Affinage

PHF6

PHD finger protein 6 · UniProt Q8IWS0

Length
365 aa
Mass
41.3 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHF6 is an X-linked nuclear, prominently nucleolar chromatin adaptor that regulates transcription across distinct genomic compartments through its two extended PHD (ePHD) zinc-finger domains (PMID:12415272, PMID:24554700). In the nucleoplasm it acts through nucleosome-remodeling complexes: it directly binds the NuRD subunit RBBP4 via a positively charged motif (residues 162–170) that inserts into the RBBP4 β-propeller, an interaction required for its transcriptional repression activity, and it also engages SWI/SNF and ISWI remodelers where it maintains active chromatin and prevents RNA Pol II stalling at promoters (PMID:22720776, PMID:24554700, PMID:25601084, PMID:39181868). In the nucleolus it occupies the rDNA gene body and suppresses rRNA transcription, recruiting the histone methyltransferases SUV39H1 and SUV4-20H2 to deposit repressive H3K9me3 and H4K20me3, with its nucleolar occupancy gated by rDNA gene-body methylation and UBF binding through ePHD1 (PMID:23229552, PMID:27165002, PMID:35847518, PMID:34520760, PMID:26286319). Its ePHD1 domain carries intrinsic E3 ubiquitin ligase activity toward H2BK120, an activity licensed by ePHD2 recognition of H2BK12 acetylation (PMID:32735658). PHF6 is recruited to DNA double-strand breaks in a PARP-dependent manner to promote classical NHEJ and G2 checkpoint recovery, and associates with heterochromatic satellite DNA and the replication machinery to safeguard genomic stability at fragile sites (PMID:31782600, PMID:35338774). In the developing cortex PHF6 cooperates with the PAF1 elongation complex and directly drives neuronal target genes including NGC/CSPG5 and Ephrin receptors to control neural stem cell self-renewal, neuronal migration and maturation (PMID:23791194, PMID:38429579, PMID:39405291); the R342X loss-of-function mutation produces brain developmental abnormalities and learning deficits (PMID:33772537). In hematopoiesis PHF6 restrains HSC self-renewal and stemness programs, in part by activating TNFα signaling and via a functional complex with PHIP, and its loss lowers the threshold for NOTCH1-driven T-ALL and mixed-lineage leukemia (PMID:28607179, PMID:30567843, PMID:30917958, PMID:40721297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 Medium

    Established the basic subcellular address of PHF6, framing it as a candidate transcriptional regulator with strong nucleolar enrichment.

    Evidence GFP-tagged PHF6 transient transfection and fluorescence imaging

    PMID:12415272

    Open questions at the time
    • Overexpression imaging only
    • No functional readout connecting localization to transcription
    • Did not resolve sub-nucleolar compartment or DNA/histone binding
  2. 2012 High

    Resolved how PHF6 acts on chromatin in two compartments — defining its nucleoplasmic NuRD association and its nucleolar UBF/rDNA repressive role.

    Evidence Flag Co-IP/MS in HEK293T (NuRD); domain-mapping pulldown, ChIP, knockdown with γH2AX and cell-cycle analysis (UBF/rDNA)

    PMID:22720776 PMID:23229552

    Open questions at the time
    • NuRD subunit directly contacted not yet identified
    • Mechanism by which PHF6 lowers UBF levels unresolved
    • Did not establish histone-mark readout
  3. 2013 High

    Connected PHF6 to transcription elongation and a concrete developmental output, placing it in the PAF1 complex driving cortical neuronal migration.

    Evidence In vivo RNAi in mouse cortex, in utero electroporation, Co-IP, electrophysiology, NGC/CSPG5 target analysis

    PMID:23791194

    Open questions at the time
    • Direct vs indirect PAF1 contact not mapped
    • How elongation activity relates to NuRD repression unclear
  4. 2014 High

    Provided the structural basis for PHF6 chromatin engagement — the ePHD2 module binds dsDNA (not histones) and contacts RBBP4 to enable repression.

    Evidence X-ray crystallography of ePHD2, in vitro binding, GAL4 repression reporter, Co-IP

    PMID:24554700

    Open questions at the time
    • DNA sequence preference of ePHD2 not defined
    • Did not localize the exact RBBP4-binding residues
  5. 2015 High

    Defined the atomic PHF6–RBBP4 interface and showed PHF6 sits upstream of miR-128 in cortical lamination and uses ePHD1 to bind UBF.

    Evidence Crystallography of RBBP4–PHF6 peptide complex with mutagenesis and reporter assays; in vivo miR-128 rescue and electrophysiology; NMR of ePHD1

    PMID:25556700 PMID:25601084 PMID:26286319

    Open questions at the time
    • Whether RBBP4 binding is the sole repression route untested
    • Full-length ePHD1 structure unsolved
  6. 2016 High

    Refined the nucleolar mechanism, showing RNA-dependent sub-nucleolar targeting and rDNA gene-body occupancy that suppresses rRNA while inducing repressive IGS transcripts.

    Evidence Immunocytochemistry after RNase/DNase/actinomycin D/DRB, ChIP-qPCR, gain-of-function rRNA quantification

    PMID:27165002

    Open questions at the time
    • RNA species mediating localization not identified
    • Causal link between IGS ncRNA and repression unproven
  7. 2017 High

    Demonstrated that PHF6 loss reprograms chromatin accessibility and lineage identity, establishing its role in enforcing cell-fate boundaries.

    Evidence ATAC-seq, RNA-seq, in vivo transplantation in Phf6-knockout B-cell leukemia

    PMID:28607179

    Open questions at the time
    • Direct vs secondary accessibility changes not separated
    • Chromatin complex responsible not pinpointed
  8. 2018 High

    Placed PHF6 as a brake on HSC self-renewal whose loss cooperates with NOTCH1 to drive T-ALL, linking its chromatin function to leukemogenesis.

    Evidence Conditional Phf6 KO, competitive transplantation, NOTCH1 T-ALL model, transcriptomics

    PMID:30567843

    Open questions at the time
    • Direct transcriptional targets in HSCs not defined
    • Mechanism of NOTCH1 cooperation unresolved
  9. 2019 High

    Identified molecular effectors of PHF6's hematopoietic role (TNFα signaling), its DNA-repair function (PARP-dependent NHEJ), and a p21-repressive activity affecting drug sensitivity.

    Evidence Conditional KO with serial transplantation and TNFα assays; RNAi checkpoint screen with live-cell DNA-damage imaging and NHEJ assays; ChIP at p21 promoter with CRISPR correction and rescue

    PMID:30551478 PMID:30917958 PMID:31782600

    Open questions at the time
    • Direct vs indirect TNFα target activation not separated
    • How PHF6 reads DNA-damage signal mechanistically unknown
    • p21 study is single-locus ChIP, single lab
  10. 2020 High

    Revealed PHF6 as an enzyme — an ePHD1 E3 ligase for H2BK120ub gated by ePHD2 reading of H2BK12Ac — and extended its repressor role to neurons in a state-dependent manner.

    Evidence In vitro ubiquitination with domain mutagenesis and ChIP (trophectoderm); cell-type-specific ChIP, RNA-seq, conditional KO and behavior in AgRP neurons; CRISPR KO in neuron-like cells

    PMID:32187544 PMID:32735658 PMID:33149206

    Open questions at the time
    • Ligase activity validated in vitro by single lab
    • Whether ligase activity operates at all PHF6 sites unknown
  11. 2021 High

    Expanded the histone-mark and methyltransferase logic of nucleolar silencing (SUV39H1, SUV4-20H2, DNMT1-dependent gating) and uncovered additional partners and disease links across leukemia and neurodevelopment.

    Evidence Co-IP/ChIP with SUV39H1 and SUV4-20H2 plus DNMT1 KO methylation mapping; PHF6-p50/NF-κB Co-IP; JAK3M511I leukemia model; R342X knock-in mouse with MRI and behavior

    PMID:33772537 PMID:34465864 PMID:34520760 PMID:35847518 PMID:37393343

    Open questions at the time
    • NF-κB/p50 and JAK3 epistasis studies are single-lab with limited orthogonal validation
    • How PHF6 selects between SUV39H1 and SUV4-20H2 recruitment unclear
  12. 2022 High

    Integrated PHF6 into a broad chromatin/replication/repair interactome and showed it associates with H3K9me3 heterochromatin and maintains genome stability at fragile sites; defined its role in reversing HSC aging.

    Evidence Interactome proteomics, native ChIP-seq, DNA fiber analysis, damage assays; aged conditional KO with scRNA-seq, transplantation, epigenomics

    PMID:35338774 PMID:37118089

    Open questions at the time
    • Direct binding partners within the remodeler/replication interactome not all validated
    • Mechanism linking PHF6 to fragile-site protection undefined
  13. 2023 Medium

    Identified context-specific PHF6 partners (RUNX1 at enhancers, HIF-1α/2α via BPTF recruitment), broadening its repertoire beyond NuRD/SWI-SNF.

    Evidence Proteomics and ChIP co-localization with RUNX1; Co-IP, ChIP-qPCR and HIF double-KO xenografts for HIF/BPTF

    PMID:36967443 PMID:38418452

    Open questions at the time
    • RUNX1 and HIF interactions are single-study, limited mechanistic dissection
    • Direct vs bridged interactions not resolved
  14. 2024 High

    Mechanistically unified PHF6's active-chromatin maintenance (SWI/SNF, Pol II progression), its direct neural targets (Ephrin receptors), its PHIP-dependent AML stemness suppression, and the consequences of its loss for cortical neuronal maturation.

    Evidence CRISPR screen with ChIP-seq/ATAC-seq/Pol II ChIP in vivo; cortical ChIP-seq with KO/KI/KD/rescue; PHF6/PHIP co-dependency with ChIP and RNA-seq in Flt3-ITD model; germline and CNS-specific KO with electrophysiology and RNA-seq

    PMID:38429579 PMID:39181868 PMID:39405291 PMID:40721297

    Open questions at the time
    • How PHF6 reconciles activating and repressive roles at different loci unresolved
    • Whether PHIP and SWI/SNF dependencies are shared or distinct unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PHF6 switches between transcriptional repression and activation, and how its enzymatic (E3 ligase), histone-reading, DNA-binding, and complex-recruitment activities are coordinated at a given locus across nucleoplasm and nucleolus.
  • No unified model integrating ePHD1 ligase activity with NuRD/SWI-SNF recruitment
  • Determinants of locus-specific activating vs repressive output unknown
  • Endogenous in vivo substrate spectrum of the H2BK120 ligase activity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0060090 molecular adaptor activity 6 GO:0003677 DNA binding 4 GO:0042393 histone binding 2 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005730 nucleolus 5 GO:0000228 nuclear chromosome 4 GO:0005654 nucleoplasm 3 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 5 R-HSA-4839726 Chromatin organization 5 R-HSA-1266738 Developmental Biology 4 R-HSA-73894 DNA Repair 2
Partners
BPTFCHD4HDAC1PHIPRBBP4RUNX1SUV39H1UBF
Complex memberships
NuRDPAF1 complexPHF6–PHIP chromatin complexSWI/SNF

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PHF6 localizes to the nucleus with prominent nucleolar accumulation, as demonstrated by transient transfection of GFP-tagged PHF6 in cells, suggesting a role in transcription. Transient transfection with GFP-tagged PHF6; fluorescence imaging Nature genetics Medium 12415272
2012 PHF6 physically associates with multiple components of the NuRD (nucleosome remodeling and deacetylation) complex, including CHD4, HDAC1, and RBBP4, and this interaction is restricted to the nucleoplasm (not the nucleolus). Flag-tag co-immunoprecipitation from HEK 293T cells followed by mass spectrometry Journal of proteome research High 22720776
2012 PHF6 is a nucleolus- and rDNA promoter-associated protein that directly interacts with UBF (upstream binding factor) through its PHD1 domain and suppresses ribosomal RNA (rRNA) transcription by affecting UBF protein levels; PHF6 knockdown causes accumulation of DNA damage at rDNA loci, increased phospho-H2AX, and G2/M arrest. Co-immunoprecipitation; domain-mapping pulldown; rRNA transcription assays; PHF6 knockdown with ChIP, γH2AX measurement, and cell cycle analysis The Journal of biological chemistry High 23229552
2013 PHF6 physically associates with the PAF1 transcription elongation complex and is required for neuronal migration in the mouse cerebral cortex in vivo; knockdown of PHF6 or PAF1 (phenocopy) causes white matter heterotopias with neuronal hyperexcitability. PHF6 drives expression of NGC/CSPG5 as a critical downstream target for migration. In vivo RNAi knockdown in mouse cerebral cortex; co-immunoprecipitation; in utero electroporation; electrophysiology Neuron High 23791194
2014 Crystal structure of PHF6 ePHD2 domain was solved at high resolution, revealing an integrated module comprising an N-terminal pre-PHD (C2HC zinc finger), a long linker, and an atypical PHD finger. ePHD2 binds dsDNA but not histones. PHF6 directly interacts with NuRD component RBBP4 via the ePHD2/NoLS region, and this interaction mediates transcriptional repression activity. X-ray crystallography; in vitro binding assays; transcriptional repression reporter assay; Co-IP The Journal of biological chemistry High 24554700
2015 Crystal structure of RBBP4 bound to PHF6 peptide (residues 162–170) was solved; PHF6 binds to the top surface of the RBBP4 β-propeller via a pair of positively charged residues inserting into a negatively charged pocket. Corresponding PHF6 mutants impair this interaction in vitro and in vivo, and knockdown of RBBP4 diminishes PHF6-mediated transcriptional repression. X-ray crystallography; in vitro binding assays; site-directed mutagenesis; GAL4 reporter assay; RBBP4 knockdown The Journal of biological chemistry High 25601084
2015 miR-128 targets PHF6 mRNA post-transcriptionally in neurons; restoring PHF6 expression counteracts the deleterious effects of miR-128 overexpression on neuronal migration, outgrowth, and intrinsic excitability, placing miR-128 upstream of PHF6 in a cortical lamination pathway. In vivo mouse cortex electroporation; miR-128 sponge inhibition; PHF6 rescue experiments; electrophysiology eLife High 25556700
2016 PHF6 is localized to the sub-nucleolar fibrillar center (FC) and dense fibrillar component (DFC) in an RNA-dependent manner; PHF6 is enriched across the entire rDNA-coding sequence (not the IGS) by ChIP-qPCR; overexpression of PHF6 decreases rRNA transcription and increases repressive IGS non-coding RNA transcripts. Immunocytochemistry after RNase A, DNase I, actinomycin D, or DRB treatment; ChIP-qPCR; rRNA quantification in gain-of-function model European journal of human genetics High 27165002
2017 Loss of Phf6 in B-cell leukemia causes systematic changes in chromatin accessibility at transcriptional start sites of B-cell- and T-cell-specific factors, leading to down-regulation of B-cell identity genes and up-regulation of T-cell signaling genes, resulting in phenotypic plasticity and mixed-lineage lymphoma in vivo. ATAC-seq; RNA-seq; in vivo transplantation; Phf6 knockout Genes & development High 28607179
2018 Genetic inactivation of Phf6 in hematopoietic cells enhances HSC long-term self-renewal and quiescence, lowers the threshold for NOTCH1-induced T-ALL, and drives leukemia stem cell transcriptional programs and enhanced T-ALL leukemia-initiating cell activity. Conditional Phf6 knockout mouse; competitive transplantation; NOTCH1-induced T-ALL model; transcriptome analysis Cancer discovery High 30567843
2019 PHF6 is rapidly recruited to sites of DNA lesions in a PARP-dependent manner and is required for efficient DNA repair through classical non-homologous end joining (NHEJ); loss of PHF6 dramatically compromises G2 checkpoint recovery. RNAi screen for chromatin regulators affecting checkpoint recovery; live-cell imaging of PHF6 recruitment to DNA damage sites; NHEJ repair assays; PARP inhibition EMBO reports High 31782600
2019 Phf6 deletion in hematopoietic cells reduces HSC numbers, increases progenitor cycling, and enhances serial transplantation reconstitution. Mechanistically, Phf6 directly and indirectly activates downstream effectors of TNFα signaling, and its deletion confers resistance to TNFα-mediated growth inhibition on HSCs. Conditional Phf6 knockout mouse; serial transplantation; RNA-seq; TNFα treatment assays Blood High 30917958
2020 PHF6 acts as an E3 ubiquitin ligase for ubiquitination of H2BK120 (H2BK120ub) via its extended PHD1 domain; the extended PHD2 domain of PHF6 recognizes H2BK12 acetylation (H2BK12Ac), and this recognition is required for PHF6 to exert its E3 ubiquitin ligase activity for H2BK120ub to activate trophectodermal genes. RNA-seq; ChIP assays; in vitro ubiquitination assay; domain mutagenesis; Co-IP Nucleic acids research High 32735658
2020 PHF6 binds to promoters of a subset of immediate-early genes (IEGs) in AgRP neurons and acts as a transcriptional repressor in a hunger state-dependent manner; Phf6 deletion in AgRP neurons causes a hunger-state-shifting transcriptional profile and decreases hunger-driven feeding motivation. Cell-type-specific ChIP; RNA-seq in AgRP neurons; conditional Phf6 knockout; behavioral assays Cell reports High 32187544
2021 PHF6 can bind to H3K9me3 and H3K27me1 on nucleolar chromatin and recruits histone methyltransferase SUV39H1 to rDNA loci; PHF6 loss decreases SUV39H1 recruitment and H3K9me3 levels at rDNA, promoting rDNA transcription. BFLS/leukemia PHF6 mutants impair SUV39H1 recruitment. Co-immunoprecipitation; ChIP-qPCR; siRNA knockdown of PHF6 and SUV39H1; rRNA transcription assays; xenograft models Acta pharmaceutica Sinica. B High 35847518
2021 PHF6 depletion inhibits NF-κB signaling in myeloid leukemia by disrupting the PHF6-p50 complex and partially inhibiting nuclear translocation of p50, thereby suppressing BCL2 expression. Co-immunoprecipitation (PHF6-p50 complex); nuclear fractionation; BCL2 expression assay; PHF6 knockdown/overexpression; NF-κB inhibitor treatment Leukemia Medium 37393343
2021 PHF6 deficiency promotes JAK3M511I-induced T-ALL progression by inhibiting the Bai1-Mdm2-p53 signaling pathway, independent of JAK3/STAT5 signaling; Phf6 KO combined with JAK3M511I accelerates leukemia in mice. Mouse leukemia model (Phf6 KO + JAK3M511I); signaling pathway analysis; pharmacologic inhibitor combination in vivo Leukemia Medium 34465864
2021 Gene body methylation maintained by DNMT1 safeguards rDNA transcription by preventing PHF6 binding to hypomethylated rDNA gene bodies; when gene body methylation is lost, PHF6 occupies the rDNA and recruits histone methyltransferase SUV4-20H2 to establish repressive H4K20me3, inhibiting rDNA transcription. MeDIP-seq; bisulfite genomic sequencing; immunofluorescence; ChIP-qPCR; DNMT1 knockdown/KO The Journal of biological chemistry High 34520760
2022 PHF6 engages multiple nucleosome remodeling complexes (NuRD, SWI/SNF, ISWI), the replication machinery, and DNA repair proteins; after DNA damage, PHF6 localizes to DNA injury sites and its loss impairs resolution of DNA breaks. Native ChIP-seq shows PHF6 associates with heterochromatin at satellite DNA regions enriched in H3K9me3, and PHF6 is required for genomic stability at fragile sites. Mass spectrometry-based proteomics (interactome); native ChIP-seq; single-molecule locus-specific DNA fiber analysis; DNA damage assays Blood High 35338774
2022 Phf6 deletion reverses age-associated HSC decline: Phf6-knockout HSCs show decreased myeloid bias, increased reconstitution capacity with preserved lymphoid potential, and epigenetic rewiring with decreased genotoxic stress signatures. Conditional Phf6 knockout in aged mice; immunophenotyping; single-cell transcriptomics; transplantation assays; epigenomics Nature aging High 37118089
2023 PHF6 physically interacts with RUNX1, and both proteins co-localize at active enhancer regions that define the context of lineage differentiation in myeloid neoplasms. Proteomics analysis; ChIP co-localization; genomic analysis of co-mutations Nature communications Medium 38418452
2023 PHF6 recruits BPTF (a NURF complex subunit) to mediate epigenetic remodeling at HIF target gene promoters to augment HIF-1α and HIF-2α transcriptional activity in breast cancer; PHF6 physically interacts with HIF-1α and HIF-2α. Co-immunoprecipitation; ChIP-qPCR; CRISPR HIF double-KO; in vivo xenograft models Journal of translational medicine Medium 36967443
2024 PHF6 co-localizes with SWI/SNF complexes at promoters and is essential for maintenance of an active chromatin state; in the absence of SMARCB1, PHF6 loss disrupts recruitment and stability of residual SWI/SNF complex members, resulting in loss of active chromatin at promoters and stalling of RNA Polymerase II progression. Genome-scale CRISPR-Cas9 depletion screen; ChIP-seq; ATAC-seq; RNA Pol II ChIP; in vivo tumor models Nature communications High 39181868
2024 PHF6 genome-wide binding in the developing cortex is associated with genes involved in CNS development; PHF6 directly promotes transcription of Ephrin receptors (EphRs) to control embryonic neural stem cell (eNSC) behavior; knockdown of EphR-A phenocopies PHF6 loss-of-function defects in eNSC self-renewal and neural progenitor numbers. Genome-wide ChIP-seq in developing cortex; conditional Phf6 KO and BFLS patient-mutation knock-in mice; eNSC functional assays; EphR knockdown and rescue EMBO reports High 38429579
2024 PHF6 represses a limited stemness gene network in AML; PHF6 requires PHIP to occupy chromatin and exert its transcriptional program; PHIP loss phenocopies PHF6 loss. PHF6 and PHIP form a common functional chromatin complex that suppresses AML stemness. PHF6 and PHIP knockout cell lines; ChIP; RNA-seq; genetic co-dependency studies; Flt3-ITD mouse leukemia model Genes & development High 40721297
2019 PHF6 represses p21 expression through direct binding to the p21 promoter region and recruiting RBBP4 (RBPP4); PHF6 loss reduces prednisolone sensitivity in T-ALL, and this can be partially reversed by p21 inhibition. ChIP (PHF6 binding at p21 promoter); CRISPR-Cas9 PHF6 point mutation correction; Western blot; MTT assay; p21 inhibitor rescue Biomedicine & pharmacotherapy Medium 30551478
2021 PHF6 R342X mutation causes reduction in PHF6 protein levels via nonsense-mediated decay (in humans) and nonsense-associated alternative splicing (in mice), resulting in brain developmental abnormalities including hypoplastic anterior pituitary, hippocampal and hypothalamic volume changes, and behavioral deficits in associative learning and spatial memory. CRISPR knock-in mouse (R342X); MRI; behavioral testing; Western blot; RT-PCR for NMD/alternative splicing Human molecular genetics Medium 33772537
2020 PHF6 knockout in human neuron-like (SK-N-BE(2)) cells impairs neuron proliferation, neurite outgrowth, and migration, with transcriptome analysis revealing broad deregulation of genes involved in chromatin/transcriptional regulation and axon/neuron development. CRISPR/Cas9 PHF6 KO; neuronal differentiation; transcriptome analysis; proliferation, neurite outgrowth, and migration assays Scientific reports Medium 33149206
2024 Loss of PHF6 in Phf6-deficient cortical neurons causes premature spontaneous neuronal activity (precocious neuronal maturation); Phf6-deficient neural precursor cells show reduced self-renewal and increased neuronal differentiation; RNA-seq shows predominantly upregulated genes in Phf6-deficient cortex including Reln, Nr4a2, Slc12a5, Phip, and ZIC family transcription factors. Germline and nervous system-specific Phf6 KO mice; spontaneous seizure recording; histology/MRI; neural precursor cell self-renewal assays; RNA-seq; electrophysiology PLoS genetics High 39405291
2015 NMR resonance assignments of the PHF6-ePHD1 domain were determined; ePHD1 is involved in nucleolus localization and directly interacts with UBF to suppress rRNA transcription. Heteronuclear multidimensional NMR spectroscopy; TALOS+ secondary structure prediction Biomolecular NMR assignments Medium 26286319

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 PHF6 mutations in T-cell acute lymphoblastic leukemia. Nature genetics 248 20228800
2002 Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome. Nature genetics 178 12415272
2015 Tau assembly: the dominant role of PHF6 (VQIVYK) in microtubule binding region repeat R3. The journal of physical chemistry. B 152 25775228
2010 PHF6 mutations in adult acute myeloid leukemia. Leukemia 141 21030981
2012 PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex. Journal of proteome research 88 22720776
2015 miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6. eLife 87 25556700
2013 The X-linked intellectual disability protein PHF6 associates with the PAF1 complex and regulates neuronal migration in the mammalian brain. Neuron 87 23791194
2012 PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis. The Journal of biological chemistry 81 23229552
1999 Fibroblast growth factor homologous factor 2 (FHF2): gene structure, expression and mapping to the Börjeson-Forssman-Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS-like patient. Human genetics 76 10071193
2011 Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica 70 21880637
2014 Structural and functional insights into the human Börjeson-Forssman-Lehmann syndrome-associated protein PHF6. The Journal of biological chemistry 63 24554700
2018 Phf6 Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL. Cancer discovery 62 30567843
2004 The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations. Clinical genetics 61 14756673
2015 A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth. Genes & development 58 25737277
2018 PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation. Blood advances 56 30530780
2014 MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia. Haematologica 53 24895337
2017 PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes. Genes & development 49 28607179
2018 Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids. Scientific reports 47 29311706
2005 Mutation screening in Borjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient. Journal of medical genetics 47 15994862
2013 A new face of Borjeson-Forssman-Lehmann syndrome? De novo mutations in PHF6 in seven females with a distinct phenotype. Journal of medical genetics 46 24092917
2019 PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia. Blood 45 30755422
2006 The Börjeson-Forssman-Lehman syndrome (BFLS, MIM #301900). European journal of human genetics : EJHG 45 16912705
2021 Aggregated Tau-PHF6 (VQIVYK) Potentiates NLRP3 Inflammasome Expression and Autophagy in Human Microglial Cells. Cells 44 34209408
2019 Membrane-mediated fibrillation and toxicity of the tau hexapeptide PHF6. The Journal of biological chemistry 44 31439664
2016 Primary Fibril Nucleation of Aggregation Prone Tau Fragments PHF6 and PHF6. The journal of physical chemistry. B 44 27776213
2010 T-cell acute lymphoblastic leukemia in association with Börjeson-Forssman-Lehmann syndrome due to a mutation in PHF6. Pediatric blood & cancer 43 20806366
2015 Structural basis of plant homeodomain finger 6 (PHF6) recognition by the retinoblastoma binding protein 4 (RBBP4) component of the nucleosome remodeling and deacetylase (NuRD) complex. The Journal of biological chemistry 39 25601084
2015 PHF6 Degrees of Separation: The Multifaceted Roles of a Chromatin Adaptor Protein. Genes 39 26103525
2016 Naphthoquinone-Tryptophan Hybrid Inhibits Aggregation of the Tau-Derived Peptide PHF6 and Reduces Neurotoxicity. Journal of Alzheimer's disease : JAD 37 26836184
2021 Effects of All-Atom Molecular Mechanics Force Fields on Amyloid Peptide Assembly: The Case of PHF6 Peptide of Tau Protein. Journal of chemical theory and computation 36 34491058
2019 The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells. Blood 36 30917958
2019 Disclosing the Mechanism of Spontaneous Aggregation and Template-Induced Misfolding of the Key Hexapeptide (PHF6) of Tau Protein Based on Molecular Dynamics Simulation. ACS chemical neuroscience 36 31661961
2021 PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression. Leukemia 35 34465864
2021 PHF6 Mutations in Hematologic Malignancies. Frontiers in oncology 34 34381727
2011 PHF6 Deletions May Cause Borjeson-Forssman-Lehmann Syndrome in Females. Molecular syndromology 32 22190899
2019 Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials. Blood advances 31 31395598
2018 Effective suppression of the modified PHF6 peptide/1N4R Tau amyloid aggregation by intact curcumin, not its degradation products: Another evidence for the pigment as preventive/therapeutic "functional food". International journal of biological macromolecules 29 30172816
2019 PHF6 promotes non-homologous end joining and G2 checkpoint recovery. EMBO reports 28 31782600
2016 Pathogenesis of Börjeson-Forssman-Lehmann syndrome: Insights from PHF6 function. Neurobiology of disease 28 27633282
2020 The chromatin-binding protein PHF6 functions as an E3 ubiquitin ligase of H2BK120 via H2BK12Ac recognition for activation of trophectodermal genes. Nucleic acids research 27 32735658
2020 Selection of a d-Enantiomeric Peptide Specifically Binding to PHF6 for Inhibiting Tau Aggregation in Transgenic Mice. ACS chemical neuroscience 26 33284003
2016 The sub-nucleolar localization of PHF6 defines its role in rDNA transcription and early processing events. European journal of human genetics : EJHG 26 27165002
2011 Somatic mutation of PHF6 gene in T-cell acute lymphoblatic leukemia, acute myelogenous leukemia and hepatocellular carcinoma. Acta oncologica (Stockholm, Sweden) 25 21736506
2006 Conformational sampling with implicit solvent models: application to the PHF6 peptide in tau protein. Biophysical journal 24 17040986
2004 Clinical and behavioral features of patients with Borjeson-Forssman-Lehmann syndrome with mutations in PHF6. The Journal of pediatrics 24 15580208
2022 Epigenetic reversal of hematopoietic stem cell aging in Phf6-knockout mice. Nature aging 22 37118089
2021 Gene body methylation safeguards ribosomal DNA transcription by preventing PHF6-mediated enrichment of repressive histone mark H4K20me3. The Journal of biological chemistry 21 34520760
2022 Functional mapping of PHF6 complexes in chromatin remodeling, replication dynamics, and DNA repair. Blood 19 35338774
2018 The depletion of PHF6 decreases the drug sensitivity of T-cell acute lymphoblastic leukemia to prednisolone. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 30551478
2009 Börjeson-Forssman-Lehmann Syndrome due to a novel plant homeodomain zinc finger mutation in the PHF6 gene. Journal of child neurology 18 19264739
2023 PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway. Leukemia 17 37393343
2013 Distinct phenotype of PHF6 deletions in females. European journal of medical genetics 17 24380767
2005 Radiation leukemia virus common integration at the Kis2 locus: simultaneous overexpression of a novel noncoding RNA and of the proximal Phf6 gene. Journal of virology 17 16103195
2023 Mapping the configurational landscape and aggregation phase behavior of the tau protein fragment PHF6. Proceedings of the National Academy of Sciences of the United States of America 16 37983502
2019 MicroRNA-214 suppresses cell proliferation and migration and cell metabolism by targeting PDK2 and PHF6 in hepatocellular carcinoma. Cell biology international 16 31329335
2016 Co-existence of PHF6 and NOTCH1 mutations in adult T-cell acute lymphoblastic leukemia. Oncology letters 16 27347093
2024 Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting. Nature communications 15 38418452
2021 LINC00958/miR-3174/PHF6 axis is responsible for triggering proliferation, migration and invasion of endometrial cancer. European review for medical and pharmacological sciences 15 34859848
2021 PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia. Acta pharmaceutica Sinica. B 13 35847518
2019 A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome. Journal of clinical research in pediatric endocrinology 13 30630810
2024 PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression. Nature communications 12 39181868
2023 PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. Journal of translational medicine 12 36967443
2024 Exploring the Aggregation Propensity of PHF6 Peptide Segments of the Tau Protein Using Ion Mobility Mass Spectrometry Techniques. Analytical chemistry 11 38517679
2023 Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6. The journal of physical chemistry. B 11 36594671
2021 Transgenic mice with an R342X mutation in Phf6 display clinical features of Börjeson-Forssman-Lehmann Syndrome. Human molecular genetics 11 33772537
2023 Identification of Aggregation Mechanism of Acetylated PHF6* and PHF6 Tau Peptides Based on Molecular Dynamics Simulations and Markov State Modeling. ACS chemical neuroscience 10 37830541
2022 On the Tracks of the Aggregation Mechanism of the PHF6 Peptide from Tau Protein: Molecular Dynamics, Energy, and Interaction Network Investigations. ACS chemical neuroscience 10 36153969
2021 LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway. Cell death & disease 10 34108447
2019 Downregulation of PHF6 Inhibits Cell Proliferation and Migration in Hepatocellular Carcinoma. Cancer biotherapy & radiopharmaceuticals 10 30888215
2014 Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis. Pathology, research and practice 10 24674452
2024 PHF6 suppresses self-renewal of leukemic stem cells in AML. Leukemia 9 39004675
2021 Notoginsenoside R1 induces DNA damage via PHF6 protein to inhibit cervical carcinoma cell proliferation. Molecular medicine reports 9 33537816
2015 The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 26561469
2023 PHF6 promotes the progression of endometrial carcinoma by increasing cancer cells growth and decreasing T-cell infiltration. Journal of cellular and molecular medicine 8 36756714
2022 Oncogenesis induced by combined Phf6 and Idh2 mutations through increased oncometabolites and impaired DNA repair. Oncogene 8 35091680
2022 Deciphering the Role of ATP on PHF6 Aggregation. The journal of physical chemistry. B 8 35759245
2022 The Role of PHF6 in Hematopoiesis and Hematologic Malignancies. Stem cell reviews and reports 8 36008597
2021 Comparison of the force fields on monomeric and fibrillar PHF6 of tau protein. Biophysical chemistry 8 34116358
2020 Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. Cell reports 8 32187544
2020 Loss of PHF6 leads to aberrant development of human neuron-like cells. Scientific reports 8 33149206
2024 PHF6-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax. Clinical cancer research : an official journal of the American Association for Cancer Research 7 37889114
2024 Molecular Dynamics Simulation Study of the Self-Assembly of Tau-Derived PHF6 and Its Inhibition by Oleuropein Aglycone from Extra Virgin Olive Oil. The journal of physical chemistry. B 7 38814052
2020 A Novel Missense Variant in PHF6 Gene Causing Börjeson-Forssman-Lehman Syndrome. Journal of molecular neuroscience : MN 7 32399860
2015 The PHF6 Mutation c.1A>G; pM1V Causes Börjeson-Forsman-Lehmann Syndrome in a Family with Four Affected Young Boys. Molecular syndromology 7 26648834
2022 Circ_0039569 contributes to the paclitaxel resistance of endometrial cancer via targeting miR-1271-5p/PHF6 pathway. Anti-cancer drugs 6 36136988
2022 PHF6 mutation is associated with poor outcome in acute myeloid leukaemia. Cancer medicine 6 36176187
2022 MiR-1306-5p promotes cell proliferation and inhibits cell apoptosis in acute myeloid leukemia by downregulating PHF6 expression. Leukemia research 5 35780573
2021 Molecular dynamics simulations reveal the disruption mechanism of a 2,4-thiazolidinedione derivative C30 against tau hexapeptide (PHF6) oligomer. Proteins 5 34331342
2024 Unraveling the Structure and Dynamics of Ac-PHF6-NH2 Tau Segment Oligomers. ACS chemical neuroscience 4 39215387
2023 Deciphering the Inhibitory Mechanism of Naphthoquinone-Dopamine on the Aggregation of Tau Core Fragments PHF6* and PHF6. ACS chemical neuroscience 4 37585669
2025 Substitution of tyrosine with electron-deficient aromatic amino acids improves Ac-PHF6 self-assembly and hydrogelation. RSC advances 3 40599564
2024 PHF6 loss reduces leukemia stem cell activity in an acute myeloid leukemia mouse model. Cancer cell international 3 38336746
2024 PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS. EMBO reports 3 38429579
2023 R274X-mutated Phf6 increased the self-renewal and skewed T cell differentiation of hematopoietic stem cells. iScience 3 37288345
2022 Effect of Trehalose and Ceftriaxone on the Stability of Aggregating-Prone Tau Peptide Containing PHF6* Sequence: An SRCD Study. International journal of molecular sciences 3 35328353
2025 Leukemia mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness. Genes & development 2 40721297
2024 A selection and optimization strategy for single-domain antibodies targeting the PHF6 linear peptide within the tau intrinsically disordered protein. The Journal of biological chemistry 2 38484799
2024 Loss of PHF6 causes spontaneous seizures, enlarged brain ventricles and altered transcription in the cortex of a mouse model of the Börjeson-Forssman-Lehmann intellectual disability syndrome. PLoS genetics 1 39405291
2022 Concurrent Mutations in SF3B1 and PHF6 in Myeloid Neoplasms. Biology 1 36671709
2015 1H, 13C and 15N resonance assignments and secondary structure of the human PHF6-ePHD1 domain. Biomolecular NMR assignments 1 26286319

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