Affinage

ACOT8

Acyl-coenzyme A thioesterase 8 · UniProt O14734

Length
319 aa
Mass
35.9 kDa
Annotated
2026-04-28
177 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACOT8 is a peroxisomal acyl-CoA thioesterase that hydrolyzes medium- and long-chain acyl-CoA esters—particularly dicarboxylyl-CoAs—to free fatty acids and CoASH, functioning in the termination of peroxisomal β-oxidation (PMID:10092594, PMID:16141203). The enzyme is targeted to peroxisomes via a C-terminal PTS1 signal, and its catalytic activity within peroxisomes is required for peroxisome biogenesis and lipid droplet formation (PMID:10092594, PMID:15194431). ACOT8 directly binds HIV-1 Nef through a defined surface on Nef's core domain, which enhances ACOT8 thioesterase activity, though ACOT8 is dispensable for Nef-mediated CD4 downmodulation (PMID:9153233, PMID:10807905, PMID:26423947). ACOT8 thioesterase activity and the free fatty acids it generates promote hepatocellular carcinoma cell growth (PMID:24788990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1997 High

    Identification of ACOT8 as a Nef-binding acyl-CoA thioesterase established it as a potential cellular mediator of HIV-1 pathogenesis and revealed that Nef binding enhances its enzymatic activity.

    Evidence Yeast two-hybrid, in vitro binding, co-immunoprecipitation, enzymatic activity assays in CEM T cells

    PMID:9153233 PMID:9299485

    Open questions at the time
    • Whether ACOT8 is causally required for Nef-mediated CD4 downmodulation versus merely correlated
    • Mechanism by which Nef binding enhances thioesterase activity
  2. 1999 High

    Demonstration that ACOT8 is a bona fide peroxisomal enzyme targeted via a PTS1 signal resolved its subcellular localization and confirmed intrinsic thioesterase activity with preference for medium-chain acyl-CoAs.

    Evidence GFP targeting assay, peroxisomal fractionation, recombinant protein activity assay

    PMID:10092594

    Open questions at the time
    • Full substrate specificity profile not yet determined
    • Physiological relevance of peroxisomal localization for Nef interaction unclear
  3. 2000 High

    Mapping the Nef–ACOT8 interaction surface and showing Nef co-localizes with ACOT8 at peroxisomes defined the structural determinants of their association, while linking these residues to CD4 and MHC-I downmodulation.

    Evidence Nef affinity purification, point mutagenesis of Nef, immunofluorescence, CD4/MHC-I functional assays

    PMID:10799608 PMID:10807905

    Open questions at the time
    • Correlation between Nef–ACOT8 binding and CD4 downmodulation does not prove causation
    • Whether Nef oligomerization requirement is specific to ACOT8 binding or a general folding defect
  4. 2004 Medium

    Overexpression studies established that ACOT8 catalytic activity within peroxisomes drives peroxisome biogenesis and lipid droplet formation, revealing a cell-biological function beyond simple fatty acid release.

    Evidence Stable overexpression in T-cell lines, catalytic and localization mutants, electron microscopy, catalase quantification

    PMID:15194431

    Open questions at the time
    • Loss-of-function (endogenous KO) confirmation of peroxisome biogenesis role not performed
    • Mechanism linking CoA hydrolysis to peroxisome proliferation signaling unknown
  5. 2005 High

    Substrate specificity profiling revealed ACOT8 preferentially hydrolyzes longer-chain dicarboxylyl-CoAs (C5–C12), positioning it as the principal enzyme terminating peroxisomal β-oxidation of dicarboxylic acids, and identifying it as a PPARα target gene.

    Evidence Recombinant protein expression, in vitro activity measurements with panel of CoA ester substrates

    PMID:16141203

    Open questions at the time
    • In vivo flux through dicarboxylic acid β-oxidation pathway upon ACOT8 loss not measured
    • Contribution of PPARα regulation to ACOT8 expression in disease states not characterized
  6. 2005 Medium

    Identification of ACOT8 as an ISG15 conjugation target during interferon-β signaling suggested a regulatory link between innate immunity and peroxisomal lipid metabolism.

    Evidence Double-affinity purification of ISG15-modified proteins, mass spectrometry in IFN-β-treated HeLa cells

    PMID:16009940

    Open questions at the time
    • Functional consequence of ISG15 modification on ACOT8 activity or stability unknown
    • Whether ISGylation alters ACOT8 peroxisomal localization not tested
  7. 2014 Medium

    Knockdown of ACOT8 in hepatocellular carcinoma cells reduced growth that was partially rescued by exogenous free fatty acids, establishing that ACOT8 thioesterase activity fuels cancer cell proliferation through fatty acid generation.

    Evidence shRNA knockdown in Huh7/Hep3B, thioesterase activity assay, anchorage-dependent/independent growth assays, myristic acid rescue

    PMID:24788990

    Open questions at the time
    • In vivo tumor model validation not performed
    • Whether specific acyl-CoA substrates or downstream lipid species mediate the growth effect is unresolved
  8. 2015 Medium

    Definitive loss-of-function experiments in primary CD4+ T cells showed ACOT8 is dispensable for Nef-mediated CD4 downmodulation despite confirmed direct interaction, resolving the long-standing question of ACOT8's functional role in this process.

    Evidence shRNA knockdown in primary CD4+ T cells, FRET confirmation of Nef–ACOT8 interaction, CD4 downmodulation assay during HIV-1 infection

    PMID:26423947

    Open questions at the time
    • Physiological significance of Nef–ACOT8 interaction remains unknown if not CD4 downmodulation
    • Whether Nef exploits ACOT8 thioesterase activity for viral replication or lipid remodeling not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological consequence of Nef–ACOT8 binding remains unresolved, the mechanism linking ACOT8 catalysis to peroxisome biogenesis is undefined, and the in vivo metabolic and oncogenic roles of ACOT8 lack genetic model validation.
  • No ACOT8 knockout animal model phenotype reported
  • Structural basis of ACOT8 substrate selectivity for dicarboxylyl-CoAs not determined
  • Functional consequence of ISG15 modification on ACOT8 activity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 5
Localization
GO:0005777 peroxisome 3
Pathway
R-HSA-1430728 Metabolism 4
Partners
HIV-1 NEF

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ACOT8 (initially named hACTE-III/hTE) was identified as a novel acyl-CoA thioesterase that binds HIV-1 Nef via the central region of Nef (amino acids 109-152), and this direct binding greatly enhances ACOT8 enzymatic activity toward a broad range of fatty acyl-CoAs. Yeast two-hybrid screen, in vitro binding assay, enzymatic activity assay Biochemical and biophysical research communications Medium 9299485
1997 ACOT8 (hTE) interacts with HIV-1 Nef in vitro and is co-immunoprecipitated with Nef in CEM cells; Nef alleles unable to down-regulate CD4 do not interact with ACOT8, and a Nef mutant selected for lack of ACOT8 interaction also fails to down-regulate CD4, suggesting ACOT8 is a cellular mediator of Nef-induced CD4 down-regulation. Yeast two-hybrid, in vitro binding, co-immunoprecipitation, functional CD4 down-regulation assay The Journal of biological chemistry High 9153233
1999 ACOT8 (hTE/PTE-1) is a peroxisomal acyl-CoA thioesterase; recombinant ACOT8 shows intrinsic thioesterase activity (6 units/mg) most active on medium-chain acyl-CoAs, and the protein is localized to peroxisomes via a type-1 peroxisomal targeting signal (PTS1). GFP targeting assay, biochemical fractionation of purified peroxisomes, recombinant protein activity assay The Journal of biological chemistry High 10092594
2000 ACOT8 (hTE) localizes to peroxisomes by immunofluorescence; co-expression of Nef with ACOT8 causes relocalization of Nef to peroxisomes. Point mutations in Nef at residues Asp108, Leu112, Phe121, Pro122, and Asp123 abolish interaction with ACOT8 and also abrogate CD4 down-regulation, defining a surface on Nef critical for both functions. Nef affinity column purification, peptide microsequence analysis, immunofluorescence, point mutagenesis, CD4 down-regulation assay The Journal of biological chemistry High 10807905
2000 Mutation of conserved residue D123 in Nef, which is required for Nef oligomerization, abolishes Nef-ACOT8 interaction and impairs Nef-induced CD4 down-regulation, MHC class I down-modulation, and enhancement of viral infectivity, suggesting Nef oligomerization is critical for ACOT8 binding and Nef function. Mutational analysis, co-immunoprecipitation, CD4/MHC class I functional assays Journal of virology High 10799608
2000 ACOT8 (PTE2, now recognized as a distinct peroxisomal thioesterase) shows intrinsic acyl-CoA thioesterase activity with a pH optimum of 8.5, is targeted to peroxisomes via a PTS1 (SKV), and displays high activity on both medium- and long-chain acyl-CoAs, in contrast to PTE1/ACOT8 which is most active on medium-chain substrates. Recombinant protein expression, thioesterase activity assay, GFP targeting assay Biochemical and biophysical research communications Medium 10944470
2004 Stable overexpression of ACOT8 (ACTEIII/PTE-1) in human and murine T-cell lines increases peroxisome number and lipid droplet formation in a dose-dependent manner. ACOT8 mutants with reduced enzymatic activity or defective peroxisomal localization do not induce peroxisome proliferation, indicating that ACOT8 catalytic activity within peroxisomes is required for peroxisome biogenesis. Stable overexpression, immunofluorescence, electron microscopy, catalase quantification, enzymatic activity mutants Experimental cell research Medium 15194431
2005 ACOT8 (peroxisomal) preferentially hydrolyzes longer dicarboxylyl-CoA esters (glutaryl-CoA, adipyl-CoA, suberyl-CoA, sebacyl-CoA, and dodecanedioyl-CoA), distinguishing it from ACOT4 which mainly hydrolyzes succinyl-CoA; both enzymes are strongly expressed in kidney and liver and are PPARα target genes, suggesting roles in termination of peroxisomal beta-oxidation of dicarboxylic acids. Recombinant protein expression, enzyme activity measurements with multiple CoA ester substrates The Journal of biological chemistry High 16141203
2005 ACOT8 is identified as an ISG15 conjugation target in IFN-beta-treated HeLa cells, indicating ACOT8 is post-translationally modified by ISG15 during antiviral innate immune responses. Double-affinity purification of ISG15-modified proteins, mass spectrometry identification, verification of ISG15 modification Proceedings of the National Academy of Sciences of the United States of America Medium 16009940
2006 Analysis of the human ACOT gene cluster reveals that ACOT8 is a peroxisomal acyl-CoA thioesterase; the human ACOT gene cluster contains only three full-length thioesterase genes (ACOT1, ACOT2, ACOT4) compared to six in mouse, with ACOT8 being a separate peroxisomal enzyme in the family. Comparative genomic analysis, expression of recombinant proteins, enzymatic activity assays FASEB journal Medium 16940157
2014 ACOT8 knockdown in Huh7 and Hep3B hepatocellular carcinoma cell lines reduces overall thioesterase activity and inhibits anchorage-dependent and -independent cell growth; this growth inhibition is partially rescued by addition of free fatty acid myristic acid, indicating ACOT8 promotes HCC cell growth through its thioesterase activity and free fatty acid generation. shRNA knockdown, thioesterase activity assay, in vitro tumorigenic assays, fatty acid rescue experiment Oncology reports Medium 24788990
2015 ACOT8 knockdown by shRNA in primary CD4+ T cells does not impair HIV-1 Nef-mediated CD4 downmodulation, while AP-2 knockdown does; FRET analysis confirmed direct interaction between Nef and ACOT8 in cells, but functional contribution to CD4 downmodulation was not supported. shRNA knockdown, FRET analysis, CD4 downmodulation assay in HIV-infected primary T cells Journal of virology Medium 26423947
2022 ACOT8 interacts with herpes simplex virus 1 ICP0 protein in both Neuro-2a and 293T cells, as validated by co-immunoprecipitation assay, suggesting ACOT8 is part of the ICP0-host protein interaction network in neuronal cells. Mass spectrometry-based interactome analysis, co-immunoprecipitation validation Frontiers in microbiology Low 35516420

Source papers

Stage 0 corpus · 177 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1114 26186194
1989 The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science (New York, N.Y.) 1109 2648569
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1077 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1010 26496610
2014 A proteome-scale map of the human interactome network. Cell 976 25416956
2020 A reference map of the human binary protein interactome. Nature 842 32296183
2006 Biochemistry of mammalian peroxisomes revisited. Annual review of biochemistry 761 16756494
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 695 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 589 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 578 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 561 33060197
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 437 15489334
2005 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proceedings of the National Academy of Sciences of the United States of America 382 16009940
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 336 34079125
2004 Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. The EMBO journal 325 14765121
2009 Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology 277 19457419
2002 The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Progress in lipid research 233 11755680
1996 Drosophila NAP-1 is a core histone chaperone that functions in ATP-facilitated assembly of regularly spaced nucleosomal arrays. Molecular and cellular biology 226 8649423
2012 Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 218 22810585
1990 Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]). American journal of respiratory cell and molecular biology 218 2189453
2010 The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions. Molecular cell 205 20347425
2004 PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins. The Journal of cell biology 205 14709540
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 200 29568061
2000 The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion. The Journal of cell biology 187 11076968
2007 SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK. The EMBO journal 168 17568778
2001 The DNA sequence and comparative analysis of human chromosome 20. Nature 168 11780052
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
1997 Control of mitotic events by Nap1 and the Gin4 kinase. The Journal of cell biology 140 9214386
2003 Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. Molecular and cellular biology 139 14560022
2014 NAP1 strain type predicts outcomes from Clostridium difficile infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 138 24604900
1992 Functional analysis of nucleosome assembly protein, NAP-1. The negatively charged COOH-terminal region is not necessary for the intrinsic assembly activity. The Journal of biological chemistry 137 1400414
2009 Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Molecular cell 135 19782028
2014 The central role of EED in the orchestration of polycomb group complexes. Nature communications 130 24457600
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
2007 Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. Cell cycle (Georgetown, Tex.) 127 17314511
1995 NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth in budding yeast. The Journal of cell biology 120 7622567
2011 The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile. PLoS pathogens 119 22022270
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 109 31753913
2021 A protein interaction landscape of breast cancer. Science (New York, N.Y.) 107 34591612
2007 Nap1: taking a closer look at a juggler protein of extraordinary skills. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 100 17317729
2008 Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction. The Journal of cell biology 96 18644894
2003 Preferential binding of the histone (H3-H4)2 tetramer by NAP1 is mediated by the amino-terminal histone tails. The Journal of biological chemistry 96 12928440
2002 The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles. Journal of cell science 94 12140259
1989 Neutrophil attractant/activation protein-1 (NAP-1) causes human basophil histamine release. Immunology letters 94 2476383
2011 Prophage-stimulated toxin production in Clostridium difficile NAP1/027 lysogens. Journal of bacteriology 93 21441508
2006 Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 91 16940157
2006 Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching. Development (Cambridge, England) 89 16831833
2000 Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions. Journal of virology 89 10799608
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 87 32707033
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2009 Nap1-mediated actin remodeling is essential for mammalian myoblast fusion. Journal of cell science 85 19706686
1997 Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation. The Journal of biological chemistry 85 9153233
2010 Evaluation of the Cepheid Xpert Clostridium difficile Epi assay for diagnosis of Clostridium difficile infection and typing of the NAP1 strain at a cancer hospital. Journal of clinical microbiology 83 20943860
2005 The identification of a succinyl-CoA thioesterase suggests a novel pathway for succinate production in peroxisomes. The Journal of biological chemistry 80 16141203
2017 A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. Cell metabolism 78 28380382
2008 A thermodynamic model for Nap1-histone interactions. The Journal of biological chemistry 78 18728017
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2004 Arabidopsis NAP1 is essential for Arp2/3-dependent trichome morphogenesis. Current biology : CB 74 15296761
2000 The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization. Genes & development 74 10766742
2013 Clostridium difficile 027/BI/NAP1 encodes a hypertoxic and antigenically variable form of TcdB. PLoS pathogens 73 23935501
2012 Tripartite motif-containing protein 38 negatively regulates TLR3/4- and RIG-I-mediated IFN-β production and antiviral response by targeting NAP1. Journal of immunology (Baltimore, Md. : 1950) 73 22539786
2006 On the mechanism of nucleosome assembly by histone chaperone NAP1. The Journal of biological chemistry 73 16531623
2016 Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators. Cell reports 72 27880917
1999 Identification of peroxisomal acyl-CoA thioesterases in yeast and humans. The Journal of biological chemistry 72 10092594
2013 ATP-dependent chromatin remodeling by Cockayne syndrome protein B and NAP1-like histone chaperones is required for efficient transcription-coupled DNA repair. PLoS genetics 71 23637612
2012 NAP1 family histone chaperones are required for somatic homologous recombination in Arabidopsis. The Plant cell 70 22534127
2011 The histone chaperones Nap1 and Vps75 bind histones H3 and H4 in a tetrameric conformation. Molecular cell 70 21329878
2006 Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways. Current biology : CB 70 16581519
2013 Chaperone Nap1 shields histone surfaces used in a nucleosome and can put H2A-H2B in an unconventional tetrameric form. Molecular cell 69 23973327
2007 Nap1-regulated neuronal cytoskeletal dynamics is essential for the final differentiation of neurons in cerebral cortex. Neuron 69 17481396
2007 A genome-wide role for CHD remodelling factors and Nap1 in nucleosome disassembly. The EMBO journal 68 17510629
1991 Chemotactic activity and receptor binding of neutrophil attractant/activation protein-1 (NAP-1) and structurally related host defense cytokines: interaction of NAP-2 with the NAP-1 receptor. Journal of leukocyte biology 68 1997632
2005 A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases. Journal of lipid research 66 16103133
2016 Arabidopsis NAP1 Regulates the Formation of Autophagosomes. Current biology : CB 62 27451899
2009 Molecular and reverse genetic characterization of NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) genes unravels their function in transcription and nucleotide excision repair in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 62 19228338
2000 The human thioesterase II protein binds to a site on HIV-1 Nef critical for CD4 down-regulation. The Journal of biological chemistry 62 10807905
2012 Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro. Proceedings of the National Academy of Sciences of the United States of America 61 22308335
2008 The coactivators CBP/p300 and the histone chaperone NAP1 promote transcription-independent nucleosome eviction at the HTLV-1 promoter. Proceedings of the National Academy of Sciences of the United States of America 60 18523016
1997 A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef. Biochemical and biophysical research communications 60 9299485
2005 Forced unraveling of nucleosomes assembled on heterogeneous DNA using core histones, NAP-1, and ACF. Journal of molecular biology 58 16002089
2005 NAP1 modulates binding of linker histone H1 to chromatin and induces an extended chromatin fiber conformation. The Journal of biological chemistry 58 16105835
1993 cDNA cloning and expression of guinea pig neutrophil attractant protein-1 (NAP-1). NAP-1 is highly conserved in guinea pig. Journal of immunology (Baltimore, Md. : 1950) 58 7504015
2010 Murine model of Clostridium difficile infection with aged gnotobiotic C57BL/6 mice and a BI/NAP1 strain. The Journal of infectious diseases 57 20977342
2008 Comparative analysis of BI/NAP1/027 hypervirulent strains reveals novel toxin B-encoding gene (tcdB) sequences. Journal of medical microbiology 57 18480336
2003 Genome-wide expression analysis of NAP1 in Saccharomyces cerevisiae. Biochemical and biophysical research communications 57 12788058
1996 The cytokines NAP-1 (IL-8), MCP-1, IL-1 beta, and GRO in rabbit inflammatory skin lesions produced by the chemical irritant sulfur mustard. Inflammation 57 8796382
2003 Involvement of nucleocytoplasmic shuttling of yeast Nap1 in mitotic progression. Molecular and cellular biology 56 12944491
2014 Proteomic analysis of a NAP1 Clostridium difficile clinical isolate resistant to metronidazole. PloS one 54 24400070
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
2018 Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1. Proceedings of the National Academy of Sciences of the United States of America 52 30459273
2011 Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix. The Journal of biological chemistry 52 22002062
2005 Interacting proteins and differences in nuclear transport reveal specific functions for the NAP1 family proteins in plants. Plant physiology 52 15980199
2004 Histone release during transcription: NAP1 forms a complex with H2A and H2B and facilitates a topologically dependent release of H3 and H4 from the nucleosome. Biochemistry 52 14992573
1999 Casein kinase 2 binds and phosphorylates the nucleosome assembly protein-1 (NAP1) in Drosophila melanogaster. Journal of molecular biology 52 10547286
2000 Molecular cloning of a novel apoptosis-related gene, human Nap1 (NCKAP1), and its possible relation to Alzheimer disease. Genomics 50 10673335
2003 Knockout targeting of the Drosophila nap1 gene and examination of DNA repair tracts in the recombination products. Genetics 49 12618400
2018 Oral cancer-derived exosomal NAP1 enhances cytotoxicity of natural killer cells via the IRF-3 pathway. Oral oncology 46 29290284
2014 Clostridium difficile infection after allogeneic hematopoietic stem cell transplant: strain diversity and outcomes associated with NAP1/027. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 43 24973628
2019 PLEKHA4/kramer Attenuates Dishevelled Ubiquitination to Modulate Wnt and Planar Cell Polarity Signaling. Cell reports 42 31091453
2017 A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling. Cell systems 42 29128334
2010 A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities. Journal of the American Chemical Society 42 20178365
2016 Gsk3β and Tomm20 are substrates of the SCFFbxo7/PARK15 ubiquitin ligase associated with Parkinson's disease. The Biochemical journal 40 27503909
2009 Nap1 and Chz1 have separate Htz1 nuclear import and assembly functions. Traffic (Copenhagen, Denmark) 37 19929865
2019 Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway. Molecular cell 36 30902546
2016 Defining the Protein-Protein Interaction Network of the Human Protein Tyrosine Phosphatase Family. Molecular & cellular proteomics : MCP 36 27432908
2015 C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle. Nature communications 35 25902731
2013 Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish. Molecular biology of the cell 35 24371087
2012 C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis. Cell cycle (Georgetown, Tex.) 35 23070519
2007 Phosphorylation by casein kinase 2 regulates Nap1 localization and function. Molecular and cellular biology 35 18086883
2001 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease. Gene 35 11418237
2016 Fast neutron-induced structural rearrangements at a soybean NAP1 locus result in gnarled trichomes. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 34 27282876
2012 NAP1-assisted nucleosome assembly on DNA measured in real time by single-molecule magnetic tweezers. PloS one 33 23050009
2022 Quantitative fragmentomics allow affinity mapping of interactomes. Nature communications 32 36115835
2022 LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus. The EMBO journal 32 36398858
2019 The RNA-mediated estrogen receptor α interactome of hormone-dependent human breast cancer cell nuclei. Scientific data 32 31527615
2014 Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. Scientific reports 32 24798879
2020 NAP1-RELATED PROTEIN1 and 2 negatively regulate H2A.Z abundance in chromatin in Arabidopsis. Nature communications 31 32513971
2016 Purification and characterization of a novel alginate lyase from the marine bacterium Cobetia sp. NAP1 isolated from brown algae. Bioscience, biotechnology, and biochemistry 31 27648685
2015 Rapid spread of Clostridium difficile NAP1/027/ST1 in Chile confirms the emergence of the epidemic strain in Latin America. Epidemiology and infection 31 25687254
2014 Fatty acid metabolic enzyme acyl-CoA thioesterase 8 promotes the development of hepatocellular carcinoma. Oncology reports 31 24788990
2024 Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD. Nature structural & molecular biology 30 38918639
2013 Spread of epidemic Clostridium difficile NAP1/027 in Latin America: case reports in Panama. Journal of medical microbiology 30 24287669
2019 Tsr4 and Nap1, two novel members of the ribosomal protein chaperOME. Nucleic acids research 29 31062022
2019 Toxin B Variants from Clostridium difficile Strains VPI 10463 and NAP1/027 Share Similar Substrate Profile and Cellular Intoxication Kinetics but Use Different Host Cell Entry Factors. Toxins 29 31212980
2011 Viruses exploiting peroxisomes. Current opinion in microbiology 29 21824805
2007 The nucleosome assembly activity of NAP1 is enhanced by Alien. Molecular and cellular biology 28 17339334
2020 SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity. Journal of immunology (Baltimore, Md. : 1950) 27 32393512
2016 Distinct roles of the histone chaperones NAP1 and NRP and the chromatin-remodeling factor INO80 in somatic homologous recombination in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 27 27352805
2015 Glutamylation of Nap1 modulates histone H1 dynamics and chromosome condensation in Xenopus. The Journal of cell biology 27 25897082
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
2015 First report of Clostridium difficile NAP1/027 in a Mexican hospital. PloS one 26 25915544
2014 Drosophila TAP/p32 is a core histone chaperone that cooperates with NAP-1, NLP, and nucleophosmin in sperm chromatin remodeling during fertilization. Genes & development 26 25228646
1995 Molecular cloning and functional characterization of a cDNA encoding nucleosome assembly protein 1 (NAP-1) from soybean. Molecular & general genetics : MGG 26 8544812
2023 Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile. Cell reports 25 37523264
2023 TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing. Neuro-oncology 24 36215168
2022 CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system. Molecular systems biology 22 35156780
2013 The Nap family proteins, CG5017/Hanabi and Nap1, are essential for Drosophila spermiogenesis. FEBS letters 22 23454210
2010 An AP-1-like transcription factor, NAP-1, regulates expression of the glutathione S-transferase and NADH:flavin oxidoreductase genes in Neurospora crassa. Bioscience, biotechnology, and biochemistry 22 20378991
2003 Yeast Nap1-binding protein Nbp2p is required for mitotic growth at high temperatures and for cell wall integrity. Genetics 22 14573466
2000 Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase. Biochemical and biophysical research communications 22 10944470
2020 Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding. Diabetes 21 32457219
2016 C-terminal acidic domain of histone chaperone human NAP1 is an efficient binding assistant for histone H2A-H2B, but not H3-H4. Genes to cells : devoted to molecular & cellular mechanisms 21 26841755
2004 Overexpression of human acyl-CoA thioesterase upregulates peroxisome biogenesis. Experimental cell research 20 15194431
2000 NBP1 (Nap1 binding protein 1), an essential gene for G2/M transition of Saccharomyces cerevisiae, encodes a protein of distinct sub-nuclear localization. Gene 20 10767562
2023 Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies. Molecular cell 19 38113892
2016 Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus. Molecular and cellular biology 19 26884462
2015 Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription. Biochemical and biophysical research communications 19 26241676
2025 Multimodal cell maps as a foundation for structural and functional genomics. Nature 18 40205054
2022 Cullin 3 Exon 9 Deletion in Familial Hyperkalemic Hypertension Impairs Cullin3-Ring-E3 Ligase (CRL3) Dynamic Regulation and Cycling. International journal of molecular sciences 18 35563538
2022 HDLBP Promotes Hepatocellular Carcinoma Proliferation and Sorafenib Resistance by Suppressing Trim71-dependent RAF1 Degradation. Cellular and molecular gastroenterology and hepatology 18 36244648
2020 NAP1-Related Protein 1 (NRP1) has multiple interaction modes for chaperoning histones H2A-H2B. Proceedings of the National Academy of Sciences of the United States of America 18 33199628
2015 AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells. Journal of virology 18 26423947
2013 Nap1 regulates proper CENP-B binding to nucleosomes. Nucleic acids research 18 23325853
2007 NAP1 catalyzes the formation of either positive or negative supercoils on DNA on basis of the dimer-tetramer equilibrium of histones H3/H4. Biochemistry 18 17595058
2022 CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment. Human genetics 14 36538041
2001 A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20. Genomics 14 11549316
2016 Prohibitin 1 regulates tumor cell apoptosis via the interaction with X-linked inhibitor of apoptosis protein. Journal of molecular cell biology 12 27025967
2022 Interactome and Ubiquitinome Analyses Identify Functional Targets of Herpes Simplex Virus 1 Infected Cell Protein 0. Frontiers in microbiology 11 35516420
2022 ALS-linked loss of Cyclin-F function affects HSP90. Life science alliance 11 36114006
2007 Nafamostat is hydrolysed by human liver cytosolic long-chain acyl-CoA hydrolase. Xenobiotica; the fate of foreign compounds in biological systems 10 17624024
2023 Fibril treatment changes protein interactions of tau and α-synuclein in human neurons. The Journal of biological chemistry 9 36634849
2023 C9orf72 protein quality control by UBR5-mediated heterotypic ubiquitin chains. EMBO reports 9 37317656
2022 TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells. Biochemical and biophysical research communications 9 35944360
2019 Cellular redox sensor HSCARG negatively regulates the translesion synthesis pathway and exacerbates mammary tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 9 31796584
2025 The solute carrier superfamily interactome. Molecular systems biology 8 40355756
2023 USP9X deubiquitinates and stabilizes CDC123 to promote breast carcinogenesis through regulating cell cycle. Molecular carcinogenesis 8 37314216
2005 Sterol Regulatory Element-Binding Protein-2 modulates human brain acyl-CoA hydrolase gene transcription. Molecular and cellular biochemistry 7 16335799
2018 Identification of Peroxisomal Protein Complexes with PTS Receptors, Pex5 and Pex7, in Mammalian Cells. Sub-cellular biochemistry 3 30378028
2025 Knockdown of SUCLG2 inhibits glioblastoma proliferation and promotes apoptosis through LMNA acetylation and the mediation of H4K16la lactylation. Cell death discovery 1 41249152
2026 Differentiation-dependent proximity proteomics identifies novel host factors linked to HPV16 E2 function. mBio 0 41524403