Affinage

PEG10

Retrotransposon-derived protein PEG10 · UniProt Q86TG7

Length
708 aa
Mass
80.2 kDa
Annotated
2026-06-10
93 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEG10 is a domesticated Ty3/gypsy LTR retrotransposon-derived gene whose Gag- and Pol-homologous open reading frames encode proteins essential for mammalian placental development (PMID:11318613, PMID:16341224). Translation produces two products via >60% efficient programmed −1 frameshifting: an ORF1 (Gag-like) protein and an ORF1/2 (Gag-Pol-like) fusion bearing an active aspartic protease (Asp-Ser-Gly active-site motif) that processes the fusion protein (PMID:17942406). In vivo these products have separable developmental roles — the ORF1/2 protease motif maintains fetal capillary integrity in mid-to-late gestation, with active-site knock-in mutation causing perinatal lethality and placental vascular defects (PMID:34559199). Structurally, a stably folded PEG10 domain matches the C-terminal capsid (CA) domain of retrotransposon Gag proteins (PMID:34357660), and the Gag domain drives vesicle budding and assembles virus-like particles that preferentially package PEG10's own mRNA through 3′ UTR sequences, enabling reprogrammable RNA delivery (PMID:30951545, PMID:34413232). PEG10 binds cellular RNAs, localizes to stress granules, associates with the ataxia proteins ATXN2 and ATXN10, and is secreted in extracellular vesicles (PMID:34467244). PEG10 protein abundance is tightly controlled post-translationally: the ORF1/2 (gag-pol) form is selectively degraded through a UBQLN2/UBE3A-dependent ubiquitin-proteasome pathway requiring specific pol-region lysines (PMID:41234208, PMID:36951542), deubiquitinated and stabilized by USP9X (PMID:38677662), and differentially ubiquitinated by SIAH1 (degradative, tumor-suppressive) versus SIAH2 (stabilizing, tumor-promoting) at distinct lysine residues in its PAIR domain (PMID:42168988). Transcriptionally, PEG10 is a direct target activated by c-MYC, E2F-1/E2F-4, and the menin-MLL1/H3K4-methylation complex, and repressed by activated androgen receptor (PMID:16423995, PMID:18625225, PMID:29142068, PMID:31013476). Functionally, PEG10 inhibits TGF-β/BMP-SMAD signaling and promotes proliferation, EMT, invasion, and apoptotic resistance across multiple cancers (PMID:29044189, PMID:28004118, PMID:33391523), and its loss accumulates in UBE3A-deficient (Angelman syndrome) neurons where it perturbs neuronal migration (PMID:34467244).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 Medium

    Established that PEG10 is not a conventional cellular gene but a domesticated retroelement, framing all later mechanistic interpretation of its Gag/Pol-derived activities.

    Evidence Sequence and genomic analysis of two overlapping ORFs homologous to Ty3/gypsy Gag and Pol

    PMID:11318613

    Open questions at the time
    • Did not demonstrate protein expression or any biochemical activity
    • Frameshifting and protease activity were inferred, not shown
  2. 2003 Medium

    First functional role assigned to PEG10 — physical sequestration of the apoptotic mediator SIAH1 — linking the Gag protein to cell survival.

    Evidence Co-immunoprecipitation and overexpression apoptosis rescue assay

    PMID:12810624

    Open questions at the time
    • Single Co-IP, single lab
    • Binding domain on PEG10 not mapped at this stage
  3. 2005 High

    Genetic proof that PEG10 is indispensable for mammalian development, showing the domesticated retroelement was co-opted for placentation.

    Evidence Peg10 knockout mice with embryonic lethality and absent spongiotrophoblast/labyrinth layers

    PMID:16341224

    Open questions at the time
    • Did not distinguish which protein product or activity drives the phenotype
    • Molecular mechanism in trophoblast not defined
  4. 2006 High

    Identified the first direct upstream transcriptional activator, connecting PEG10 to oncogenic MYC signaling.

    Evidence ChIP, MYC RNAi, and E-box site-directed mutagenesis at the PEG10 first intron

    PMID:16423995

    Open questions at the time
    • Downstream consequences of MYC-driven PEG10 not established here
  5. 2007 High

    Demonstrated the predicted retroviral translational and enzymatic mechanisms are real in vivo: efficient −1 frameshifting and a catalytically active aspartic protease that processes the fusion protein.

    Evidence In vivo frameshift reporter assay plus active-site (Asp-Ser-Gly) mutagenesis in mouse/human placenta

    PMID:17942406

    Open questions at the time
    • Substrates of the protease beyond autoprocessing not identified
    • Developmental requirement of the protease not yet tested in vivo
  6. 2007 High

    Extended PEG10 regulation to androgen signaling and broadened its functional reach beyond placenta to adipogenesis and hepatocarcinogenesis.

    Evidence AR ChIP, AR/PEG10 siRNA, xenografts (HCC); separate RNAi in 3T3-L1 adipocyte differentiation

    PMID:17369855 PMID:17707377

    Open questions at the time
    • Mechanism by which PEG10 protein executes proliferation/anti-apoptosis not defined
    • Adipogenesis link relies on a single RNAi study
  7. 2008 Medium

    Placed PEG10 within the E2F/RB transcriptional network controlling proliferation and apoptosis.

    Evidence ChIP for E2F-1/E2F-4 at the promoter with apoptosis assays

    PMID:18625225

    Open questions at the time
    • Functional output of E2F-driven PEG10 described only phenomenologically
  8. 2010 Medium

    Revealed additional translational complexity through a non-AUG upstream start codon, indicating multiple PEG10 protein isoforms.

    Evidence Mutational analysis of translation start sites with reporter constructs

    PMID:20084274

    Open questions at the time
    • Functional distinction of non-AUG vs AUG products not established
    • Not independently replicated
  9. 2016 Medium

    Connected PEG10 to TGF-β-driven EMT and chemoresistance, and uncovered miRNA-level control of PEG10 protein output.

    Evidence shRNA/overexpression with TGF-β1 stimulation (HCC EMT); miR-122 3′UTR reporter and knockout mouse

    PMID:27370270 PMID:28004118

    Open questions at the time
    • Direction of PEG10–TGF-β relationship appears context-dependent across studies
    • Molecular mechanism of PEG10 action on EMT effectors unclear
  10. 2017 Medium

    Defined PEG10 as a repressor of both TGF-β and BMP SMAD branches in a mutually inhibitory loop and added epigenetic (menin-MLL1/H3K4me) and E2F-1/cell-cycle regulatory layers.

    Evidence SMAD reporter assays, siRNA, phospho-SMAD blots (chondrosarcoma); menin-MLL1 ChIP with MI-503 (HCC); E2F-1 ChIP with cell-cycle/invasion assays (pancreatic)

    PMID:28193232 PMID:29044189 PMID:29142068

    Open questions at the time
    • Whether PEG10 represses SMAD signaling directly or via a partner unresolved
    • Opposing TGF-β reports across tissues not reconciled
  11. 2018 Medium

    Mechanistically linked PEG10's TGF-β/BMP antagonism to specific kinase cascades and identified TSG101 as a protein-level stabilizer.

    Evidence AKT/p38 inhibitor rescue and MMP analysis (chondrosarcoma); TSG101 Co-IP and degradation assays

    PMID:30094509 PMID:30450735

    Open questions at the time
    • TSG101 stabilization mechanism (direct vs proteasome-shielding) not fully defined
    • Kinase-pathway link is correlative through inhibitor rescue
  12. 2019 Medium

    Demonstrated the Gag domain retains capsid-like vesicle-budding and RNA-binding activity, tying these directly to trophoblast differentiation, and identified USP9X as a deubiquitinating regulator.

    Evidence Vesicle budding assay, RNA-IP, PEG10-deficient trophoblast stem cell differentiation, USP9X Co-IP

    PMID:30951545

    Open questions at the time
    • RNA cargo selectivity mechanism not yet defined
    • USP9X functional consequence on PEG10 levels not quantified here
  13. 2020 Medium

    Showed gag-pol self-cleavage liberates a nucleus-targeted nucleocapsid fragment affecting axon-remodeling genes and identified UBQLN2 as a regulator, opening the neurodegeneration axis.

    Evidence Protein fractionation, nuclear imaging, expression profiling, UBQLN2 perturbation in cells and spinal cord; plus D370A protease mutagenesis in proliferation assays

    PMID:32244497 PMID:36951542

    Open questions at the time
    • Nuclear fragment's direct gene targets unmapped
    • Protease's role in viability is bidirectional and incompletely explained
  14. 2021 High

    Crystallography confirmed capsid homology and biochemistry established self-mRNA encapsidation, while disease-context studies tied PEG10 to UBE3A/Angelman neurons, stress granules, and an IGF2BP1/m6A stabilization-to-cell-cycle axis.

    Evidence X-ray structure vs Gag CA; VLP purification, RNA-seq, UTR-swap delivery; proteomics with UBE3A ASO and ATXN2/10 Co-IP; RIP-seq/m6A/p16-p18 promoter binding

    PMID:33391523 PMID:34357660 PMID:34413232 PMID:34467244

    Open questions at the time
    • How nuclear PEG10 binds p16/p18 promoters mechanistically unclear
    • Stress-granule and EV roles not yet integrated with placental function
  15. 2021 High

    Genetically separated the two protein products in vivo, showing the ORF1/2 protease motif specifically maintains fetal capillary architecture, and added AR-repression/neuroendocrine and CTCL oncogenic contexts.

    Evidence Protease active-site knock-in mice with vascular histology; AR enhancer ChIP in NEPC; 7q21.3 amplification and PEG10/KLF2/NF-κB axis in CTCL

    PMID:31013476 PMID:34559199 PMID:34582557

    Open questions at the time
    • Protease substrate in fetal capillary maintenance not identified
    • ORF1-specific developmental role not yet dissected at this point
  16. 2023 High

    Resolved the selectivity of PEG10 turnover: only the gag-pol fusion is degraded via UBQLN2/UBE3A-dependent, lysine-specific ubiquitination, distinguishing it from the stable gag protein.

    Evidence Co-IP, ubiquitination assays, pol-region lysine mutagenesis, proteasome inhibition, UBE3A siRNA

    PMID:41234208

    Open questions at the time
    • Why gag escapes degradation despite UBQLN2 binding not fully explained
    • Physiological tissue where this control dominates not defined
  17. 2024 Medium

    Identified opposing capsid-domain partners and a stabilizing deubiquitinase, refining how PEG10 VLP formation and protein levels are tuned.

    Evidence RTL8 VLP incorporation/Co-IP and VLP quantification; USP9X Co-IP, ubiquitination assay, and in vivo CTCL model

    PMID:38677662 PMID:39775359

    Open questions at the time
    • Physiological role of RTL8 inhibition of VLPs unknown
    • USP9X mechanism studied only in CTCL
  18. 2026 High

    Established that SIAH1 and SIAH2 ubiquitinate the same PAIR domain at distinct lysines to produce opposite fates, providing a molecular basis for PEG10's bidirectional role in HCC.

    Evidence Co-IP, ubiquitination assays with site-specific lysine mutagenesis, xenografts, clinical correlation

    PMID:42168988

    Open questions at the time
    • How K48 vs K63 linkages at shared/distinct lysines yield opposite stability not mechanistically resolved
    • Interplay with UBQLN2/USP9X pathways untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PEG10's distinct activities — placental morphogenesis, capsid/RNA encapsidation, stress-granule/EV biology, neuronal splicing, and oncogenic signaling — are partitioned between its ORF1 and ORF1/2 products and coordinated in vivo remains unresolved.
  • Substrate repertoire of the aspartic protease unidentified
  • Direct nuclear/promoter targets of liberated PEG10 fragments unmapped
  • Neuronal splicing role (NRG3) and stress-granule functions rest on preprints awaiting peer review

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0016787 hydrolase activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ATXN2RTL8SIAH1SIAH2TSG101UBE3AUBQLN2USP9X
Complex memberships
stress granulevirus-like particle

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Peg10 knockout mice exhibit early embryonic lethality due to severe placental defects, specifically absence of both the spongiotrophoblast and labyrinth layers, establishing PEG10 as essential for placental formation in mammals. Gene knockout in mice (loss-of-function) with histological phenotypic readout Nature genetics High 16341224
2001 PEG10 encodes two overlapping open reading frames (ORF1 and ORF2) with homology to the Gag and Pol proteins of Ty3/gypsy LTR retrotransposons, establishing it as a retrotransposon-derived domesticated gene. Sequence analysis of predicted ORFs, genomic localization Genomics Medium 11318613
2007 PEG10 undergoes programmed −1 frameshifting during translation with >60% efficiency in developing mouse placenta and amniotic membrane, producing both the ORF1 protein and an ORF1-2 fusion protein. Mutagenesis of the active-site motif (Asp-Ser-Gly) of the putative aspartic protease within ORF2 demonstrated that this enzyme is active and participates in post-translational processing of the ORF1-2 protein. In vivo frameshifting reporter assay, active-site mutagenesis, protein detection in mouse and human placenta The Journal of biological chemistry High 17942406
2003 PEG10 protein physically associates with SIAH1 (a mediator of apoptosis), and overexpression of PEG10 decreases SIAH1-mediated cell death, establishing PEG10 as an inhibitor of SIAH1-dependent apoptosis. Co-immunoprecipitation, overexpression with functional apoptosis assay Cancer research Medium 12810624
2006 c-MYC directly binds to an E-box-containing region in the PEG10 first intron and activates PEG10 transcription; site-directed mutagenesis of the most proximal E-box abolished promoter activity, placing PEG10 as a direct transcriptional target of MYC. Chromatin immunoprecipitation (ChIP), RNAi knockdown of MYC, site-directed mutagenesis of E-box Cancer research High 16423995
2007 Androgen receptor (AR) directly binds to androgen-responsive elements in the promoter and exon 2 regions of the PEG10 gene in hepatoma cells (demonstrated by ChIP), and DHT-stimulated AR activates PEG10 expression to enhance HCC cell growth and apoptotic resistance and upregulate hTERT in a PEG10-dependent manner. ChIP assay, siRNA knockdown of AR and PEG10, AR transfection into AR-lacking cells, in vivo nude mouse xenograft Oncogene High 17369855
2008 Transcription factors E2F-1 and E2F-4 directly bind to the PEG10 promoter and regulate its expression, as shown by ChIP; PEG10 is involved in repression of apoptosis induced by serum deprivation and chemotherapeutic drugs. ChIP, promoter binding assay, functional apoptosis assay FEBS letters Medium 18625225
2017 E2F-1 directly enhances PEG10 expression by binding to the PEG10 promoter (shown by ChIP), and PEG10 knockdown causes G0/G1 arrest mediated by p21 and p27 upregulation, and reduces pancreatic cancer cell invasion via the ERK/MMP7 pathway. ChIP assay, siRNA knockdown, cell cycle and invasion assays Journal of experimental & clinical cancer research Medium 28193232
2010 PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon, adding a new layer to its translational complexity. Molecular cloning and mutational analysis of translation start sites, promoter-reporter constructs PloS one Medium 20084274
2019 The Gag domain of PEG10 promotes vesicle budding similar to HIV p24 Gag protein. PEG10 binds to numerous cellular RNAs including Hbegf mRNA, and loss of PEG10 in trophoblast stem cells reduces Hbegf expression and impairs differentiation into placental lineages. PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X. Vesicle budding assay, RNA immunoprecipitation/proteomics (Verschueren et al.), PEG10-deficient TSC differentiation assay, Co-IP for USP9X interaction PloS one Medium 30951545
2021 PEG10 is a mammalian Gag homolog that preferentially binds and facilitates vesicular secretion of its own mRNA via sequences in its 3′ UTR. The mRNA cargo of PEG10 can be reprogrammed by flanking genes of interest with PEG10's untranslated regions, enabling selective endogenous encapsidation for cellular delivery (SEND). Biochemical purification of virus-like particles, RNA sequencing of particle contents, UTR-flanking reporter assays, functional delivery assays in mouse and human cells Science (New York, N.Y.) High 34413232
2021 PEG10 protein increase (but not RNA) is dependent on UBE3A and proteasome function; UBE3A loss (as in Angelman syndrome neurons) leads to PEG10 protein accumulation. PEG10 binds to RNA and to ataxia-associated proteins ATXN2 and ATXN10, localizes to stress granules, and is secreted in extracellular vesicles where it modulates vesicle content. Overexpression of PEG10 during mouse brain development alters neuronal migration. Unbiased proteomics, antisense oligonucleotide modulation of UBE3A, Co-IP for ATXN2/ATXN10, stress granule localization imaging, extracellular vesicle purification, in vivo neuronal migration assay Cell reports. Medicine High 34467244
2021 The viral aspartic protease (DSG) motif in the POL-like region (ORF2) of PEG10 is essential for maintenance of fetal capillary structure in mid-to-late gestation placenta. Mice with a mutation in this motif show perinatal lethality with fetal vascular defects, specifically in the three trophoblast layers surrounding fetal capillary endothelial cells where PEG10 is expressed. Active-site knock-in mutagenesis in mice, histological analysis of placental vasculature, in situ expression localization Development (Cambridge, England) High 34559199
2020 The PEG10 gag-pol protein undergoes retrotransposon-like self-cleavage to generate a liberated 'nucleocapsid' fragment that uniquely localizes to the nucleus and alters expression of genes involved in axon remodeling. UBQLN2 regulates PEG10 gag-pol protein levels in human cells and spinal cord tissue. Protein fractionation, nuclear localization imaging, gene expression profiling, UBQLN2 knockdown/overexpression eLife Medium 36951542
2021 X-ray crystal structures of a stably folded domain of PEG10 reveal high structural similarity to the C-terminal capsid (CA) domain of cognate Gag proteins from LTR retrotransposons, confirming PEG10 as a domesticated Gag and suggesting possible preservation of capsid-assembly interactions. X-ray crystallography with structural comparison Proteins High 34357660
2020 The aspartic protease domain of PEG10 ORF1/2 (containing the -Asp-Ser-Gly- active-site motif) is functionally active; overexpression of the ORF1/2 form increases cellular proliferation but also has a detrimental effect on cell viability, while an active-site D370A mutant alters these effects, indicating the protease domain modulates proliferation and viability. Active-site mutagenesis (D370A), cell transfection, proliferation and viability assays in HEK293T and HaCaT cells International journal of molecular sciences Medium 32244497
2017 The menin-MLL1 complex binds the PEG10 promoter and promotes H3K4 methylation to activate PEG10 transcription; pharmacological inhibition of the menin-MLL interaction with MI-503 displaces the complex from the PEG10 promoter, reduces H3K4 methylation, and transcriptionally represses PEG10 in HCC models. ChIP assay for menin-MLL1 at PEG10 promoter and H3K4me marks, small-molecule inhibitor treatment, in vivo xenograft Molecular cancer therapeutics Medium 29142068
2016 PEG10 is required for TGF-β1-induced epithelial-mesenchymal transition (EMT) in HCC cells; cells with PEG10 knocked down do not undergo EMT upon TGF-β1 stimulation and show reduced migration and invasion. Conversely, TGF-β1 upregulates PEG10 expression, and PEG10 overexpression confers chemoresistance. Adenoviral shRNA knockdown, overexpression, TGF-β1 stimulation, migration/invasion assays, EMT marker analysis Oncology reports Medium 28004118
2017 PEG10 represses TGF-β and BMP-SMAD signaling pathways (both SMAD2/3 and SMAD1/5/9 branches) in chondrosarcoma cells; PEG10 knockdown increases phospho-SMAD3 and phospho-SMAD1/5/9, and reporter assays show PEG10 directly represses TGF-β and BMP signaling while TGF-β1 in turn suppresses PEG10 expression, establishing a mutually inhibitory relationship. Luciferase reporter assays for SMAD pathway activity, siRNA knockdown, immunoblotting for phospho-SMADs, microarray Scientific reports Medium 29044189
2018 PEG10 knockdown in chondrosarcoma cells augments TGF-β1-induced motility via AKT phosphorylation (reversed by AKT inhibitor MK2206), and augments BMP-6-induced invasion via p38 MAPK and AKT pathways and upregulation of MMP-1, -3, and -13, identifying PEG10 as an inhibitor of TGF-β/BMP-driven motility and invasion through these kinase cascades. siRNA knockdown, AKT and p38 inhibitors, MMP inhibitors, invasion assays, immunoblotting Journal of bone and mineral metabolism Medium 30094509
2018 TSG101 physically interacts with PEG10 and protects it from proteasomal degradation; knockdown of TSG101 reduces PEG10 protein levels and downstream effectors p53, p21, and MMPs, while overexpression has opposite effects. Co-immunoprecipitation, iTRAQ proteomics, siRNA knockdown, overexpression, immunoblotting Journal of cellular and molecular medicine Medium 30450735
2019 Activated AR binds to the PEG10 enhancer (confirmed by ChIP assay) and represses PEG10 expression. Antagonism of AR increases PEG10 expression followed by increased neuroendocrine (NE) markers; androgen supplementation reverses this. PEG10 knockdown reduces NE markers and attenuates tumor growth in vitro and in vivo. ChIP assay, AR agonist/antagonist treatment, siRNA knockdown, in vivo xenograft Journal of molecular endocrinology Medium 31013476
2021 IGF2BP1 recognizes m6A sites in the 3′ UTR of PEG10 mRNA and recruits PABPC1 to enhance PEG10 mRNA stability, consequently increasing PEG10 protein expression; a large proportion of PEG10 protein then binds p16 and p18 gene promoter sequences to repress their expression and accelerate the cell cycle. RNA-binding protein immunoprecipitation sequencing (RIP-seq), methylated RIP-seq, RNA-seq, Co-immunoprecipitation and mass spectrometry, xenograft Theranostics Medium 33391523
2016 miR-122 suppresses PEG10 protein expression via direct binding to the 3′ UTR of the PEG10 transcript (translational repression rather than mRNA degradation), demonstrated by reporter assay; deficiency of miR-122 in knockout mice is associated with increased PEG10 and HCC progression. Luciferase reporter assay, miR-122 overexpression, miR-122 knockout mouse model, qRT-PCR and western blot Journal of translational medicine Medium 27370270
2007 peg10 expression is induced early in adipocyte differentiation; peg10 RNAi inhibits 3T3-L1 differentiation into lipid-laden adipocytes, reduces C/EBPβ and C/EBPδ expression, and inhibits mitotic clonal expansion, establishing PEG10 as essential for adipogenesis at the immediate early stage. RNAi knockdown, adipocyte differentiation assay, gene expression analysis FEBS letters Medium 17707377
2022 PEG10 overexpression in cutaneous T-cell lymphoma increases cell size, promotes cell proliferation, and confers treatment resistance via a PEG10/KLF2/NF-κB signaling axis, driven by 7q21.3 amplification in large-cell transformation. Genomic hybridization, in vitro and in vivo models, pathway analysis (PEG10/KLF2/NF-κB), pharmacological targeting Blood Medium 34582557
2024 USP9X (a deubiquitinase) interacts with PEG10 and deubiquitinates it, thereby stabilizing PEG10 protein levels. Knockdown or pharmacological inhibition of USP9X leads to downregulation of PEG10 and its downstream pathway in CTCL, and impairs tumor growth in vivo. Co-immunoprecipitation, ubiquitination assay, USP9X knockdown/inhibitor, in vivo tumor model The Journal of investigative dermatology Medium 38677662
2023 UBQLN2 regulates proteasomal degradation of the PEG10 gag-pol protein specifically (not the gag protein). Both forms bind UBQLN2 independently of ubiquitination, but only gag-pol is degraded in a UBQLN2-, ubiquitin-, and proteasome-dependent fashion. Gag-pol ubiquitination is dependent on E3 ubiquitin ligase UBE3A, which requires UBQLN2 to regulate gag-pol levels; mutation of key lysine residues in the pol region renders gag-pol insensitive to UBQLN2. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis of lysine residues, proteasome inhibitor treatment, UBE3A siRNA knockdown Journal of cell science High 41234208
2026 SIAH1 and SIAH2 both bind to the PAIR domain of PEG10 and promote its polyubiquitination, but with opposing functional consequences: SIAH1 mediates K48-linked ubiquitination at Lys36 and K63-linked at Lys170, leading to decreased PEG10 levels and suppression of HCC; SIAH2 mediates K48-linked ubiquitination at Lys36 and K63-linked at Lys19 and Lys155, resulting in net accumulation of PEG10 and promotion of HCC. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis of lysine residues, xenograft models, clinical sample correlation Cell communication and signaling High 42168988
2024 RTL8, a related Mart-family gene whose protein shares homology with the N-terminal gag-like capsid domain of PEG10, is incorporated into PEG10-derived virus-like particles (VLPs) and inhibits PEG10 VLP formation or release by binding to the N-terminal domain of PEG10 capsid, decreasing VLP abundance and increasing intracellular PEG10. VLP purification by iodixanol ultracentrifugation, Co-IP of RTL8 with PEG10, RTL8 overexpression/knockdown with VLP quantification PloS one Medium 39775359
2023 PEG10 knockdown in trophoblast stem cells (hTSCs) reduces activation of the canonical TGF-β signaling effector SMAD binding element (luciferase assay), indicating that PEG10 positively regulates canonical TGF-β signaling in trophoblasts. siRNA knockdown of PEG10 in hTSCs, SMAD binding element luciferase reporter assay Reproductive biology and endocrinology Low 37464405
2015 The AR and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at distinct stages of neuroendocrine prostate cancer development; PEG10 promotes G0/G1 cell-cycle progression in the context of TP53 loss and regulates Snail expression via TGF-β signaling to promote invasion. Patient-derived xenograft model of NEPC, siRNA knockdown, cell cycle analysis, invasion assay Cell reports Medium 26235627
2021 Menin displaces the menin-MLL1 complex from the PEG10 promoter upon pharmacological inhibition, reducing H3K4 methylation and causing transcriptional repression of PEG10 (replicated finding, corroborating the Kempinska 2017 paper). ChIP assay, MI-503 inhibitor treatment Acta pharmacologica Sinica Low 34876700
2025 PEG10-ORF1 (Gag-like protein) plays an essential and distinct role in labyrinth trophoblast precursor (LaTP) cell development and mid-to-late gestational labyrinthine microarchitecture; mice retaining only the ORF1/2 fusion but lacking ORF1 protein show placental labyrinth underdevelopment and growth retardation, distinguishing the roles of the two PEG10 protein products. Genetic mouse model with selective ablation of ORF1 while preserving ORF1/2 protein, histological placental analysis, cell lineage analysis bioRxivpreprint Medium bio_10.1101_2025.10.08.681076
2024 PEG10, as a core component of stress granules, drives recruitment of UBQLN2 to stress granules (requires RTL8 co-expression), remodels kinetics of stress granule disassembly, and alters stress granule composition by incorporating extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles. Stress granule imaging, UBQLN2 co-localization, VLP detection within condensates, RTL8 knockdown/overexpression bioRxivpreprint Low bio_10.1101_2024.10.24.620053
2026 PEG10 overexpression in neurons selectively binds U/G-rich RNAs and causes widespread mRNA splicing changes, including an exon-skipping event in neuregulin 3 (NRG3), reducing NRG3 protein levels along cellular processes and impairing NRG3/ERBB4 signaling. These splicing changes partially overlap with changes seen in UBQLN2-associated and sporadic ALS patient samples. RNA-seq after PEG10 overexpression, RNA-binding selectivity assay, immunofluorescence for NRG3, comparison with ALS patient data bioRxivpreprint Low 42239172

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nature genetics 351 16341224
2021 Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science (New York, N.Y.) 330 34413232
2015 The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer. Cell reports 237 26235627
2001 A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics 215 11318613
2021 IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. Theranostics 175 33391523
2003 Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer research 143 12810624
2007 Mammalian gene PEG10 expresses two reading frames by high efficiency -1 frameshifting in embryonic-associated tissues. The Journal of biological chemistry 96 17942406
2006 PEG10 is a c-MYC target gene in cancer cells. Cancer research 86 16423995
2003 Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta. Biology of reproduction 72 12620933
2019 The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification. PloS one 62 30951545
2003 Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers. Journal of biomedical science 62 14576465
2018 PEG10 as an oncogene: expression regulatory mechanisms and role in tumor progression. Cancer cell international 60 30123090
2007 Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia. International journal of cancer 59 17621626
2017 PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer. Journal of experimental & clinical cancer research : CR 50 28193232
2016 PEG10 promotes human breast cancer cell proliferation, migration and invasion. International journal of oncology 50 26934961
2015 Long noncoding RNA PEG10 regulates proliferation and invasion of esophageal cancer cells. Cancer gene therapy 50 25591808
2021 Secreted retrovirus-like GAG-domain-containing protein PEG10 is regulated by UBE3A and is involved in Angelman syndrome pathophysiology. Cell reports. Medicine 45 34467244
2018 The effects of Curcumin on HCT-116 cells proliferation and apoptosis via the miR-491/PEG10 pathway. Journal of cellular biochemistry 45 29058812
2017 Pharmacologic Inhibition of the Menin-MLL Interaction Leads to Transcriptional Repression of PEG10 and Blocks Hepatocellular Carcinoma. Molecular cancer therapeutics 45 29142068
2006 Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma. Cancer letters 44 17126992
2004 PEG10 activation by co-stimulation of CXCR5 and CCR7 essentially contributes to resistance to apoptosis in CD19+CD34+ B cells from patients with B cell lineage acute and chronic lymphocytic leukemia. Cellular & molecular immunology 44 16225771
2010 Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation. PloS one 40 20084274
2007 Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells. Oncogene 37 17369855
2020 LncRNA SNAI3-AS1 promotes PEG10-mediated proliferation and metastasis via decoying of miR-27a-3p and miR-34a-5p in hepatocellular carcinoma. Cell death & disease 36 32826862
2008 PEG10 directly regulated by E2Fs might have a role in the development of hepatocellular carcinoma. FEBS letters 35 18625225
2007 peg10, an imprinted gene, plays a crucial role in adipocyte differentiation. FEBS letters 34 17707377
2021 PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta. Development (Cambridge, England) 33 34559199
2019 PEG10 is associated with treatment-induced neuroendocrine prostate cancer. Journal of molecular endocrinology 33 31013476
2017 The H19-PEG10/IGF2BP3 axis promotes gastric cancer progression in patients with high lymph node ratios. Oncotarget 32 29088808
2023 UBQLN2 restrains the domesticated retrotransposon PEG10 to maintain neuronal health in ALS. eLife 30 36951542
2022 LncRNA NALT1 promotes colorectal cancer progression via targeting PEG10 by sponging microRNA-574-5p. Cell death & disease 28 36385135
2019 RETRACTED: lncRNA PEG10 promotes cell survival, invasion and migration by sponging miR-134 in human bladder cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 30953817
2018 TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10. Journal of cellular and molecular medicine 24 30450735
2012 PEG10 promotes the migration of human Burkitt's lymphoma cells by up-regulating the expression of matrix metalloproteinase-2 and -9. Clinical and investigative medicine. Medecine clinique et experimentale 23 22673314
2013 Regulation of murine placentogenesis by the retroviral genes Syncytin-A, Syncytin-B and Peg10. Differentiation; research in biological diversity 22 23807393
2017 Overexpression of long noncoding RNA PEG10 promotes proliferation, invasion and metastasis of hypopharyngeal squamous cell carcinoma. Oncology letters 21 28928830
2010 PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. Cancer genetics and cytogenetics 21 20362226
2022 PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma. Blood 20 34582557
2019 LncRNA PEG10 aggravates cardiac hypertrophy through regulating HOXA9. European review for medical and pharmacological sciences 19 31389601
2016 PEG10 is imperative for TGF-β1-induced epithelial‑mesenchymal transition in hepatocellular carcinoma. Oncology reports 19 28004118
2015 Partial Loss of Genomic Imprinting Reveals Important Roles for Kcnq1 and Peg10 Imprinted Domains in Placental Development. PloS one 19 26241757
2020 Functional Study of the Retrotransposon-Derived Human PEG10 Protease. International journal of molecular sciences 18 32244497
2016 miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma. Journal of translational medicine 18 27370270
2023 Roles of retrovirus-derived PEG10 and PEG11/RTL1 in mammalian development and evolution and their involvement in human disease. Frontiers in cell and developmental biology 17 37842090
2020 Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer. Diseases of the colon and rectum 17 33149023
2017 TGF-β signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells. Scientific reports 16 29044189
2020 Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion, and Survival of Bladder Cancer. Molecular cancer therapeutics 15 32847979
2021 Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression. International ophthalmology 13 34633608
2020 Long Non-Coding RNA Paternally Expressed Imprinted Gene 10 (PEG10) Elevates Diffuse Large B-Cell Lymphoma Progression by Regulating Kinesin Family Member 2A (KIF2A) via Targeting MiR-101-3p. Medical science monitor : international medical journal of experimental and clinical research 13 32976381
2019 Knockdown long non-coding RNA PEG10 inhibits proliferation, migration and invasion of glioma cell line U251 by regulating miR-506. General physiology and biophysics 13 31241046
2019 PEG10 Promoter-Driven Expression of Reporter Genes Enables Molecular Imaging of Lethal Prostate Cancer. Cancer research 13 31530569
2021 Transcriptional regulator CTR9 promotes hepatocellular carcinoma progression and metastasis via increasing PEG10 transcriptional activity. Acta pharmacologica Sinica 12 34876700
2021 Folate deficiency disturbs PEG10 methylation modifications in human spina bifida. Pediatric research 12 34934172
2018 Knockdown of long non-coding RNA PEG10 inhibits growth, migration and invasion of gastric carcinoma cells via up-regulating miR-3200. Neoplasma 12 29940767
2018 PEG10 counteracts signaling pathways of TGF-β and BMP to regulate growth, motility and invasion of SW1353 chondrosarcoma cells. Journal of bone and mineral metabolism 12 30094509
2011 Elevated expression of PEG10 in human placentas from preeclamptic pregnancies. Acta histochemica 12 22137777
2007 Imprinting analyses of the porcine GATM and PEG10 genes in placentas on days 75 and 90 of gestation. Genes & genetic systems 12 17660697
2023 Targeting PEG10 as a novel therapeutic approach to overcome CDK4/6 inhibitor resistance in breast cancer. Journal of experimental & clinical cancer research : CR 11 38017459
2020 The Landscape of Genomic Imprinting at the Porcine SGCE/PEG10 Locus from Methylome and Transcriptome of Parthenogenetic Embryos. G3 (Bethesda, Md.) 11 32878957
2015 HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators. PloS one 11 26447468
2019 Long noncoding RNA PEG10 facilitates bladder cancer cells proliferation, migration, and invasion via repressing microRNA-29b. Journal of cellular physiology 10 30941768
2022 Silencing of long chain noncoding RNA paternally expressed gene (PEG10) inhibits the progression of neuroblastoma by regulating microRNA-449a (miR-449a)/ribosomal protein S2 (RPS2) axis. Bioengineered 9 35212607
2023 Paternal Expressed Gene 10 (PEG10) is decreased in early-onset preeclampsia. Reproductive biology and endocrinology : RB&E 7 37464405
2023 GPC3 and PEG10 peptides associated with placental gp96 elicit specific T cell immunity against hepatocellular carcinoma. Cancer immunology, immunotherapy : CII 7 37932427
2022 Influences of fresh and frozen embryo transfer on neonatal birthweight and the expression of imprinted genes PEG10 /L3MBTL1 in placenta. Reproductive biology 7 35714554
2021 Structural evidence that MOAP1 and PEG10 are derived from retrovirus/retrotransposon Gag proteins. Proteins 7 34357660
2014 Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia. Genetics and molecular research : GMR 7 25526181
1990 Extragenic suppressors of mar2(sir3) mutations in Saccharomyces cerevisiae. Genetics 7 2199314
2021 Expression and DNA Methylation Status of the Imprinted Genes PEG10 and L3MBTL1 in the Umbilical Cord Blood and Placenta of the Offspring of Assisted Reproductive Technology. Reproductive sciences (Thousand Oaks, Calif.) 6 33515207
2010 Molecular and DNA methylation analysis of Peg10 and Xist gene in sheep. Molecular biology reports 6 21113679
2024 The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles. PloS one 5 39775359
2008 [Genetic imprinted gene PEG10 expression in deciduas from inevitable abortion]. Yi chuan = Hereditas 4 18550496
2025 Roles of PEG10 in cancer and neurodegenerative disorder (Review). Oncology reports 3 40183369
2024 Abrogation of USP9X Is a Potential Strategy to Decrease PEG10 Levels and Impede Tumor Progression in Cutaneous T-Cell Lymphoma. The Journal of investigative dermatology 3 38677662
2022 CRISPR activation screen identifies TGFβ-associated PEG10 as a crucial tumor suppressor in Ewing sarcoma. Scientific reports 3 35739280
2011 [The methylation status of PEG10 in placentas of cloned transgenic calves]. Yi chuan = Hereditas 3 21586401
2010 Biallele expression of PEG10 gene in primordial germ cells derived from day 27 porcine fetuses. Reproduction in domestic animals = Zuchthygiene 3 20345586
2024 NAP1L5 promotes epithelial-mesenchymal transition by regulating PEG10 expression in acute myeloid leukaemia. Leukemia research 2 39579659
2010 [MiR-122 regulates the expression of PEG10 in hepatoma cell lines]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 2 20460050
2009 Suppressive effects of genomic imprinted gene PEG10 on hydrogen peroxide-induced apoptosis in L02 cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 2 20037811
2025 Evolutionary dynamics of PEG10 and its interacting proteins during early and late-stage placental development in ruminants. International journal of biological macromolecules 1 40180104
2025 UBQLN2 is necessary for UBE3A-mediated proteasomal degradation of the domesticated retroelement PEG10. Journal of cell science 1 41234208
2009 [Establishment of PEG10 transgenic mouse and effects of PEG10 on growth, metastasis of transplanted tumor in mice]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 19567027
2007 [Construction of recombinant plasmid human imprinted gene PEG10 and the primary functional identification in transfected cell lines]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 17456318
2026 Placenta-Driven Evolution: Viral Gene Acquisition and PEG10's Essential Roles in Eutherian Placenta. Biomolecules 0 41594701
2026 Polyubiquitination and accumulation of PEG10 regulated by SIAH1/2 affiliates the progression of hepatocellular carcinoma. Cell communication and signaling : CCS 0 42168988
2026 miR-379-5p promotes ovarian granulosa cell apoptosis in primary ovarian insufficiency by targeting KNDC1 and PEG10. Frontiers in genetics 0 42205180
2026 The retroelement-derived human protein PEG10 is a regulator of mRNA splicing in neurons. bioRxiv : the preprint server for biology 0 42239172
2025 Construction of a TAT-Cas9-EGFP Site-Specific Integration Eukaryotic Cell Line Using Efficient PEG10 Modification. International journal of molecular sciences 0 39941098
2025 Knockdown of FOXD3-AS1 inhibits the progression of prostate cancer by targeting miR-491-5p/PEG10. Journal of cancer research and clinical oncology 0 41291383
2025 PEG10 loss of function causes Silver-Russell syndrome: a familial case with paternal deletion. Scientific reports 0 41429883
2024 The landscape of allelic expression and DNA methylation at the bovine SGCE/PEG10 locus. Animal genetics 0 38594908
2010 [The imprinting status of genetic imprinted gene PEG10 in human hepatocellular carcinomas]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 0 21205473

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