Affinage

HERC5

E3 ISG15--protein ligase HERC5 · UniProt Q9UII4

Length
1024 aa
Mass
116.9 kDa
Annotated
2026-06-10
48 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HERC5 is the principal cellular E3 ligase for ISG15 conjugation (ISGylation) in human cells and a central effector of interferon-induced innate antiviral immunity (PMID:16407192, PMID:38303729). It is an interferon-induced HECT-type ligase whose catalytic activity depends on an active-site cysteine, Cys994, in its C-terminal HECT domain; this residue is essential, since its substitution abolishes ISGylation, and HERC5 reconstitutes robust ISG15 conjugation together with the E1 UBE1L and E2 UbcH8 (PMID:16815975, PMID:16407192). As a ribosome-associated ligase, HERC5 ISGylates a broad spectrum of nascent polypeptides cotranslationally, modifying thousands of lysines across over a thousand proteins, with sequence-context preferences distinct from the mouse homolog HERC6 (PMID:38303729). Through this activity HERC5 amplifies innate immune signaling by ISGylating pathway components: it modifies IRF3 to block its Pin1-dependent degradation and sustain antiviral gene expression (PMID:20308324, PMID:40505230), promotes cGAS oligomerization and enzymatic activity (PMID:38421872), and drives MDA5 CARD-domain oligomerization required for downstream signaling [PMID:bio_10.1101_2024.09.20.614144]. HERC5 also directly restricts viruses by ISGylating viral proteins to disrupt their function — blocking influenza NS1 and SARS-CoV-2 nucleocapsid oligomerization and targeting SARS-CoV-2 nsp8 for degradation (PMID:20385878, PMID:39194248, PMID:39149229, PMID:40409630). A second, ISGylation-independent antiviral activity resides in its N-terminal RCC1-like domain, which inhibits Rev/RRE-dependent nuclear RNA export and reduces RanGTP levels to restrict HIV-1 (PMID:24693865). Beyond antiviral defense, HERC5-mediated ISGylation regulates cellular substrates including PTEN, β-catenin, IFI16, and UGDH, linking it to inflammatory signaling and cancer-associated pathways (PMID:37279284, PMID:28744352, PMID:35671810, PMID:40045362).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 Medium

    Established that HERC5 is an active ubiquitin-pathway E3 ligase, providing the first biochemical evidence of its enzymatic activity before its ISG15-specific role was known.

    Evidence In vitro ubiquitin ligase assay with UbcH5a and protein/mRNA quantification in endothelial cells

    PMID:15331633

    Open questions at the time
    • Did not identify ISG15 as the relevant conjugate
    • No active-site mutagenesis
    • Physiological substrates unknown
  2. 2005 High

    Identified HERC5 as the enzyme required for the bulk of cellular ISG15 conjugation, defining its function as a general ISG15 E3 ligase rather than a generic ubiquitin ligase.

    Evidence siRNA knockdown, four-component reconstitution, and active-site plus RCC1-deletion mutants in human cells

    PMID:16407192

    Open questions at the time
    • Substrate selection mechanism unresolved
    • Did not map specific modified lysines
  3. 2006 High

    Defined the catalytic and enzymatic logic of HERC5 ISGylation by pinpointing the essential HECT active-site Cys994 and showing it physically binds and stimulates ISGylation of targets with E1/E2 dependence.

    Evidence C994A mutagenesis, co-transfection reconstitution, proteomic substrate identification and reciprocal Co-IP

    PMID:16815975 PMID:16884686

    Open questions at the time
    • Mechanism conferring ISG15 over ubiquitin specificity not explained
    • Functional consequence of ISGylation on substrates not yet defined
  4. 2010 High

    Showed that HERC5 ISGylation can stabilize a substrate to amplify signaling, establishing a positive-regulatory role in innate immunity through IRF3 modification.

    Evidence Co-IP, IRF3 lysine-site mutagenesis, and Sendai virus infection assays linking ISGylation to blocked Pin1-mediated degradation

    PMID:20308324

    Open questions at the time
    • Did not establish in vivo physiological requirement
    • Interplay with deISGylases not addressed
  5. 2010 High

    Demonstrated a direct antiviral mechanism whereby ISGylation of a viral protein disrupts its function, exemplified by influenza NS1.

    Evidence Mass spectrometry site mapping, mutagenesis, homodimerization assay, and viral replication assays in cells and mice

    PMID:20385878

    Open questions at the time
    • Generality of oligomerization-blocking mechanism across viral substrates untested at the time
  6. 2014 High

    Revealed a second, catalytically independent antiviral activity in the N-terminal RCC1-like domain, separating HERC5's ligase function from its control of nuclear RNA export.

    Evidence Domain mutagenesis, Rev/RRE nuclear export assays, RanGTP and RanBP1 measurements, and localization imaging for HIV-1

    PMID:22093708 PMID:24693865

    Open questions at the time
    • Molecular target of the RCC1-like domain on the Ran cycle not defined
    • Generality beyond HIV-1 untested in these studies
  7. 2023 Medium

    Extended HERC5 ISGylation to destabilizing substrates and to antibacterial defense, showing ISGylation can target proteins for degradation to reprogram signaling.

    Evidence Co-IP, KO macrophages, PI3K-AKT analysis, and bacterial growth assays for PTEN; viral-hijacking Co-IP and in vivo assays for JAK1 ubiquitination

    PMID:37279284 PMID:37417777

    Open questions at the time
    • JAK1 ubiquitination represents virus-directed hijacking distinct from ISGylation
    • Determinants of degradative vs stabilizing outcome unclear
  8. 2024 High

    Established HERC5 as a ribosome-associated cotranslational ISGylation machine acting on nascent polypeptides at proteome scale, defining the operating mode of the enzyme.

    Evidence Large-scale mass spectrometry ISGylome profiling in IFN-β-stimulated cells with sequence-context analysis and HERC6 comparison

    PMID:38303729

    Open questions at the time
    • How cotranslational targeting reconciles with selective regulatory substrates is unresolved
    • Determinants of site selection beyond local sequence unclear
  9. 2024 Medium

    Showed ISGylation can activate immune sensors by promoting oligomerization, generalizing the positive-regulatory role across the cGAS-STING and RIG-I-like receptor pathways.

    Evidence Mass spectrometry site mapping, domain mapping, oligomerization and enzymatic activity assays, and KO/knock-in mouse infection models for cGAS and MDA5

    PMID:38421872 PMID:bio_10.1101_2024.09.20.614144

    Open questions at the time
    • MDA5 evidence is from a preprint
    • Stoichiometry of ISGylation needed for oligomerization not quantified
  10. 2024 Medium

    Defined the antagonism between HERC5 ISGylation and viral deISGylases, showing SARS-CoV-2 proteins are ISGylated to block oligomerization and target replication factors for degradation, countered by PLpro.

    Evidence Mass spectrometry, mutagenesis, replicon systems, oligomerization assays, and PLpro deISGylation assays for N protein and nsp8

    PMID:39194248 PMID:40409630

    Open questions at the time
    • Relative contribution of N vs nsp8 ISGylation to restriction unresolved
    • In vivo relevance not established
  11. 2025 Medium

    Provided a structural basis for HERC5's exclusive ISGylation specificity, explaining why UbcH8~ISG15 engages HECT but not RING/RBR E3s.

    Evidence Structural and biochemical analysis of UbcH8~ISG15 conformation and trans-thiolation specificity (preprint)

    PMID:bio_10.1101_2025.09.26.678755

    Open questions at the time
    • Preprint not peer-reviewed
    • No high-resolution complex structure of HERC5 with charged E2
    • Awaits independent confirmation
  12. 2025 Medium

    Implicated HERC5 in non-antiviral cellular contexts including cancer-associated substrate regulation and retrotransposon control via ISGylation-independent RNA binding.

    Evidence Co-IP and ISGylation/xenograft assays for UGDH; retrotransposition, RNA-IP, and catalytic-mutant analyses for LINE-1 ORF1p

    PMID:40045362 PMID:42055552

    Open questions at the time
    • Mechanism of ISGylation-independent RNA binding undefined
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HERC5 reconciles broad cotranslational ISGylation of nascent chains with selective, functionally consequential modification of specific regulatory and viral substrates, and how its HECT trimerization and RCC1-like domain are coordinated, remain open.
  • No unified model linking cotranslational targeting to substrate-specific outcomes
  • Functional role of HECT trimerization undemonstrated
  • Regulation of the two distinct antiviral mechanisms not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0031386 protein tag activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 1 GO:0005840 ribosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 2
Partners
CGASCTNNB1IRF3ISG15MDA5PTENUBA7UBCH8

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 HERC5 (also known as Ceb1) is an IFN-induced HECT-type E3 protein ligase that mediates ISGylation. Its active-site cysteine (Cys-994) in the HECT domain is required for E3 ligase activity, as a C994A substitution completely abrogates ISGylation. HERC5 coexpression with Ube1L (E1) and UbcH8 (E2) reconstitutes ISG15 conjugation in vivo independent of IFN stimulation. Active-site mutagenesis (C994A), siRNA knockdown, co-transfection reconstitution, in vivo ISGylation assay Proceedings of the National Academy of Sciences of the United States of America High 16815975
2005 Herc5 is required for ISG15 conjugation to a broad spectrum of target proteins in human cells. siRNA knockdown of Herc5 abolishes the vast majority of ISG15 conjugation. Co-transfection of ISG15, Ube1L, UbcH8, and Herc5 reconstitutes robust ISG15 conjugation in non-IFN-treated cells. The active-site cysteine mutant of Herc5 and a mutant lacking the RCC1 repeat region do not support ISG15 conjugation. siRNA knockdown, co-transfection reconstitution, active-site mutagenesis, domain deletion mutagenesis The Journal of biological chemistry High 16407192
2004 HERC5 possesses ubiquitin ligase activity in vitro and requires the ubiquitin-conjugating enzyme UbcH5a for its activity. HERC5 protein is subject to enhanced degradation upon LPS stimulation of endothelial cells despite upregulation of its mRNA. In vitro ubiquitin ligase assay, subcellular fractionation/western blot, differential mRNA/protein quantification Journal of cell science Medium 15331633
2006 Herc5 functions as a general E3 ISG15 ligase that physically binds target proteins and stimulates their ISGylation in a UBE1L- and UbcH8-dependent manner. Six novel ISGylation substrates were identified by proteomics and confirmed by immunoblot. Proteomic identification of substrates, co-immunoprecipitation, immunoblot, E1/E2 dependency assay Biochemical and biophysical research communications Medium 16884686
2010 HERC5 binds IRF3 (identified by immunoprecipitation) and catalyzes ISGylation of IRF3 at Lys193, Lys360, and Lys366. This ISGylation attenuates the interaction between Pin1 and IRF3, preventing IRF3 polyubiquitination and degradation, thereby sustaining IRF3 activation and antiviral gene expression. Co-immunoprecipitation, site-directed mutagenesis of IRF3 lysines, siRNA knockdown, overexpression, Sendai virus infection assay Molecular and cellular biology High 20308324
2010 Herc5 catalyzes ISGylation of influenza A virus NS1 protein at Lys20, Lys41, Lys108, Lys110, Lys126, Lys217, and Lys219. ISGylated NS1 fails to form homodimers and its antiviral inhibitory functions are blocked. Knockdown of Herc5 partially alleviates IFN-β-induced antiviral activity, while ectopic expression of the Herc5-mediated ISGylation system potentiates antiviral effects. Mass spectrometry mapping of ISGylation sites, mutagenesis, homodimerization assay, siRNA knockdown, viral replication assay, mouse infection model Journal of immunology High 20385878
2011 HERC5 inhibits HIV-1 Gag particle production. E3 ligase activity of HERC5 is required for this restriction, which correlates with ISGylation of HIV-1 Gag. HERC5 interacts with HIV-1 Gag but does not alter Gag trafficking to the plasma membrane. Electron microscopy shows HIV-1 Gag particle assembly is arrested at the plasma membrane at an early stage. HERC5 also restricts murine leukemia virus Gag particle production. Overexpression, siRNA knockdown, co-immunoprecipitation, electron microscopy, Gag particle production assay, active-site mutant analysis Retrovirology High 22093708
2014 HERC5 inhibits HIV-1 particle production by a second mechanism distinct from ISGylation: it targets nuclear export of Rev/RRE-dependent RNA via its RCC1-like domain (N-terminal), without requiring E3 ligase activity. This inhibition correlates with reduced intracellular RanGTP levels and/or impaired RanGTP–RanBP1 interaction, and with altered subcellular localization of HIV-1 Rev. A region in the RCC1-like domain under strong positive evolutionary selection is required for this activity. Domain deletion/mutagenesis, Rev/RRE-dependent nuclear export assay, RanGTP level measurement, RanBP1 interaction assay, subcellular localization imaging, positive selection analysis Retrovirology High 24693865
2017 HERC5 physically interacts with β-catenin (immunoprecipitation) and mediates ISGylation of β-catenin, promoting its proteasomal degradation. CYP1B1 suppresses Herc5 expression, thereby stabilizing β-catenin and activating Wnt/β-catenin signaling in HeLa cells. Co-immunoprecipitation, RT-PCR, western blot, siRNA knockdown, CYP1B1 overexpression/inhibition Toxicological research Medium 28744352
2021 HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein (HBx) at Lys91, Lys95, and Lys140. This ISGylation promotes pro-viral HBV replication and contributes to IFN-α resistance, as silencing ISG15 markedly reduced HBV replication in IFN-α-treated cells while silencing USP18 (de-ISGylase) increased replication. Immunoblot, site-directed mutagenesis, expression plasmids for E3 ligases, siRNA knockdown, HBV replication assay The Journal of general virology Medium 34661519
2021 HERC5 recruits an adaptor protein (CREB-binding protein) to ubiquitinate CtBP1 in non-cancerous colon cells. Downregulation of HERC5 in colorectal cancer attenuates CtBP1 ubiquitination, allowing CtBP1 to accumulate and assemble a transcriptional complex with HDAC1 and c-MYC that represses pro-apoptotic genes (BAX, BIK, PUMA). Co-immunoprecipitation, ubiquitination assay, western blot, siRNA knockdown, overexpression, promoter binding assay, in vivo xenograft Carcinogenesis Medium 34147029
2023 HERC5 (human) and mHERC6 (mouse) mediate ISGylation of the phosphatase PTEN in macrophages, promoting PTEN degradation and thereby increasing PI3K-AKT signaling and proinflammatory cytokine synthesis, enhancing antimycobacterial responses. Co-immunoprecipitation, ISGylation assay, siRNA knockdown, KO macrophages, PI3K-AKT pathway analysis, bacterial growth assay in vitro and in vivo Science signaling Medium 37279284
2023 African swine fever virus MGF-360-10L recruits HERC5 to mediate K48-linked ubiquitination (not ISGylation) of JAK1 at Lys245 and Lys269, leading to JAK1 proteasomal degradation and suppression of STAT1/2 signaling. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, viral deletion mutant, in vivo virulence assay mBio Medium 37417777
2024 HERC5 ISGylates cGAS at Lys21, Lys187, Lys219, and Lys458, promoting cGAS oligomerization and enhancing cGAS enzymatic activity. The interaction depends on the cGAS C-terminal domain and RCC1-4/RCC1-5 domains of HERC5. ISGylation deficiency attenuates cGAS-STING-mediated inflammatory gene expression and antiviral defense in mouse and human cells. Co-immunoprecipitation, mass spectrometry site identification, mutagenesis, cGAS activity assay, oligomerization assay, ISGylation assay, KO mouse model (HSV-1 infection) Cell reports High 38421872
2024 HERC5 ISGylates SARS-CoV-2 nucleocapsid (N) protein at Lys266, Lys355, Lys387, and Lys388 (preferentially the phosphorylated form), impeding N protein oligomerization and inhibiting viral RNA synthesis. This ISGylation is reversed by PLpro (NSP3) deISGylation activity. Mutant N-4KR abolishes ISGylation and alleviates restriction in a replicon system. Mass spectrometry, site-directed mutagenesis, SARS-CoV-2 replicon system, oligomerization assay, ISGylation assay, PLpro activity assay Journal of virology High 39149229 39194248
2024 hHERC5 broadly ISGylates proteins cotranslationally as a ribosome-associated HECT E3 ligase. Over 2,000 modified lysines in over 1,100 proteins were characterized in IFN-β-stimulated cells. hHERC5 and mouse HERC6 have distinct amino acid sequence context preferences surrounding ISGylation sites. mHERC6 also cotranslationally modifies nascent polypeptides. Mass spectrometry ISGylome profiling, IFN-β stimulation, sequence context analysis, comparison with mHERC6 iScience High 38303729
2022 HERC5 interacts with IFI16 and mediates ISGylation of IFI16 at Lys274, facilitating IFI16 proteasomal degradation. IFI16 acts as a tumor suppressor downstream of HERC5, and IFI16 is positively correlated with p53 expression, defining a HERC5/IFI16/p53 signaling pathway in breast cancer cells. Co-immunoprecipitation, proteomic analysis, western blot, siRNA knockdown, site mutagenesis, cell proliferation/migration assays Life sciences Medium 35671810
2021 HERC5 inhibits Ebola virus (EBOV) VLP replication by depleting EBOV mRNAs. The RCC1-like domain of HERC5 is necessary and sufficient for this inhibition and does not require zinc finger antiviral protein (ZAP). EBOV glycoprotein (Zaire strain) antagonizes HERC5 early during infection. Transcription- and replication-competent VLP system, domain deletion analysis, ZAP-deficient cell assay, EBOV GP antagonism assay Cells Medium 34572049
2025 HERC5 ISGylates SARS-CoV-2 nsp8 (a viral replication factor) at its N2 domain lysine residues, facilitating proteasome-dependent nsp8 degradation and suppressing viral replication. SARS-CoV-2 PLpro counteracts this by deconjugating ISG15 from nsp8, preventing its degradation. The full ISGylation system (HERC5, UBA7, ISG15) suppresses replication of multiple SARS-CoV-2 variants including Omicron. Mass spectrometry, mutagenesis, overexpression, PLpro deISGylation assay, proteasome inhibition, viral replication assay International journal of biological macromolecules Medium 40409630
2025 HERC5 catalyzes ISGylation of UGDH (UDP-glucose 6-dehydrogenase) via its HECT domain active-site Cys994, facilitating UGDH phosphorylation and enhancing SNAI1 mRNA stability, thereby promoting OSCC cell invasion and cisplatin resistance. Co-immunoprecipitation, ISGylation assay, site mutagenesis (C994A), siRNA knockdown, overexpression, in vivo xenograft Biology direct Medium 40045362
2025 HERC5 inhibits LINE-1 (L1) retrotransposition through an ISGylation-independent mechanism. HERC5 interacts with L1 RNA and selectively reduces ORF1p protein levels, decreasing L1 translation efficiency and altering L1 RNP composition. L1 retrotransposition assay, HERC5 domain/catalytic mutant analysis, RNA immunoprecipitation, ORF1p level quantification, RNP composition analysis Nucleic acids research Medium 42055552
2025 UbcH8~ISG15 exhibits striking specificity for HECT-family E3 ligases (particularly HERC5) but is inactive with RING or RBR E3s, in contrast to UbcH8~Ub which preferentially engages RBR E3s. A unique closed conformation of UbcH8~ISG15 enables trans-thiolation selectively mediated by HECT E3s. HERC5's C-lobe specifically recognizes donor ISG15 for lysine conjugation, explaining its exclusive ISGylation activity and lack of ubiquitination function. Structural analysis (biochemical studies), in vitro thiolation assay, comparative E3 ligase specificity assay bioRxivpreprint Medium bio_10.1101_2025.09.26.678755
2025 SAXS analysis reveals that the HERC5 HECT domain predominantly adopts a trimeric assembly in solution, suggesting trimerization may play a regulatory role in HERC5 functional activity. Small-angle X-ray scattering (SAXS), size-exclusion chromatography, Guinier/Kratky analysis, ab initio shape reconstruction bioRxivpreprint Low bio_10.1101_2025.03.22.644726
2024 HERC5 (human) and HERC6 (mouse functional homolog) are the primary E3 ligases responsible for ISGylation of MDA5 at Lys23 and Lys43 within its CARD domain. ISGylation at these sites promotes MDA5 oligomeric assembly and downstream antiviral signaling; knock-in mice with K23R/K43R MDA5 mutations show abrogated ISGylation, impaired MDA5 oligomerization, blunted cytokine responses, and increased mortality upon EMCV infection. MDA5 K23R/K43R knock-in mice, ISGylation assay, MDA5 oligomerization assay, cytokine measurement, viral infection survival assay, E3 ligase identification bioRxivpreprint Medium bio_10.1101_2024.09.20.614144
2025 HERC5 interacts with and ISGylates IRF3, preventing IRF3 ubiquitination and degradation. This stabilizes IRF3 and sustains IFN-β production and overactivation in podocytes, contributing to lupus nephritis pathology. Co-immunoprecipitation, siRNA knockdown, overexpression, ISGylation assay, IFN-β quantification, podocyte injury assay International immunopharmacology Medium 40505230

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo. PLoS genetics 302 19424434
2006 HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proceedings of the National Academy of Sciences of the United States of America 246 16815975
2005 Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells. The Journal of biological chemistry 243 16407192
2010 Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. Molecular and cellular biology 229 20308324
1994 Complex recombination events at the hypermutable minisatellite CEB1 (D2S90). The EMBO journal 151 8039512
2010 Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein. Journal of immunology (Baltimore, Md. : 1950) 127 20385878
2011 Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag. Retrovirology 72 22093708
2006 Identification and Herc5-mediated ISGylation of novel target proteins. Biochemical and biophysical research communications 63 16884686
2021 HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response. Viruses 62 34207696
2014 Structure and conformational dynamics of a stacked dimeric G-quadruplex formed by the human CEB1 minisatellite. Journal of the American Chemical Society 62 24742225
2004 HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells. Journal of cell science 62 15331633
2012 Stimulation of gross chromosomal rearrangements by the human CEB1 and CEB25 minisatellites in Saccharomyces cerevisiae depends on G-quadruplexes or Cdc13. PLoS genetics 59 23133402
1999 Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks. Nature genetics 51 10545956
2000 Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90). American journal of human genetics 38 10869237
2017 CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells. Toxicological research 36 28744352
2024 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate immunity. Cell reports 35 38421872
2000 Somatic versus germline mutation processes at minisatellite CEB1 (D2S90) in humans and transgenic mice. Genomics 29 10783256
2023 African swine fever virus MGF-360-10L is a novel and crucial virulence factor that mediates ubiquitination and degradation of JAK1 by recruiting the E3 ubiquitin ligase HERC5. mBio 26 37417777
2015 Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase. The Journal of general virology 25 26361997
2014 Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export. Retrovirology 25 24693865
2014 Identification of HERC5 and its potential role in NSCLC progression. International journal of cancer 24 25353388
2020 Rapid Evolution of HERC6 and Duplication of a Chimeric HERC5/6 Gene in Rodents and Bats Suggest an Overlooked Role of HERCs in Mammalian Immunity. Frontiers in immunology 22 33391270
2024 ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis. Journal of virology 19 39194248
2017 HZ-6d targeted HERC5 to regulate p53 ISGylation in human hepatocellular carcinoma. Toxicology and applied pharmacology 19 28919514
2002 The human minisatellites MS1, MS32, MS205 and CEB1 integrated into the yeast genome exhibit different degrees of mitotic instability but are all stabilised by RAD27. Current genetics 18 12185499
2022 HERC5/IFI16/p53 signaling mediates breast cancer cell proliferation and migration. Life sciences 17 35671810
2024 HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis. Journal of experimental & clinical cancer research : CR 13 38605423
2024 Cellular targets and lysine selectivity of the HERC5 ISG15 ligase. iScience 12 38303729
2022 The Neuropeptide-Related HERC5/TAC1 Interactions May Be Associated with the Dysregulation of lncRNA GAS5 Expression in Gestational Diabetes Mellitus Exosomes. Disease markers 12 35178132
2023 LincRNA-ROR/miR-145/ZEB2 regulates liver fibrosis by modulating HERC5-mediated p53 ISGylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 37144417
2021 Downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis in colorectal cancer cells. Carcinogenesis 11 34147029
2021 HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein to promote viral replication. The Journal of general virology 11 34661519
2023 The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN. Science signaling 7 37279284
2021 Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein. Cells 7 34572049
2024 CircJPH1 regulates the NF-κB/HERC5 axis to promote the malignant progression of esophageal squamous cell carcinoma through binding to XRCC6. Cellular signalling 6 39255925
2007 New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia. British journal of cancer 6 17387343
2025 E3 ligase HERC5-catalyzed UGDH isgylation promotes SNAI1-mediated tumor metastasis and cisplatin resistance in oral squamous cell carcinoma. Biology direct 4 40045362
2025 HERC5-mediated ISGylation of SARS-CoV-2 nsp8 facilitates its degradation and inhibits viral replication. International journal of biological macromolecules 4 40409630
2025 HERC5/ISG15 Enhances Glioblastoma Stemness and Tumor Progression by mediating SERBP1protein stability. Neuromolecular medicine 3 39776018
2025 HERC5 induces podocyte injury in LN by mediated IRF3 ISGylation to promote the production and overactivation of IFN-β in podocytes. International immunopharmacology 2 40505230
2021 Overexpression of Survivin-1, TAG-72 and HERC5 in patients diagnosed with hepatocellular carcinoma in the Black Sea coast geographical area. Experimental and therapeutic medicine 2 33603891
2010 Comparison of germ line minisatellite mutation detection at the CEB1 locus by Southern blotting and PCR amplification. Mutagenesis 2 20228094
2017 HECT Domain and RCC1-Like Domain-Containing Protein 5 (HERC-5) Gene Polymorphisms in HIV-1-Infected Individuals: A Study from India. AIDS research and human retroviruses 1 28737979
2026 The interferon-stimulated gene product HERC5 inhibits human LINE-1 retrotransposition with an ISGylation-independent mechanism. Nucleic acids research 0 42055552
2025 Albendazole Suppresses SARS-CoV-2 Replication by Enhancing HERC5-Mediated ISGylation of Nucleocapsid Protein. Journal of medical virology 0 41404913
2025 HERC5, IFI6, IFIT3, and OASL as potential diagnostic biomarkers for systemic lupus erythematosus: an integrated bioinformatics, machine learning and clinical validation. Clinical rheumatology 0 41432807
2024 ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis. bioRxiv : the preprint server for biology 0 39149229
2014 [Analysis of genome instability in offspring of "Mayak" workers families: minisatellite CEB1]. Genetika 0 25739289

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