Affinage

HNRNPK

Heterogeneous nuclear ribonucleoprotein K · UniProt P61978

Length
463 aa
Mass
51.0 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPK is a multifunctional nucleic acid-binding protein that integrates signal transduction with gene expression at transcriptional, splicing, and translational levels, acting as a central hub whose subcellular localization and target engagement are dynamically controlled by post-translational modifications. In the nucleus, hnRNPK serves as a transcriptional coactivator of p53—regulated by SUMOylation (PIAS3-mediated) and Aurora-A phosphorylation at Ser379 (PMID:23092970, PMID:21821029)—recruits PCGF3/5-PRC1 to Xist B-repeats to initiate X-chromosome silencing (PMID:29220657), and regulates alternative splicing of targets including MRPL33 and G6PD (PMID:28869607, PMID:24352616). ERK-mediated phosphorylation at Ser284/353 drives cytoplasmic accumulation where hnRNPK silences DICE-containing mRNA translation, promotes IRES-dependent MYC translation, and stabilizes or destabilizes specific mRNAs through KH-domain and RGG-domain recognition of C-rich sequences—activities further modulated by Src phosphorylation at Tyr458 (releasing bound mRNAs), SCF^Fbxo4-mediated K63-polyubiquitylation (limiting cytoplasmic mRNA binding), O-GlcNAcylation (promoting nuclear retention), and arginine methylation at Arg296/299 (blocking PKCδ-dependent apoptotic signaling) (PMID:11231586, PMID:16293596, PMID:24642125, PMID:36329064, PMID:30444036, PMID:25104022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Establishing how signaling controls hnRNPK localization and function: ERK phosphorylation at Ser284/353 was shown to be the switch driving nuclear-to-cytoplasmic translocation and enabling DICE-dependent translational silencing, linking MAPK signaling directly to post-transcriptional gene regulation.

    Evidence In vitro kinase assay, phosphoacceptor mutagenesis, subcellular fractionation, and translational reporter assays in serum-stimulated cells

    PMID:11231586

    Open questions at the time
    • Identity of all physiological DICE-containing target mRNAs unknown
    • Structural basis of how phosphorylation alters nuclear export not defined
  2. 2002 Medium

    Demonstrating that hnRNPK functions as a transcriptional regulator by binding single-stranded DNA elements, established through its repression of the CD43 promoter together with Purα.

    Evidence EMSA, promoter-reporter assays, and ChIP in leukocyte activation model

    PMID:12411317

    Open questions at the time
    • Genome-wide scope of ssDNA-binding transcriptional regulation not determined
    • Mechanism of single-strand DNA recognition versus RNA recognition not distinguished structurally
  3. 2005 High

    Connecting hnRNPK to oncogenic signaling: BCR/ABL was shown to upregulate hnRNPK via ERK, and hnRNPK was demonstrated to promote IRES-dependent MYC mRNA translation, establishing a mechanistic link between tyrosine kinase oncogenes and MYC translational control.

    Evidence siRNA knockdown, dominant-negative constructs, IRES reporter assays, and in vivo leukemogenesis in primary patient cells

    PMID:16293596

    Open questions at the time
    • Direct binding site on MYC IRES not mapped
    • Whether hnRNPK recruits specific translation initiation factors to the IRES not determined
  4. 2006 High

    Revealing a cytoskeletal regulatory role: hnRNPK was found to directly interact with N-WASP via its KI domain and negatively regulate N-WASP-dependent actin-mediated cell spreading, expanding hnRNPK function beyond nucleic acid metabolism.

    Evidence Reciprocal co-immunoprecipitation, domain-deletion mapping, co-localization imaging, and cell spreading assays

    PMID:16574661

    Open questions at the time
    • Whether hnRNPK inhibits N-WASP by sequestration or allosteric mechanism not resolved
    • Physiological contexts beyond spreading initiation centers not explored
  5. 2011 Medium

    Defining kinase-specific modulation of the p53 axis: Aurora-A phosphorylation at Ser379 was shown to disrupt the hnRNPK–p53 interaction without affecting localization, providing a mechanism distinct from ERK-mediated cytoplasmic redistribution.

    Evidence In vitro kinase assay, Ser379 mutagenesis, co-immunoprecipitation

    PMID:21821029

    Open questions at the time
    • In vivo significance during mitosis not validated
    • Whether Ser379 phosphorylation affects other hnRNPK interactions not tested
  6. 2011 High

    Establishing hnRNPK as a translational regulator during myelination: integrin α6β1 was shown to interact with hnRNPK, and integrin activation relieved hnRNPK-mediated translational repression of MBP mRNA, connecting extracellular matrix signaling to myelin protein synthesis.

    Evidence Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, translational assay in oligodendrocytes

    PMID:21357748

    Open questions at the time
    • Mechanism by which integrin engagement releases hnRNPK from MBP mRNA not defined
    • Whether this extends to other myelin-related mRNAs not tested
  7. 2012 High

    Elucidating how DNA damage stabilizes hnRNPK for p53 activation: PIAS3-mediated SUMOylation (ATR-dependent) was shown to block HDM2-mediated ubiquitination, stabilize hnRNPK, and increase its affinity for p53, with SENP2 providing temporal termination of the response.

    Evidence Purified SUMOylated hnRNPK binding assays, SUMOylation-defective mutants, siRNA epistasis with PIAS3/SENP2, cell-cycle analysis

    PMID:23092970

    Open questions at the time
    • SUMOylation sites on hnRNPK not fully mapped
    • Whether SUMOylation affects hnRNPK RNA-binding activity not tested
  8. 2014 High

    Demonstrating crosstalk between arginine methylation and phosphorylation: methylation at Arg296/299 was shown to inhibit PKCδ phosphorylation at Ser302, suppressing apoptosis after DNA damage and revealing a PTM switch governing cell fate decisions.

    Evidence Site-directed mutagenesis, in vitro methylation/phosphorylation assays, caspase activation assays in engineered U2OS lines

    PMID:25104022

    Open questions at the time
    • Identity of the arginine methyltransferase responsible in vivo not established
    • Whether this crosstalk operates in non-cancer cell contexts unknown
  9. 2014 High

    Establishing Src-mediated release of mRNA targets: Ang1-stimulated Src phosphorylation at Tyr458 was reconstituted in vitro and shown to prevent hnRNPK binding to UCP2 mRNA, providing a general mechanism for signal-induced translational derepression.

    Evidence In vitro Src kinase assay with purified proteins, Y458 mutagenesis, RNA binding assay, UCP2 translational readout in endothelial cells

    PMID:24642125

    Open questions at the time
    • Scope of mRNAs released by Tyr458 phosphorylation not determined genome-wide
    • Structural basis of how Tyr458 phosphorylation disrupts RNA contact not known
  10. 2015 High

    Expanding the pathogen interface: Ehrlichia EtpE-C was shown to recruit cytoplasmic hnRNPK to activate N-WASP-dependent actin polymerization for bacterial entry, and separately, hnRNPK was found to suppress HCV particle production by sequestering viral RNA from virion assembly.

    Evidence In vitro actin polymerization reconstitution, intracellular nanobody ablation, domain-mapping rescue for HCV, RIP

    PMID:25569684 PMID:26530384

    Open questions at the time
    • Whether hnRNPK–N-WASP activation during infection uses the same KI domain interface as endogenous regulation not confirmed
    • Mechanism of hnRNPK viral RNA sequestration not structurally characterized
  11. 2017 High

    Defining hnRNPK as the key adaptor in Xist-mediated X-chromosome silencing: hnRNPK was shown to bind the Xist B-repeat and recruit PCGF3/5-PRC1 for chromosome-wide H2AK119 ubiquitylation, with synthetic tethering sufficient to rescue silencing.

    Evidence CLIP, deletion mapping, tethering rescue, ChIP, co-immunoprecipitation in mouse ES cell X-inactivation system

    PMID:29220657

    Open questions at the time
    • Whether hnRNPK directly contacts PCGF3/5 or requires bridging factors not resolved
    • Stoichiometry of hnRNPK on the B-repeat not determined
  12. 2017 High

    Identifying hnRNPK as a splicing regulator with mitochondrial consequences: hnRNPK promotes MRPL33 exon 3 inclusion, and its depletion phenocopies MRPL33-L loss with mitochondrial dysfunction, directly linking hnRNPK splicing activity to energy metabolism.

    Evidence siRNA/shRNA knockdown, MRPL33-L rescue overexpression, RT-PCR splicing assay, xenograft model, mitochondrial assays

    PMID:28869607

    Open questions at the time
    • Direct binding site of hnRNPK on MRPL33 pre-mRNA not mapped
    • Whether other mitochondrial gene splicing events are co-regulated not explored
  13. 2019 High

    Establishing dual nuclear mechanisms in epidermal progenitor maintenance: hnRNPK was shown to both promote DDX6-mediated degradation of differentiation mRNAs and facilitate RNA Pol II binding at proliferation gene loci, revealing coordinated transcriptional and post-transcriptional control.

    Evidence RIP, ChIP-seq, mRNA stability assays, epidermal organoid/differentiation models with siRNA knockdown

    PMID:31519929

    Open questions at the time
    • Whether hnRNPK directly recruits Pol II or acts through intermediaries not determined
    • Mechanism of DDX6 recruitment by hnRNPK not characterized
  14. 2019 Medium

    Demonstrating O-GlcNAcylation as a localization determinant: O-GlcNAc modification was shown to promote hnRNPK nuclear retention, with loss of this modification causing cytoplasmic accumulation and altered migration/invasion phenotypes.

    Evidence Click chemistry O-GlcNAc proteomics, sWGA pulldown, subcellular fractionation, migration assays in cholangiocarcinoma cells

    PMID:30444036

    Open questions at the time
    • Specific O-GlcNAcylation sites not mapped
    • Whether O-GlcNAcylation competes with other PTMs at the same residues unknown
  15. 2020 High

    Resolving domain contributions to RNA binding: the RG/RGG domain was shown to be essential for RNA (but not DNA) binding, KH3 alone was neither necessary nor sufficient, and multiple KH domains cooperate; Xist B-repeat recognition requires C-patch elements constrained by RNA secondary structure.

    Evidence In vitro RNA binding assays with systematic domain deletion/mutant constructs, biophysical binding measurements

    PMID:32813011

    Open questions at the time
    • Full structural model of multi-KH domain engagement with RNA not available
    • How arginine methylation of RGG domain modulates RNA affinity in this framework not tested
  16. 2022 High

    Identifying a ubiquitin-based regulatory mechanism for cytoplasmic hnRNPK: SCF^Fbxo4-mediated K63-linked polyubiquitylation was shown to restrict hnRNPK mRNA-binding activity, and loss of this modification increased c-Myc translation and metastasis.

    Evidence Ubiquitin chain-type analysis, RIP-seq, polysome fractionation, in vivo metastasis assays

    PMID:36329064

    Open questions at the time
    • K63-ubiquitylation sites on hnRNPK not mapped
    • Mechanism by which K63-Ub blocks RNA binding not structurally explained
    • Whether other E3 ligases provide redundant cytoplasmic control unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and quantitative model of how multiple PTMs are integrated on a single hnRNPK molecule to coordinate its diverse nuclear and cytoplasmic functions remains unestablished.
  • No full-length structural model of hnRNPK bound to RNA or DNA exists
  • Combinatorial PTM code (SUMOylation, phosphorylation, methylation, O-GlcNAcylation, ubiquitylation) not systematically dissected
  • Genome-wide identification of direct transcriptional versus post-transcriptional targets in a single system not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 14 GO:0045182 translation regulator activity 9 GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 11 GO:0005634 nucleus 7 GO:0005694 chromosome 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-392499 Metabolism of proteins 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2
Partners
DDX3XDDX6FBXO4PCGF3PIAS3TP53WASLYAP1
Complex memberships
PCGF3/5-PRC1hnRNPK-p53 transcriptional complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MAPK/ERK phosphorylates hnRNPK at serines 284 and 353 both in vitro and in vivo, driving its cytoplasmic accumulation; ERK phosphoacceptor site mutations abolish cytoplasmic localization and prevent hnRNPK from silencing translation of mRNAs containing a differentiation-control element (DICE) in the 3' UTR. In vitro kinase assay, site-directed mutagenesis, serum stimulation / MEK1 overexpression, pharmacological ERK inhibition, subcellular fractionation, translational reporter assays Nature cell biology High 11231586
2017 hnRNPK binds the Xist B-repeat element (XR-PID) and is required to recruit the PCGF3/5-PRC1 complex to the inactive X chromosome, enabling chromosome-wide H2AK119 ubiquitylation; synthetic tethering of hnRNPK to Xist lacking XR-PID is sufficient to restore Polycomb recruitment and gene silencing. CLIP, deletion mapping, co-immunoprecipitation, ChIP, RNA tethering rescue experiment, chromatin accessibility assays Molecular cell High 29220657
2012 UV-induced SUMOylation of hnRNPK by the E3 ligase PIAS3 (in an ATR-dependent manner) prevents HDM2-mediated ubiquitination and proteasomal degradation of hnRNPK, stabilizing it; SUMOylated hnRNPK shows reduced affinity for HDM2 and increased affinity for p53, enabling p21-dependent cell-cycle arrest. SENP2 subsequently removes SUMO to terminate the response. SUMOylation-defective mutants, purified SUMOylated hnRNPK binding assays, siRNA knockdown, co-immunoprecipitation, cell-cycle analysis The EMBO journal High 23092970
2005 BCR/ABL activates hnRNPK expression and activity via the MAPK(ERK1/2) pathway; hnRNPK promotes IRES-dependent MYC mRNA translation, and inhibition of hnRNPK's translation-regulatory function impairs BCR/ABL-driven proliferation and leukemogenesis. siRNA knockdown, dominant-negative constructs, in vivo leukemogenesis assay, IRES reporter assays, pharmacological ERK inhibition Blood High 16293596
2011 During oligodendrocyte differentiation, α6β1-integrin interacts with hnRNPK; hnRNPK binds MBP mRNA and translocates from the nucleus to the myelin sheath; integrin activation reverses the inhibitory effect of hnRNPK on MBP mRNA translation, and hnRNPK knockdown inhibits MBP protein synthesis during myelination. Co-immunoprecipitation, subcellular fractionation/imaging, siRNA knockdown, in situ hybridization, translational assay The Journal of cell biology High 21357748
2014 Arginine methylation of hnRNPK at Arg296 and Arg299 inhibits nearby Ser302 phosphorylation by the pro-apoptotic kinase PKCδ; methylation-defective hnRNPK mutant cells show increased apoptosis through both intrinsic and extrinsic pathways after DNA damage, demonstrating that arginine methylation negatively regulates PKCδ-mediated apoptotic signaling. Site-directed mutagenesis, engineered U2OS cell lines, apoptosis assays (caspase activation), in vitro methylation and phosphorylation assays Nucleic acids research High 25104022
2006 hnRNPK directly interacts with N-WASP via the N-WASP WH1 domain and the hnRNPK KI domain; co-localization occurs at the spreading initiation center; hnRNPK co-expression reverses N-WASP-stimulated cell spreading and reduces filopodia formation, identifying hnRNPK as a negative regulator of N-WASP. Co-immunoprecipitation, domain-deletion mapping, co-localization imaging, cell spreading and filopodia assays with overexpression/co-expression The Journal of biological chemistry High 16574661
2015 HNRNPK suppresses HCV particle production (but not RNA replication) by interacting specifically with HCV RNA; domains required for RNA interaction are also required for suppression; in HCV-infected cells, HNRNPK redistributes to sites adjacent to lipid droplets and colocalizes with core protein and HCV RNA, suggesting it limits viral RNA availability for virion incorporation. siRNA screen, knock-down rescue with domain mutants, RNA immunoprecipitation, subcellular localization imaging, viral production assays PLoS pathogens High 25569684
2011 Aurora-A kinase phosphorylates hnRNPK at serine 379; this phosphorylation disrupts the hnRNPK–p53 interaction without affecting post-transcriptional activity or cellular localization of hnRNPK, providing a mechanism by which Aurora-A suppresses p53 activity during DNA damage. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, immunofluorescence FEBS letters Medium 21821029
2013 Tcl1 promotes G6PD pre-mRNA splicing in an hnRNPK-dependent manner; PTEN forms a complex with hnRNPK to inhibit G6PD pre-mRNA splicing; PTEN also inactivates Tcl1 via GSK3β-mediated phosphorylation, establishing a PTEN/Tcl1/hnRNPK/G6PD axis that regulates the pentose phosphate pathway in hepatocarcinogenesis. Co-immunoprecipitation, mass spectrometry, splicing assays, siRNA knockdown, biochemical flux measurements Gut Medium 24352616
2017 hnRNPK regulates alternative splicing of MRPL33 pre-mRNA to promote inclusion of exon 3 (generating MRPL33-L); hnRNPK knockdown phenocopies MRPL33-L depletion (impaired proliferation, increased apoptosis, mitochondrial dysfunction including decreased ATP and increased ROS); overexpression of MRPL33-L rescues hnRNPK-depleted cells. siRNA/shRNA knockdown, rescue overexpression, RT-PCR splicing assay, xenograft model, mitochondrial function assays Oncogene High 28869607
2019 HNRNPK maintains epidermal progenitor cells by two distinct mechanisms: (1) promoting DDX6 binding to and degradation of differentiation-promoting mRNAs (GRHL3, KLF4, ZNF750); (2) facilitating RNA Polymerase II binding to proliferation/self-renewal gene loci (MYC, CYR61, EGFR, cyclins). HNRNPK siRNA knockdown, RIP, ChIP-seq (RNA Pol II), mRNA stability assays, epidermal organoid/differentiation models Nature communications High 31519929
2015 During RANKL-induced osteoclast differentiation, PI3K/Akt-mediated Ser9 phosphorylation of GSK3β triggers ERK-dependent nuclear-to-cytoplasmic translocation of hnRNPK; cytoplasmic hnRNPK interacts with GSK3β and modulates NF-κB activation, NFATc1 expression, and tubulin acetylation; hnRNPK localizes to the actin belt and is required for mature osteoclast formation. Co-immunoprecipitation, subcellular fractionation, immunofluorescence, siRNA knockdown, osteoclast differentiation assays, TRAP staining Scientific reports Medium 26638989
2002 hnRNP-K and Purα act together to repress CD43 gene promoter transcriptional activity during leukocyte activation; both proteins bind single-stranded DNA within the CD43 promoter, and their recruitment coincides with repression of CD43 mRNA levels. Electrophoretic mobility shift assay (EMSA), promoter-reporter assays, chromatin immunoprecipitation, single-stranded DNA binding assays Blood Medium 12411317
2013 hnRNPK promotes metastasis by regulating extracellular matrix, cell motility, and angiogenesis gene expression programs; hnRNPK-overexpressing cells show enhanced malignancy in vitro and in vivo, while hnRNPK-compromised cells show delayed tumor growth; cytoplasmic accumulation of hnRNPK is crucial for its metastatic role. Loss-of-function (intracellular antibody screen), stable overexpression/knockdown cell lines, cDNA microarray, in vivo xenograft, migration assays The Journal of biological chemistry Medium 17483488 23564449
2017 hnRNPK regulates PLK1 expression post-transcriptionally through KH1- and KH2-dependent binding to cytosine-rich sequences in the PLK1 mRNA 3'UTR; hnRNPK competes with miR-149-3p and miR-193b-5p at the same C-rich motif, and loss of hnRNPK reduces PLK1 levels, decreases clonogenicity, and induces apoptosis. RIP, 3'UTR reporter assays, Ago2 immunoprecipitation, siRNA knockdown/overexpression, domain deletion (KH1/KH2) Cell death and differentiation Medium 28708135
2013 hnRNPK interacts with SERT mRNA distal polyadenylation element; trophic factor S100β induces Src-family kinase-mediated tyrosine phosphorylation of hnRNPK, increasing SERT protein expression; genetic manipulation of hnRNPK alters SERT protein levels, establishing hnRNPK as a translational regulator of SERT. RNA immunoprecipitation, in vitro binding assay, Src kinase inhibition, genetic knockdown/overexpression, western blot Proceedings of the National Academy of Sciences of the United States of America Medium 23798440
2016 hnRNPK translocates from nucleus to cytoplasm upon TRAIL treatment in an ERK1/2-dependent manner (requiring Ser284/353 phosphorylation); cytoplasmic hnRNPK inhibits GSK3β Ser9 phosphorylation by PKC, thereby activating GSK3β and stabilizing c-FLIP, contributing to TRAIL resistance; hnRNPK also upregulates XIAP in this context. Subcellular fractionation, immunofluorescence, ERK inhibition (U0126), phospho-site mutants, co-immunoprecipitation, TRAIL resistance assays Scientific reports Medium 26972480
2019 In pancreatic β cells under glucolipotoxic/metabolic stress, MEK/ERK phosphorylates hnRNPK, which then binds the polyC motif in JUND mRNA 3'UTR and recruits the RNA helicase DDX3X; this ERK/hnRNPK/DDX3X pathway promotes efficient JUND mRNA translation, upregulating pro-oxidant and pro-inflammatory genes and affecting β cell survival. RNA immunoprecipitation, co-immunoprecipitation, Phos-tag analysis, TRAP-seq, CRISPR-Cas9 gene depletion in primary islets, pharmacological MEK inhibition Molecular metabolism High 31178390
2008 ASFV p30 protein interacts with hnRNP-K through the KH1 and KH2 RNA-binding domains (residues 35–197) of hnRNPK; infection alters hnRNPK subcellular distribution and decreases incorporation of 5-fluorouridine into nascent RNA, suggesting p30-hnRNPK interaction contributes to host mRNA translation downregulation. cDNA library screening, co-localization imaging, 5-fluorouridine incorporation assay, transient p30 expression FEBS letters Medium 18775702
2005 In smooth muscle cells, hnRNPK protein levels increase upon serum stimulation; subcellular localization cycles through the cell cycle with nuclear-to-cytoplasmic translocation; cytoplasmic hnRNPK forms a multiprotein complex with calponin and ERK1/2, suggesting a role in growth-stimulated post-transcriptional regulation. Subcellular fractionation, cycloheximide chase, co-immunoprecipitation, cell cycle synchronization Journal of cellular biochemistry Medium 15962305
2009 TCR activation triggers ERK-dependent phosphorylation of hnRNP-K in T-cell nuclei; siRNA knockdown of hnRNPK abrogates IL-2 production; hnRNPK knockdown also causes increased proteolysis of the essential T-cell activator Vav1, suggesting hnRNPK protects Vav1 from activation-induced degradation. Proteomic analysis of nuclear proteins, siRNA knockdown, ERK inhibition, IL-2 ELISA, western blot of Vav1 proteolysis International immunology Medium 19880579
2019 O-GlcNAcylation of hnRNP-K promotes its nuclear localization in cholangiocarcinoma cells; suppression of O-GlcNAcylation retains hnRNPK in the cytoplasm and reduces cell migration/invasion; nuclear hnRNPK modulates cyclin D1, XIAP, EMT markers, and MMP2/MMP7 expression. Click chemistry-based O-GlcNAc proteomics (LC-MS/MS), immunoprecipitation, sWGA pulldown, siRNA knockdown, subcellular fractionation, migration assays Molecular oncology Medium 30444036
2014 Angiopoietin-1 (Ang1) stimulates Src-family kinase recruitment to hnRNP-K and tyrosine phosphorylation of hnRNP-K (at Tyr458); phosphorylation by Src prevents hnRNP-K binding to UCP2 mRNA in vitro, releasing UCP2 mRNA from its translationally inactive state and increasing UCP2 protein expression in endothelial cells. Co-immunoprecipitation, in vitro Src kinase assay, direct RNA binding assay (purified proteins), site-directed mutagenesis (Y458), western blot, ROS measurement Cellular signalling High 24642125
2020 hnRNPK and PTBP1 are essential RNA-binding proteins that mediate SINEUP long non-coding RNA function; they contribute to SINEUP subcellular distribution and assembly of translational initiation complexes, leading to enhanced target mRNA translation. Co-transfection, RNA immunoprecipitation, co-immunoprecipitation, subcellular localization assays, translational reporter assays, siRNA knockdown Nucleic acids research Medium 33130894
2020 The KH3 domain of hnRNPK is neither necessary nor sufficient for RNA binding; the RG/RGG domain provides essential contributions to RNA (but not DNA) binding affinity; multiple KH domains cooperate for high-affinity RNA interaction; hnRNPK binds Xist B-repeat RNA through C-patch recognition constrained by RNA secondary structure. NMR (implied), in vitro RNA binding assays with domain deletion/mutant constructs, CLIP data analysis, biophysical binding measurements Nucleic acids research High 32813011
2018 Smchd1 localizes to the inactive X chromosome via the Xist-HnrnpK-PRC1 pathway in an H2AK119ub-dependent manner; perturbation of this interaction destabilizes Smchd1 and has genome-wide consequences for gene silencing. ChIP, conditional knockouts, co-localization imaging, H2AK119ub dependency assays Cell reports Medium 30428357
2021 hnRNPK acts downstream of TNFR2 signaling to directly interact with and stabilize YAP on target gene promoters genome-wide, co-regulating YAP target gene expression during HPC malignant transformation; SGLT2 separately promotes hnRNPK nuclear translocation to enhance hnRNPK-induced YAP1 transcription in pancreatic cancer. Co-immunoprecipitation, ChIP-seq, scRNA-seq, LC-MS, siRNA knockdown, in vivo tumor models Cancer research / Cancer letters Medium 33619115 34314754
2021 circ-GALNT16 binds the KH3 domain of hnRNPK and promotes its SUMOylation; enhanced SUMOylation of hnRNPK facilitates formation of the hnRNPK-p53 transcriptional complex and increases its sequence-specific DNA binding ability; SENP2-mediated deSUMOylation of hnRNPK reverses this, and circ-GALNT16 suppresses CRC progression through this mechanism. RNA pulldown, RIP, co-immunoprecipitation, ChIP, RNA-seq, domain binding assays (KH3) Journal of experimental & clinical cancer research Medium 34452628
2022 SCFFbxo4 E3 ubiquitin ligase restricts hnRNPK pro-oncogenic activity via K63-linked polyubiquitylation, limiting its ability to bind target mRNAs; loss of SCFFbxo4 leads to hnRNPK-dependent increase in c-Myc translation, enhanced invasion and metastasis; cytoplasmic redistribution of hnRNPK correlates with loss of this ubiquitylation. Co-immunoprecipitation, ubiquitin chain-type analysis, RIP-seq, siRNA/shRNA knockdown, in vivo metastasis assays, polysome fractionation Nature communications High 36329064
2021 In C9orf72 ALS, HNRNPK undergoes cytoplasmic mislocalization; HNRNPK overexpression reverses C9 repeat RNA toxicity in a subcellular localization- and RNA-recognition-dependent manner; HNRNPK regulates RRM2 (a DNA damage response gene), and increasing HNRNPK or RRM2 mitigates DNA damage in the C9 RNA toxicity zebrafish model. Zebrafish toxicity model, patient fibroblasts and iPSC-derived motor neurons, post-mortem tissue, subcellular fractionation, genetic overexpression rescue Acta neuropathologica Medium 35895140
2019 hnRNPK promotes gastric cancer tumorigenesis by activating transcription of the splicing regulator SRSF1 (binding −65 to −77 site upstream of the start codon), which in turn increases production of the oncogenic CD44E splice isoform (CD44v8-v10). ChIP, dual-luciferase reporter assay, siRNA knockdown, RT-PCR splicing assay, TCGA data validation Cancer cell international Medium 31857793
2021 In C9orf72 ALS patient fibroblasts, HNRNPK is mislocalized to the cytoplasm; increasing HNRNPK or its downstream target RRM2 (involved in DNA damage response) is sufficient to mitigate DNA damage, linking HNRNPK subcellular localization to DNA damage repair capacity. Patient fibroblast/iPSC-motor neuron analysis, zebrafish rescue, AAV-mediated overexpression, γH2AX foci quantification Acta neuropathologica Medium 35895140
2023 Keratin 19 (K19) directly interacts with HNRNPK and sequesters it in the cytoplasm; in K19 knockout cells, HNRNPK fails to localize in the cytoplasm, reducing cell proliferation; cytoplasmic K19-retained HNRNPK increases stability of target mRNAs bound at 3'UTR C-rich elements, protecting pro-tumorigenic transcripts from degradation. Co-immunoprecipitation, K19 knockout, HNRNPK knockdown, CLIP-seq (HNRNPK binding map), western blot, proliferation assays BMC molecular and cell biology Medium 37592256
2021 hnRNPK directly interacts with YAP1 promoter and stabilizes YAP on target gene chromatin; downstream of TNFR2 signaling, hnRNPK co-regulates YAP target genes essential for hepatic progenitor cell malignant transformation. ChIP-seq, co-immunoprecipitation, siRNA knockdown, scRNA-seq, in vivo liver tumorigenesis model Cancer research Medium 33619115
2024 KH1 and KH2 domains of Hnrnpk bind and promote degradation of WWC1 mRNA; Hnrnpk deletion increases WWC1 expression, activating Hippo signaling and aggravating osteoarthritis; AAV-mediated Hnrnpk overexpression protects against OA in mice. Domain-specific binding assays, conditional knockout mice, RNA stability assays, intra-articular AAV delivery, histology Molecular therapy Medium 38414246
2022 In chondrocytes, Hnrnpk binds Hif1a mRNA and promotes its degradation; Hnrnpk deletion upregulates Hif1α, causing excessive glycolysis and impairing chondrocyte survival and differentiation during growth plate development. Conditional KO mice, RIP, mRNA stability assays, glycolytic flux measurements, histology Cell death & disease Medium 36127325
2015 EtpE-C (Ehrlichia outer membrane protein) recruits hnRNP-K to drive bacterial entry; cytoplasmic hnRNP-K activates N-WASP-dependent actin polymerization; functional ablation of hnRNP-K by intracellular antibody markedly attenuates bacterial entry; EtpE-C stimulates in vitro actin polymerization in an N-WASP- and DNase X-dependent manner. Affinity pulldown, far-western blotting, co-immunoprecipitation, intracellular nanobody ablation, in vitro actin polymerization assay, time-lapse imaging mBio High 26530384
2021 hnRNPK binds and sorts miR-4732-3p into fucosylated exosomes in NSCLC cells; hnRNPK knockdown suppresses NSCLC cell proliferation and retains miR-4732-3p intracellularly; the interaction between miR-4732-3p and hnRNPK for selective sorting was validated by RIP and miRNA pull-down. RNA immunoprecipitation (RIP), miRNA pulldown, hnRNPK knockdown, exosome isolation, nanoparticle tracking analysis, functional cell assays Journal of experimental & clinical cancer research Medium 38654325

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochemical and biophysical research communications 431 9207191
1996 Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. The Journal of biological chemistry 303 8626550
2017 hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb-Mediated Chromosomal Silencing. Molecular cell 257 29220657
2001 ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation. Nature cell biology 249 11231586
2016 Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer. Cancer letters 206 27012187
1996 Differential activation of ERK, JNK/SAPK and P38/CSBP/RK map kinase family members during the cellular response to arsenite. Free radical biology & medicine 185 8902523
1997 Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase. Bioorganic & medicinal chemistry 171 9043657
2005 A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation. Blood 161 16293596
2023 Dissection of FOXO1-Induced LYPLAL1-DT Impeding Triple-Negative Breast Cancer Progression via Mediating hnRNPK/β-Catenin Complex. Research (Washington, D.C.) 145 38111678
2019 The emerging roles of hnRNPK. Journal of cellular physiology 124 31538344
2013 PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis. Gut 110 24352616
1998 Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorganic & medicinal chemistry letters 102 9873686
2018 Exosomal lncRNA 91H is associated with poor development in colorectal cancer by modifying HNRNPK expression. Cancer cell international 101 29410604
1996 Activation of the HIV-1 long terminal repeat by cytokines and environmental stress requires an active CSBP/p38 MAP kinase. The Journal of biological chemistry 95 8940070
2011 Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K. The Journal of cell biology 94 21357748
2021 A TNFR2-hnRNPK Axis Promotes Primary Liver Cancer Development via Activation of YAP Signaling in Hepatic Progenitor Cells. Cancer research 93 33619115
2013 Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) promotes tumor metastasis by induction of genes involved in extracellular matrix, cell movement, and angiogenesis. The Journal of biological chemistry 84 23564449
1994 Identification, molecular cloning, expression and chromosome mapping of a family of transformation upregulated hnRNP-K proteins derived by alternative splicing. Journal of molecular biology 84 8107114
2018 Long Noncoding RNA pancEts-1 Promotes Neuroblastoma Progression through hnRNPK-Mediated β-Catenin Stabilization. Cancer research 82 29311158
2019 Post-translational modification control of RNA-binding protein hnRNPK function. Open biology 80 30836866
2018 LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK. Stem cells (Dayton, Ohio) 76 30372559
2012 SUMOylation of hnRNP-K is required for p53-mediated cell-cycle arrest in response to DNA damage. The EMBO journal 73 23092970
2022 PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK. International journal of biological sciences 71 35342346
2007 Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proceedings of the National Academy of Sciences of the United States of America 71 17483488
2019 New Insights into the Interplay between Non-Coding RNAs and RNA-Binding Protein HnRNPK in Regulating Cellular Functions. Cells 66 30658384
2021 CircFAM73A promotes the cancer stem cell-like properties of gastric cancer through the miR-490-3p/HMGA2 positive feedback loop and HNRNPK-mediated β-catenin stabilization. Journal of experimental & clinical cancer research : CR 65 33731207
2012 Identification of ZNF217, hnRNP-K, VEGF-A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma. International journal of cancer 65 22815235
2018 Genomic analysis reveals recurrent deletion of JAK-STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides. Genes, chromosomes & cancer 61 30144205
2015 GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK. Human mutation 60 26173930
2017 MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression. Oncogene 57 28869607
2018 Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. Cell reports 56 30428357
2011 Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β-catenin signaling in prostate cancer cells. International journal of cancer 56 22015967
2015 Identification of HNRNPK as regulator of hepatitis C virus particle production. PLoS pathogens 54 25569684
2014 Withanone-rich combination of Ashwagandha withanolides restricts metastasis and angiogenesis through hnRNP-K. Molecular cancer therapeutics 53 25236891
2014 Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation. Nucleic acids research 51 25104022
2020 Circular RNA (circ-0075804) promotes the proliferation of retinoblastoma via combining heterogeneous nuclear ribonucleoprotein K (HNRNPK) to improve the stability of E2F transcription factor 3 E2F3. Journal of cellular biochemistry 49 32065448
2021 SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis. Cancer letters 48 34314754
2019 HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs. Nature communications 48 31519929
2021 Caveolin-1-driven membrane remodelling regulates hnRNPK-mediated exosomal microRNA sorting in cancer. Clinical and translational medicine 47 33931969
2021 Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK. Journal of experimental & clinical cancer research : CR 46 34452628
2020 SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies. Nucleic acids research 46 33130894
2008 African swine fever virus protein p30 interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP-K) during infection. FEBS letters 46 18775702
2002 hnRNP-K and Pur(alpha) act together to repress the transcriptional activity of the CD43 gene promoter. Blood 45 12411317
2013 Heme oxygenase-1 regulates postnatal lung repair after hyperoxia: role of β-catenin/hnRNPK signaling. Redox biology 42 24024157
2016 A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia. Clinical genetics 40 26954065
2017 HnRNPK/miR-223/FBXW7 feedback cascade promotes pancreatic cancer cell growth and invasion. Oncotarget 38 28423622
2015 Cytoplasmic hnRNPK interacts with GSK3β and is essential for the osteoclast differentiation. Scientific reports 38 26638989
2017 Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2. International journal of cancer 37 28335083
2017 Regulation of PLK1 through competition between hnRNPK, miR-149-3p and miR-193b-5p. Cell death and differentiation 37 28708135
2010 Comprehensive analysis of the palindromic motif TCTCGCGAGA: a regulatory element of the HNRNPK promoter. DNA research : an international journal for rapid publication of reports on genes and genomes 37 20587588
2020 hnRNPK recognition of the B motif of Xist and other biological RNAs. Nucleic acids research 36 32813011
2013 Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK. Proceedings of the National Academy of Sciences of the United States of America 35 23798440
2019 O-GlcNAc-induced nuclear translocation of hnRNP-K is associated with progression and metastasis of cholangiocarcinoma. Molecular oncology 34 30444036
2019 SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC. Redox biology 34 31121493
2019 hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing. Cancer cell international 33 31857793
2019 Metabolic stress activates an ERK/hnRNPK/DDX3X pathway in pancreatic β cells. Molecular metabolism 32 31178390
2021 hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2. Cell death & disease 30 33731671
2020 Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression. Cancer letters 28 32866608
2019 LncRNA RMST activates TAK1-mediated NF-κB signaling and promotes activation of microglial cells via competitively binding with hnRNPK. IUBMB life 28 31329361
2019 LncRNA RMST-mediated miR-107 transcription promotes OGD-induced neuronal apoptosis via interacting with hnRNPK. Neurochemistry international 28 31852624
2017 HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway. Oncotarget 27 29262567
2016 hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells. Scientific reports 27 26972480
2022 An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome. American journal of human genetics 26 36130591
2020 FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/β-catenin signaling via regulating miR-129-5p/HNRNPK axis. Life sciences 26 32585241
2016 Nujiangexathone A, a novel compound from Garcinia nujiangensis, suppresses cervical cancer growth by targeting hnRNPK. Cancer letters 26 27424288
2006 Interaction of N-WASP with hnRNPK and its role in filopodia formation and cell spreading. The Journal of biological chemistry 26 16574661
2015 EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin. mBio 25 26530384
2011 Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53. FEBS letters 25 21821029
2017 Clinical spectrum of Kabuki-like syndrome caused by HNRNPK haploinsufficiency. Clinical genetics 24 28374925
2005 Compartmentalization of hnRNP-K during cell cycle progression and its interaction with calponin in the cytoplasm. Journal of cellular biochemistry 24 15962305
2022 HNRNPK/CLCN3 axis facilitates the progression of LUAD through CAF-tumor interaction. International journal of biological sciences 23 36439880
2024 LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis. Journal of experimental & clinical cancer research : CR 22 38238853
2017 Knockdown of hnRNPK leads to increased DNA damage after irradiation and reduces survival of tumor cells. Carcinogenesis 22 28426877
2024 Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression. Journal of experimental & clinical cancer research : CR 21 38654325
2015 RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK. Oncotarget 21 26305187
2013 Transcriptome sequencing of Chinese and Caucasian population identifies ethnic-associated differential transcript abundance of heterogeneous nuclear ribonucleoprotein K (hnRNPK). Genomics 21 24373910
2022 HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS. Acta neuropathologica 19 35895140
2018 hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells. International journal of oncology 19 30106132
2023 Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer. Communications biology 18 36681772
2021 DNA-methylation-induced silencing of DIO3OS drives non-small cell lung cancer progression via activating hnRNPK-MYC-CDC25A axis. Molecular therapy oncolytics 18 34761103
2014 Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation. Biochemical and biophysical research communications 18 24508256
2014 The RNA binding protein hnRNP-K mediates post-transcriptional regulation of uncoupling protein-2 by angiopoietin-1. Cellular signalling 18 24642125
2018 The multifunctional RNA-binding protein hnRNPK is critical for the proliferation and differentiation of myoblasts. BMB reports 17 29898807
2009 hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation. International immunology 17 19880579
2021 Arginine Methylation of hnRNPK Inhibits the DDX3-hnRNPK Interaction to Play an Anti-Apoptosis Role in Osteosarcoma Cells. International journal of molecular sciences 15 34575922
2019 miR-1249-3p accelerates the malignancy phenotype of hepatocellular carcinoma by directly targeting HNRNPK. Molecular genetics & genomic medicine 15 31429522
2023 MGCG regulates glioblastoma tumorigenicity via hnRNPK/ATG2A and promotes autophagy. Cell death & disease 14 37460467
2022 Tumor suppressor mediated ubiquitylation of hnRNPK is a barrier to oncogenic translation. Nature communications 14 36329064
2021 SnoRD126 promotes the proliferation of hepatocellular carcinoma cells through transcriptional regulation of FGFR2 activation in combination with hnRNPK. Aging 14 33891563
2019 Okamoto syndrome has features overlapping with Au-Kline syndrome and is caused by HNRNPK mutation. American journal of medical genetics. Part A 14 30793470
2017 hnRNPK-regulated PTOV1-AS1 modulates heme oxygenase-1 expression via miR-1207-5p. BMB reports 14 28228215
2024 Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway. Molecular therapy : the journal of the American Society of Gene Therapy 13 38414246
2022 Deletion of Hnrnpk Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis. Cells 13 35455958
2022 LncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK in colorectal cancer. Cell & bioscience 13 35907898
2010 Hnrnpk, a protein differentially expressed in immature rat ovarian development, is required for normal primordial follicle assembly and development. Endocrinology 13 21190960
2023 BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axis†. Biology of reproduction 12 36617174
2023 Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer. BMC molecular and cell biology 12 37592256
2022 Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis. Cell death & disease 12 36127325
2020 LncSSBP1 Functions as a Negative Regulator of IL-6 Through Interaction With hnRNPK in Bronchial Epithelial Cells Infected With Talaromyces marneffei. Frontiers in immunology 12 31998294
2017 ERK1/2-mediated Cytoplasmic Accumulation of hnRNPK Antagonizes TRAIL-induced Apoptosis through Upregulation of XIAP in H1299 Cells. Biomedical and environmental sciences : BES 12 28756806