Affinage

HOOK1

Protein Hook homolog 1 · UniProt Q9UJC3

Round 2 corrected
Length
728 aa
Mass
84.6 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOOK1 is a coiled-coil microtubule-binding protein that functions as both a dynein–dynactin activating adaptor for minus-end-directed transport and an endosomal cargo adaptor that sorts clathrin-independent endocytic (CIE) cargo into recycling tubules. Its conserved N-terminal domain binds microtubules and the dynein–dynactin complex to form processive transport complexes with longer run lengths than BICD2-based complexes (PMID:27365401), while its divergent C-terminal domain engages organellar cargo—including CD147, CD98, and CD44—cooperating with Rab22a to direct these CIE cargoes into recycling tubules away from EEA1-positive early endosomes (PMID:23589492, PMID:34897470). HOOK1 participates in the FTS/Hook/FHIP complex that links to the HOPS complex to regulate early-to-late endosome/lysosome trafficking (PMID:18799622), negatively regulates SHP2 phosphatase activity to modulate TGF-β-induced epithelial–mesenchymal transition (PMID:25331952), and is essential in haploid male germ cells for organizing the microtubular manchette and flagellum during spermatogenesis, as demonstrated by the azh mutant mouse (PMID:12075009).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Establishing the domain architecture of the Hook protein family—a conserved N-terminal microtubule-binding domain and a divergent C-terminal organelle-binding domain—provided the structural framework for understanding how Hook proteins bridge cytoskeletal transport to membrane cargo.

    Evidence In vitro organelle-binding assays, overexpression, and immunofluorescence in cultured mammalian cells

    PMID:11238449

    Open questions at the time
    • Only Hook3–Golgi binding was shown in detail; Hook1 organelle targets remained uncharacterized
    • No structural resolution of the N-terminal domain
  2. 2002 High

    The azh mutant mouse revealed that Hook1 is essential for spermatogenesis: loss of Hook1 causes ectopic manchette microtubules, abnormal sperm head morphology, and sperm decapitation, establishing the first in vivo function for a mammalian Hook protein.

    Evidence Mouse genetics (azh deletion of exons 10–11), cDNA cloning, immunohistochemistry on spermatids

    PMID:12075009

    Open questions at the time
    • Molecular cargo(s) engaged by Hook1 in spermatids not identified
    • Whether Hook1-manchette function requires dynein was untested
  3. 2004 Medium

    Identification of Hook1 interactions with endosomal Rab GTPases (Rab7, Rab9, Rab11) and CLN3 connected Hook1 to membrane trafficking and suggested relevance to Batten disease pathogenesis.

    Evidence Co-immunoprecipitation and in vitro binding assay in mammalian cells

    PMID:15471887

    Open questions at the time
    • CLN3 interaction was weak by a single assay; no reciprocal validation
    • Functional consequence of Rab interactions on trafficking not shown
    • Connection to Batten disease lacks genetic/patient evidence for Hook1 itself
  4. 2008 High

    Discovery of the FTS/Hook/FHIP (FHF) complex and its interaction with the HOPS complex defined a multimeric assembly through which Hook proteins regulate early-to-late endosome trafficking and lysosomal clustering.

    Evidence Affinity purification/mass spectrometry, yeast two-hybrid, co-IP, siRNA knockdown with EGF trafficking assay

    PMID:18799622

    Open questions at the time
    • Relative contributions of Hook1 vs. Hook2 vs. Hook3 within the FHF complex not resolved
    • Direct structural interface between FHF and HOPS not mapped
  5. 2013 High

    Hook1 was identified as a specific cargo adaptor for clathrin-independent endocytic recycling: it recognizes the cytoplasmic tail of CD147 and, together with Rab22a and microtubules, sorts CD44, CD98, and CD147 into recycling tubules, with functional consequences for cell spreading.

    Evidence siRNA depletion, cargo-specific recycling assays, immunofluorescence, tail-truncation mutants

    PMID:23589492

    Open questions at the time
    • Structural basis of Hook1–CD147 tail recognition unknown
    • Whether dynein motor activity is required for tubule formation was not tested
  6. 2014 Medium

    Identification of Hook1 as a direct binding partner and endogenous negative regulator of SHP2 phosphatase activity established a signaling function for Hook1 beyond vesicle trafficking, linking Hook1 downregulation to TGF-β-induced EMT.

    Evidence Reciprocal co-IP, domain-mapping pull-downs, phosphatase activity assay, siRNA/overexpression in A549 cells

    PMID:25331952

    Open questions at the time
    • Structural basis of inhibition not resolved
    • Whether SHP2 regulation operates through Hook1's trafficking function or is independent remains unclear
  7. 2016 High

    Reconstitution of Hook1 as a dynein activating adaptor demonstrated that Hook1 bridges dynein and dynactin into a processive minus-end-directed transport complex, resolving the molecular basis of Hook1-dependent organelle motility.

    Evidence Optogenetic peroxisome recruitment, co-IP, single-molecule TIRF motility assays

    PMID:27365401

    Open questions at the time
    • Cryo-EM structure of dynein–dynactin–Hook1 complex not yet available
    • How cargo-binding and dynein-activating functions are coordinated on the same molecule is unclear
  8. 2017 Medium

    Identification of Ccdc181 as a Hook1-interacting protein in the testicular manchette expanded the spermatogenesis interactome of Hook1 and linked it to PP1 phosphatase regulation in motile cilia.

    Evidence Yeast two-hybrid with testicular library, FRET validation, immunofluorescence on spermatids

    PMID:28283191

    Open questions at the time
    • Functional consequence of Ccdc181–Hook1 interaction for manchette dynamics not tested by loss-of-function
    • Whether the interaction operates in somatic cilia is unknown
  9. 2022 Medium

    Discovery that γ-taxilin binds Hook1's C-terminal region and inhibits Hook1–CD98 interaction defined a negative regulatory mechanism for Hook1-mediated endosomal sorting, operating through Rab10 and Rab22a.

    Evidence siRNA epistasis experiments, co-IP, domain mapping, tubular formation and recycling assays

    PMID:34897470

    Open questions at the time
    • Physiological signals controlling γ-taxilin–Hook1 interaction are unknown
    • Whether γ-taxilin also modulates Hook1's dynein-adaptor function is untested
  10. 2023 Medium

    In renal cell carcinoma, HOOK1 was shown to suppress tumor growth, metastasis, and angiogenesis through both canonical TGF-β/Smad3 and non-canonical MEK/ERK/c-Myc pathways, and to promote ubiquitin-proteasome-dependent degradation of TNFSF13B.

    Evidence siRNA/overexpression, xenograft models, ubiquitin-proteasome assays, pathway inhibitors, promoter analysis

    PMID:37085921

    Open questions at the time
    • Direct E3 ligase responsible for TNFSF13B degradation downstream of HOOK1 not identified
    • Whether these tumor-suppressive effects depend on Hook1's trafficking or dynein-adaptor function is unclear
  11. 2024 Medium

    CRISPR knockout of HOOK1 in ovarian cancer cells revealed a role in maintaining protein homeostasis; loss of HOOK1 triggers ER stress and UPR-mediated cell death selectively in cancer stem cells, creating a synthetic vulnerability with proteasome inhibitors.

    Evidence CRISPR/Cas9 KO, xenograft, tumorsphere assays, proteomics, UPR/ER stress markers

    PMID:38807192

    Open questions at the time
    • Mechanism by which HOOK1 maintains proteostasis is undefined
    • Whether ER stress is a direct or indirect consequence of disrupted endosomal trafficking is unknown
    • Findings not yet replicated across cancer types

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of Hook1's dual function as dynein activator and cargo adaptor, how cargo engagement and motor activation are coordinated, and the physiological signals that regulate Hook1 availability (e.g., via γ-taxilin or post-translational modifications) in different cellular contexts.
  • No high-resolution structure of Hook1 in complex with dynein–dynactin
  • No defined post-translational regulatory code for Hook1
  • Relative contributions of Hook1 vs. Hook3 in somatic cell trafficking remain ambiguous

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0038024 cargo receptor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1474165 Reproduction 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-9612973 Autophagy 1
Partners
BSGCCDC181DCTN1DYNC1H1FHIP1AFTSPTPN11RAB22A
Complex memberships
Dynein–dynactin–Hook1 transport complexFTS/Hook/FHIP (FHF) complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Hook proteins constitute a novel family of cytosolic coiled-coil proteins with a conserved N-terminal domain that binds microtubules and a divergent C-terminal domain that binds organelles; Hook3 specifically binds Golgi membranes and its overexpression causes Golgi fragmentation, establishing the domain architecture of the Hook family to which Hook1 belongs. In vitro organelle-binding assays, overexpression in cultured cells, immunofluorescence, Brefeldin A treatment The Journal of Cell Biology High 11238449
2002 Hook1 is predominantly expressed in haploid male germ cells and localizes to the microtubular manchette and flagellum in elongating spermatids; loss of Hook1 function (deletion of exons 10–11) in the azh mutant mouse causes ectopic positioning of microtubular structures, abnormal sperm head shape, tail abnormalities, and decapitation of sperm heads, demonstrating an essential role for Hook1 in linking the manchette and flagellum to cellular structures during spermatogenesis. Mouse genetics (azh mutant), cDNA cloning, genomic mapping, immunohistochemistry, RT-PCR Human Molecular Genetics High 12075009
2004 Human Hook1 physically interacts with endocytic Rab GTPases Rab7, Rab9, and Rab11 by co-immunoprecipitation; overexpression of CLN3 induces aggregation of Hook1 and its dissociation from microtubules; a weak direct interaction between Hook1 and the cytoplasmic segments of CLN3 was demonstrated by in vitro binding assay, linking Hook1 to membrane trafficking events and to Batten disease pathogenesis. Co-immunoprecipitation, in vitro binding assay, overexpression/aggregation assay, endocytosis assay Human Molecular Genetics Medium 15471887
2005 Hook1 interacts with Ankyrin G (an adaptor protein linking proteins to the spectrin-actin cytoskeleton) as demonstrated by co-localization and interaction assays; despite a nearly threefold increase in Hook1 expression in Cln3-knockout mouse tissue, the Hook1–Ankyrin G interaction and localization are not disrupted, suggesting Hook1 and Ankyrin G function in a CLN3-independent manner. Protein interaction assay, co-localization by immunofluorescence, Cln3-knockout mouse tissue analysis Biochemical and Biophysical Research Communications Low 15823567
2006 Btn2, the yeast Saccharomyces cerevisiae ortholog of Hook1, mediates specific protein retrieval from late endosomes to the Golgi (e.g., Yif1); Btn2 was found by immunoprecipitation to bind the endocytic SNARE complex (Snc1/2, Tlg1, Tlg2, Vti1), the sorting nexin Snx4, and retromer subunits (Vps26, Vps35); direct binding of recombinant Btn2 to GST-Snc1 and GST-Vps26 was shown in vitro; Btn2 localizes to a late endosomal compartment adjacent to the vacuole. Yeast two-hybrid, immunoprecipitation, in vitro GST pull-down with recombinant protein, fluorescence colocalization, btn2Δ genetic analysis Molecular and Cellular Biology High 17101785
2008 Hook1, Hook2, and Hook3 form a multiprotein FHF complex (~500 kDa) with FTS (Fused Toes) and FHIP (FTS and Hook Interacting Protein); Hook proteins interact with FTS via a conserved C-terminal motif, form homo- and heterodimers, and the complex interacts with both class B and class C components of the HOPS complex; depletion of FTS by RNAi impairs EGF trafficking from early to late endosomes/lysosomes and reduces HOPS-driven lysosomal clustering. Affinity purification/mass spectrometry, yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, EGF trafficking assay Molecular Biology of the Cell High 18799622
2013 Hook1 acts as a cargo adaptor for clathrin-independent endocytosis (CIE), recognizing the cytoplasmic tail of CD147 to sort CD147 and CD98 into Rab22a-dependent tubules for recycling back to the plasma membrane; depletion of Hook1 redirects CD44, CD98, and CD147 toward EEA1-positive compartments, impairs CD98 recycling, and inhibits cell spreading, while MHC-I trafficking (which normally goes to EEA1 compartments) is unaffected. siRNA depletion, immunofluorescence, recycling assays, cell spreading assay, cytoplasmic tail truncation mutants The Journal of Cell Biology High 23589492
2013 Hook1 works together with microtubules and Rab22a in a coordinated manner to sort specific CIE cargo proteins (CD44, CD98, CD147) into recycling endosomal tubules; Hook1 serves as an endosomal cargo adaptor determining the post-endocytic fate of CIE cargo proteins. Review/commentary integrating data from siRNA, imaging, and trafficking assays from the companion primary paper Bioarchitecture Medium 24284901
2016 Mammalian Hook1 (and Hook3) function as dynein activator adaptors: optogenetic recruitment of Hook1 to peroxisomes drives rapid minus-end-directed transport; biochemically, Hook proteins interact with both dynein and dynactin, stabilizing a supramolecular dynein–dynactin–Hook complex; the N-terminal domain (calponin-homology-like) mediates this interaction; single-molecule TIRF assays show Hook1 and Hook3 induce longer run lengths and higher velocities than BICD2. Optogenetics (organelle recruitment), co-immunoprecipitation, single-molecule TIRF microscopy, biochemical pull-down The Journal of Biological Chemistry High 27365401
2017 Ccdc181 (coiled-coil domain containing protein 181) is a novel Hook1 interacting protein identified by yeast two-hybrid screen of a testicular library; the interaction was verified by FRET analysis; Ccdc181 localizes to the microtubular manchette of elongating spermatids (like Hook1), to sperm flagella, and to the basal half of motile cilia (but not primary cilia); Ccdc181 also interacts directly with microtubules and with catalytic subunits of PP1, suggesting a role in ciliary motility. Yeast two-hybrid, FRET analysis, immunofluorescence, microtubule co-sedimentation, RNA expression analysis European Journal of Cell Biology Medium 28283191
2017 Hook1 is downregulated in hepatocellular carcinoma; knockdown of Hook1 promotes TGF-β-induced epithelial-mesenchymal transition (EMT) and reduces sensitivity to doxorubicin, while Hook1 expression is decreased after TGF-β-induced EMT, indicating that Hook1 acts as a suppressor of EMT in hepatocellular carcinoma cells. siRNA knockdown, TGF-β-induced EMT model, RT-PCR, drug sensitivity assay Tumour Biology Low 28718370
2017 The human dynein interactome established by BioID proximity labeling places Hook proteins (including Hook1) as proximity interactors of the dynein machinery, consistent with their role as dynein activators/adaptors. BioID proximity labeling, mass spectrometry eLife Low 28718761
2014 SHP2 (protein-tyrosine phosphatase) directly interacts with Hook1 via both its PTP domain and N-terminal SH2 domain; Hook1 is downregulated during TGF-β1-induced EMT in A549 lung epithelial cells; overexpression of Hook1 inhibits EMT while knockdown promotes it; downregulation of Hook1 increases SHP2 phosphatase activity, identifying Hook1 as an endogenous negative regulator of SHP2. Co-immunoprecipitation, siRNA knockdown, overexpression, domain-mapping pull-downs, phosphatase activity assay The Journal of Biological Chemistry Medium 25331952
2018 Hypoxia enhances the interaction between CD147 and Hook1 in neuronal cells; interference with the CD147–Hook1 interaction (via Rab22a knockdown) suppresses hypoxia-induced accumulation of amyloid-β (Aβ40/Aβ42) in exosomes, implicating the CD147–Hook1–Rab22a axis in exosomal Aβ secretion. Co-immunoprecipitation, siRNA knockdown of Rab22a, ELISA for Aβ in exosomes, in vivo hypoxia mouse model American Journal of Translational Research Medium 29423001
2022 γ-Taxilin is a novel negative regulator of Hook1-mediated endosomal sorting: γ-taxilin binds the C-terminal region of Hook1 and inhibits Hook1's interaction with CD98, thereby blocking sorting of CD98 and CD147 into recycling endosomal tubules; γ-taxilin depletion promotes tubular formation and CD98 recycling in a Hook1-, Rab10-, and Rab22a-dependent manner. siRNA depletion, co-immunoprecipitation, domain-mapping, tubular formation assay, recycling assay Journal of Cell Science Medium 34897470
2023 HOOK1 inhibits renal cell carcinoma (RCC) tumor growth and metastasis via the canonical TGF-β/ALK5/p-Smad3 and non-canonical TGF-β/MEK/ERK/c-Myc pathways; HOOK1 also inhibits RCC angiogenesis and sunitinib resistance by promoting ubiquitin-proteasome-dependent degradation of TNFSF13B; HOOK1 transcription is regulated by E2F3 in a VHL-dependent manner; an agonist compound (meletin) that upregulates HOOK1 shows antitumor activity. siRNA/overexpression, xenograft mouse models, pathway inhibitor experiments, ubiquitin-proteasome assays, promoter analysis Advanced Science Medium 37085921
2024 Reducing HOOK1 levels in ovarian cancer cells (by CRISPR/Cas9) decreases in vitro growth, migration, and in vivo tumor formation; HOOK1 reduction decreases cancer stem cell properties through increased endoplasmic reticulum (ER) stress and unfolded protein response (UPR)-induced cell death in the CSC population; proteomic analysis reveals that HOOK1 maintains protein homeostasis, and HOOK1 loss synergizes with proteasome inhibitors. CRISPR/Cas9 knockout, in vivo xenograft, tumorsphere assay, proteomics/mass spectrometry, UPR/ER stress markers, flow cytometry Journal of Experimental & Clinical Cancer Research Medium 38807192

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2006 Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular psychiatry 345 17043677
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2015 mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Cell reports 327 26119735
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
1980 Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. International journal of cancer 210 6259064
2001 The Golgi-associated hook3 protein is a member of a novel family of microtubule-binding proteins. The Journal of cell biology 166 11238449
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2002 The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse. Human molecular genetics 136 12075009
2004 Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. Human molecular genetics 121 15471887
2017 The human cytoplasmic dynein interactome reveals novel activators of motility. eLife 118 28718761
2016 SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes. Cell reports 115 27545878
2013 Microtubule-dependent endosomal sorting of clathrin-independent cargo by Hook1. The Journal of cell biology 109 23589492
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2022 HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. Nature metabolism 103 36192599
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2008 An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Molecular biology of the cell 95 18799622
1998 Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from the mHk1 gene and the HK1-S protein is localized mainly in the sperm tail. Molecular reproduction and development 92 9508088
2016 Hook Adaptors Induce Unidirectional Processive Motility by Enhancing the Dynein-Dynactin Interaction. The Journal of biological chemistry 85 27365401
2014 Cr(VI) reduction and Cr(III) immobilization by Acinetobacter sp. HK-1 with the assistance of a novel quinone/graphene oxide composite. Environmental science & technology 80 25296002
2011 The hybrid histidine kinase Hk1 is part of a two-component system that is essential for survival of Borrelia burgdorferi in feeding Ixodes scapularis ticks. Infection and immunity 80 21606185
2008 Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study. PLoS genetics 77 19096518
2003 Centrally administered hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils. Neuropharmacology 69 12842130
2006 Btn2, a Hook1 ortholog and potential Batten disease-related protein, mediates late endosome-Golgi protein sorting in yeast. Molecular and cellular biology 67 17101785
2020 BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells. Cellular signalling 61 33253911
2014 A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa. Investigative ophthalmology & visual science 55 25190649
2013 Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Hormone research in paediatrics 52 23859901
2017 MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1. Gene 50 29054762
2020 Anti-inflammation activity of exopolysaccharides produced by a medicinal fungus Cordyceps sinensis Cs-HK1 in cell and animal models. International journal of biological macromolecules 49 32035153
2019 An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1-HK2+ Multiple Myeloma. Cancer research 49 30885978
1997 Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2. The Journal of biological chemistry 47 9368023
2014 SHP2 positively regulates TGFβ1-induced epithelial-mesenchymal transition modulated by its novel interacting protein Hook1. The Journal of biological chemistry 42 25331952
2017 Ccdc181 is a microtubule-binding protein that interacts with Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia. European journal of cell biology 41 28283191
2022 Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. Nature genetics 40 36333503
2014 A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa. Investigative ophthalmology & visual science 37 25316723
2013 Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin-independent endocytic cargo proteins on endosomes. Bioarchitecture 35 24284901
2016 Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells. BMC genetics 32 28105937
2015 NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells. PloS one 31 25974126
2023 Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment. Phytotherapy research : PTR 25 36772986
2018 Hexokinase 2 is targetable for HK1 negative, HK2 positive tumors from a wide variety of tissues of origin. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 29880505
2023 HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 37085921
2018 Hypoxia increases amyloid-β level in exosomes by enhancing the interaction between CD147 and Hook1. American journal of translational research 23 29423001
2014 Evaluation of in vitro efficacy for decolorization and degradation of commercial azo dye RB-B by Morganella sp. HK-1 isolated from dye contaminated industrial landfill. Chemosphere 23 24480425
2023 Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota. Toxicology and applied pharmacology 22 37001609
2001 Downeast anemia (dea), a new mouse model of severe nonspherocytic hemolytic anemia caused by hexokinase (HK(1)) deficiency. Blood cells, molecules & diseases 21 11783948
2024 Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 38367425
2013 Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia. Journal of applied genetics 20 23996628
1979 Increased HK1 activity levels in the red cells of a patient with a de novo trisomy 10p: t(Y;10)(p11;p12). Human genetics 20 468260
2022 KLF2 mediates the suppressive effect of BDNF on diabetic intimal calcification by inhibiting HK1 induced endothelial-to-mesenchymal transition. Cellular signalling 19 35364229
2005 Elevation of Hook1 in a disease model of Batten disease does not affect a novel interaction between Ankyrin G and Hook1. Biochemical and biophysical research communications 19 15823567
1983 Chromosome localization of the genes for ENO1, HK1, ADK, ACP2, MPI, ITPA, ACON1 and α-GAL in the American mink (Mustela vison). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 19 24258481
2018 MeCP2 AT-Hook1 mutations in patients with intellectual disability and/or schizophrenia disrupt DNA binding and chromatin compaction in vitro. Human mutation 17 29431277
2015 Structural characterization and modeling of the Borrelia burgdorferi hybrid histidine kinase Hk1 periplasmic sensor: A system for sensing small molecules associated with tick feeding. Journal of structural biology 17 26321039
2013 Characterization of histidine-aspartate kinase HK1 and identification of histidine phosphotransfer proteins as potential partners in a Populus multistep phosphorelay. Physiologia plantarum 17 23330606
2013 Fine mapping and identification of blast resistance gene Pi-hk1 in a broad-spectrum resistant japonica rice landrace. Phytopathology 17 23718837
1999 Anti-tumor effect of angiogenesis inhibitor TNP-470 on the human nasopharyngeal carcinoma cell line NPC/HK1. Oncology 17 10394123
2007 Preservation of ejaculated mouse spermatozoa from fertile C57BL/6 and infertile Hook1/Hook1 mice collected from the uteri of mated females. Biology of reproduction 16 17314312
2020 Cytotoxic Activity of Boesenbergia rotunda Extracts against Nasopharyngeal Carcinoma Cells (HK1). Cardamonin, a Boesenbergia rotunda Constituent, Inhibits Growth and Migration of HK1 Cells by Inducing Caspase-Dependent Apoptosis and G2/M-Phase Arrest. Nutrition and cancer 15 32270712
2019 Fubp1 supports the lactate-Akt-mTOR axis through the upregulation of Hk1 and Hk2. Biochemical and biophysical research communications 15 30871777
2019 New Naphtho-γ-Pyrones Isolated from Marine-Derived Fungus Penicillium sp. HK1-22 and Their Antimicrobial Activities. Marine drugs 15 31159234
2022 Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency. Frontiers in oncology 14 35646662
2021 Isolation and Assessment of a Highly-Active Anti-Inflammatory Exopolysaccharide from Mycelial Fermentation of a Medicinal Fungus Cs-HK1. International journal of molecular sciences 14 33671052
2018 Protection of Bifidobacterial cells against antibiotics by a high molecular weight exopolysaccharide of a medicinal fungus Cs-HK1 through physical interactions. International journal of biological macromolecules 14 30036626
2016 Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress. International journal of molecular sciences 14 27941652
2023 ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion. Medical oncology (Northwood, London, England) 13 37079118
2023 Targeted isolation of prenylated indole alkaloids from the marine-derived fungus Penicillium janthinellum HK1‑6 using molecular networking. Natural product research 10 36718098
2020 High-resolution photoreceptor imaging analysis of patients with autosomal dominant retinitis pigmentosa (adRP) caused by HK1 mutation. Ophthalmic genetics 10 32814480
2017 Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 28718370
2015 Insights into B-type RR members as signaling partners acting downstream of HPt partners of HK1 in the osmotic stress response in Populus. Plant physiology and biochemistry : PPB 10 26126081
2014 An antioxidative galactomannan-protein complex isolated from fermentation broth of a medicinal fungus Cs-HK1. Carbohydrate polymers 10 25129769
2013 Family-based association study between SLC2A1, HK1, and LEPR polymorphisms with myelomeningocele in Chile. Reproductive sciences (Thousand Oaks, Calif.) 10 23427181
1978 10q(q23 leads to qter) duplication: GOTs, HK1, and other gene markers. Human genetics 10 669709
2025 FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway. Nature communications 9 39934129
2023 Intermittent Hypoxia Promotes TAM-Induced Glycolysis in Laryngeal Cancer Cells via Regulation of HK1 Expression through Activation of ZBTB10. International journal of molecular sciences 9 37834257
2019 Epigenome-wide association study of asthma and wheeze characterizes loci within HK1. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 9 31367216
2016 Molecular characterization of six new cases of red blood cell hexokinase deficiency yields four novel mutations in HK1. Blood cells, molecules & diseases 9 27282571
2015 High 18F-FDG uptake in PMAH correlated with normal expression of Glut1, HK1, HK2, and HK3. Acta radiologica (Stockholm, Sweden : 1987) 9 25766729
2022 ASSOCIATION OF PIGMENTED PARAVENOUS RETINOCHOROIDAL ATROPHY WITH A PATHOGENIC VARIANT IN THE HK1 GENE. Retinal cases & brief reports 8 33165303
2021 Modification and enhanced anti-inflammatory activity by Bifidobacterial fermentation of an exopolysaccharide from a medicinal fungus Cs-HK1. International journal of biological macromolecules 8 34403670
2011 Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes. BMC medical genetics 8 21781351
2024 Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect. Biochemical pharmacology 7 38996929
2024 Anti-Inflammatory Effects of Cordyceps Cs-HK1 Fungus Exopolysaccharide on Lipopolysaccharide-Stimulated Macrophages via the TLR4/MyD88/NF-κB Pathway. Nutrients 7 39599671
1992 The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene. Human genetics 7 1487251
2024 PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice. European journal of pharmacology 6 38346469
2024 MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism. Stem cell research & therapy 6 39080798
2023 Induced Expression of CYP51a and HK1 Genes Associated with Penconazole and Fludioxonil Resistance in the Potato Pathogen Fusarium oxysporum. Microorganisms 6 37317231
2023 Suppression of hnRNP A1 binding to HK1 RNA leads to glycolytic dysfunction in Alzheimer's disease models. Frontiers in aging neuroscience 6 37744386
2023 Insecticidal Effect of the Entomopathogenic Fungus Lecanicillium araneicola HK-1 in Aphis craccivora (Hemiptera: Aphididae). Insects 6 37999059
2023 Phlorizin ameliorates myocardial fibrosis by inhibiting pyroptosis through restraining HK1-mediated NLRP3 inflammasome activation. Heliyon 6 38027628
2020 Novel pathogenic variant c.2714C>A (p. Thr905Lys) in the HK1 gene causing severe haemolytic anaemia with developmental delay in an Indian family. Journal of clinical pathology 6 33361148
2017 Clinical, Molecular, and Computational Analysis in Patients With a Novel Double Mutation and a New Synonymous Variant in MeCP2: Report of the First Missense Mutation Within the AT-hook1 Cluster in Rett Syndrome. Journal of child neurology 6 28399682
2024 Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy. Journal of experimental & clinical cancer research : CR 5 38807192
2023 Cichoric acid improves isoproterenol-induced myocardial fibrosis via inhibition of HK1/NLRP3 inflammasome-mediated signaling pathways by reducing oxidative stress, inflammation, and apoptosis. Food science & nutrition 5 38268894
2022 Regulation of Hook1-mediated endosomal sorting of clathrin-independent cargo by γ-taxilin. Journal of cell science 5 34897470
2022 A de novo hexokinase 1 (HK1) variant presenting as Boucher-Neuhäuser syndrome. American journal of medical genetics. Part A 5 36541585
2018 In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines. Natural product research 5 30507306
1989 HincII RFLP at the human hexokinase I (HK1) locus on chromosome 10. Nucleic acids research 5 2571978
2025 Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity. Genome medicine 4 40033430
2024 MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of Borrelia burgdorferi. PLoS pathogens 4 39775665
2023 Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants. European journal of medical genetics 4 36639056
2023 LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins. Acta biochimica et biophysica Sinica 4 37222534
2023 MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway. Aging 4 37414399
2019 Eleven-year follow-up of a Japanese retinitis pigmentosa patient with an HK1 gene mutation. Ophthalmic genetics 4 31621442
2023 Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors. Scientific reports 3 38016997
2016 Establishment and Analysis of the 3-dimensional (3D) Spheroids Generated from the Nasopharyngeal Carcinoma Cell Line HK1. Tropical life sciences research 3 27965750
2002 Inhibition of EGF-mediated receptor activity and cell proliferation by HK1-ceramide, a stable analog of the ganglioside GM3-lactone. Glycobiology 3 12145192
2025 NAT10-mediated N4-acetylcytosine modification promotes the progression of retinoblastoma by improving the HK1 mRNA stability to enhance glycolysis. Clinics (Sao Paulo, Brazil) 2 40344913
2024 Two Japanese Families with Pigmented Paravenous Retinochoroidal Atrophy and HK1 Mutation: A Case Report. Case reports in ophthalmology 2 38179148
2024 Malus toringoides (Rehd.) Hughes decoction alleviates isoproterenol-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3 signaling pathway. Bioscience, biotechnology, and biochemistry 2 38697933
2024 Regulation of macrophage polarization and glucose metabolism by the ERK/MAPK-HK1 signaling pathway in paraquat-induced acute lung injury. Chemico-biological interactions 2 38763349
2024 MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of Borrelia burgdorferi. bioRxiv : the preprint server for biology 2 38915556
2024 DNA methylation-regulated HK1 overexpression contributes to irradiation-resistance by promoting glycolysis in non-small cell lung cancer. American journal of cancer research 1 39417179