Affinage

HK1

Hexokinase-1 · UniProt P19367

Length
917 aa
Mass
102.5 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HK1 (hexokinase 1) catalyzes the committed first step of glycolysis (glucose → glucose-6-phosphate) and is the rate-limiting glycolytic enzyme whose activity sustains cell viability and proliferation, acting redundantly with HK2 such that loss of one is buffered by compensatory upregulation of the other (PMID:28105937, PMID:29880505). A single gene generates multiple transcripts through alternative splicing of distinct 5' exons, including a testis-specific isoform (HK1-S/hHKI-td) driven by a separate upstream promoter that lacks the porin-binding domain required for mitochondrial outer-membrane association and instead localizes to the sperm fibrous sheath (PMID:9508088, PMID:10978502). HK1 is subject to extensive post-translational and post-transcriptional control: Parkin (PRKN) ubiquitylates mitochondrial HK1 upon loss of membrane potential to target it for proteasomal degradation (PMID:23068103), PARP-1-mediated PARylation inhibits its catalytic activity during cerebral ischemia/reperfusion (PMID:38346469), and TGF-β-induced palmitoylation promotes its secretion from hepatic stellate cells via TSG101-dependent large extracellular vesicles, after which it is imported by hepatocellular carcinoma cells to fuel glycolysis (PMID:36192599). At the mRNA level, HK1 transcript stability and expression are governed by hnRNP A1 binding (PMID:37744386), m6A and ac4C modifications (PMID:38996929, PMID:40344913), and promoter activation by the transcription factor ZBTB10 (PMID:37834257), while KLF2 directly binds HK1 to restrain glycolytic hyperactivation (PMID:35364229). Upstream, mTORC1 drives HK1-dependent glycolysis required for NLRP3 inflammasome activation in macrophages (PMID:26119735). Loss-of-function HK1 mutations cause red-cell hexokinase deficiency and nonspherocytic hemolytic anemia (PMID:11783948, PMID:27282571), non-coding variants in an intron 2 cis-regulatory element derepress HK1 in pancreatic beta-cells to cause congenital hyperinsulinism (PMID:36333503), and a dominant missense variant (p.E847K) located outside the catalytic domains causes autosomal dominant retinitis pigmentosa without altering enzymatic activity, implicating a non-catalytic retina-specific function (PMID:25190649, PMID:25316723).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Established that the single HK1 gene produces a spermatogenic isoform whose alternative splicing removes the porin-binding domain, redirecting localization from mitochondria to the sperm fibrous sheath and decoupling HK1 isoform identity from its canonical subcellular targeting.

    Evidence Alternative exon mapping by molecular cloning and immunolocalization in mouse sperm

    PMID:9508088

    Open questions at the time
    • Functional consequence of fibrous-sheath localization for sperm metabolism not defined
    • Human isoform behavior inferred from mouse
  2. 2000 High

    Showed the human HK1 locus uses a separate upstream promoter to generate testis-specific transcripts including a unique hHKI-td isoform, defining the genomic basis for tissue-restricted HK1 variants.

    Evidence Cosmid mapping, genomic mapping, and cDNA sequencing from human sperm

    PMID:10978502

    Open questions at the time
    • Protein-level function of hHKI-td not characterized
    • Regulation of the alternative promoter unknown
  3. 2001 High

    Linked reduced HK1 expression to disease by showing a transposon insertion disrupting Hk1 splicing causes erythroid hexokinase deficiency and hemolytic anemia, establishing HK1 as essential for red-cell glycolysis.

    Evidence Linkage, Southern blot, sequencing, and enzyme activity assays in the dea mouse model

    PMID:11783948

    Open questions at the time
    • Erythroid-specific transcript regulation not detailed
    • Translation to human variants pending
  4. 2014 Medium

    Identified a dominant non-catalytic disease mechanism: the p.E847K mutation outside catalytic domains causes retinitis pigmentosa without altering enzymatic activity or protein stability, implying a retina-specific function distinct from glycolysis.

    Evidence Exome sequencing, segregation across five families, and biochemical glycolysis/stability assays

    PMID:25190649 PMID:25316723

    Open questions at the time
    • The non-catalytic retinal function remains uncharacterized
    • Gain-of-function versus dominant-negative mechanism unresolved
    • Single lab
  5. 2015 High

    Positioned HK1 within innate immune signaling by demonstrating mTORC1-driven HK1-dependent glycolysis is required for NLRP3 inflammasome activation, connecting metabolic flux to caspase-1/IL-1β processing.

    Evidence Pharmacologic inhibition and shRNA knockdown of HK1/Raptor with caspase-1/IL-1β readouts in macrophages

    PMID:26119735

    Open questions at the time
    • Direct molecular link between HK1 metabolite output and NLRP3 assembly not defined
    • In vivo relevance not addressed here
  6. 2017 Medium

    Defined functional redundancy between HK1 and HK2 in cancer, showing dual inactivation reduces viability and that HK2 loss triggers compensatory HK1 upregulation, explaining glycolytic resilience in tumors.

    Evidence shRNA knockdown of HK1/HK2/HK3 individually and combined with viability/apoptosis assays in colorectal cancer and melanoma cells

    PMID:28105937

    Open questions at the time
    • Mechanism of compensatory HK1 induction unknown
    • Single lab
  7. 2012 High

    Revealed regulated turnover of mitochondrial HK1 by identifying it as a Parkin substrate ubiquitylated upon mitochondrial depolarization for proteasomal degradation, linking HK1 stability to mitochondrial quality control.

    Evidence Substrate screen, Co-IP, ubiquitylation assay, Parkin mutant analysis, and endogenous confirmation in cells

    PMID:23068103

    Open questions at the time
    • Ubiquitylation site mapping not reported
    • Physiological setting of HK1 degradation in vivo not defined
  8. 2019 High

    Extended HK1/HK2 redundancy to therapeutic logic, showing HK2 dependence emerges only in HK1-negative cancers, with HK1 status predicting response to HK2 targeting.

    Evidence HK2 knockdown/CRISPR knockout in HK1+ and HK1- lines with proliferation, xenograft, and 18F-FDG PET assays

    PMID:29880505

    Open questions at the time
    • Determinants of HK1 expression status across tumors unclear
    • Does not address combined HK1/HK2 inhibition therapeutically
  9. 2022 High

    Uncovered a secretory, non-canonical role for HK1: TGF-β-induced palmitoylation enables TSG101-dependent vesicular secretion from hepatic stellate cells and paracrine glycolytic support of hepatocellular carcinoma, with the Nur77/ABHD17B axis controlling palmitoylation.

    Evidence Co-IP, EV proteomics, palmitoylation assays, TSG101/Nur77/ABHD17B perturbation, and xenografts

    PMID:36192599

    Open questions at the time
    • Palmitoylation site(s) on HK1 not mapped
    • Mechanism of HK1 uptake by recipient cells undefined
  10. 2022 High

    Established a regulatory-element disease mechanism by showing de novo variants in an intron 2 cis-element derepress HK1 in pancreatic beta-cells, causing inappropriate insulin secretion and congenital hyperinsulinism.

    Evidence Gene-agnostic non-coding screening, epigenomic mapping, loss-of-repression assays, and 14 de novo variants

    PMID:36333503

    Open questions at the time
    • Identity of the repressor binding the element not determined
    • Mechanism of beta-cell-specific silencing not fully resolved
  11. 2022 Medium

    Identified KLF2 as a direct HK1 interactor that restrains glycolytic hyperactivation, placing HK1 downstream of BDNF/TrkB/KLF2 signaling in endothelial-to-mesenchymal transition.

    Evidence Co-IP, KLF2 and HK1 perturbation, and glycolysis/EndMT readouts in HUVECs

    PMID:35364229

    Open questions at the time
    • Interaction not reciprocally validated with full controls
    • Mechanism by which KLF2 binding inhibits HK1 activity unclear
    • Single lab
  12. 2023 Medium

    Defined transcriptional and post-transcriptional inputs to HK1: ZBTB10 directly activates the HK1 promoter, and hnRNP A1 directly binds and stabilizes HK1 mRNA to sustain neuronal glycolysis.

    Evidence ChIP and luciferase for ZBTB10; RIP and CLIP-qPCR with rescue for hnRNP A1 in cancer and neuronal models

    PMID:37744386 PMID:37834257

    Open questions at the time
    • Crosstalk between transcriptional and mRNA-stability control unaddressed
    • Single labs
  13. 2024 High

    Defined inhibitory post-translational and pharmacological control of HK1 catalysis: PARP-1 PARylates HK1 to suppress activity during ischemia, while the natural product oridonin covalently modifies Cys-813 near the glucose-binding domain to inhibit glycolysis.

    Evidence Co-IP/MS for PARylation in MCAO/R mice; proteome microarray, BLI, MS adduct ID, and CETSA for oridonin in bladder cancer

    PMID:38346469 PMID:38367425

    Open questions at the time
    • PARylation residue(s) not mapped
    • Selectivity of oridonin for HK1 versus other hexokinases not fully resolved
  14. 2025 Medium

    Expanded RNA-modification control of HK1 by showing m6A (FTO demethylation and KIAA1429/HuR writing/reading) and NAT10-mediated ac4C tune HK1 mRNA stability and expression across osteoclast, liver, and retinoblastoma contexts.

    Evidence m6A/ac4C quantification, MeRIP-seq, RIP, reporter and stability assays, knockdown/rescue, and xenografts

    PMID:38996929 PMID:39934129 PMID:40344913

    Open questions at the time
    • Whether these modifications co-regulate the same transcripts or act context-specifically is unclear
    • Direct mapping of modified residues on HK1 mRNA incomplete
    • Single labs
  15. 2025 Medium

    Connected a circular-RNA circuit to HK1 turnover, showing circST6GALNAC6 recruits FUS to stabilize PRKN mRNA and thereby enhance Parkin-mediated HK1 degradation to limit glycolysis in bladder cancer.

    Evidence RIP, Co-IP, glycolysis assays, and xenografts with PRKN rescue

    PMID:39960214

    Open questions at the time
    • Indirect multi-step circuit
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The non-catalytic, retina-specific function of HK1 disrupted by p.E847K remains mechanistically undefined, as does the identity of the beta-cell repressor acting on the intron 2 cis-element.
  • No molecular partner or pathway identified for the retinal HK1 function
  • Repressor of the disallowed-gene cis-element unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5
Localization
GO:0005739 mitochondrion 2 GO:0005576 extracellular region 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 1
Partners
HNRNP A1KIAA1429KLF2NAT10PARP1PRKNTSG101ZBTB10

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Mouse spermatogenic cell-specific HK1 (HK1-S) is encoded by alternative splicing from the single mHk1 gene using alternative exons; the resulting protein lacks the porin-binding domain (PBD) required for mitochondrial outer membrane binding and is localized to the fibrous sheath in the sperm tail rather than to mitochondria in the midpiece. Alternative exon identification by molecular cloning, immunolocalization by direct imaging/fractionation in mouse sperm Molecular reproduction and development High 9508088
2000 A single human HK1 gene spanning at least 100 kb encodes multiple transcripts generated by alternative splicing of different 5' exons; testis-specific transcripts are produced by a separate upstream promoter and include a novel isoform (hHKI-td) with both a testis-specific 5' sequence and an additional unique sequence not present in somatic HK1. Cosmid library screening, genomic mapping, cDNA isolation and sequencing from human sperm Biochimica et biophysica acta High 10978502
2001 In the downeast anemia (dea) mouse model, a spontaneous early transposon (ETn) insertion in intron 4 of the Hk1 gene disrupts normal splicing, markedly decreases HK1 expression, and causes severe nonspherocytic hemolytic anemia due to hexokinase deficiency in erythroid tissues. Linkage analysis, Southern blotting, direct sequencing, hexokinase enzyme activity assay in mouse erythroid tissues Blood cells, molecules & diseases High 11783948
2012 Mitochondrial hexokinase 1 (HKI) is a substrate of the Parkin E3 ubiquitin ligase; following dissipation of mitochondrial membrane potential, Parkin ubiquitylates HKI leading to its proteasomal degradation. Disease-relevant Parkin mutations hinder this ubiquitylation, and endogenous HKI is ubiquitylated upon membrane potential loss in cells expressing genuine Parkin. Substrate screen, co-immunoprecipitation, ubiquitylation assay in cells, Parkin mutant analysis, endogenous ubiquitylation confirmation Biochemical and biophysical research communications High 23068103
2014 A dominant HK1 missense mutation (p.Glu847Lys) causes autosomal dominant retinitis pigmentosa; the mutation is located outside the catalytic domains at a highly conserved position, and no systemic abnormalities in glycolysis were detected, suggesting the pathogenic effect is retina-specific and may not involve loss of enzymatic activity. Exome sequencing, linkage mapping, candidate gene screening, segregation analysis across five families, biochemical glycolysis assay Investigative ophthalmology & visual science Medium 25190649
2014 The HK1 E847K missense mutation does not affect hexokinase enzymatic activity or protein stability, suggesting the mutation causes retinitis pigmentosa through an uncharacterized non-catalytic function or gain of function, not via loss of glycolytic enzyme activity. Biochemical enzyme activity assay, protein stability assessment in mutant vs. wild-type HK1 Investigative ophthalmology & visual science Medium 25316723
2015 mTORC1-induced upregulation of HK1-dependent glycolysis is required for NLRP3 inflammasome activation in macrophages; inhibition of Raptor/mTORC1 or HK1 suppresses both pro-IL-1β maturation and caspase-1 activation in response to LPS and ATP. Pharmacological inhibition (rapamycin, HK inhibitors), shRNA knockdown of HK1/Raptor, caspase-1 and IL-1β processing assays in macrophages Cell reports High 26119735
2022 TGF-β stimulates palmitoylation of HK1 in hepatic stellate cells (HSCs), facilitating its secretion via large extracellular vesicles in a TSG101-dependent manner; the secreted HK1 is taken up by hepatocellular carcinoma (HCC) cells to accelerate glycolysis and HCC progression. The nuclear receptor Nur77 transcriptionally activates depalmitoylase ABHD17B to inhibit HK1 palmitoylation, and TGF-β-activated Akt phosphorylates and degrades Nur77 to repress this inhibitory axis. Co-IP, extracellular vesicle isolation and proteomic analysis, palmitoylation assay, TSG101 knockdown, Nur77/ABHD17B functional assays, Akt inhibition, xenograft models Nature metabolism High 36192599
2022 Non-coding de novo variants in a 42-bp conserved cis-regulatory element in intron 2 of HK1 cause loss of repression of HK1 in pancreatic beta-cells (a 'disallowed gene' context), leading to inappropriate HK1 expression, insulin secretion during hypoglycemia, and congenital hyperinsulinism. Gene-agnostic non-coding region screening, epigenomic analysis of regulatory elements, functional demonstration of loss of beta-cell repression, identification of 14 de novo variants Nature genetics High 36333503
2016 Simultaneous shRNA-mediated inactivation of HK1 and HK2 in colorectal cancer and melanoma cells leads to decreased cell viability and proliferation; HK2 inactivation alone induces compensatory upregulation of HK1, demonstrating functional redundancy between HK1 and HK2 in sustaining glycolysis in these cancers. shRNA lentiviral knockdown of HK1, HK2, and HK3 individually and in combination; cell viability and apoptosis assays BMC genetics Medium 28105937
2024 Oridonin forms a covalent bond with Cys-813 of HK1, located adjacent to the glucose-binding domain, suppressing HK1 enzymatic activity and reducing glycolysis in bladder cancer cells; this leads to apoptosis and inhibits lactate-induced PD-L1 expression. Human Proteome Microarray, streptavidin-agarose affinity assay, biolayer interferometry, mass spectrometry identifying Cys-813 adduct, cellular thermal shift assay, extracellular acidification rate measurement, xenograft models Phytomedicine High 38367425
2024 PARP-1 activation during cerebral ischemia/reperfusion causes poly(ADP-ribosyl)ation (PARylation) of hexokinase-1, which inhibits HK1 enzymatic activity and contributes to energy metabolism collapse in neurons; PARP-1 inhibition restores hexokinase activity. Immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, 3D-modeling, hexokinase activity assay in MCAO/R mouse model European journal of pharmacology High 38346469
2025 FTO-mediated m6A demethylation of HK1 mRNA enhances the glycolytic pathway in osteoclasts, which stabilizes RANK protein via USP14 deubiquitinase activity, promoting osteoclastogenesis and alveolar bone resorption in apical periodontitis. m6A quantification, FTO knockdown/overexpression, HK1 manipulation, Co-IP for USP14/RANK interaction, glycolysis assays, BMDM-derived osteoclast models, rat AP model, pharmacological inhibition (Dac51, 2-DG) Nature communications Medium 39934129
2023 The RNA-binding protein hnRNP A1 directly binds to the 2605-2821 region of HK1 mRNA, stabilizing it; inhibition of hnRNP A1 downregulates HK1 mRNA and protein expression, impairs glycolysis in neurons, and overexpression of hnRNP A1 rescues Aβ-induced neuronal glycolytic dysfunction via the hnRNP A1/HK1/pyruvate pathway. RNA immunoprecipitation (RIP), CLIP-qPCR, hnRNP A1 inhibitor treatment, lentiviral hnRNP A1 overexpression, glycolysis assays in HT22 cells and AD mouse model Frontiers in aging neuroscience Medium 37744386
2025 NAT10-mediated N4-acetylcytosine (ac4C) modification of HK1 mRNA increases its stability and expression, thereby promoting glycolysis and retinoblastoma cell proliferation; NAT10 knockdown decreases ac4C modification and stability of HK1 mRNA, and HK1 overexpression reverses the glycolytic inhibition caused by NAT10 knockdown. Dot blot assay for ac4C levels, RNA immunoprecipitation, immunofluorescence, dual luciferase reporter, NAT10 knockdown, HK1 overexpression rescue, xenograft mouse model Clinics (Sao Paulo, Brazil) Medium 40344913
2019 HK1 and HK2 are functionally redundant for sustaining aerobic glycolysis and tumor growth; in HK1-expressing cancers, HK2 knockdown does not inhibit proliferation or tumor progression, but in HK1-negative (HK1-HK2+) cancers, HK2 knockdown inhibits proliferation, colony formation, and xenograft tumor progression. HK2 shRNA knockdown and CRISPR knockout in HK1+ and HK1- cancer cell lines; cell proliferation, colony formation, xenograft tumor assays, 18F-FDG PET/CT; Cancer Cell Line Encyclopedia expression analysis Journal of nuclear medicine High 29880505
2016 Four novel pathogenic HK1 missense and splice-site mutations cause red blood cell hexokinase deficiency with severe hemolytic anemia; structural modeling and biochemical analysis confirmed pathogenicity, and splice-site mutation c.873-2A>G was confirmed to disrupt pre-mRNA processing at the protein level. Molecular genetic analysis, 3D structural modeling, biochemical enzyme activity assays, pre-mRNA processing analysis Blood cells, molecules & diseases Medium 27282571
2022 KLF2 directly interacts with HK1 and reduces HK1-mediated hyperactivation of glycolysis; BDNF acting through the TrkB/KLF2 pathway downregulates HK1 expression, thereby suppressing HK1-induced glucose metabolism reprogramming and the endothelial-to-mesenchymal transition (EndMT) process in vascular endothelial cells. Co-immunoprecipitation (KLF2-HK1 interaction), HK1 knockdown, KLF2 silencing/overexpression, BDNF/TrkB pathway inhibition, glycolysis assays (ECAR, glucose uptake, lactate), EndMT markers in HUVECs Cellular signalling Medium 35364229
2023 The transcription factor ZBTB10 directly binds to the HK1 promoter and regulates its transcriptional activity; knockdown of ZBTB10 decreases HK1 expression and reduces glycolysis in laryngeal cancer cells, whereas ZBTB10 overexpression increases HK1 expression. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), ZBTB10 knockdown/overexpression, HK1 mRNA/protein quantification, glycolysis assays International journal of molecular sciences Medium 37834257
2025 CircST6GALNAC6 promotes PRKN (Parkin)-mediated ubiquitination and degradation of HK1 in bladder cancer cells by recruiting FUS to stabilize PRKN mRNA; overexpression of circST6GALNAC6 reduces HK1 protein levels, inhibits glycolysis and proliferation, and the effect is reversed by PRKN knockdown. RNA immunoprecipitation, co-immunoprecipitation, colony formation assay, glycolysis assays (glucose intake, lactate, ATP, ECAR), xenograft mouse model Molecular carcinogenesis Medium 39960214
2024 KIAA1429 (an m6A writer) directly binds HK1 mRNA and, cooperating with the m6A reader HuR, enhances HK1 mRNA stability and upregulates HK1 expression to promote the Warburg effect in liver cancer; KIAA1429 depletion decreases HK1 expression and increases sorafenib sensitivity. RNA-seq and MeRIP-seq (m6A-seq), RIP assay, KIAA1429 knockdown, HK1 mRNA stability assay, glycolysis functional assays, in vivo xenograft Biochemical pharmacology Medium 38996929

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer research 519 15173008
2015 mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Cell reports 328 26119735
2009 A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 232 19318484
1980 Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. International journal of cancer 210 6259064
2007 Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer cell 191 17613438
2008 The development of HKI-272 and related compounds for the treatment of cancer. Archiv der Pharmazie 130 18493974
2006 Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer research 114 16818618
2022 HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. Nature metabolism 112 36192599
2012 Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Annals of oncology : official journal of the European Society for Medical Oncology 93 22967996
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
2007 The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Oncogene 86 17311002
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
2013 Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. British journal of cancer 71 23632474
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
2012 Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase. Biochemical and biophysical research communications 65 23068103
2020 BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells. Cellular signalling 64 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 54 23859901
2017 MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1. Gene 51 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 50 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
2022 Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. Nature genetics 45 36333503
2010 Characterization of HKI-272 covalent binding to human serum albumin. Drug metabolism and disposition: the biological fate of chemicals 45 20400660
2007 HKI-272 in non small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 45 17671147
2014 A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa. Investigative ophthalmology & visual science 37 25316723
2016 Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells. BMC genetics 33 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
2014 Genomics-guided discovery of endophenazines from Kitasatospora sp. HKI 714. Journal of natural products 27 24617951
2024 Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1. Phytomedicine : international journal of phytotherapy and phytopharmacology 26 38367425
2023 Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment. Phytotherapy research : PTR 26 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 26 29880505
2008 HKI 46F08, a novel potent histone deacetylase inhibitor, exhibits antitumoral activity against embryonic childhood cancer cells. Anti-cancer drugs 26 18765999
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 23 37001609
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
2012 Neratinib (HKI-272) in the treatment of breast cancer. Future oncology (London, England) 23 22764764
2013 Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia. Journal of applied genetics 21 23996628
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
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
2000 Structure of the 5' region of the human hexokinase type I (HKI) gene and identification of an additional testis-specific HKI mRNA. Biochimica et biophysica acta 19 10978502
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
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
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 16 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
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 15 30036626
2023 ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion. Medical oncology (Northwood, London, England) 14 37079118
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
2016 Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress. International journal of molecular sciences 14 27941652
2025 FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway. Nature communications 13 39934129
2009 Ampullosporin A, a peptaibol from Sepedonium ampullosporum HKI-0053 with neuroleptic-like activity. Behavioural brain research 12 19450625
2023 Targeted isolation of prenylated indole alkaloids from the marine-derived fungus Penicillium janthinellum HK1‑6 using molecular networking. Natural product research 10 36718098
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 10 37834257
2020 High-resolution photoreceptor imaging analysis of patients with autosomal dominant retinitis pigmentosa (adRP) caused by HK1 mutation. Ophthalmic genetics 10 32814480
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
2021 Modification and enhanced anti-inflammatory activity by Bifidobacterial fermentation of an exopolysaccharide from a medicinal fungus Cs-HK1. International journal of biological macromolecules 9 34403670
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
2024 PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice. European journal of pharmacology 8 38346469
2023 Suppression of hnRNP A1 binding to HK1 RNA leads to glycolytic dysfunction in Alzheimer's disease models. Frontiers in aging neuroscience 8 37744386
2022 ASSOCIATION OF PIGMENTED PARAVENOUS RETINOCHOROIDAL ATROPHY WITH A PATHOGENIC VARIANT IN THE HK1 GENE. Retinal cases & brief reports 8 33165303
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
2003 New quinones and hydroquinones from Malbranchea cinnamomea HKI 286 and HKI 296 and interaction with Tax/CREB expression system in yeast. The Journal of antibiotics 8 14763557
2025 Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity. Genome medicine 7 40033430
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
2009 Complete genome sequence of Beutenbergia cavernae type strain (HKI 0122). Standards in genomic sciences 7 21304633
1992 The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene. Human genetics 7 1487251
2024 MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism. Stem cell research & therapy 6 39080798
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 6 39775665
2023 Induced Expression of CYP51a and HK1 Genes Associated with Penconazole and Fludioxonil Resistance in the Potato Pathogen Fusarium oxysporum. Microorganisms 6 37317231
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
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 6 38268894
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
2023 MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway. Aging 5 37414399
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
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
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 CircST6GALNAC6 Inhibits Glycolysis of Bladder Cancer by Regulating PRKN/HK1 Signaling Pathway. Molecular carcinogenesis 2 39960214
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
2022 HKI-272 contributes to gemcitabine-mediated anti-proliferative and anti-metastatic effects through EGFR suppression in gallbladder cancer. Molecular therapy oncolytics 2 36321135

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