Affinage

HNRNPK

Heterogeneous nuclear ribonucleoprotein K · UniProt P61978

Length
463 aa
Mass
51.0 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPK is a multifunctional KH-domain RNA/DNA-binding protein that integrates signaling inputs with post-transcriptional and transcriptional gene control across proliferation, differentiation, apoptosis, and chromatin silencing (PMID:11231586, PMID:31519929). It recognizes cytosine-rich (C-patch) sequences cooperatively through its multiple KH domains, with the RG/RGG domain providing essential affinity for RNA but not DNA, and C-patch accessibility is gated by RNA secondary structure (PMID:32813011). Subcellular partitioning is the central control point: MAPK/ERK phosphorylation at S284/S353 drives cytoplasmic accumulation required for translational repression of DICE-element mRNAs (PMID:11231586), while O-GlcNAcylation promotes nuclear translocation (PMID:30444036). In the nucleus HNRNPK functions as a transcriptional co-activator of p53 — UV-induced SUMOylation by PIAS3 (reversed by SENP2) stabilizes it and shifts its affinity toward p53 to drive p21-mediated cell-cycle arrest (PMID:23092970), an interaction independently disrupted by Aurora-A phosphorylation at S379 (PMID:21821029). It also binds single-stranded promoter DNA with Purα to repress transcription (PMID:12411317) and recruits PCGF3/5-PRC1 to the Xist B-repeat to establish X-chromosome silencing (PMID:29220657). In the cytoplasm it acts as a sequence-specific regulator of mRNA fate, repressing or activating translation depending on partner and modification state — promoting IRES-dependent MYC translation (PMID:16293596), stabilizing or destabilizing specific transcripts via its KH domains (e.g., promoting WWC1 and Hif1a mRNA decay (PMID:38414246, PMID:36127325)), and recruiting helicase partners such as DDX3X to activate JUND translation (PMID:31178390). HNRNPK additionally regulates alternative splicing (e.g., MRPL33 isoform choice (PMID:28869607)) and directly inhibits N-WASP through its KI domain to control actin-based cell spreading and migration (PMID:16574661). Its pro-oncogenic mRNA-binding activity is restrained by SCF-Fbxo4-mediated K63-linked ubiquitylation (PMID:36329064). Loss of HNRNPK function is linked to cartilage and skeletal pathology through dysregulated Hippo signaling and glycolysis (PMID:38414246, PMID:36127325), and its activity counteracts C9orf72-associated RNA toxicity by transcriptionally controlling RRM2 to limit DNA damage (PMID:35895140).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Established that ERK phosphorylation is the switch coupling extracellular signaling to HNRNPK's cytoplasmic translational-repressor function, defining subcellular partitioning as the core regulatory principle.

    Evidence In vitro kinase assay, S284/S353 mutagenesis, ERK inhibition and subcellular fractionation

    PMID:11231586

    Open questions at the time
    • Did not identify the import/export machinery executing the relocalization
    • DICE-mRNA target repertoire not enumerated
  2. 2002 Medium

    Showed HNRNPK acts directly on chromatin as a transcriptional repressor by binding single-stranded promoter DNA with Purα, establishing a DNA-templated function distinct from its RNA roles.

    Evidence EMSA, transcriptional reporter assays and Co-IP at the CD43 promoter in K562 cells

    PMID:12411317

    Open questions at the time
    • Mechanism of single-stranded DNA generation at the promoter unresolved
    • Genome-wide promoter occupancy not mapped
  3. 2005 High

    Linked HNRNPK's translation-regulatory (not transcription-regulatory) activity to oncogenic IRES-dependent MYC translation downstream of BCR/ABL-ERK signaling, separating its two functional arms.

    Evidence Dominant-negative dissection, IRES reporters and in vivo leukemogenesis assays

    PMID:16293596

    Open questions at the time
    • Direct binding site within the MYC IRES not mapped
    • Co-factors for IRES activation not identified
  4. 2006 High

    Defined a non-nucleic-acid effector function: direct KI-domain inhibition of N-WASP, placing HNRNPK in cytoskeletal control of cell spreading and filopodia.

    Evidence Domain-mapped Co-IP, co-localization and spreading/filopodia assays

    PMID:16574661

    Open questions at the time
    • Whether N-WASP regulation is coupled to HNRNPK's RNA roles unknown
    • Structural basis of KI–WH1 contact not solved
  5. 2012 High

    Established the SUMO switch (PIAS3/SENP2, ATR-dependent) that stabilizes HNRNPK and biases it toward p53 co-activation for p21-driven arrest, defining its DNA-damage co-activator function.

    Evidence SUMO-defective mutants, purified-protein binding assays and PIAS3/SENP2 knockdown

    PMID:23092970

    Open questions at the time
    • SUMO acceptor lysine choreography with other PTMs not integrated
    • Promoter selectivity of the HNRNPK–p53 complex not defined here
  6. 2011 Medium

    Showed Aurora-A phosphorylation at S379 selectively disrupts the HNRNPK–p53 interaction without altering localization, providing a counter-regulatory brake on p53 transcriptional activity.

    Evidence In vitro kinase assay, Co-IP and S379 mutagenesis

    PMID:21821029

    Open questions at the time
    • Single-lab finding without reciprocal in vivo validation
    • Interplay with SUMO-driven p53 stabilization untested
  7. 2014 High

    Demonstrated arginine methylation (R296/R299) suppresses adjacent PKCδ-mediated S302 phosphorylation to dampen apoptosis, revealing a PTM crosstalk node controlling cell death independently of p53.

    Evidence Methylation-defective mutants, in vitro kinase assays and apoptosis readouts in U2OS cells

    PMID:25104022

    Open questions at the time
    • Responsible arginine methyltransferase not identified
    • Downstream apoptotic effectors not mapped
  8. 2017 High

    Identified HNRNPK as the principal Xist B-repeat (XR-PID) binding factor that recruits PCGF3/5-PRC1 to initiate X-chromosome silencing, defining a chromatin-establishing role bridging RNA recognition and Polycomb deposition.

    Evidence RNA deletion mutagenesis, knockdown, and synthetic tethering rescue with chromatin accessibility assays

    PMID:29220657

    Open questions at the time
    • Molecular bridge between HNRNPK and PRC1 not biochemically defined
    • Contribution of HNRNPK PTMs to this activity untested
  9. 2017 High

    Showed HNRNPK governs both splicing isoform choice (MRPL33-L) and 3'UTR-mediated mRNA stability (PLK1, competing with miRNAs at a shared C-rich motif), establishing KH-domain C-patch recognition as the common engine of its post-transcriptional control.

    Evidence Knockdown/rescue epistasis, RT-PCR splicing assays, 3'UTR mutants, Ago2-IP and reporter assays

    PMID:28708135 PMID:28869607

    Open questions at the time
    • Determinants selecting activation vs. repression at a given target unknown
    • miRNA competition generality across targets not established
  10. 2020 High

    Resolved the biochemical logic of target recognition: cooperative multi-KH C-patch binding with an essential RG/RGG contribution for RNA, gated by RNA structure, explaining differential RNA vs. DNA and structured vs. unstructured target engagement.

    Evidence In vitro domain-deletion binding assays, quantitative measurements and iCLIP/NMR-informed analysis on Xist B-repeat and C-patch RNAs

    PMID:32813011

    Open questions at the time
    • High-resolution structure of the multi-KH–RNA complex not solved
    • How PTMs modulate C-patch affinity not tested
  11. 2022 High

    Established SCF-Fbxo4 K63-linked ubiquitylation as a brake on HNRNPK's mRNA-binding pro-oncogenic activity, connecting ubiquitin signaling to MYC translation and metastasis.

    Evidence Linkage-specific ubiquitylation assays, polysome profiling, genetic KO and invasion assays

    PMID:36329064

    Open questions at the time
    • Ubiquitin acceptor sites not mapped
    • How K63 chains mechanically impair RNA binding unresolved
  12. 2022 Medium

    Defined HNRNPK-dependent destabilization of Hif1a (and later WWC1) mRNA via KH domains as physiologically essential for chondrocyte metabolism and cartilage homeostasis, linking its mRNA-decay activity to skeletal disease.

    Evidence Conditional KO mice, RIP, mRNA stability and metabolic assays; later WWC1 RNAi rescue in OA models

    PMID:36127325 PMID:38414246

    Open questions at the time
    • Decay machinery recruited by HNRNPK at these targets not identified
    • Tissue-specific target selectivity mechanism unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the combinatorial PTM code (ERK/Src/Aurora-A phosphorylation, SUMO, arginine methylation, O-GlcNAc, K63-ubiquitin) is integrated to select among HNRNPK's transcriptional, splicing, translational, mRNA-stability, and cytoskeletal outputs at any given time and locus remains unresolved.
  • No unified model relating PTM state to target choice
  • Structural basis of partner-switching between p53, N-WASP, DDX3X, and PRC1 unknown
  • Genome/transcriptome-wide direct target maps not integrated across conditions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0140110 transcription regulator activity 6 GO:0045182 translation regulator activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 6 GO:0005634 nucleus 4 GO:0005856 cytoskeleton 3 GO:0000228 nuclear chromosome 1 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-4839726 Chromatin organization 1
Partners
DDX3XFBXO4GSK3BPIAS3SENP2TP53WASLYAP1
Complex memberships
PCGF3/5-PRC1 (recruited to Xist)hnRNPK-p53 transcriptional complex

Evidence

Reading pass · 41 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; this phosphorylation drives cytoplasmic accumulation of hnRNPK, which is required for its ability to silence mRNA translation of transcripts containing a differentiation-control element (DICE) in the 3' UTR. Mutation of ERK phosphoacceptor sites abolishes cytoplasmic accumulation and translational repression. In vitro kinase assay, site-directed mutagenesis, pharmacological ERK inhibition, subcellular fractionation, constitutively active MEK1 overexpression Nature cell biology High 11231586
2017 hnRNPK is the principal binding factor for the Xist RNA Polycomb Interaction Domain (XR-PID, encompassing the B-repeat element) and is required to recruit PCGF3/5-PRC1 to the inactive X chromosome. Deletion of XR-PID abolishes Polycomb recruitment, Xist-mediated gene silencing, and chromatin inaccessibility; synthetic tethering of hnRNPK to Xist RNA lacking XR-PID restores Polycomb recruitment. RNA deletion mutagenesis, hnRNPK knockdown, synthetic tethering rescue, chromatin accessibility assays, RNA-protein interaction studies 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 and increasing its affinity for p53 over HDM2, thereby enabling hnRNPK to act as a transcriptional co-activator of p53 for p21-mediated cell-cycle arrest. Later, SENP2 removes SUMO from hnRNPK, destabilizing it and releasing the cell-cycle arrest. SUMOylation-defective mutant analysis, purified SUMOylated hnRNPK binding assays, siRNA knockdown of PIAS3/SENP2, co-immunoprecipitation The EMBO journal High 23092970
2014 Arginine methylation of hnRNPK at Arg296 and Arg299 inhibits nearby Ser302 phosphorylation mediated by the pro-apoptotic kinase PKCδ, thereby negatively regulating apoptosis following DNA damage. Cells expressing methylation-defective hnRNPK mutants show increased apoptosis through both intrinsic and extrinsic pathways in a p53-independent manner. Site-directed mutagenesis (Arg296/299), in vitro kinase assays, engineered U2OS cell lines, apoptosis assays Nucleic acids research High 25104022
2011 During oligodendrocyte differentiation and myelination, α6β1-integrin activation interacts with hnRNP-K, which binds MBP mRNA and translocates from the nucleus to the myelin sheath, reversing the inhibitory effect of the MBP mRNA 3'UTR on translation; knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Co-immunoprecipitation, siRNA knockdown, subcellular fractionation/live imaging, in vitro translation assays The Journal of cell biology High 21357748
2005 BCR/ABL activates hnRNPK expression and activity via the MAPK/ERK1/2 pathway; elevated hnRNPK enhances IRES-dependent MYC mRNA translation, contributing to leukemogenic proliferation and clonogenic potential. Interference with hnRNPK translation-regulatory activity (but not transcription-regulatory activity) impairs BCR/ABL-driven leukemogenesis. siRNA knockdown, dominant-negative constructs distinguishing translation vs. transcription functions, in vivo leukemogenesis assays, IRES reporter assays Blood High 16293596
2006 hnRNPK directly interacts with N-WASP via the WH1 domain of N-WASP and the KI domain of hnRNPK; co-expression of hnRNPK with N-WASP reverses N-WASP-stimulated cell spreading and reduces filopodia formation, identifying hnRNPK as a negative regulator of N-WASP at the spreading initiation center. Co-immunoprecipitation, domain mapping, co-localization imaging, cell spreading and filopodia assays The Journal of biological chemistry High 16574661
2011 Aurora-A kinase phosphorylates hnRNPK at serine 379; this phosphorylation disrupts the interaction of hnRNPK with p53 without affecting hnRNPK post-transcriptional activity or cellular localization, providing a mechanism by which Aurora-A reduces p53 transcriptional activity during DNA damage. In vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis (S379) FEBS letters Medium 21821029
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 regulates NF-κB activation, NFATc1 expression, and tubulin acetylation, all critical for osteoclast differentiation. hnRNPK is also localized in the actin belt of mature osteoclasts. Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, immunofluorescence localization, osteoclast differentiation assays Scientific reports Medium 26638989
2019 HNRNPK is necessary for DDX6-mediated binding and degradation of a subset of mRNAs encoding differentiation-promoting transcription factors (GRHL3, KLF4, ZNF750) in epidermal progenitor cells, preventing premature differentiation. HNRNPK is also required for RNA Polymerase II binding to proliferation/self-renewal genes (MYC, CYR61, FGFR1, EGFR, cyclins) to sustain progenitor proliferative capacity. HNRNPK siRNA knockdown, RNA-seq, ChIP for RNA Pol II, mRNA stability assays, RIP for DDX6 Nature communications High 31519929
2015 HNRNPK interacts directly with HCV RNA (but not Dengue virus RNA), and mutations that impair this RNA interaction also reduce HNRNPK's ability to suppress HCV particle production. In HCV-infected cells, HNRNPK is redistributed to sites adjacent to lipid droplets, co-localizing with core protein and HCV plus-strand RNA. The mechanism involves limiting viral RNA availability for incorporation into virions. siRNA knockdown, domain mapping rescue experiments, RNA-protein interaction assays, co-localization imaging, virion production assays PLoS pathogens High 25569684
2013 hnRNPK, together with Tcl1, promotes G6PD pre-mRNA splicing and increases G6PD protein expression; PTEN forms a complex with hnRNPK and inhibits this G6PD pre-mRNA splicing, thereby antagonizing the Tcl1/hnRNPK-mediated enhancement of the pentose phosphate pathway in hepatocellular carcinoma. Co-immunoprecipitation, mass spectrometry, splicing assays, siRNA knockdown, biochemical complex analysis Gut Medium 24352616
2021 hnRNPK acts downstream of TNFα-TNFR2 signaling to directly interact with and stabilize YAP on target gene promoters genome-wide, co-regulating YAP target gene expression in hepatic progenitor cells. TNFR1 does not mediate this effect. Co-immunoprecipitation, ChIP-seq, siRNA knockdown, single-cell RNA sequencing Cancer research Medium 33619115
2017 hnRNPK regulates alternative splicing of MRPL33 pre-mRNA to promote inclusion of exon 3, producing the long isoform MRPL33-L; knockdown of hnRNPK phenocopies MRPL33-L depletion (impaired proliferation, increased apoptosis, mitochondrial dysfunction), and overexpression of MRPL33-L can rescue hnRNPK-depleted cells, placing hnRNPK upstream of MRPL33-L in a cancer-relevant splicing pathway. siRNA knockdown, overexpression rescue, RT-PCR splicing assay, mitochondrial functional assays, xenograft model Oncogene High 28869607
2002 hnRNP-K and Purα act together to repress transcriptional activity of the CD43 gene promoter during K562 cell activation by binding single-stranded DNA sequences in the promoter. Transcriptional reporter assays, electrophoretic mobility shift assays (EMSA), co-immunoprecipitation Blood Medium 12411317
2019 In pancreatic β cells under glucolipotoxic metabolic stress, MEK/ERK signaling phosphorylates hnRNPK, which then binds the 3'UTR poly-C motif of JUND mRNA and recruits the RNA helicase DDX3X as a binding partner to promote efficient JUND mRNA translation. Loss of hnRNPK blocks post-transcriptional JUND upregulation, and hnRNPK loss reduces DDX3X association with translation machinery. RNA immunoprecipitation, co-immunoprecipitation, Phos-tag analysis, TRAP-qPCR, CRISPR-Cas9 KO, lentiviral delivery Molecular metabolism High 31178390
2013 hnRNP-K promotes tumor metastasis by regulating extracellular matrix, cell motility, and angiogenesis gene-expression pathways (including Cck, Mmp-3, Ptgs2, and Ctgf), as established in hnRNP-K-overexpressing and -underexpressing cell lines with in vitro and in vivo metastasis assays. Stable hnRNPK overexpression/knockdown cell lines, cDNA microarray, pathway analysis, in vivo metastasis assays The Journal of biological chemistry Medium 23564449
2017 hnRNPK regulates PLK1 expression post-transcriptionally through KH1- and KH2-dependent interactions with cytosine-rich sequences in the 3'UTR of PLK1 mRNA, and competes with miR-149-3p and miR-193b-5p for this shared C-rich motif to influence PLK1 mRNA stability and Ago2 association. siRNA knockdown, overexpression, Ago2 immunoprecipitation, 3'UTR deletion mutants, luciferase reporter assays Cell death and differentiation Medium 28708135
2016 hnRNPK translocated from nucleus to cytoplasm (via MAPK/ERK) binds to and inhibits Ser9 phosphorylation of GSK3β by PKC, thereby maintaining GSK3β in an active state that stabilizes c-FLIP protein and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells. Subcellular fractionation, co-immunoprecipitation, co-localization imaging, GSK3β phosphorylation assays, c-FLIP stability assays, tissue microarray Scientific reports Medium 26972480
2005 Cytoplasmic hnRNP-K forms a multi-protein complex with calponin and ERK1/2 in smooth muscle cells; nuclear-to-cytoplasmic translocation of hnRNP-K is cell cycle-dependent, with cytoplasmic hnRNP-K appearing at later cell cycle stages, partly by translocation from the nucleus. Subcellular fractionation across cell cycle, cycloheximide chase, co-immunoprecipitation Journal of cellular biochemistry Medium 15962305
2008 African swine fever virus protein p30 interacts with hnRNP-K through the KH1 and KH2 domains (residues 35–197) of hnRNP-K; this interaction occurs mainly in the nucleus, alters hnRNP-K subcellular distribution, and decreases nascent RNA synthesis in infected cells. Yeast two-hybrid, co-localization imaging, domain mapping, 5-fluorouridine incorporation assay FEBS letters Medium 18775702
2013 hnRNP-K binds the distal polyadenylation element of SERT mRNA; Src-family kinase-mediated tyrosine phosphorylation of hnRNPK (induced by trophic factor S100β) is associated with increased SERT protein expression, suggesting hnRNPK holds SERT mRNA in a translationally repressed state that is relieved upon tyrosine phosphorylation. RNA-protein binding assays, genetic manipulation of hnRNPK, pharmacological Src inhibition, western blot for SERT protein Proceedings of the National Academy of Sciences of the United States of America Medium 23798440
2014 Angiopoietin-1 stimulates Src-family kinase recruitment to hnRNP-K and tyrosine phosphorylation of hnRNP-K (requiring Tyr458); this phosphorylation prevents hnRNP-K from binding UCP2 mRNA, releasing it for translation and increasing UCP2 protein expression in endothelial cells without changing total UCP2 mRNA levels. In vitro Src phosphorylation of purified hnRNP-K, RIP, site-directed mutagenesis (Y458), co-immunoprecipitation, western blot Cellular signalling High 24642125
2021 CAV1 (non-caveolar, in the absence of CAVIN1) drives localization of hnRNPK to multi-vesicular bodies (MVBs), recruiting AsUGnA motif-containing miRNAs for selective loading into exosomes; knockdown of hnRNPK abolishes PC3 extracellular vesicle-induced osteoclastogenesis, establishing hnRNPK as a miRNA sorting factor for exosomal release. hnRNPK knockdown, co-localization imaging, cholesterol depletion, miRNA pulldown, osteoclastogenesis assay Clinical and translational medicine Medium 33931969
2021 hnRNPK facilitates cytoplasmic interaction with and stabilization of β-catenin by inhibiting its proteasome-mediated degradation; lncRNA pancEts-1 promotes this interaction by binding hnRNPK and facilitating its physical interaction with β-catenin. Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor assays, lncRNA pulldown Cancer research (reported in PMID:29311158) Medium 29311158
2022 SCFFbxo4 E3 ubiquitin ligase restricts hnRNPK pro-oncogenic activity via K63-linked polyubiquitylation, limiting hnRNPK's ability to bind target mRNAs. Loss of SCFFbxo4 leads to hnRNPK-dependent increase in c-Myc mRNA translation, enhanced cell invasion, and tumor metastasis. Co-immunoprecipitation, ubiquitylation assays (K63 linkage), polysome profiling, siRNA/genetic KO, invasion assays Nature communications High 36329064
2019 hnRNPK activates transcription of the SRSF1 splicing regulator by binding to a motif upstream of the start codon (−65 to −77 site), thereby increasing expression of the oncogenic CD44E isoform (CD44v8-v10) in gastric cancer cells. ChIP assay, dual luciferase reporter assay, siRNA knockdown, RT-PCR splicing analysis Cancer cell international Medium 31857793
2015 hnRNP-K interacts with Ehrlichia entry-triggering protein EtpE-C via CD147 and cytoplasmic hnRNP-K; hnRNP-K activates N-WASP-dependent actin polymerization to drive bacterial entry. Functional ablation of cytoplasmic hnRNP-K by intracellular nanobody markedly attenuated Ehrlichia entry and infection. Affinity pulldown, far-Western blot, co-immunoprecipitation, shRNA knockdown, intracellular nanobody, in vitro actin polymerization assay, time-lapse imaging mBio High 26530384
2009 TCR-activated ERK phosphorylates hnRNP-K in the nucleus of T cells; hnRNP-K knockdown abrogates IL-2 production and causes increased proteolysis of Vav1 (a binding target of hnRNP-K), suggesting hnRNPK protects Vav1 from activation-induced degradation and is required for T cell activation. Proteomic analysis of TCR-activated nuclear proteins, siRNA knockdown, western blot for Vav1 International immunology Medium 19880579
2017 hnRNPK binds to the miR-223 promoter, and siRNA knockdown of hnRNPK reduces miR-223 levels in pancreatic cancer cells. FBXW7 interacts with hnRNPK and promotes its degradation via GSK3-mediated phosphorylation at threonine 1695, forming a feedback cascade. ChIP, siRNA knockdown, co-immunoprecipitation, GSK3 phosphorylation assay Oncotarget Medium 28423622
2021 Circ-GALNT16 binds the KH3 domain of hnRNPK and promotes its SUMOylation, thereby enhancing formation of an hnRNPK-p53 transcriptional complex; SUMOylation of hnRNPK inhibited by SENP2 reduces sequence-specific DNA binding of the hnRNPK-p53 complex, regulating Serpine1 transcription. RNA pulldown, RIP, co-immunoprecipitation, ChIP, RNA sequencing, domain mapping (KH3) Journal of experimental & clinical cancer research Medium 34452628
2022 hnRNPK alleviates RNA toxicity in C9orf72 ALS by counteracting DNA damage; HNRNPK subcellular localization (cytoplasmic mislocalization observed in patient cells) and RNA recognition are required for this function. hnRNPK transcriptionally controls RRM2 (ribonucleotide reductase regulatory subunit M2), and increasing either hnRNPK or RRM2 expression mitigates DNA damage in a C9orf72 RNA toxicity zebrafish model. Zebrafish overexpression model, patient fibroblasts/iPSC-derived motor neurons, post-mortem tissue, DNA damage assays, subcellular fractionation Acta neuropathologica Medium 35895140
2024 The KH1 and KH2 domains of hnRNPK bind and promote degradation of WWC1 mRNA; hnRNPK deletion increases WWC1 expression, activating Hippo signaling and aggravating osteoarthritis. Intra-articular AAV5-hnRNPK protects against OA, and WWC1 RNAi rescues cartilage degeneration caused by hnRNPK deletion. Conditional KO mice, AAV rescue, RIP/domain mapping, in vivo OA models, mRNA stability assays Molecular therapy Medium 38414246
2022 hnRNPK binds Hif1a mRNA and promotes its degradation via its KH domains; hnRNPK deletion in chondrocytes increases Hif1α protein, leading to exorbitant glycolysis and impaired chondrocyte survival and differentiation, causing dwarfism. Conditional chondrocyte KO mice, RIP, mRNA stability assay, metabolic assays Cell death & disease Medium 36127325
2021 SGLT2 interacts with hnRNPK and promotes hnRNPK nuclear translocation, thereby enhancing hnRNPK-induced YAP1 transcription, activating Hippo signaling in pancreatic cancer cells. Liquid chromatography-mass spectrometry, co-immunoprecipitation, subcellular fractionation, siRNA knockdown, transcription reporter assay Cancer letters Medium 34314754
2019 O-GlcNAcylation of hnRNP-K is required for its nuclear translocation; suppression of O-GlcNAcylation retains hnRNP-K in the cytoplasm in cholangiocarcinoma cells, reducing their migratory capabilities. Click chemistry enzymatic labeling, LC-MS/MS proteomics, anti-OGP/anti-hnRNPK immunoprecipitation, sWGA pulldown, siRNA knockdown, subcellular fractionation Molecular oncology Medium 30444036
2014 SET protein directly interacts with hnRNPK and increases hnRNPK's binding to nucleic acids; SET accumulation promotes hnRNPK nuclear localization and enhances Bcl-xS repression. Co-immunoprecipitation, overexpression/knockdown, nucleic acid binding assays, subcellular fractionation Biochemical and biophysical research communications Low 24508256
2021 Arginine methylation of hnRNPK inhibits the DDX3-hnRNPK interaction; DDX3 C-terminus preferentially binds unmethylated hnRNPK and promotes apoptosis in osteosarcoma cells. A small molecule docking at the DDX3 ATP-binding site promotes DDX3-hnRNPK interaction and induces apoptosis. Co-immunoprecipitation with methylation mutants, apoptosis assays, in silico docking, domain-deletion constructs International journal of molecular sciences Medium 34575922
2020 hnRNPK and PTBP1 are essential RNA-binding proteins for SINEUP lncRNA function; they contribute to SINEUP sub-cellular distribution and assembly of translational initiation complexes, leading to enhanced target mRNA translation. Co-transfection, co-localization imaging, siRNA knockdown, polysome/translational complex analysis Nucleic acids research Medium 33130894
2019 hnRNPK decreases α-tubulin K40 acetylation in cells by downregulating HDAC6 expression; hnRNPK deficiency increases HDAC6 mRNA and protein, enhancing autophagosome-lysosome fusion and selective quality-control autophagy under basal (but not starvation) conditions. CRISPR-Cas9 KO, siRNA, overexpression, autophagy flux assays, co-localization, HDAC6 inhibitor rescue International journal of oncology Medium 30106132
2020 hnRNPK recognition of multi-cytosine-patch (C-patch) RNA is mediated cooperatively by multiple KH domains, with the RG/RGG domain providing essential contributions to RNA (but not DNA) binding affinity; KH3 alone is neither necessary nor sufficient. For the Xist B-repeat RNA, C-patch recognition is conformationally restricted within hairpin structures but relieved in unstructured RNA. In vitro binding assays with domain deletion mutants, quantitative RNA-protein interaction measurements, NMR-informed analysis, iCLIP crosslinking data analysis Nucleic acids research High 32813011

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 264 29220657
2001 ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation. Nature cell biology 250 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 208 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.) 150 38111678
2019 The emerging roles of hnRNPK. Journal of cellular physiology 131 31538344
2013 PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis. Gut 110 24352616
2018 Exosomal lncRNA 91H is associated with poor development in colorectal cancer by modifying HNRNPK expression. Cancer cell international 102 29410604
1998 Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorganic & medicinal chemistry letters 102 9873686
2011 Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K. The Journal of cell biology 96 21357748
2021 A TNFR2-hnRNPK Axis Promotes Primary Liver Cancer Development via Activation of YAP Signaling in Hepatic Progenitor Cells. Cancer research 95 33619115
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
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 83 29311158
2019 Post-translational modification control of RNA-binding protein hnRNPK function. Open biology 81 30836866
2018 LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK. Stem cells (Dayton, Ohio) 77 30372559
2012 SUMOylation of hnRNP-K is required for p53-mediated cell-cycle arrest in response to DNA damage. The EMBO journal 74 23092970
2022 PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK. International journal of biological sciences 73 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 69 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 67 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 62 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 61 26173930
2018 Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. Cell reports 59 30428357
2017 MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression. Oncogene 59 28869607
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 55 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
2021 Caveolin-1-driven membrane remodelling regulates hnRNPK-mediated exosomal microRNA sorting in cancer. Clinical and translational medicine 50 33931969
2021 SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis. Cancer letters 50 34314754
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 50 32065448
2019 HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs. Nature communications 49 31519929
2020 SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies. Nucleic acids research 48 33130894
2021 Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK. Journal of experimental & clinical cancer research : CR 47 34452628
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 41 26954065
2015 Cytoplasmic hnRNPK interacts with GSK3β and is essential for the osteoclast differentiation. Scientific reports 39 26638989
2017 HnRNPK/miR-223/FBXW7 feedback cascade promotes pancreatic cancer cell growth and invasion. Oncotarget 38 28423622
2020 hnRNPK recognition of the B motif of Xist and other biological RNAs. Nucleic acids research 37 32813011
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
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 36 23798440
2019 hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing. Cancer cell international 35 31857793
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
2021 hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2. Cell death & disease 32 33731671
2019 Metabolic stress activates an ERK/hnRNPK/DDX3X pathway in pancreatic β cells. Molecular metabolism 32 31178390
2020 Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression. Cancer letters 29 32866608
2019 LncRNA RMST activates TAK1-mediated NF-κB signaling and promotes activation of microglial cells via competitively binding with hnRNPK. IUBMB life 29 31329361
2017 HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway. Oncotarget 29 29262567
2019 LncRNA RMST-mediated miR-107 transcription promotes OGD-induced neuronal apoptosis via interacting with hnRNPK. Neurochemistry international 28 31852624
2016 hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells. Scientific reports 28 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 27 36130591
2020 FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/β-catenin signaling via regulating miR-129-5p/HNRNPK axis. Life sciences 27 32585241
2016 Nujiangexathone A, a novel compound from Garcinia nujiangensis, suppresses cervical cancer growth by targeting hnRNPK. Cancer letters 26 27424288
2015 EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin. mBio 26 26530384
2006 Interaction of N-WASP with hnRNPK and its role in filopodia formation and cell spreading. The Journal of biological chemistry 26 16574661
2011 Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53. FEBS letters 25 21821029
2024 LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis. Journal of experimental & clinical cancer research : CR 24 38238853
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
2022 HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS. Acta neuropathologica 22 35895140
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
2021 DNA-methylation-induced silencing of DIO3OS drives non-small cell lung cancer progression via activating hnRNPK-MYC-CDC25A axis. Molecular therapy oncolytics 21 34761103
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
2023 Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer. Communications biology 19 36681772
2018 hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells. International journal of oncology 19 30106132
2018 The multifunctional RNA-binding protein hnRNPK is critical for the proliferation and differentiation of myoblasts. BMB reports 18 29898807
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
2021 Arginine Methylation of hnRNPK Inhibits the DDX3-hnRNPK Interaction to Play an Anti-Apoptosis Role in Osteosarcoma Cells. International journal of molecular sciences 17 34575922
2009 hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation. International immunology 17 19880579
2019 miR-1249-3p accelerates the malignancy phenotype of hepatocellular carcinoma by directly targeting HNRNPK. Molecular genetics & genomic medicine 16 31429522
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 15 38414246
2022 LncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK in colorectal cancer. Cell & bioscience 15 35907898
2022 Tumor suppressor mediated ubiquitylation of hnRNPK is a barrier to oncogenic translation. Nature communications 15 36329064
2021 SnoRD126 promotes the proliferation of hepatocellular carcinoma cells through transcriptional regulation of FGFR2 activation in combination with hnRNPK. Aging 15 33891563
2023 MGCG regulates glioblastoma tumorigenicity via hnRNPK/ATG2A and promotes autophagy. Cell death & disease 14 37460467
2022 Deletion of Hnrnpk Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis. Cells 14 35455958
2022 Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis. Cell death & disease 14 36127325
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
2010 Hnrnpk, a protein differentially expressed in immature rat ovarian development, is required for normal primordial follicle assembly and development. Endocrinology 14 21190960
2023 BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axis†. Biology of reproduction 13 36617174
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 13 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 13 28756806
2007 Sequence and transcriptional study of HNRPK pseudogenes, and expression and molecular modeling analysis of hnRNP K isoforms. Genome 12 17612614

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