Affinage

PA2G4

Proliferation-associated protein 2G4 · UniProt Q9UQ80

Length
394 aa
Mass
43.8 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PA2G4/EBP1 is a multifunctional RNA- and protein-binding protein built on a catalytically inactive methionine aminopeptidase (pita-bread) fold coupled to a C-terminal extension that supplies its protein-, RNA-, and lipid-binding surfaces (PMID:17690690, PMID:17765895). It functions across translation, ribosome biogenesis, and transcriptional control, partitioning into two isoforms (p48, p42) with distinct localization and opposing effects on proliferation (PMID:16832058). At the translational level, EBP1 occupies the 60S peptide exit tunnel as a high-occupancy ribosome-associated factor that engages eL19, uL23, and 28S rRNA, modulating ribosome occupancy during start-codon initiation and early elongation and is displaced by emerging signal sequences, thereby biasing synthesis of membrane-targeted proteins (PMID:33357414, PMID:33479117). In the nucleolus it joins pre-ribosomal RNP complexes through a dsRNA-binding region and partners with nucleophosmin/B23 and TIF-IA/TIF-90 to drive rRNA synthesis (PMID:15064750, PMID:16631606, PMID:17951246, PMID:30793766). As a transcriptional co-repressor, EBP1 binds Rb, the androgen receptor, and HNF4α, and represses E2F1- and AR-regulated promoters by recruiting Sin3A and HDAC2 to target chromatin (PMID:11268000, PMID:12165860, PMID:12682367, PMID:15073182, PMID:16254079, PMID:31362984); it also represses DNMT1 and HDAC1 transcription, controlling the epigenetic state during neural development (PMID:31748268, PMID:32283721). EBP1 is heavily regulated by post-translational modification—PKC-mediated phosphorylation at S360 governing Akt binding and anti-apoptotic activity, PAK1-mediated T261 phosphorylation controlling repression and tamoxifen sensitivity, TLS/FUS-mediated SUMOylation of p42 driving its nuclear, anti-proliferative function, and PRKN-mediated K376 ubiquitination directing mitophagy after ischemic injury (PMID:16642037, PMID:18283314, PMID:19946338, PMID:37712850). Through isoform-specific routing it acts as both an oncogenic factor—stabilizing MYCN and sequestering FBXW7α (p48)—and a tumor suppressor—degrading the p85 PI3K subunit via HSP70/CHIP (p42) (PMID:24651434, PMID:28209614, PMID:31501192). Mouse genetics ties EBP1 to neurodevelopment, where its loss disrupts cerebellar architecture and produces schizophrenia-like behaviors rescuable by wild-type but not a patient-derived EBP1-E183Ter mutant (PMID:35165395).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established EBP1's first physiological context by showing it is a receptor-associated protein released to the nucleus upon growth-factor signaling, linking a membrane receptor to a downstream transcriptional regulator.

    Evidence Yeast two-hybrid, in vitro binding, and fractionation/immunofluorescence of EBP1–ErbB3 and heregulin-induced translocation

    PMID:10682683

    Open questions at the time
    • Did not define EBP1's nuclear function once translocated
    • Mechanism coupling dissociation to nuclear import unresolved
  2. 2003 High

    Defined EBP1 as a transcriptional co-repressor by mapping its C-terminal recruitment of HDAC activity, explaining how it silences E2F1- and AR-regulated genes.

    Evidence Co-IP with Rb/AR/E2F1, GST pulldown of HDAC2, ChIP, EMSA, and promoter reporter assays across multiple studies

    PMID:11268000 PMID:12165860 PMID:12682367 PMID:15073182

    Open questions at the time
    • Whether HDAC2 contact is direct or bridged was unclear from early work
    • Specificity for E2F1 vs AR target subsets not fully resolved
  3. 2005 High

    Identified Sin3A as the direct corepressor scaffold linking EBP1 to HDAC, resolving the architecture of the repressive complex and demonstrating in vivo tumor suppression in prostate cancer.

    Evidence Recombinant direct binding, reciprocal Co-IP, ChIP of co-occupancy, microarray, and LNCaP xenografts in SCID mice

    PMID:15994225 PMID:16254079

    Open questions at the time
    • Direct vs indirect HDAC2 engagement still implies Sin3A bridging
    • AR downregulation mechanism beyond promoter recruitment incomplete
  4. 2006 High

    Revealed EBP1's roles in RNA metabolism and translation, showing it binds dsRNA and bcl-2 ARE transcripts, associates with ribosomes, and modulates eIF2alpha phosphorylation.

    Evidence Domain mutagenesis, RNA affinity/EMSA, RIP, mRNA decay assays, ribosome fractionation, and in vitro PKR kinase assay

    PMID:16396631 PMID:16631606

    Open questions at the time
    • Structural basis of ribosome engagement not yet defined
    • Direct vs indirect effect on eIF2alpha kinase activity unresolved
  5. 2006 High

    Established the p48/p42 isoform dichotomy and the S360-phosphorylation/Akt axis as the molecular switch between EBP1's anti-apoptotic and differentiation functions.

    Evidence Subcellular fractionation, cell-free apoptotic assays, site-directed mutagenesis (S360A/D), and isoform-specific binding assays

    PMID:16642037 PMID:16832058 PMID:17316401

    Open questions at the time
    • How isoform abundance is regulated in tissues not addressed
    • Kinase-independent Akt mechanism mechanistically incomplete
  6. 2007 High

    Provided the structural foundation by solving murine and human EBP1 crystal structures, defining a catalytically dead MetAP-like fold whose C-terminal extension carries the RNA/protein-binding determinants.

    Evidence X-ray crystallography of murine and human EBP1 with RNA-binding and IRES translation assays

    PMID:17690690 PMID:17765895

    Open questions at the time
    • Structure did not capture ribosome- or partner-bound conformations
    • No catalytic activity, leaving the fold's enzymatic legacy unexplained
  7. 2007 High

    Connected EBP1 to ribosome biogenesis and antiviral functions, showing B23/nucleophosmin partnership for rRNA synthesis and inhibition of influenza and FMDV polymerase/IRES activities.

    Evidence Co-IP/mutagenesis with B23, siRNA ribosome biogenesis assays, in vitro polymerase and IRES translation assays

    PMID:17295834 PMID:17690690 PMID:17951246

    Open questions at the time
    • Whether antiviral activity is physiologically deployed in infection unclear
    • Coupling of nucleolar RNP role to cytoplasmic translation not integrated
  8. 2009 High

    Defined the post-translational regulatory network controlling EBP1 stability, localization, and repressive output through PAK1 phosphorylation, hBRE1 ubiquitination, and TLS/FUS-mediated SUMOylation.

    Evidence In vitro kinase, ubiquitination, and SUMOylation assays with phospho/SUMO-site mutagenesis and reporter assays

    PMID:11325528 PMID:17786317 PMID:18283314 PMID:19037095 PMID:19946338

    Open questions at the time
    • Interplay/hierarchy among modifications not established
    • In vivo relevance of individual modifications largely untested
  9. 2014 High

    Mechanistically separated the oncogenic and tumor-suppressive activities of the two isoforms through CDK2-mediated p48 S34 phosphorylation versus p42-driven p85-PI3K degradation.

    Evidence Co-IP, in vitro kinase assays, domain mapping, PI3K lipid kinase and ubiquitination assays with proliferation/xenograft readouts

    PMID:21098709 PMID:24651434 PMID:25154617

    Open questions at the time
    • What dictates p48 vs p42 production in a given tumor unresolved
    • Whether p85 degradation and p53/HDM2 effects co-occur in the same cells unknown
  10. 2017 Medium

    Extended isoform-specific function to ubiquitin-ligase regulation, showing p48 sequesters FBXW7α while p42 acts as an FBXW7 adapter, and that p48 stabilizes oncogenic MYCN in a feedback loop.

    Evidence Domain-mapped Co-IP, ubiquitination assays, surface plasmon resonance, ChIP, and in vivo tumor models

    PMID:28209614 PMID:31501192

    Open questions at the time
    • FBXW7 adapter/sequestration model rests on a single lab
    • Generality of MYCN stabilization beyond neuroblastoma untested
  11. 2020 High

    Resolved EBP1's principal molecular role at near-atomic resolution as a 60S peptide-exit-tunnel factor that shapes ribosome occupancy and the synthesis of membrane-targeted proteins during neurodevelopment.

    Evidence Cryo-EM of EBP1–80S ribosome, ribosome profiling, pSILAC/BONCAT proteomics, and loss-of-function

    PMID:33357414 PMID:33479117

    Open questions at the time
    • How exit-tunnel occupancy integrates with its nucleolar/transcriptional roles unclear
    • Selectivity for specific nascent chains incompletely defined
  12. 2022 High

    Defined EBP1's essential neurodevelopmental functions and disease relevance, linking its loss to FBXW7/PTF1A and DNMT1/HDAC1 dysregulation, cerebellar defects, and schizophrenia-like behavior rescuable by wild-type but not a patient mutant.

    Evidence Conditional and heterozygous KO mice, ChIP, methylation analysis, and rescue with WT vs EBP1-E183Ter mutant

    PMID:31748268 PMID:32283721 PMID:35165395 PMID:37712850

    Open questions at the time
    • Causal human genetic link to schizophrenia rests on mouse rescue with a patient-derived mutant
    • Cell-type-specific contributions of translational vs transcriptional roles not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EBP1's distinct molecular roles—ribosome exit-tunnel occupancy, nucleolar rRNA synthesis, transcriptional corepression, and ubiquitin-ligase modulation—are coordinated within a single cell, and how isoform choice and PTM combinations are decoded, remains unresolved.
  • No unified model integrating translational and transcriptional functions
  • Regulation of p48/p42 ratio and PTM hierarchy in physiological settings unknown
  • Direct human disease-causing mutations not established beyond mouse-validated candidates

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0045182 translation regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 3 GO:0005829 cytosol 3 GO:0005840 ribosome 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
ARERBB3HDAC2HNF4AMYCNNPM1RB1SIN3A
Complex memberships
Sin3A-HDAC2 corepressor complexZFP809-TRIM28 retroviral silencing complexpre-ribosomal RNP / 60S ribosome (peptide exit tunnel)

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 EBP1 (PA2G4) interacts with the juxtamembrane domain of ErbB-3; the first 15 amino acids of ErbB-3's juxtamembrane domain are essential for EBP1 binding in vitro. Treatment of cells with the ErbB-3 ligand heregulin causes dissociation of EBP1 from ErbB-3 and translocation of EBP1 from the cytoplasm to the nucleus. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, cellular fractionation/immunofluorescence British journal of cancer High 10682683
2001 EBP1 binds the retinoblastoma protein (Rb) both in vivo and in vitro; the 72 C-terminal amino acids of EBP1 are sufficient for Rb binding. Dephosphorylation of EBP1 enhances the interaction with Rb. EBP1 overexpression inhibits the E2F1-regulated cyclin E promoter, and EBP1 binds E2F1 indirectly via Rb. Co-immunoprecipitation, GST pulldown, promoter reporter assay Journal of cellular physiology High 11268000
2002 EBP1 binds androgen receptor (AR) in vitro and in vivo via its C-terminal 79 amino acids; this binding is increased by androgen treatment. The N-terminal domain of AR is responsible for binding EBP1. EBP1 overexpression inhibits ligand-mediated transcriptional activation of AR-regulated promoters, and an LXXLL motif mutation abolishes this repression. GST pulldown, co-immunoprecipitation, transient transfection reporter assay, mutagenesis Oncogene High 12165860
2003 EBP1 represses E2F1-mediated transcription through its C-terminal domain, which recruits histone deacetylase (HDAC) activity. EBP1 binds HDAC2 (but not HDAC1) in vitro. HDAC inhibitors significantly reduce EBP1-mediated repression. An EBP1 mutant lacking the HDAC binding domain fails to inhibit transcription. Reporter assay, GST pulldown, HDAC activity assay, mutagenesis Nucleic acids research High 12682367
2004 EBP1 is localized to the cytoplasm and nucleolus; its nucleolar localization requires sequences at both the amino- and carboxy-terminus. EBP1 is part of pre-ribosomal ribonucleoprotein complexes and associates with different rRNA species. EBP1 overexpression inhibits proliferation of human fibroblasts, linked to its nucleolar localization. Subcellular fractionation, immunofluorescence, mass spectrometry, deletion mutagenesis, proliferation assay Oncogene High 15064750
2004 EBP1 (contained in nuclear lysates) associates with E2F1 consensus sequences in the E2F1 promoter in complex with E2F1, Rb, and HDAC2. Heregulin regulates the association of EBP1 with E2F promoter sequences and enhances EBP1-mediated transcriptional repression. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), reporter assay The Journal of biological chemistry High 15073182
2005 EBP1 interacts with the corepressor Sin3A both in vitro and in vivo; the C-terminal domain of EBP1 is necessary and sufficient for Sin3A binding, mapping to the PAH4/HDAC-interacting domain of Sin3A. Recombinant Sin3A binds EBP1 directly but recombinant HDAC2 does not bind EBP1 directly. EBP1 and Sin3A co-occupy PSA and E2F1 promoters; Sin3A enhances EBP1-mediated repression of AR- and E2F1-regulated genes. GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assay, recombinant protein binding Nucleic acids research High 16254079
2005 EBP1 overexpression down-regulates AR and six AR-regulated genes in LNCaP prostate cancer cells. EBP1 is recruited to the PSA promoter in response to the androgen antagonist bicalutamide (demonstrated by ChIP). EBP1 overexpression reduces LNCaP tumor incidence and growth in SCID mice. Microarray, chromatin immunoprecipitation (ChIP), reporter assay, xenograft mouse model Proceedings of the National Academy of Sciences of the United States of America High 15994225
2006 EBP1 contains a dsRNA-binding domain (dsRBD) that mediates interaction with dsRNA; deletion of the dsRBD impairs nucleolar localization and RNP complex formation. EBP1 is associated with mature ribosomes in the cytoplasm and inhibits phosphorylation of eIF2alpha at serine 51. EBP1 interacts with and is phosphorylated by PKR kinase. Mutagenesis, RNA binding assay, co-immunoprecipitation, in vitro kinase assay, ribosome fractionation, western blot Biochemical and biophysical research communications High 16631606
2006 Nuclear Akt interacts with EBP1 to prevent DNA fragmentation by caspase-activated DNase (CAD). EBP1 phosphorylation by PKC at serine 360 (S360) is required for EBP1 to bind nuclear Akt; S360A mutant barely binds Akt or inhibits DNA fragmentation, while S360D mutant strongly binds Akt and suppresses apoptosis. Nuclear (not cytoplasmic) Akt enhances EBP1 antiapoptotic action independent of Akt kinase activity. Cell-free apoptotic assay, co-immunoprecipitation, site-directed mutagenesis, knockdown, overexpression The EMBO journal High 16642037
2006 EBP1 exists as two isoforms, p48 and p42. p48 localizes in both cytoplasm and nucleus and suppresses apoptosis; p42 predominantly resides in the cytoplasm and promotes cell differentiation. EGF strongly stimulates p42 (but not p48) to bind ErbB3, dependent on PKC-mediated phosphorylation. p42 and p48 have opposing effects on cell proliferation. Subcellular fractionation, co-immunoprecipitation, overexpression, kinase inhibitor treatment, neurite outgrowth assay Proceedings of the National Academy of Sciences of the United States of America High 16832058
2006 EBP1 binds bcl-2 mRNA AU-rich elements (AREs) in vitro; it is present in bcl-2 mRNA-containing ribonucleoprotein complexes in HL-60 cells and co-precipitates with nucleolin in cytoplasmic extracts. EBP1 decreases the rate of decay of bcl-2 ARE-containing transcripts in cell extracts. RNA affinity chromatography, MALDI-MS identification, EMSA, RNA co-immunoprecipitation, co-IP, RNA decay assay The Biochemical journal High 16396631
2007 Crystal structure of murine EBP1 (p48 isoform) reveals a core domain homologous to methionine aminopeptidases (pita bread fold) coupled to a C-terminal extension containing protein- and RNA-binding motifs. The primary RNA-binding site is a Lys-rich motif in the C-terminus mediating interaction with the FMDV IRES. EBP1 has a specific functional requirement in FMDV IRES-directed translation independent of direct interaction with PTB. X-ray crystallography, RNA binding assay, IRES reporter translation assay, mutagenesis The EMBO journal High 17690690
2007 Crystal structure of human EBP1 at 1.6 Å resolution reveals the conserved pita bread fold of methionine aminopeptidases without catalytic activity, providing a structural platform for multiple protein and RNA interactions. X-ray crystallography FEBS letters High 17765895
2007 EBP1 specifically interacts with the PB1 subunit of influenza virus RNA polymerase in vitro and in vivo; the EBP1 contact site on PB1 maps to its transcription primer binding site. EBP1 inhibits in vitro RNA synthesis by the influenza virus RNA polymerase (3P complex) but does not inhibit capped RNA endonuclease or RNA-cap binding activities. EBP1 overexpression interferes with virus production. Yeast two-hybrid, in vitro binding, in vitro RNA polymerase assay, overexpression viral replication assay Genes to cells High 17295834
2007 EBP1 forms a complex with nucleophosmin/B23. p42 isoform associates with B23 upon EGF stimulation in a manner dependent on Ser360 phosphorylation, while p48 constitutively binds B23 in the nucleolus requiring B23 Lys263 sumoylation. Knockdown of B23 or EBP1 substantially decreases ribosome biogenesis and cell survival. Co-immunoprecipitation, mutagenesis, siRNA knockdown, ribosome biogenesis assay The Journal of biological chemistry High 17951246
2007 PKC-delta phosphorylates EBP1 and protects it from apoptotic degradation by caspase-3. EBP1 is cleaved by active caspase-3 at D53 and D196 sites; cleavage at D196 is prerequisite for subsequent D53 cleavage. PKC phosphorylation at S360 suppresses caspase-3 cleavage. D196A mutant protects cells from apoptosis. Cell-free apoptotic assay, site-directed mutagenesis, PKC-delta knockout cells, in vitro caspase cleavage assay Journal of neurochemistry High 17316401
2007 Serine 363 of EBP1 is phosphorylated in vivo; EBP1 phosphorylated at S363 localizes exclusively to the nucleus. S363A mutation significantly decreases EBP1-mediated transcriptional repression and abolishes its ability to inhibit cell growth. S363A EBP1 fails to bind HDAC2 and mSin3a, though it still associates with the E2F1 promoter. Phospho-specific antibody, mutagenesis, reporter assay, co-immunoprecipitation, chromatin immunoprecipitation International journal of oncology Medium 17786317
2008 hBRE1 (human BRE1) is an E3 ubiquitin ligase for EBP1; hBRE1 promotes EBP1 polyubiquitination and degradation. EBP1 polyubiquitination in cancer cells is regulated by its phosphorylation. Depletion of hBRE1 blocks EBP1 polyubiquitination and elevates EBP1 protein levels. hBRE1 binds EBP1 and suppresses its repressive effect on E2F-1. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, western blot Molecular biology of the cell High 19037095
2008 PAK1 phosphorylates EBP1 in vitro and in vivo at threonine 261. EGF/heregulin treatment and constitutively active PAK1 enhance threonine phosphorylation of EBP1. EBP1 binds endogenous PAK1, enhanced by heregulin. T261E mutation (mimicking phosphorylation) abolishes EBP1-mediated transcriptional repression, growth inhibition, and tamoxifen sensitivity. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, reporter assay, cell growth assay British journal of cancer High 18283314
2009 EBP1 p42 isoform can be sumoylated on K93 and K298 residues; sumoylation mediates its nuclear translocation and is required for anti-proliferative activity. TLS/FUS has SUMO1 E3 ligase activity for EBP1 p42 and directly binds EBP1; EBP1 sumoylation is triggered by genotoxic stress. Overexpression of TLS enhances EBP1 sumoylation; depletion of TLS abolishes it. Unsumoylatable EBP1 mutants fail to suppress E2F-1-regulated transcription. Sumoylation assay, co-immunoprecipitation, mutagenesis, siRNA knockdown, reporter assay, subcellular localization Oncogene High 19946338
2010 EBP1 p48 isoform binds the p53 E3 ligase HDM2, enhancing the HDM2-p53 association and thereby promoting p53 polyubiquitination and degradation, reducing steady-state p53 levels and activity in glioblastoma cells. Co-immunoprecipitation, ubiquitination assay, western blot, xenograft model Cancer research Medium 21098709
2014 EBP1 p42 interacts with the cSH2 domain of the p85 regulatory subunit of PI3K, inhibiting its lipid kinase activity. p42 promotes p85 degradation by recruiting the HSP70/CHIP E3 ligase complex, coupling p85 to ubiquitin-proteasomal degradation. Co-immunoprecipitation, PI3K lipid kinase assay, ubiquitination assay, domain mapping, western blot Cell death & disease High 24651434
2014 CDK2 specifically interacts with p48 EBP1 (but not p42) through p48's N-terminal domain and phosphorylates p48 at serine 34. This CDK2-mediated phosphorylation is required for the tumorigenic function of p48; the phospho-ablated S34A mutant antagonizes cell proliferation and transformation. Co-immunoprecipitation, in vitro kinase assay, mutagenesis, cell proliferation assay, xenograft model Molecular carcinogenesis Medium 25154617
2015 GTP-bound TIF-IA (transcription initiation factor I) binds EBP1, and together they enhance transcription of PCNA. GTP binding by TIF-IA and EBP1 phosphorylation by protein kinase C delta are both required for optimal PCNA expression. GTP depletion inhibits ribosomal RNA synthesis in T cells by inhibiting TIF-IA. Protein binding assay, kinase inhibitor treatment, GTP depletion, reporter/quantitative expression assay Blood Medium 25691158
2016 EBP1 binds directly to several polyphosphoinositides (PPIns) via two distinct lysine-rich PPIn-binding sites at the N- and C-termini. The C-terminal PPIn-binding motif contributes most to nucleolar localization. A K372N point mutation in the C-terminal motif (found in endometrial tumors) is sufficient to alter nucleolar targeting. EBP1 associates with PtdIns(3,4,5)P3 in the nucleolus via electrostatic and hydrophobic interactions. Lipid pulldown, mutagenesis, NMR spectroscopy, immunofluorescence/localization The Biochemical journal High 27118868
2017 EBP1 p48 binds the WD domain of FBXW7 as an oncogenic substrate, sequestering FBXW7α to the cytosol and attenuating its tumor suppressor function. EBP1 p42 binds the F-box domain of FBXW7 and acts as an adapter that stabilizes FBXW7-substrate interactions, promoting FBXW7-mediated degradation of oncogenic targets. Co-immunoprecipitation, domain mapping, ubiquitination assay, subcellular fractionation, functional tumor assays Cancer research Medium 28209614
2019 PA2G4 directly binds MYCN protein, blocking MYCN proteolysis and enhancing colony formation in a MYCN-dependent manner. MYCN occupies the PA2G4 gene promoter, stimulating transcription (positive feedback). The MYCN-PA2G4 interaction site was mapped to a 14 amino acid MYCN sequence and a surface crevice of PA2G4 by molecular modeling, surface plasmon resonance, and mutagenesis. Competitive chemical inhibition of the MYCN-PA2G4 interface reduces neuroblastoma tumorigenesis in vivo. Chromatin immunoprecipitation, surface plasmon resonance, mutagenesis, molecular modeling, co-immunoprecipitation, in vivo tumor model Cancer research High 31501192
2019 EBP1 p48 interacts with TIF-90 (a splice variant of TIF-IA/RNA polymerase I transcription factor), regulating ribosomal RNA synthesis. EBP1 expression is essential for Akt-protected TIF-90 stability by preventing TIF-90 ubiquitination by MDM2 and proteasomal degradation. Co-immunoprecipitation, ubiquitination assay, ribosomal RNA synthesis assay, siRNA knockdown, western blot Journal of cellular physiology Medium 30793766
2019 EBP1 represses DNMT1 transcription by binding to its promoter region, interrupting DNMT1-mediated methylation at the Survivin promoter. Loss of EBP1 in embryonic mice caused global DNA methylation increase with elevated Suv39H1/DNMT1 levels, massive apoptosis, and developmental defects including brain malformation. Chromatin immunoprecipitation, promoter reporter assay, Ebp1 knockout mouse, methylation analysis Proceedings of the National Academy of Sciences of the United States of America High 31748268
2019 EBP1 binds HNF4α via its LXXLL motif in a manner that competes with HNF4α coactivators for the same binding pocket on HNF4α's ligand-binding domain, thereby suppressing expression of HNF4α target genes implicated in insulin secretion. Crystal structure of the HNF4α ligand-binding domain in complex with an EBP1 LXXLL peptide at 3.15 Å resolution. Yeast two-hybrid, GST pulldown, mammalian two-hybrid, X-ray crystallography, reporter assay The Journal of biological chemistry High 31362984
2020 Cryo-EM structure at near-atomic resolution shows EBP1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis in the developing neocortex. Ribosome profiling shows EBP1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy. Membrane-targeting signal sequences emerging from the 60S tunnel displace EBP1. EBP1 especially impacts synthesis of membrane-targeted cell adhesion molecules. Cryo-electron microscopy, ribosome profiling, pSILAC/BONCAT mass spectrometry, loss-of-function Molecular cell High 33357414
2021 Cryo-EM structure of human EBP1 (p48) bound to the human 80S ribosome at 3.3 Å resolution reveals EBP1 binding near the peptide exit tunnel, centered on interactions with ribosomal proteins eL19 and uL23 and 28S rRNA. EBP1-ribosome association is enhanced upon puromycin-mediated translational inhibition. EBP1 can rotate around its insert domain, allowing multiple conformations while maintaining ribosome interaction. Cryo-electron microscopy, ribosome binding assay, chemical translational inhibition RNA High 33479117
2021 EBP1 directly interacts with Suv39H1 and recruits the E3 ligase MDM2, promoting ubiquitin-proteasome system-dependent degradation of Suv39H1, thereby governing heterochromatin assembly during neural development. Co-immunoprecipitation, ubiquitination assay, western blot, neural differentiation model BMB reports Medium 33691908
2022 PA2G4/EBP1 is ubiquitinated at lysine 376 by PRKN/PARKIN on damaged mitochondria following cerebral ischemia-reperfusion injury. Ubiquitinated PA2G4 interacts with receptor protein SQSTM1/p62, promoting mitophagy induction. Neuron-specific knockout of Pa2g4 impairs mitophagy and increases infarct volume; AAV-mediated re-expression of PA2G4 rescues this. Co-immunoprecipitation, ubiquitination assay with site mutagenesis, conditional KO mouse, AAV rescue, mitophagy assay Autophagy High 37712850
2001 PKC phosphorylates EBP1 on serine/threonine residues in vitro and in vivo; basal EBP1 phosphorylation in breast cancer cells is PKC-dependent. PKC activity is required for EBP1 to associate with ErbB3 in serum-starved cells; PKC inhibition abrogates this association. Heregulin-induced EBP1 phosphorylation occurs predominantly in a PKC-independent manner. In vitro kinase assay, PKC inhibitor treatment, co-immunoprecipitation, metabolic phosphate labeling Molecular and cellular endocrinology Medium 11325528
2013 EBP1 is a novel component of the ZFP809-TRIM28 retroviral silencing complex; EBP1 depletion reduces PBS-mediated retroviral silencing in embryonic cells. Co-immunoprecipitation, shRNA knockdown, retroviral reporter assay Journal of virology Medium 24227866
2016 Pa2G4 (EBP1) binds Six1 transcription factor and interferes with the Six1-Eya1 complex. Knockdown of Pa2G4 in Xenopus embryos downregulates neural border zone, neural crest, and cranial placode genes. Gain-of-function expands neural crest and alters cranial placode domains. Co-immunoprecipitation in HEK293 cells, morpholino knockdown, mRNA overexpression, in situ hybridization in Xenopus embryos Developmental biology Medium 27940157
2022 PA2G4 stabilizes FYN mRNA by binding to m6A-modified FYN mRNA in a YTHDF2-dependent manner, increasing FYN protein expression. EBP1 co-immunoprecipitates with YTHDF2; RIP assays demonstrate PA2G4 binding to FYN mRNA. YTHDF2's m6A catalytic activity is indispensable for PA2G4-mediated FYN regulation. Co-immunoprecipitation, RIP assay, MeRIP assay, dual-luciferase reporter, mRNA half-life assay Cell & bioscience Medium 35526051
2025 PA2G4 interacts with NF110; CRAPIR (a piRNA) competes with NF110 for binding to PA2G4, preventing PA2G4-mediated interaction with the NF110-NF45 heterodimer and reducing NF110 degradation, thereby promoting cardiomyocyte proliferation. Co-immunoprecipitation, RNA-protein binding assay, genetic ablation, overexpression Nature cardiovascular research Medium 39814981
2017 p48 EBP1 physically interacts with beta-tubulin (but not alpha-tubulin) and accumulates in distal microtubule growth cone regions. Introduction of p48 EBP1 in injured hippocampal slices promotes axon regeneration. Co-immunoprecipitation, immunofluorescence, ex vivo axon regeneration assay BMB reports Low 27916024
2013 PAK1 inhibitor IPA-3 sensitizes breast cancer cells to tamoxifen only when EBP1 is ectopically expressed; phosphorylation of EBP1 at T261 by PAK1 induces tamoxifen resistance. An EBP1 T261A mutant (non-phosphorylatable) ameliorates PAK1-induced tamoxifen resistance, while T261E (phosphomimetic) increases ErbB2 protein levels. Pharmacological inhibition, mutagenesis, cell viability assay, western blot British journal of cancer Medium 23361053
2019 EBP1 binds to the DNMT1 promoter region and represses DNMT1 transcription; it also binds to the HDAC1 promoter and suppresses HDAC1 expression. In Ebp1+/- mice, elevated DNMT1 and HDAC1 leads to reduced GAD67 expression, contributing to schizophrenia-like behavior. Chromatin immunoprecipitation, reporter assay, heterozygous KO mouse, western blot International journal of molecular sciences Medium 32283721
2022 Loss of EBP1 in CNS-specific knockout mice causes aberrant Fbxw7 gene expression, resulting in proteasomal degradation of PTF1A and leading to reduced cerebellar volume, Purkinje cell loss, and schizophrenia-like behaviors. Reinstatement of wild-type EBP1 (but not a SZ-patient mutant EBP1-E183Ter) rescued cerebellar architecture. Conditional KO mouse, western blot, rescue experiment with wild-type vs. mutant EBP1, behavioral assays Molecular psychiatry High 35165395
2018 EBP1 (p48) is the strongest candidate binding partner of DPPA4 in human embryonic stem cells; DPPA4 preferentially binds p48 (not p42) in a SAP-domain-mediated manner in pluripotent cells but not non-pluripotent cells. EBP1 p48 binding attenuates DPPA4's transcriptional repressive function; SAP-domain mutant DPPA4 abolishes this effect. Proteomics screening, co-immunoprecipitation, reporter assay, siRNA knockdown, domain mutagenesis Stem cells Medium 29327467

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1. The EMBO journal 195 3138113
2006 EBP1 regulates organ size through cell growth and proliferation in plants. The EMBO journal 143 17024182
2000 Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin. British journal of cancer 113 10682683
2004 EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes. Oncogene 110 15064750
2006 Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase. The EMBO journal 106 16642037
2006 Ebp1 isoforms distinctively regulate cell survival and differentiation. Proceedings of the National Academy of Sciences of the United States of America 102 16832058
2007 Structural insights into the transcriptional and translational roles of Ebp1. The EMBO journal 91 17690690
2005 The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America 84 15994225
2003 Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nucleic acids research 83 12682367
2001 Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation. Journal of cellular physiology 82 11268000
2000 Ectopic expression of the ErbB-3 binding protein ebp1 inhibits growth and induces differentiation of human breast cancer cell lines. Journal of cellular physiology 82 10797306
2019 Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription. Molecular cancer 76 31752867
2005 The ErbB3 binding protein Ebp1 interacts with Sin3A to repress E2F1 and AR-mediated transcription. Nucleic acids research 74 16254079
2006 Ebp1 is a dsRNA-binding protein associated with ribosomes that modulates eIF2alpha phosphorylation. Biochemical and biophysical research communications 68 16631606
2002 Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1. Oncogene 66 12165860
2008 Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor. Molecular biology of the cell 65 19037095
2018 EBP1 nuclear accumulation negatively feeds back on FERONIA-mediated RALF1 signaling. PLoS biology 63 30339663
2007 The crystal structure of Ebp1 reveals a methionine aminopeptidase fold as binding platform for multiple interactions. FEBS letters 61 17765895
1988 Identification and purification of EBP1: a HeLa cell protein that binds to a region overlapping the 'core' of the SV40 enhancer. Genes & development 60 2844627
2008 EBP1, an ErbB3-binding protein, is decreased in prostate cancer and implicated in hormone resistance. Molecular cancer therapeutics 54 18852121
2008 Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice. BMC cell biology 54 19094237
2013 ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic differentiation of muscle stem cells. Developmental biology 53 24275324
2006 Identification of Ebp1 as a component of cytoplasmic bcl-2 mRNP (messenger ribonucleoprotein particle) complexes. The Biochemical journal 53 16396631
2010 Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors. Cancer research 52 21098709
2007 Ebp1 association with nucleophosmin/B23 is essential for regulating cell proliferation and suppressing apoptosis. The Journal of biological chemistry 51 17951246
2004 Heregulin regulates the ability of the ErbB3-binding protein Ebp1 to bind E2F promoter elements and repress E2F-mediated transcription. The Journal of biological chemistry 48 15073182
2023 PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia. Autophagy 47 37712850
2014 P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP. Cell death & disease 46 24651434
1997 Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a protein highly homologous to the mouse cell cycle protein p38-2G4. Cytogenetics and cell genetics 44 9345902
2009 Ebp1 sumoylation, regulated by TLS/FUS E3 ligase, is required for its anti-proliferative activity. Oncogene 42 19946338
2020 Protein Synthesis in the Developing Neocortex at Near-Atomic Resolution Reveals Ebp1-Mediated Neuronal Proteostasis at the 60S Tunnel Exit. Molecular cell 41 33357414
2001 Analysis of the expression pattern of Ebp1, an ErbB-3-binding protein. Biochemical and biophysical research communications 41 11708806
1990 Interaction of enhancer-binding protein EBP1 (NF-kappa B) with the human immunodeficiency virus type 1 enhancer. Journal of virology 41 2406459
1989 Sequence requirement for specific interaction of an enhancer binding protein (EBP1) with DNA. Nucleic acids research 41 2536920
2007 Differential regulation of primitive myelopoiesis in the zebrafish by Spi-1/Pu.1 and C/ebp1. Zebrafish 40 18041923
2013 Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. Oncogene 37 23975429
2007 Host factor Ebp1: selective inhibitor of influenza virus transcriptase. Genes to cells : devoted to molecular & cellular mechanisms 37 17295834
2005 Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling. British journal of cancer 36 15583694
2015 Regulation of ribosomal RNA synthesis in T cells: requirement for GTP and Ebp1. Blood 35 25691158
2016 A polybasic motif in ErbB3-binding protein 1 (EBP1) has key functions in nucleolar localization and polyphosphoinositide interaction. The Biochemical journal 30 27118868
2008 Inhibition of heregulin mediated MCF-7 breast cancer cell growth by the ErbB3 binding protein EBP1. Cancer letters 30 18355957
2007 Suppression of salivary adenoid cystic carcinoma growth and metastasis by ErbB3 binding protein Ebp1 gene transfer. International journal of cancer 30 17266032
2017 Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer. Cancer research 29 28209614
2022 PA2G4 promotes the metastasis of hepatocellular carcinoma by stabilizing FYN mRNA in a YTHDF2-dependent manner. Cell & bioscience 28 35526051
2020 A structural view of PA2G4 isoforms with opposing functions in cancer. The Journal of biological chemistry 27 32952126
2019 Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface. Cancer research 26 31501192
2001 Regulation of the ErbB3 binding protein Ebp1 by protein kinase C. Molecular and cellular endocrinology 25 11325528
2016 Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development. Developmental biology 23 27940157
2015 P42 Ebp1 functions as a tumor suppressor in non-small cell lung cancer. BMB reports 23 24998263
1989 Enhancer binding protein (EBP1) makes base and backbone contacts over one complete turn of the DNA double helix. Journal of molecular biology 23 2544731
2010 The ErbB3 binding protein EBP1 regulates ErbB2 protein levels and tamoxifen sensitivity in breast cancer cells. Breast cancer research and treatment 22 20379846
2013 EBP1, a novel host factor involved in primer binding site-dependent restriction of moloney murine leukemia virus in embryonic cells. Journal of virology 20 24227866
2011 EBP1 inhibits translation of androgen receptor mRNA in castration resistant prostate cancer cells. Anticancer research 20 21965718
2007 Ebp1-mediated inhibition of cell growth requires serine 363 phosphorylation. International journal of oncology 20 17786317
2007 Role of host protein Ebp1 in influenza virus growth: intracellular localization of Ebp1 in virus-infected and uninfected cells. Journal of biotechnology 20 17884219
2015 A novel Anxa2-interacting protein Ebp1 inhibits cancer proliferation and invasion by suppressing Anxa2 protein level. Molecular and cellular endocrinology 19 25917452
2013 Regulation of tamoxifen sensitivity by a PAK1-EBP1 signalling pathway in breast cancer. British journal of cancer 19 23361053
2008 Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells. British journal of cancer 19 18283314
2014 Phosphorylation of the N-terminal domain of p48 Ebp1 by CDK2 is required for tumorigenic function of p48. Molecular carcinogenesis 18 25154617
2012 Expression of ERBB3 binding protein 1 (EBP1) in salivary adenoid cystic carcinoma and its clinicopathological relevance. BMC cancer 18 23110497
2022 Loci on chromosome 12q13.2 encompassing ERBB3, PA2G4 and RAB5B are associated with polycystic ovary syndrome. Gene 17 36423778
2021 Dynamic association of human Ebp1 with the ribosome. RNA (New York, N.Y.) 17 33479117
2020 The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease. Experimental & molecular medicine 17 32719408
2011 EBP1 and DRBP76/NF90 binding proteins are included in the major histocompatibility complex class II RNA operon. Nucleic acids research 16 21624892
2015 EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells. International journal of oncology 15 26081906
2012 ErbB3-binding protein EBP1 decreases ErbB2 levels via a transcriptional mechanism. Oncology reports 15 23242156
2019 Ebp1 p48 promotes oncogenic activities in human colon cancer cells through regulation of TIF-90-mediated ribosomal RNA synthesis. Journal of cellular physiology 14 30793766
2008 Ebp1 expression in benign and malignant prostate. Cancer cell international 14 19025630
2019 Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control. Proceedings of the National Academy of Sciences of the United States of America 13 31748268
2010 p48 Ebp1 acts as a downstream mediator of Trk signaling in neurons, contributing neuronal differentiation. Neurochemistry international 13 21145366
2007 Protein kinase C-delta phosphorylates Ebp1 and prevents its proteolytic degradation, enhancing cell survival. Journal of neurochemistry 13 17316401
2022 LINC00987 knockdown inhibits the progression of acute myeloid leukemia by suppressing IGF2BP2-mediated PA2G4 expression. Anti-cancer drugs 12 34407052
2021 HER2-intronic miR-4728-5p facilitates HER2 expression and accelerates cell proliferation and migration by targeting EBP1 in breast cancer. PloS one 12 33529238
2021 EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development. BMB reports 12 33691908
2018 ERBB3-Binding Protein 1 (EBP1) Is a Novel Developmental Pluripotency-Associated-4 (DPPA4) Cofactor in Human Pluripotent Cells. Stem cells (Dayton, Ohio) 12 29327467
2017 Neuron-specific expression of p48 Ebp1 during murine brain development and its contribution to CNS axon regeneration. BMB reports 12 27916024
2014 LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. PLoS neglected tropical diseases 12 24421916
2021 Ebp1 p48 promotes oncogenic properties in hepatocellular carcinoma through p38 MAPK/HIF1α activation and p53 downregulation. Molecular carcinogenesis 11 33634940
2015 ErbB3 binding protein 1 (EBP1) participates in the regulation of intestinal inflammation via mediating Akt signaling pathway. Molecular immunology 11 26256794
2021 Increased PA2G4 Expression Is an Unfavorable Factor in Nasopharyngeal Carcinoma. Applied immunohistochemistry & molecular morphology : AIMM 10 33605574
2016 C-terminal domain of p42 Ebp1 is essential for down regulation of p85 subunit of PI3K, inhibiting tumor growth. Scientific reports 10 27464702
2015 EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26008146
2007 Expression, purification, crystallization and preliminary crystallographic analysis of the proliferation-associated protein Ebp1. Acta crystallographica. Section F, Structural biology and crystallization communications 10 17768350
2025 The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice. Nature cardiovascular research 9 39814981
2019 ErbB3-binding protein 1 (EBP1) represses HNF4α-mediated transcription and insulin secretion in pancreatic β-cells. The Journal of biological chemistry 9 31362984
2017 Ebp1 regulates myogenic differentiation of myoblast cells via SMAD2/3 signaling pathway. Development, growth & differentiation 9 28707296
2013 HIV-1 viral protein R downregulates Ebp1 and stabilizes p53 in glioblastoma U87MG cells. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 9 23828502
2023 LINC00173 facilitates tumor progression by stimulating RAB1B-mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma. Molecular oncology 8 36606322
2022 Cerebellar dysfunction and schizophrenia-like behavior in Ebp1-deficient mice. Molecular psychiatry 8 35165395
2020 Pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect glioblastoma cell viability and apoptosis. Life sciences 8 33220287
2014 Upregulated expression of ebp1 contributes to schwann cell differentiation and migration after sciatic nerve crush. Journal of molecular neuroscience : MN 8 24878627
2019 YC-1 Antagonizes Wnt/β-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma. Cancers 7 31086087
2019 Somatic Mutations and Intratumoral Heterogeneity of Cancer-Related Genes NLK, YY1 and PA2G4 in Gastric and Colorectal Cancers. Pathology oncology research : POR 7 31828582
2014 Androgen receptor (AR) inhibitor ErbB3-binding protein-1 (Ebp1) is not targeted by the newly identified AR controlling signaling axis heat-shock protein HSP27 and microRNA miR-1 in prostate cancer cells. World journal of urology 7 24798454
2010 EBP1 is a novel E2F target gene regulated by transforming growth factor-β. PloS one 7 21085677
2025 FKBP12-EBP1-Mediated Regulation of Salinity Tolerance in Rice. Plant, cell & environment 6 40344235
2020 Dysregulation of Epigenetic Control Contributes to Schizophrenia-Like Behavior in Ebp1+/- Mice. International journal of molecular sciences 6 32283721
2015 The ErbB3-binding protein EBP1 modulates lapatinib sensitivity in prostate cancer cells. Molecular and cellular biochemistry 6 25876877
2013 Expression of ErbB3-binding protein-1 (EBP1) during primordial follicle formation: role of estradiol-17ß. PloS one 6 23840586
2021 The GpIA7 effector from the potato cyst nematode Globodera pallida targets potato EBP1 and interferes with the plant cell cycle programme. Journal of experimental botany 5 34310681

Missed literature

Know a paper Affinage missed for PA2G4? Flag it for the maintainers and the community.

No submissions yet.