioscience Medium 35642004
2024 KPNA3 (importin alpha 4) is a specific importin that drives nuclear import of NPAT by binding to its nuclear localization signal (NLS). NPAT undergoes phase separation mediated by a C-terminal self-interaction facilitator (C-SIF) motif binding to the middle 431–1030 sequence. KPNA3 binding to the NLS sterically blocks C-SIF-dependent NPAT self-association, thereby suppressing aberrant cytoplasmic NPAT condensation and ensuring that histone locus body formation occurs in the nucleus. Co-immunoprecipitation, domain mapping, phase separation assays, nuclear import assays, fluorescence microscopy, mutagenesis The Journal of cell biology High 39621428
2026 Exportin CRM1 binds NPAT via a nuclear export signal (NES) within the LisH domain and drives its nuclear export. The LisH domain mediates NPAT self-association and condensation. CRM1 competitively occupies self-association sites in the NES motif, thereby suppressing NPAT condensation and HLB formation. Recurrent CRM1 E571K and E571G cancer mutants cannot bind the NPAT NES and therefore fail to regulate NPAT condensation. A LisH-derived peptide designed to compete with NPAT self-association perturbs HLB formation. Co-immunoprecipitation, phase separation assays, nuclear export assays, mutagenesis (CRM1 mutants), peptide competition assay, fluorescence microscopy The Journal of cell biology High 41481226
2026 In TP53-mutated AML, XPO7 (exportin 7) retains NPAT within the nucleus. NPAT depletion induces genome-wide histone loss, compromises genomic integrity, and triggers replication catastrophe in TP53-mutated AML cells. The XPO7-NPAT axis is validated as essential for TP53-mutated AML cell survival in patient-derived xenograft models. CRISPR/Cas9 dropout screens, siRNA knockdown, transcriptomic and proteomic analyses, patient-derived xenograft models Blood Medium 41160778
2024 Cigarette smoke exposure promotes proteasome-dependent degradation of NPAT protein in C2C12 myoblasts, leading to reduced replication-dependent histone transcription and S-phase arrest. The proteasome inhibitor MG132 reverses NPAT loss and restores myoblast proliferation, demonstrating that NPAT stability is regulated by proteasomal degradation. Immunoblotting, proteasome inhibitor (MG132) treatment, RT-PCR, flow cytometry, overexpression rescue Current research in toxicology Medium 38496008

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. Genes & development 379 10995386
2000 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Genes & development 302 10995387
1998 Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry. Genes & development 193 9472014
1992 A high percentage yield of tyrosine hydroxylase-positive cells from rat E14 mesencephalic cell culture. Brain research 75 1355697
2003 The cyclin E/Cdk2 substrate and Cajal body component p220(NPAT) activates histone transcription through a novel LisH-like domain. Molecular and cellular biology 74 12724424
1987 Transplant-derived astrocytes migrate into host lumbar and cervical spinal cord after implantation of E14 fetal cerebral cortex into adult thoracic spinal cord. Journal of neuroscience research 67 3305970
2008 FLASH and NPAT positive but not Coilin positive Cajal Bodies correlate with cell ploidy. Cell cycle (Georgetown, Tex.) 66 18677100
2011 Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma. Blood 61 21562039
2007 Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. European journal of cancer (Oxford, England : 1990) 60 17449237
2007 Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells. Journal of cellular physiology 53 17520687
2007 Transcriptional activation of histone genes requires NPAT-dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition. Molecular and cellular biology 53 17967892
2004 Analysis of the lambdoid prophage element e14 in the E. coli K-12 genome. BMC microbiology 53 14733619
2003 NPAT expression is regulated by E2F and is essential for cell cycle progression. Molecular and cellular biology 52 12665581
1984 A Mu gin complementing function and an invertible DNA region in Escherichia coli K-12 are situated on the genetic element e14. Journal of bacteriology 47 6233259
1999 Apoptosis in primary cultures of E14 rat ventral mesencephala: time course of dopaminergic cell death and implications for neural transplantation. Experimental neurology 39 10630193
1985 Excision and reintegration of the Escherichia coli K-12 chromosomal element e14. Journal of bacteriology 39 2982786
2010 Induced G1 cell-cycle arrest controls replication-dependent histone mRNA 3' end processing through p21, NPAT and CDK9. Oncogene 37 20190802
1998 Ataxia-telangiectasia and T-cell leukemias: no evidence for somatic ATM mutation in sporadic T-ALL or for hypermethylation of the ATM-NPAT/E14 bidirectional promoter in T-PLL. Cancer research 36 9622061
1996 Cloning of a gene encoding cinnamoyl ester hydrolase from the ruminal bacterium Butyrivibrio fibrisolvens E14 by a novel method. FEMS microbiology letters 35 8837463
1997 Expression of a Butyrivibrio fibrisolvens E14 gene (cinB) encoding an enzyme with cinnamoyl ester hydrolase activity is negatively regulated by the product of an adjacent gene (cinR). Microbiology (Reading, England) 34 9141683
1989 Use of the isocitrate dehydrogenase structural gene for attachment of e14 in Escherichia coli K-12. Journal of bacteriology 34 2661545
2013 Dynamic expression of MEIS1 homeoprotein in E14.5 forebrain and differentiated forebrain-derived neural stem cells. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 33 23756022
2010 Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells. Journal of cellular physiology 33 19890848
2014 Effects of combined netupitant and palonosetron (NEPA), a cancer supportive care antiemetic, on the ECG of healthy subjects: an ICH E14 thorough QT trial. SpringerPlus 28 25105088
1986 SOS-associated division inhibition gene sfiC is part of excisable element e14 in Escherichia coli. Journal of bacteriology 28 3531184
1988 Attachment site of the genetic element e14. Journal of bacteriology 27 3283103
2008 The geometric control of E14 and R1 mouse embryonic stem cell pluripotency by plasma polymer surface chemical gradients. Biomaterials 25 19010532
1997 Proviral inactivation of the Npat gene of Mpv 20 mice results in early embryonic arrest. Molecular and cellular biology 25 9199343
2015 Cyclin E2 is the predominant E-cyclin associated with NPAT in breast cancer cells. Cell division 20 25741376
2013 N-glycoproteome of E14.Tg2a mouse embryonic stem cells. PloS one 20 23405203
2006 Anti-HER2 antibody trastuzumab inhibits CDK2-mediated NPAT and histone H4 expression via the PI3K pathway. Cell cycle (Georgetown, Tex.) 20 16861913
2020 Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis. FEBS letters 19 31845319
2010 Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy. International journal of radiation oncology, biology, physics 18 21050672
2020 The Rad53CHK1/CHK2-Spt21NPAT and Tel1ATM axes couple glucose tolerance to histone dosage and subtelomeric silencing. Nature communications 17 32814778
1997 Integration specificities of two lambdoid phages (21 and e14) that insert at the same attB site. Journal of bacteriology 17 9294425
2009 Satellite DNA spatial localization and transcriptional activity in mouse embryonic E-14 and IOUD2 stem cells. Cytogenetic and genome research 16 19556780
1997 The structure and organization of the human NPAT gene. Genomics 16 9205109
2015 Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription. The Journal of biological chemistry 15 26429916
2010 Differentiation of E14 mouse embryonic stem cells into thyrocytes in vitro. Thyroid : official journal of the American Thyroid Association 15 19886789
2004 Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry. Biochemical and biophysical research communications 14 15555599
2023 The New S7B/E14 Q&A Document Provides Additional Opportunities to Replace the Thorough QT Study. Journal of clinical pharmacology 13 37455487
2024 Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities? Clinical pharmacology and therapeutics 12 38362953
2014 High-throughput single nucleotide variant discovery in E14 mouse embryonic stem cells provides a new reference genome assembly. Genomics 12 25004115
2010 Comprehensive characterization of a novel intronic pseudo-exon inserted within an e14/a2 BCR-ABL rearrangement in a patient with chronic myeloid leukemia. The Journal of molecular diagnostics : JMD 12 20508029
2006 Construction of mouse 129/Ola BAC library for targeting experiments using E14 embryonic stem cells. Genes & genetic systems 12 16755138
2022 hERG block potencies for 5 positive control drugs obtained per ICH E14/S7B Q&As best practices: Impact of recording temperature and drug loss. Journal of pharmacological and toxicological methods 11 35792285
2019 Npat-dependent programmed Sertoli cell proliferation is indispensable for testis cord development and germ cell mitotic arrest. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 31084574
2022 Mxc, a Drosophila homolog of mental retardation-associated gene NPAT, maintains neural stem cell fate. Cell & bioscience 10 35642004
2021 The venous system of E14.5 mouse embryos-reference data and examples for diagnosing malformations in embryos with gene deletions. Journal of anatomy 10 34435363
2020 Structural Analysis of the SANT/Myb Domain of FLASH and YARP Proteins and Their Complex with the C-Terminal Fragment of NPAT by NMR Spectroscopy and Computer Simulations. International journal of molecular sciences 10 32722282
2009 E14-F55 combination in M2 protein: a putative molecular determinant responsible for swine-origin influenza A virus transmission in humans. PLoS currents 10 20029615
1998 Lead exposures increases oxidative stress in serum deprived E14 mesencephalic cultures. Role of metallothionein and glutathione. Restorative neurology and neuroscience 10 12671303
2018 Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5. PloS one 9 29543863
2006 Hb Marineo [beta70(E14)Ala-->Val]: a silent hemoglobin variant with a mutation within the heme pocket. Hemoglobin 9 16798637
2022 NPAT Supports CD8+ Immature Single-Positive Thymocyte Proliferation and Thymic Development. Journal of immunology (Baltimore, Md. : 1950) 8 35922064
2012 Site E14 in hemoglobins and myoglobins: a key residue that affects hemin loss and lipid oxidation capacity. Journal of agricultural and food chemistry 8 22681513
1998 Effect of lead on cytoskeletal proteins expressed in E14 mesencephalic primary cultures. Neurochemistry international 7 9596558
1983 Three closely linked latent rabbit IgG allotype gene products: a1, d12, e14. Journal of immunology (Baltimore, Md. : 1950) 7 6413580
2024 KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT. The Journal of cell biology 6 39621428
2020 Metabolic remodeling in Escherichia coli MG1655. A prophage e14-encoded small RNA, co293, post-transcriptionally regulates transcription factors HcaR and FadR. The FEBS journal 6 32061118
2014 Transcriptome analysis of the mouse E14.5 (TS23) developing humerus and differential expression in muscle-less mutant embryos lacking mechanical stimulation. Genomics data 5 26484063
2024 Germline NPAT inactivating variants as cause of hereditary colorectal cancer. European journal of human genetics : EJHG 4 38778081
2024 Drug-induced long QT syndrome: Concept and nonclinical models for predicting the onset of drug-induced torsade de pointes in patients in compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E14/S7B guidance. The Journal of pharmacology and experimental therapeutics 4 40023597
2005 Two unstable beta chain variants associated with beta-thalassemia: Hb Miami [beta116(G18)his-->Pro], and Hb Hershey [beta70(E14)Ala-->Gly], and a second unstable Hb variant at 170: Hb Abington [beta70(E14)Ala-->Pro]. Hemoglobin 4 16370483
2023 Safety pharmacology 2023 and implementation of the ICH E14/S7B Q&A guidance document. Journal of pharmacological and toxicological methods 3 37524151
2020 The Effect of (E)-1-(4'-aminophenyl)-3-phenylprop-2-en-1-one on MicroRNA-18a, Dicer1, and MMP-9 Expressions against DMBA-Induced Breast Cancer. Asian Pacific journal of cancer prevention : APJCP 3 32458624
2014 High-throughput whole-genome sequencing of E14 mouse embryonic stem cells. Genomics data 3 26484140
2002 Characterization of functional regions for nuclear localization of NPAT. Journal of biochemistry 3 12473189
2018 CD24 and CD49f expressions of E14.5 mouse mammary anlagen cells define putative distribution of earlier embryonic mammary stem cell activities. Biochemistry and cell biology = Biochimie et biologie cellulaire 2 29620414
2026 The XPO7-NPAT axis represents key vulnerabilities in TP53-mutated acute myeloid leukemia. Blood 1 41160778
2024 Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression. Current research in toxicology 1 38496008
2021 Hb Maruchi [α165 (E14) Ala>Pro; HBA1: c.196G>C]: A new thalassemia hemoglobinopathy related to the alpha1 globin gene. Clinical biochemistry 1 33675809
2012 Differences in chimera formation and germline transmission between E14 and C2J embryonic stem cells in mice. Zygote (Cambridge, England) 1 22805319
2010 Co-inheritance of Hb Hershey [beta70(E14) Ala-->Gly] and Hb La Pommeraie [beta133(H11)Val-->Met] in a Sicilian subject. European journal of haematology 1 20059533
2008 Vasculogeneic maturation of E14 embryonic stem cells with evidence of early vascular endothelial growth factor independency. Differentiation; research in biological diversity 1 18681864
2004 [E14 mouse embryonic stem cells differentiate into hepatocyt ESC]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 15619335
2026 CRM1 inhibits NPAT condensation and histone locus body formation via a competitive occupation strategy. The Journal of cell biology 0 41481226
2021 The genetic association of the transcription factor NPAT with glycemic response to metformin involves regulation of fuel selection. PloS one 0 34197485

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