Affinage

PRMT3

Protein arginine N-methyltransferase 3 · UniProt O60678

Length
531 aa
Mass
59.9 kDa
Annotated
2026-06-10
50 papers in source corpus 33 papers cited in narrative 33 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

PRMT3 is a predominantly cytoplasmic type I protein arginine methyltransferase that catalyzes asymmetric dimethylarginine on protein substrates and thereby controls ribosome biogenesis, innate immune signaling, metabolism, and a broad set of cancer-associated pathways (PMID:15175657, PMID:37639603, PMID:41629293). Its catalytic core adopts a two-domain architecture—an AdoMet-binding domain and a barrel-like domain forming a cone-shaped active-site pocket with a conserved double-E loop and a His-Asp proton relay—and the enzyme acts distributively, releasing monomethylated intermediates between successive methyl transfers (PMID:10899106, PMID:19158082). Substrate selection is governed by an N-terminal C2H2 zinc finger that is necessary and sufficient for recognition of RNA-associated substrates and, in particular, the 40S ribosomal protein RPS2/uS5, which the zinc finger binds and stabilizes against proteasomal degradation (PMID:10931850, PMID:15473865, PMID:18573314). RPS2 is a bona fide in vivo substrate whose methylation maintains 40S:60S subunit balance and supports translation, including BDNF-induced dendritic translation in neurons (PMID:15175657, PMID:17439947, PMID:20647003). Beyond ribosomes, PRMT3 methylates a wide range of substrates with distinct physiological consequences: it methylates RIG-I (R730), MDA5 (R822), and cGAS (R111) to dampen type I interferon production and antiviral defense (PMID:37639603); PCSK9 (R582) to block CHIP-mediated ubiquitination and drive aortic valve calcification (PMID:41797709); and the mitochondrial citrate transporter SLC25A1 to promote feeding-driven lipogenic metabolism (PMID:41629293). PRMT3 also functions through methylation-independent mechanisms, acting as a direct transcriptional coactivator of LXRα to promote lipogenic gene expression and binding/inhibiting ALDH1A1 (PMID:25187371, PMID:33495566). Its activity and localization are modulated by partner proteins: ZNF200 stabilizes PRMT3 and drives its nuclear translocation, while DAL-1/4.1B binds the catalytic core and inhibits methylation (PMID:39513743, PMID:15334060). PRMT3 is a target of the selective allosteric inhibitor SGC707, which binds a site distinct from the substrate and cofactor pockets (PMID:23445220, PMID:25728001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Establishing the structural and catalytic basis of PRMT3 was needed to understand how it transfers methyl groups; the crystal structure defined a two-domain fold and the active-site machinery.

    Evidence X-ray crystallography of the rat PRMT3 catalytic core with AdoHcy at 2.0 Å

    PMID:10899106

    Open questions at the time
    • Structure was of the catalytic core only, not the full-length enzyme with its N-terminal zinc finger
    • Did not address substrate-specific recognition
  2. 2000 Medium

    It was unknown how PRMT3 chooses its substrates; the N-terminal C2H2 zinc finger was shown to be required for recognition of RNA-associated substrates but dispensable for an artificial GAR substrate, distinguishing PRMT3 from other PRMTs.

    Evidence In vitro methylation assays with zinc-finger mutants and cysteine-modifying inhibitors in RAT1 extracts

    PMID:10931850

    Open questions at the time
    • Physiological RNA-associated substrate not yet identified
    • Single in vitro system
  3. 1999 High

    Early substrate identification asked what PRMT3 methylates; PABP2 was shown to be methylated at non-canonical Arg-Xaa-Arg clusters producing asymmetric dimethylarginine.

    Evidence In vitro methylation with recombinant PRMT3, MS site mapping and deletion analysis

    PMID:10224081

    Open questions at the time
    • In vitro only; physiological relevance of PABP2 methylation not established
    • No cellular or in vivo validation
  4. 2005 High

    The first physiological substrate and a cellular role were defined: PRMT3 binds RPS2/uS5 through its zinc finger and methylates it, linking the enzyme to ribosome subunit homeostasis, validated from yeast to human cytoplasm.

    Evidence TAP-MS, FLAG pulldown, in vitro methylation, deletion mapping, sucrose-gradient sedimentation, genetic disruption (idx 3, 4)

    PMID:15175657 PMID:15473865

    Open questions at the time
    • How methylation affects ribosome function mechanistically not resolved
    • Other co-fractionating substrates unidentified
  5. 2007 High

    In vivo confirmation was needed; PRMT3-knockout mice showed RPS2 is hypomethylated with no compensation by other PRMTs and a transient Minute-like growth phenotype, cementing RPS2 as a dedicated in vivo substrate.

    Evidence Knockout mouse with MS/immunoblot methylation readout and ribosome fractionation

    PMID:17439947

    Open questions at the time
    • Molecular cause of transient small-size phenotype unclear
    • Identity of additional ribosome-associated substrates unresolved
  6. 2009 High

    The catalytic mechanism for multi-arginine substrates was clarified: PRMT3 acts distributively, releasing monomethyl intermediates between transfers rather than processively dimethylating.

    Evidence In vitro kinetics and MS analysis of methylation intermediates across substrates

    PMID:19158082

    Open questions at the time
    • In vitro kinetics may not reflect cellular processivity
    • Does not address substrate-specific kinetic differences in vivo
  7. 2008 Medium

    A methylation-independent role emerged: the PRMT3 N-terminal domain binds and stabilizes RPS2 by inhibiting its ubiquitin-mediated degradation, decoupling substrate binding from catalysis.

    Evidence Domain deletion, in vitro binding, cellular ubiquitination assay, in vitro enzyme assay

    PMID:18573314

    Open questions at the time
    • E3 ligase mediating RPS2 ubiquitination not identified
    • Single lab
  8. 2010 Medium

    Determinants of substrate engagement and a neuronal function were defined: Tyr87 in the substrate-binding domain is critical for RPS2 binding and activity, and PRMT3 promotes BDNF-induced neuronal translation and dendritic spine morphology through RPS2 methylation.

    Evidence Site-directed mutagenesis with binding/activity assays (idx 10); siRNA knockdown in rat hippocampal neurons with methylation-resistant RPS2 rescue (idx 9)

    PMID:20647003 PMID:21059412

    Open questions at the time
    • Whether Tyr87 is physiologically phosphorylated is unresolved (no Tyr87 phosphorylation detected)
    • Neuronal phenotypes from a single lab
  9. 2013 High

    Pharmacological control of PRMT3 was established by discovering an allosteric site distinct from substrate and cofactor pockets, enabling selective inhibition.

    Evidence X-ray crystallography with compound 14u and non-competitive kinetic analysis (idx 11); crystal structure with SGC707, IC50 31 nM, broad selectivity panel and cellular activity (idx 13)

    PMID:23445220 PMID:25728001

    Open questions at the time
    • Allosteric mechanism of catalytic suppression not fully defined
    • Cellular off-target effects of inhibitors not exhaustively excluded
  10. 2014 Medium

    A non-catalytic transcriptional function was uncovered: PRMT3 binds LXRα methylation-independently and coactivates lipogenic transcription, with palmitic acid driving its nuclear translocation.

    Evidence Co-IP, luciferase assays, PRMT3 KO MEFs, and LXRα KO mice

    PMID:25187371

    Open questions at the time
    • Structural basis of LXRα binding not defined
    • Signal triggering nuclear translocation not fully mapped
  11. 2018 Medium

    Regulation of RPS2 handling was extended: ZNF277 competes with PRMT3 for uS5/RPS2 using the same zinc-finger recognition mode, indicating shared control of nascent ribosomal protein binding.

    Evidence Quantitative proteomics, Co-IP competition assays, live-cell imaging, nascent-chain analysis

    PMID:30530495

    Open questions at the time
    • Functional consequence of PRMT3/ZNF277 competition on methylation output unclear
    • Single lab
  12. 2023 High

    A defined role in innate immunity was established: PRMT3 methylates RIG-I (R730), MDA5 (R822), and cGAS (R111) to impair nucleic-acid sensing and suppress type I interferon, with genetic and pharmacological loss conferring antiviral resistance.

    Evidence Site-specific in vitro methylation with mutagenesis, RNA/DNA binding and oligomerization assays, Prmt3 heterozygous mice, viral infection assays

    PMID:37639603

    Open questions at the time
    • Upstream signals controlling PRMT3 engagement of immune sensors not defined
    • Relative contribution of each substrate to phenotype not separated
  13. 2024 Medium

    PRMT3 was shown to control mitochondrial integrity by methylating HSP60 at R446 to drive oligomerization, with loss triggering mtDNA leakage and cGAS/STING-driven anti-tumor immunity.

    Evidence Co-IP, site-specific methylation, oligomerization and mtDNA leakage assays, in vivo HCC models

    PMID:39256398

    Open questions at the time
    • Structural mechanism by which R446 methylation promotes oligomerization unresolved
    • Single lab
  14. 2025 Medium

    Mechanisms of PRMT3-driven tumor phenotypes were extended through substrate-specific methylation of metabolic and transcriptional regulators (PDHK1 R363/368 driving lactylation-linked PD-L1, TFAP2A enhancing IDO1, IGF2BP1 R452 stabilizing HEG1 mRNA, METTL14) and histone H4R3me2a-driven programs.

    Evidence Site-specific methylation, kinase/ChIP/mRNA-stability assays, CRISPR screen, in vivo cancer models (idx 24, 27, 20, 21)

    PMID:37024475 PMID:37973560 PMID:40050608 PMID:41129671

    Open questions at the time
    • Each axis validated by a single lab in a specific cancer context
    • Generalizability across tumor types untested
  15. 2026 High

    Disease-relevant substrate methylation in metabolic and cardiovascular contexts was defined: PRMT3 methylates PCSK9 at R582 to block CHIP-mediated degradation and promote valve calcification, and methylates SLC25A1 under feeding/insulin-pAKT to drive lipogenic metabolism.

    Evidence Site-specific methylation with catalytically dead and substrate mutants, ubiquitination rescue, haploinsufficient and adipocyte-specific KO mice, SGC707/PROTAC (idx 30, 31)

    PMID:41629293 PMID:41797709

    Open questions at the time
    • Whether the same axes operate in human disease tissue beyond models is untested
    • Interplay of metabolic and ribosomal substrate pools unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PRMT3 selects among its expanding catalytically and non-catalytically engaged substrates in different compartments and cell types, and what signals partition its cytoplasmic ribosome-regulatory role from its nuclear, transcription-associated functions.
  • No unified model of substrate selection beyond the zinc-finger/RPS2 paradigm
  • Triggers and regulators of nuclear translocation incompletely defined
  • Most disease-substrate axes rest on single-lab studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 6 GO:0140096 catalytic activity, acting on a protein 6 GO:0042393 histone binding 3 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005840 ribosome 3
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ALDH1A1DAL-1/4.1BLXRΑMETTL14RPS2TEAD4ZNF200ZNF277

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of the rat PRMT3 catalytic core in complex with AdoHcy at 2.0 Å resolution reveals a two-domain architecture: an AdoMet-binding domain (compact version of the consensus AdoMet-dependent methyltransferase fold) and a barrel-like domain. The active site is in a cone-shaped pocket between the two domains, with a conserved double-E loop containing two invariant Glu residues and a His-Asp proton-relay system. Crystal packing and solution behavior indicate dimer formation of the PRMT3 core. X-ray crystallography at 2.0 Å resolution The EMBO journal High 10899106
2000 PRMT3 contains a single C2H2 zinc-finger domain in its N-terminus that is required for recognition of RNA-associated substrates in RAT1 cell extracts but not for methylation of an artificial GST-GAR substrate. PRMT3 activity is inhibited by ZnCl2 and N-ethylmaleimide (cysteine-modifying reagents), distinguishing it from PRMT1 and CARM1/PRMT4. In vitro methylation assay, zinc-finger domain mutagenesis, pharmacological inhibition The Journal of biological chemistry Medium 10931850
1999 PRMT3 methylates Poly(A)-binding protein II (PABP2) in vitro at Arg-Xaa-Arg clusters in its C-terminal domain using S-adenosyl-L-methionine as methyl donor, producing asymmetric dimethylarginine at sites distinct from canonical RGG motifs. In vitro methylation assay with recombinant PRMT3, mass spectrometry, protein sequencing The Journal of biological chemistry High 10224081
2004 Fission yeast PRMT3 ortholog associates with components of the translational machinery and methylates the 40S ribosomal protein S2 (rpS2) as its first identified physiological substrate. A fraction of PRMT3 co-sediments with free 40S ribosomal subunits by sucrose gradient velocity centrifugation. Loss of PRMT3 causes accumulation of free 60S subunits and imbalance of the 40S:60S free subunit ratio without affecting pre-rRNA processing. Tandem affinity purification, mass spectrometry, sucrose gradient sedimentation, genetic disruption of PRMT3 The EMBO journal High 15175657
2005 Mammalian PRMT3 binds rpS2 via its N-terminal zinc-finger domain (which is necessary and sufficient for this interaction), methylates rpS2 in vitro at N-terminal Arg-Gly repeat residues, and both proteins co-sediment with free ribosomal subunits. PRMT3 is exclusively cytoplasmic. FLAG pulldown from HeLa extracts, MS identification, in vitro methylation assay, deletion analysis, sucrose gradient sedimentation, subcellular fractionation The Biochemical journal High 15473865
2007 In PRMT3-knockout mice, rpS2 is hypomethylated, confirming rpS2 as a bona fide in vivo PRMT3 substrate that cannot be compensated by other PRMTs. Loss of PRMT3 causes a Minute-like small-size phenotype in embryos that normalizes postnatally. Total ribosome levels (40S, 60S, 80S, polysomes) are unaffected in adults. Additional unidentified proteins that co-fractionate with ribosomes are also dedicated PRMT3 substrates. Targeted gene disruption (knockout mouse), methylation analysis by mass spectrometry/immunoblot, sucrose gradient sedimentation The Journal of biological chemistry High 17439947
2004 Tumor suppressor DAL-1/4.1B interacts with PRMT3 via the C-terminal catalytic core domain of PRMT3, confirmed by yeast two-hybrid and co-immunoprecipitation in lung and breast cancer cells. DAL-1/4.1B is not a PRMT3 substrate but inhibits PRMT3-mediated methylation of GST-GAR in vitro and inhibits cellular substrate methylation when DAL-1/4.1B is induced in MCF-7 cells. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, in vitro methylation assay, inducible expression system Oncogene Medium 15334060
2008 PRMT3's N-terminal domain (not its catalytic core) is required for binding to rpS2 and for stabilizing rpS2 by inhibiting its ubiquitin-mediated proteasomal degradation. Overexpressed rpS2 is ubiquitinated; co-expression of PRMT3 reduces ubiquitination. Recombinant PRMT3 forms an active enzyme complex with endogenous rpS2 in vitro, and excess rpS2 modestly stimulates PRMT3 enzymatic activity. Domain deletion analysis, in vitro binding assay, ubiquitination assay in cells, in vitro enzyme activity assay Biochimica et biophysica acta Medium 18573314
2009 PRMT3 (and PRMT1) methylate arginine residues in a distributive manner — releasing the monomethylated intermediate between each methyl transfer step — even with substrates containing multiple methyl-accepting arginines (including one with 13 such residues). PRMT3 does not prefer pre-methylated substrates. In vitro methylation kinetics, mass spectrometry analysis of methylation intermediates, multiple substrate constructs The Journal of biological chemistry High 19158082
2010 In rat hippocampal neurons, PRMT3 knockdown causes deformed dendritic spine morphology without changing spine number, reduces BDNF-induced translational upregulation of αCaMKII, and diminishes rpS2 protein stability. Overexpression of methylation-resistant rpS2 (Arg-Gly repeat deleted) phenocopies PRMT3 knockdown, indicating PRMT3 promotes neuronal translation through rpS2 methylation. siRNA knockdown in primary rat hippocampal neurons, morphological analysis, immunoblot, translational reporter assay Brain research Medium 20647003
2010 Tyrosine 87 (Tyr87) in the substrate-binding domain of PRMT3 is critical for its interaction with rpS2 and full enzymatic activity. Tyr87Cys and Tyr87Glu (phosphomimetic) substitutions markedly decrease affinity for RPS2 and reduce methyltransferase activity, while Tyr87Phe (non-phosphorylatable) retains full activity. Mass spectrometry detected phosphorylation of Ser25 and Ser27 of PRMT3 but no Tyr87 phosphorylation. Site-directed mutagenesis, in vitro binding assay, methyltransferase activity assay, mass spectrometry Biochimica et biophysica acta Medium 21059412
2013 PRMT3 possesses an allosteric binding site distinct from the substrate and cofactor binding sites. Inhibitors occupying this site are non-competitive with both the peptide substrate and AdoMet. X-ray crystal structure of PRMT3 with compound 14u confirmed occupation of this allosteric site. X-ray crystallography, biochemical inhibition assays (IC50, mechanism of inhibition), structure-activity relationship studies Journal of medicinal chemistry High 23445220
2014 PRMT3 directly binds LXRα (liver X receptor α) in a methylation-independent manner and acts as a transcriptional coactivator to increase LXRα-driven lipogenic gene expression. Palmitic acid treatment translocates PRMT3 from the cytoplasm to the nucleus. In LXRα KO mice, high-fat diet does not increase PRMT3-LXRα binding, confirming LXRα dependence. Co-immunoprecipitation, luciferase transcriptional activity assay, PRMT3 KO mouse embryonic fibroblasts, subcellular fractionation, LXRα KO mouse model Diabetes Medium 25187371
2015 Crystal structure of PRMT3 in complex with the allosteric inhibitor SGC707 confirms the allosteric inhibition mode; SGC707 inhibits PRMT3 with IC50 = 31 nM (KD = 53 nM) and is selective against 31 other methyltransferases and >250 non-epigenetic targets. SGC707 engages PRMT3 and inhibits its cellular methyltransferase activity. X-ray crystallography, biochemical IC50 assay, biophysical binding assay (KD), selectivity panel, cellular methylation assay Angewandte Chemie (International ed. in English) High 25728001
2018 ZNF277 is identified as a new binding partner of uS5/RPS2 using quantitative proteomics. ZNF277 uses its C2H2-type zinc finger domain (same recognition mode as PRMT3) to bind uS5 in the cytoplasm and nucleolus. ZNF277 and PRMT3 compete for uS5 binding: overexpression of PRMT3 inhibits ZNF277-uS5 complex formation and vice versa. ZNF277 recognizes nascent uS5 cotranslationally. Quantitative proteomics, co-immunoprecipitation, live-cell imaging, competition binding assay, ribosome nascent-chain analysis The Journal of biological chemistry Medium 30530495
2019 PRMT3 methylates histone H4 at arginine 3 (H4R3me2a) at the promoter region of miR-3648, activating its expression during MSC osteogenesis. PRMT3 overexpression promotes osteogenic differentiation; PRMT3 depletion or SGC707 treatment causes osteopenia in mice. Overexpression of miR-3648 rescues impaired osteogenesis in PRMT3-deficient cells. ChIP assay, siRNA/shRNA knockdown, overexpression, SGC707 pharmacological inhibition, in vivo mouse bone phenotype analysis Cell death & disease Medium 31378783
2021 PRMT3 interacts with ALDH1A1 (retinal dehydrogenase 1) via specific residues in PRMT3's catalytic domain binding to ALDH1A1's C-terminal region. PRMT3 inhibits ALDH1A1 enzymatic activity and negatively regulates retinoic acid-responsive gene expression in a methyltransferase-activity-independent manner. Yeast two-hybrid, co-immunoprecipitation, GST pull-down, molecular docking, site-directed mutagenesis, ALDH1A1 enzymatic activity assay, gene expression analysis Communications biology Medium 33495566
2021 PRMT3 stabilizes c-MYC protein, and the pro-tumorigenic function of PRMT3 in colorectal cancer cells is dependent on c-MYC; PRMT3 knockdown reduces c-MYC levels and suppresses proliferation, migration, and invasion. siRNA knockdown, overexpression, immunoblot for c-MYC protein stability Gene Low 33991650
2022 PRMT3 reprograms metabolic pathways in glioblastoma stem cells (GSCs) by promoting glycolysis and upregulating its transcriptional regulator HIF1α; PRMT3 knockdown reduces proliferation and migration of GBM cells and inhibits tumor growth in xenografts. siRNA/shRNA knockdown, overexpression, metabolic assays (glycolysis), xenograft mouse model, SGC707 pharmacological inhibition Cell death & disease Medium 36351894
2021 PRMT3 methylates HIF-1α at R282, which is required for HIF-1α stabilization and oncogenic function in colorectal cancer; PRMT3-mediated tumorigenesis is HIF-1α methylation-dependent. Site-specific methylation assay, mutagenesis of R282, protein stability assay, tumor xenograft model Cell death & disease Medium 34753906
2023 PRMT3 methylates IGF2BP1 at arginine R452, stabilizing IGF2BP1 protein and enabling it to stabilize HEG1 mRNA, thereby promoting oxaliplatin resistance in hepatocellular carcinoma. The PRMT3-IGF2BP1-HEG1 axis was validated by CRISPR screen, transcriptomics, and functional in vitro/in vivo assays. CRISPR/Cas9 activation library screen, site-specific methylation assay (R452), mRNA stability assay, in vitro and in vivo functional rescue experiments Nature communications Medium 37024475
2023 PRMT3 interacts with METTL14 and mediates its arginine methylation; PRMT3 inhibition leads to METTL14 overexpression, which promotes m6A methylation via YTHDF2-dependent reduction of GPX4 mRNA stability, increasing lipid peroxidation and ferroptosis in endometrial cancer cells. Co-immunoprecipitation, arginine methylation assay, m6A methylation assay, mRNA stability assay, xenograft models (CDX and PDX) Advanced science Medium 37973560
2023 PRMT3 methylates RIG-I at R730, MDA5 at R822, and cGAS at R111 with asymmetric dimethylarginine marks. These modifications reduce RNA-binding of RIG-I and MDA5 and reduce DNA-binding and oligomerization of cGAS, suppressing type I interferon production. Mice with Prmt3 haploinsufficiency or SGC707 treatment are more resistant to RNA and DNA virus infection. Co-immunoprecipitation, in vitro methylation assay, RNA/DNA binding assay, oligomerization assay, Prmt3 heterozygous KO mouse model, viral infection assay Proceedings of the National Academy of Sciences of the United States of America High 37639603
2024 PRMT3 methylates HSP60 at R446, inducing HSP60 oligomerization and maintaining mitochondrial homeostasis. Inhibition of PRMT3 disrupts mitochondrial integrity, increases mitochondrial DNA leakage, and activates cGAS/STING-mediated anti-tumor immunity in hepatocellular carcinoma. Co-immunoprecipitation, site-specific methylation assay (R446), HSP60 oligomerization assay, mitochondrial integrity/mtDNA leakage assay, cGAS/STING pathway readout, in vivo HCC mouse models Nature communications Medium 39256398
2024 PRMT3 methylates PDHK1 at R363 and R368, increasing PDHK1 kinase activity, promoting lactate production, and driving PD-L1 expression via H3K18 lactylation at the PD-L1 promoter in hepatocellular carcinoma. R363/368K mutant or PDHK1 inhibitor blocks PRMT3-dependent lactate production. Co-immunoprecipitation, site-specific methylation assay (R363/368), kinase activity assay, R363/368K mutant, ChIP assay, hepatocyte-specific Prmt3 KO mouse model Cell death & disease Medium 40050608
2024 ZNF200 interacts with PRMT3 via PRMT3's N-terminal zinc finger domain binding to ZNF200's C-terminal zinc finger regions. ZNF200 stabilizes PRMT3 by inhibiting proteasomal degradation and promotes PRMT3 nuclear translocation, leading to global increase of H4R3me2a modifications. Yeast two-hybrid, co-immunoprecipitation, GST pull-down, molecular docking, proteasome inhibitor assay, subcellular fractionation, H4R3me2a immunoblot The Biochemical journal Medium 39513743
2025 PRMT3 interacts with FOXO1 and methylates it at arginine R253, promoting FOXO1 degradation and inhibiting its nuclear translocation, thereby impairing decidualization in endometriosis through an oxidative stress mechanism. SGC707 inhibits endometriosis and promotes deciduoma formation in mice. Co-immunoprecipitation, site-specific methylation assay (R253), protein stability assay, nuclear translocation assay, in vivo mouse model with SGC707 Cellular and molecular life sciences Medium 41455763
2025 PRMT3 methylates transcription factor TFAP2A, enhancing TFAP2A binding to the IDO1 promoter. Methylated TFAP2A has prolonged half-life, increased nuclear localization, and enhanced dimer formation, leading to elevated IDO1 expression and kynurenine synthesis that promotes radioresistance and immunosuppression in non-small cell lung cancer. Arginine methylation assay, ChIP assay, protein stability assay, nuclear fractionation, dimerization assay, combined PRMT3+IDO1 pharmacological inhibition Cancer research Medium 41129671
2025 PRMT3 promotes chromatin accessibility and transcription at the HIV-1 promoter by increasing H4R3me2a levels and recruiting P-TEFb. PRMT3 forms a transcriptional hub with TEAD4 and P-TEFb at the viral promoter via direct physical interactions among the three proteins, reversing HIV-1 latency. dCas9-targeted locus-specific protein analysis, ChIP assay, co-immunoprecipitation, ATAC-seq (chromatin accessibility), HIV-1 latency cell models and primary cells from infected persons Nature communications Medium 40374607
2025 PRMT3-mediated H4R3me2a upregulates miR-448, which suppresses IGF1R and activates GSK3β via PI3K/AKT/GSK3β signaling, driving tau hyperphosphorylation in primary age-related tauopathy. SGC707 reduces tau hyperphosphorylation in this model. Transcriptomic profiling of postmortem tissue, in vitro and in vivo functional validation, ChIP assay, miR-448 overexpression, IGF1R suppression assay, SGC707 treatment Advanced science Medium 40344412
2026 PRMT3 catalyzes asymmetric dimethylation of PCSK9 at R582, which prevents E3 ligase CHIP from binding PCSK9 at K575, thereby blocking ubiquitination-mediated degradation and stabilizing PCSK9 (a procalcific factor) to promote aortic valve calcification. Prmt3 haploinsufficiency ameliorates aortic valve calcification in ApoE-/- mice. Co-immunoprecipitation coupled with LC-MS/MS, enzymatically inactive PRMT3 mutant, arginine-to-lysine and lysine-to-alanine PCSK9 substitution mutants, protein half-life assay, ubiquitination assay, Prmt3 haploinsufficient mouse model, SGC707 and PROTAC treatment in vivo Circulation High 41797709
2026 Feeding upregulates PRMT3 via insulin-pAKT signaling; PRMT3 drives expression of mitochondrial citrate transporter SLC25A1 through direct arginine methylation during feeding. PRMT3 inhibition attenuates diet-induced obesity and enhances adipocyte glycolysis in male mice. Adipocyte-specific Slc25a1 deletion protects against diet-induced obesity. Pharmacological PRMT3 inhibition, adipocyte-specific Slc25a1 KO mouse, arginine methylation assay for SLC25A1, metabolic phenotyping, insulin/AKT signaling assays Nature communications Medium 41629293
2023 PRMT3 is localized predominantly in the cytoplasm; PRMT3 regulates histone H4R3me2a in the context of breast cancer invasive micropapillary carcinoma by facilitating this epigenetic mark to regulate the endoplasmic reticulum stress signaling pathway. ChIP-sequencing, RNA sequencing, mass spectrometry, targeted metabolomics, xenograft tumorigenic capacity with PRMT3 inhibitor Cancer science Low 36637351

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Crystal structure of the conserved core of protein arginine methyltransferase PRMT3. The EMBO journal 264 10899106
2004 PRMT3 is a ribosomal protein methyltransferase that affects the cellular levels of ribosomal subunits. The EMBO journal 146 15175657
2005 Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine methyltransferase 3). The Biochemical journal 141 15473865
1999 Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3. The Journal of biological chemistry 141 10224081
2007 Ribosomal protein rpS2 is hypomethylated in PRMT3-deficient mice. The Journal of biological chemistry 115 17439947
2000 PRMT3 is a distinct member of the protein arginine N-methyltransferase family. Conferral of substrate specificity by a zinc-finger domain. The Journal of biological chemistry 112 10931850
2015 A potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angewandte Chemie (International ed. in English) 103 25728001
2004 DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Oncogene 97 15334060
2023 PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer. Nature communications 80 37024475
2023 PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 64 37973560
2022 PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. Cell death & disease 58 36351894
2019 Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell death & disease 57 31378783
2013 Exploiting an allosteric binding site of PRMT3 yields potent and selective inhibitors. Journal of medicinal chemistry 54 23445220
2014 PRMT3 regulates hepatic lipogenesis through direct interaction with LXRα. Diabetes 41 25187371
2008 PRMT3 inhibits ubiquitination of ribosomal protein S2 and together forms an active enzyme complex. Biochimica et biophysica acta 40 18573314
2024 Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling. Nature communications 39 39256398
2009 Type I Arginine Methyltransferases PRMT1 and PRMT-3 Act Distributively. The Journal of biological chemistry 35 19158082
2018 Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3). Journal of medicinal chemistry 34 29244490
2021 PRMT3 promotes tumorigenesis by methylating and stabilizing HIF1α in colorectal cancer. Cell death & disease 33 34753906
2010 PRMT3 is essential for dendritic spine maturation in rat hippocampal neurons. Brain research 31 20647003
2020 Zebrafish prmt3 negatively regulates antiviral responses. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 32643209
2018 The 40S ribosomal protein uS5 (RPS2) assembles into an extraribosomal complex with human ZNF277 that competes with the PRMT3-uS5 interaction. The Journal of biological chemistry 29 30530495
2025 PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma. Cell death & disease 27 40050608
2021 Arginine methyltransferase PRMT3 promote tumorigenesis through regulating c-MYC stabilization in colorectal cancer. Gene 27 33991650
2021 PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling. Communications biology 24 33495566
2024 PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease. Molecular medicine (Cambridge, Mass.) 20 38200452
2023 Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America 20 37639603
2023 PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast. Cancer science 16 36637351
2011 The C. elegans PRMT-3 possesses a type III protein arginine methyltransferase activity. Journal of receptor and signal transduction research 13 21385054
2019 Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochimica et biophysica acta. Molecular basis of disease 12 30776415
2022 PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. Scientific reports 11 35013582
2024 Discovery of PRMT3 Degrader for the Treatment of Acute Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39120042
2025 PRMT3 and CARM1: Emerging Epigenetic Targets in Cancer. Journal of cellular and molecular medicine 7 39964832
2023 Arginine methyltransferases PRMT2 and PRMT3 are essential for biosynthesis of plant-polysaccharide-degrading enzymes in Penicillium oxalicum. PLoS genetics 7 37523410
2014 PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced β-cell death. Transplantation proceedings 6 24815167
2010 Tyrosine 87 is vital for the activity of human protein arginine methyltransferase 3 (PRMT3). Biochimica et biophysica acta 6 21059412
2019 Cisplatin-induced ototoxicity involves interaction of PRMT3 and cannabinoid system. Archives of toxicology 5 31256211
2025 PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub. Nature communications 3 40374607
2026 PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer. Cancer research 2 41129671
2026 PRMT3 at the crossroads of inflammation: dual roles in metabolic reprogramming and immune dysregulation in chronic diseases. Frontiers in immunology 2 41583428
2025 CircERBB3 Targets miR-194-5p/PRMT3 to Promote Hepatocellular Carcinoma Progression. Journal of physiological investigation 2 40616280
2025 Interplay of PRMTs and Identification of Biomarkers Through Machine Learning Algorithms in Pan-Cancer, Highlighting PRMT3 as a Biomarker in Pancreatic Cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 41099588
2025 PRMT3-Mediated H4R3me2a Promotes Primary Age-Related Tauopathy by Driving Tau Hyperphosphorylation in Neuron. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40344412
2025 PRMT3-mediated FOXO1 arginine methylation exacerbates oxidative stress-induced decidualization defects in the eutopic endometrium of endometriosis. Cellular and molecular life sciences : CMLS 1 41455763
2024 Chicken PRMT3 facilitates IBDV replication. Poultry science 1 38981362
2021 Identification of a cartilage specific novel miRNA which directly targets PRMT3 in rats. Osteoarthritis and cartilage open 1 36474992
2026 PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility. Nature communications 0 41629293
2026 PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification. Circulation 0 41797709
2026 PRMT3 in cancer: arginine methylation as a driver of tumor metabolism, immune evasion, and therapeutic resistance. Frontiers in immunology 0 42148077
2024 The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation. The Biochemical journal 0 39513743

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