Affinage

MORC3

MORC family CW-type zinc finger protein 3 · UniProt Q14149

Length
939 aa
Mass
107.1 kDa
Annotated
2026-06-10
49 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MORC3 is a GHKL-family nuclear ATPase that couples ATP-dependent self-assembly to chromatin recognition, acting as a chromatin-compaction and gene-silencing factor at H3K4me3-marked promoters and repeat elements (PMID:27528681, PMID:27653685). Crystallographic and enzymatic work shows that its N-terminal ATPase domain dimerizes upon ATP binding, while an adjacent CW zinc-finger domain reads H3K4me3 through an aromatic cage; the CW domain also autoinhibits catalysis by docking onto the ATPase domain and sterically blocking DNA access, an 'off' state that is released when CW engages the histone H3 tail, freeing the DNA-binding surface required for DNA-stimulated ATPase activity (PMID:27528681, PMID:27653685, PMID:30850548). This ATPase-driven, DNA-dependent activity in turn drives formation of liquid-like nuclear condensates and assembly of nuclear domains (PMID:31284181). MORC3 self-assembles into PML-independent nuclear domains and then associates with PML nuclear bodies through SUMO1–SIM interactions and SUMOylation at multiple sites, where its ATPase activity is needed to recruit p53 and Sp100 and to drive p53-dependent cellular senescence (PMID:17332504, PMID:20501696). As a silencing effector, SUMOylated MORC3 recruits the H3.3 chaperone DAXX to enable H3.3 deposition, repressing endogenous retroviruses and a PU.1-bound tandem-repeat enhancer adjacent to IFNB1; loss of MORC3 opens these elements and triggers IRF3/IRF7-independent interferon induction, defining a self-guarded antiviral circuit (PMID:34759314, PMID:34650047, PMID:42249047). MORC3 directly restricts herpesviruses at viral genome entry sites and immediate-early promoters and is itself degraded or deSUMOylated by viral factors such as HSV-1 ICP0 and HCMV LUNA, linking its destruction to de-repression of interferon (PMID:27440897, PMID:34759314, PMID:35879101, PMID:38009611). The CW aromatic cage is also hijacked by influenza NS1, which competes with H3 for the same site to relieve autoinhibition (PMID:31006586). MORC3 is further required for T cell development, controlling chromatin accessibility at T cell transcription factor loci including TCF1, with both ATPase and CW functions required [PMID:bio_10.1101_2025.03.05.641591].

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 Medium

    Established MORC3 (NXP-2) as a multidomain nuclear matrix protein with RNA-dependent anchoring, the first description of its modular architecture before any enzymatic role was known.

    Evidence GFP-tagged truncation mapping, Northwestern analysis, and RNase-sensitive nuclear matrix fractionation

    PMID:11927593

    Open questions at the time
    • No enzymatic activity defined
    • Functional consequences of RNA binding and matrix anchoring untested
    • Domain boundaries predate the later ATPase/CW framework
  2. 2006 Medium

    Connected MORC3 to SUMO biology and transcriptional repression, showing it binds SUMO-2 and represses transcription when tethered, foreshadowing its SUMO-dependent silencing roles.

    Evidence GST-SUMO-2 affinity chromatography with MS and Gal4-tethering repression assay

    PMID:16567619

    Open questions at the time
    • Endogenous SUMO-modified targets not identified
    • Mechanism linking SUMO binding to repression unresolved
    • No chromatin context
  3. 2007 High

    Defined a functional output for MORC3's ATPase activity—recruitment of p53 and Sp100 to PML bodies and induction of p53-dependent senescence—establishing it as an active enzyme with cell-fate consequences.

    Evidence ATPase-dead E35A mutant, siRNA knockdown, Morc3-/- fibroblasts, immunofluorescence and senescence assays

    PMID:17332504

    Open questions at the time
    • Direct substrate of the ATPase not defined
    • How ATPase activity mechanistically recruits p53 unclear
    • PML-body assembly steps not yet resolved
  4. 2010 High

    Resolved how MORC3 reaches PML bodies, defining a two-step ATP-driven self-assembly followed by SUMO1-SIM/SUMOylation-dependent PML association, mechanistically separating its self-assembly from its PML targeting.

    Evidence Pml-/- cells, ATPase/SIM/SUMO-site mutants, live-cell imaging and fractionation

    PMID:20501696

    Open questions at the time
    • Identity of the SUMO E3/ligase machinery not defined
    • Relationship of nuclear domains to chromatin targets unresolved
  5. 2016 High

    Provided the structural and enzymatic basis of MORC3 function: ATP-dependent ATPase dimerization, CW-domain reading of H3K4me3, genome-wide promoter localization, and CW-mediated autoinhibition of DNA-stimulated ATPase activity.

    Evidence X-ray crystallography of ATPase-CW with AMPPNP, native MS, in vitro peptide binding, ATPase assays with domain mutants, and ChIP-seq

    PMID:27528681 PMID:27653685

    Open questions at the time
    • In vivo substrate of ATPase remodeling activity unknown
    • How H3K4me3 binding and DNA-stimulated catalysis are coordinated on chromatin not fully resolved
  6. 2016 High

    Showed MORC3 is an intrinsic antiviral restriction factor at herpesvirus genomes and a target of viral countermeasures, as HSV-1 ICP0 degrades it via its RING E3 ligase activity.

    Evidence MORC3 depletion with plaque assays, immunofluorescence colocalization at viral entry sites, and ICP0 RING-finger mutant analysis across HSV-1 and HCMV

    PMID:27440897

    Open questions at the time
    • Mechanism of MORC3 recruitment to incoming viral genomes unresolved
    • Whether restriction uses chromatin compaction or PML-body assembly not separated
  7. 2016 Low

    Linked MORC3 to bone homeostasis and the haematopoietic niche through an osteoclast phenotype and altered subcellular localization in mutant mice.

    Evidence ENU mutagenesis screen, immunofluorescence, ex vivo bone assays and osteoclastogenesis

    PMID:27188231

    Open questions at the time
    • Single lab phenotypic study with limited mechanistic depth
    • Causal chromatin targets in osteoclasts not identified
    • STAT1 link correlative
  8. 2019 High

    Defined the conformational switch governing MORC3 activity, showing the CW:ATPase interface enforces an autoinhibited 'off' state that H3-tail binding disrupts to license DNA binding and catalysis, with ATP-induced dimerization strictly required.

    Evidence Crystallography of the autoinhibited complex, NMR, mutagenesis and enzymatic assays

    PMID:30850548

    Open questions at the time
    • Cellular triggers that supply the activating H3 tail in vivo not mapped
    • Kinetics of the off/on transition on nucleosomes unresolved
  9. 2019 Medium

    Established that MORC3's enzymatic switch drives biophysical behavior, with ATPase- and DNA-dependent, autoinhibition-released formation of dynamic liquid-like nuclear condensates.

    Evidence Live-cell imaging, in vitro phase-separation assays with ATPase mutants

    PMID:31284181

    Open questions at the time
    • Functional role of condensates in silencing vs. PML-body biology not separated
    • Condensate composition in cells not defined
  10. 2019 High

    Revealed a viral exploitation of the activation switch: influenza NS1 occupies the CW aromatic cage like H3, competing for the site and capable of relieving MORC3 autoinhibition.

    Evidence Crystal structure of MORC3-CW:NS1 complex with quantitative binding measurements and cellular analyses

    PMID:31006586

    Open questions at the time
    • Whether NS1 binding activates MORC3 catalysis in infected cells not directly demonstrated
    • Downstream consequence for viral replication via this site unresolved
  11. 2021 High

    Defined MORC3's silencing mechanism at endogenous retroviruses and male germline retrotransposons, showing SUMO-dependent recruitment of the DAXX/H3.3 chaperone system to deposit H3.3 and compact chromatin, partly downstream of or parallel to TRIM28/SETDB1.

    Evidence Genome-wide sgRNA screens, Morc3 KO/mutant ESCs, ChIP-seq (H3K9me3, H3.3), ATAC-seq, proteomics, MIWI2 co-IP and piRNA/DNA-methylation analyses

    PMID:34650047 PMID:34650118 PMID:34706774

    Open questions at the time
    • How ATPase activity drives H3.3 deposition mechanistically unresolved
    • Order of MORC3, TRIM28/SETDB1, and DAXX action at individual loci not fully ordered
  12. 2021 High

    Integrated restriction and immune repression into a single 'self-guarded' antiviral logic, showing MORC3 represses a cis IFNB1-adjacent element whose de-repression upon MORC3 loss or ICP0-mediated degradation triggers IRF3/IRF7-independent interferon.

    Evidence CRISPR screen, MORC3 KO, ICP0 overexpression, IFNB1 reporter assays in IRF3/IRF7 KO cells

    PMID:34759314

    Open questions at the time
    • Identity of the transcription factor driving the IRF-independent response not yet defined here
    • Generality of the self-guard model across pathogens untested
  13. 2022 High

    Extended antiviral function to HCMV, showing MORC3 suppresses the major immediate-early promoter with PML assistance and is transiently degraded by the proteasome during early infection.

    Evidence siRNA, CRISPR KO, overexpression, MIEP reporter assays, proteasome inhibitors

    PMID:35879101

    Open questions at the time
    • Viral factor mediating early MORC3 degradation not identified
    • Mechanism of PML cooperation at MIEP unresolved
  14. 2023 High

    Showed MORC3 is required to establish HCMV latency by forming nuclear bodies at viral genomes, and that the viral LUNA deSUMOylase counteracts MORC3 to license reactivation, tying SUMOylation directly to latency control.

    Evidence CRISPR epigenetic-library screen, MORC3 KO, GFP-MIEP reporter, immunofluorescence and LUNA deSUMOylase-mutant analysis in myeloid cells

    PMID:38009611

    Open questions at the time
    • Which MORC3 SUMO sites govern latency not pinpointed
    • How deSUMOylation reverses MORC3-body assembly mechanistically unresolved
  15. 2024 Low

    Implicated MORC3 in tumor immune signaling, with its loss upregulating PD-L1, STAT1 and IFN genes through a downstream lncRNA LINC00880.

    Evidence RNAi knockdown, RNA-seq, qRT-PCR and LINC00880 silencing epistasis in head and neck cancer cells

    PMID:39329063

    Open questions at the time
    • No protein-level mechanistic assays linking MORC3 to PD-L1
    • Pathway placement indirect
    • Single lab, single cancer context
  16. 2026 High

    Defined the chromatin substrate of MORC3 repression at tandem-repeat enhancers, showing PU.1 recruits MORC3 to deposit DAXX/H3.3 and that MORC3 loss converts a homotypic PU.1-motif repeat into a potent IRF-independent IFNB1 enhancer.

    Evidence ATAC-seq, ChIP-seq, CRISPR deletion of the tandem repeat, motif analysis, DAXX interaction and H3.3 incorporation assays

    PMID:42249047

    Open questions at the time
    • How MORC3 ATPase activity compacts the repeat element mechanistically unresolved
    • Whether the PU.1 axis generalizes to other tandem-repeat enhancers untested
  17. 2025 Medium

    Established a developmental requirement for MORC3 in T cell lineage commitment, with loss arresting development at DN1 and TCF1 re-expression rescuing the defect, dependent on both ATPase and CW functions.

    Evidence Morc3 loss-of-function mouse model, flow cytometry, ATAC-seq, TCF1 rescue, ATPase/CW domain mutants (preprint)

    PMID:bio_10.1101_2025.03.05.641591

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct MORC3 binding at the TCF1 locus vs. indirect effect not fully separated
    • Whether silencing or activation of T cell loci is the primary action unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MORC3's ATP-dependent dimerization and DNA-stimulated catalysis mechanistically translate into nucleosome compaction and DAXX/H3.3 deposition at its target loci remains the central open question.
  • No defined biochemical chromatin substrate or remodeling product of the ATPase
  • Order of recruitment among SUMO machinery, DAXX/H3.3 and TRIM28/SETDB1 not resolved
  • Coupling of phase separation to silencing function not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 4 GO:0016787 hydrolase activity 3 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 4 GO:0005654 nucleoplasm 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
DAXXMIWI2P53PMLPU.1SP100SUMO1SUMO2
Complex memberships
PML nuclear bodies

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 NXP-2/MORC3 contains three structurally distinct functional domains: a nuclear matrix-binding domain (amino acids 326-353) with a hydrophobic cluster similar to known nuclear matrix targeting signals, an RNA-binding domain (amino acids 500-591) identified by Northwestern analysis, and a coiled-coil domain (amino acids 682-876). The protein localizes to the nuclear matrix and is released by RNase A treatment, indicating RNA-dependent anchoring. GFP-tagged truncation mutants, Northwestern analysis, nuclear matrix fractionation with RNase A treatment The Journal of biological chemistry Medium 11927593
2006 NXP-2/MORC3 binds preferentially to SUMO-2 in a manner dependent on SUMO-2 lysines K33, K35, and K42; when tethered to a promoter via Gal4 fusion, NXP-2 represses transcription, consistent with a role in SUMO-mediated transcriptional repression. GST-SUMO-2 affinity chromatography followed by LC-MS; Gal4 tethering transcription repression assay Proceedings of the National Academy of Sciences of the United States of America Medium 16567619
2007 MORC3 ATPase activity is required to recruit p53 and Sp100 (but not CBP) to PML nuclear bodies; loss of ATPase activity (E35A mutant) or siRNA knockdown of MORC3 impairs p53 and Sp100 localization at PML-NBs. MORC3 activates p53 transcriptional activity and induces cellular senescence in a p53-dependent manner; genotoxic stress fails to activate p53 transcriptionally in Morc3-/- fibroblasts. ATPase-deficient mutant (E35A) expression, siRNA knockdown, immunofluorescence, Morc3-/- fibroblasts, senescence assay Molecular biology of the cell High 17332504
2010 MORC3 colocalizes with PML nuclear bodies via a two-step mechanism: (1) ATPase cycle-driven formation of PML-independent MORC3 nuclear domains, and (2) SUMO1-SIM (SUMO-interacting motif)-mediated association with PML. ATP binding induces MORC3 dimerization ('molecular clamp') and ND formation; ATP hydrolysis mediates diffusion and nuclear matrix binding. SUMOylation of MORC3 at five sites is required for its association with PML. PML-deficient cells, ATPase mutants, SIM mutants, SUMO site mapping, live-cell imaging, fractionation Journal of cell science High 20501696
2015 NXP2/MORC3 associates with influenza A virus polymerase and viral ribonucleoproteins (RNPs) during infection, as shown by co-immunoprecipitation and immunofluorescence. Downregulation of NXP2/MORC3 reduces viral titers and viral RNA/mRNA levels. In a minireplicon system, MORC3 knockdown reduces viral mRNA and CAT protein but not genomic vRNA, indicating a specific role in supporting influenza virus transcription. Co-immunoprecipitation, immunofluorescence, shRNA knockdown, minireplicon transcription/replication assay Journal of virology Medium 26202233
2016 MORC3 is recruited to HSV-1 genome entry sites in the nucleus and is required for fully efficient recruitment of PML, Sp100, hDaxx, and γH2AX to those sites. Depletion of MORC3 increases replication of ICP0-null HSV-1 and wild-type HCMV. MORC3 is degraded by ICP0 via its RING finger domain (ubiquitin E3 ligase activity), and no other HSV-1 protein is required for this degradation. MORC3 depletion (knockdown), plaque assay, immunofluorescence colocalization, ICP0 RING finger mutant analysis Journal of virology High 27440897
2016 Crystal structure of mouse MORC3 ATPase-CW domain bound to AMPPNP shows ATP-dependent dimerization of the N-terminal ATPase domain. The CW domain uses an aromatic cage to bind trimethylated H3K4 (H3K4me3) and forms extensive hydrogen bonds with the H3 tail. MORC3 localizes genome-wide to promoters marked by H3K4me3, consistent with its in vitro H3K4me3 binding. X-ray crystallography, native mass spectrometry, ChIP-seq, in vitro peptide binding Proceedings of the National Academy of Sciences of the United States of America High 27528681
2016 MORC3 possesses intrinsic ATPase activity that requires DNA for stimulation. The CW domain negatively regulates ATPase activity by interacting with the ATPase domain and sterically impeding its access to DNA. H3K4me3 binding by CW is essential for MORC3 recruitment to chromatin and accumulation in nuclear bodies. MORC3 is significantly upregulated in Down syndrome. ATPase activity assays, domain interaction biochemistry, chromatin recruitment assays (ChIP/immunofluorescence), genetic analysis Cell reports High 27653685
2016 Morc3 protein shifts from nuclear membrane localization to the cytoplasm in Morc3 mutant osteoclasts, and Morc3 mutant mice exhibit reduced osteoclast numbers and bone resorption, increased β-galactosidase senescence activity reduction, decreased STAT1 upregulation in osteoclast lineage, and altered osteoblast differentiation — indicating a role in bone homeostasis and haematopoietic stem cell niche. ENU mutagenesis screen, immunofluorescence localization, ex vivo bone assays, in vitro osteoclastogenesis Scientific reports Low 27188231
2019 Crystal structure of MORC3 ATPase-CW domain in complex with non-hydrolyzable ATP analog shows the ATPase and CW domains are directly coupled via an extensive interface that stabilizes the fold but inhibits catalytic activity (autoinhibited 'off' state). NMR, enzymatic, mutational, and biochemical analyses demonstrate that CW sterically blocks DNA binding required for catalysis. Binding of CW to histone H3 tail disrupts the ATPase:CW interface, freeing the DNA-binding site (active 'on' state). ATP-induced ATPase dimerization is strictly required for catalytic activity. X-ray crystallography, NMR, mutagenesis, enzymatic assays, biochemical binding assays Proceedings of the National Academy of Sciences of the United States of America High 30850548
2019 MORC3 forms phase-separated condensates with liquid-like properties in the cell nucleus. The ATPase activity of MORC3 drives phase separation in vitro and requires DNA binding. Releasing CW domain-dependent autoinhibition through H3 association is required for phase separation. MORC3 condensates are heterogeneous and undergo dynamic morphological changes during the cell cycle. Fluorescence live-cell imaging, in vitro phase separation assay, ATPase mutants iScience Medium 31284181
2019 The CW domain of MORC3 is directly targeted by the C-terminal tail of influenza H3N2 NS1 protein. Crystal structure of MORC3-CW:NS1 complex shows NS1 occupies the same aromatic cage binding site as histone H3. NS1 and H3 peptides bind MORC3-CW with comparable affinities, suggesting NS1 can compete with H3 for CW binding, thereby releasing MORC3 autoinhibition and activating its catalytic ATPase function. X-ray crystallography, binding affinity measurements (ITC/fluorescence), cellular analyses Structure (London, England : 1993) High 31006586
2021 ICP0 (HSV-1 virulence factor) degrades MORC3, leading to de-repression of a MORC3-regulated DNA element (MRE) adjacent to the IFNB1 locus. This MRE is required in cis for IFNB1 induction via the MORC3 pathway. Loss of MORC3 recapitulates an IRF3- and IRF7-independent IFN response. MORC3 thus functions as both a direct HSV-1 restriction factor (primary anti-viral function) and a repressor of IFN induction (secondary function), constituting a 'self-guarded' immune pathway. CRISPR screen, MORC3 knockout, ICP0 overexpression, reporter assays for IFNB1 induction, IRF3/IRF7 knockout cells Nature High 34759314
2021 Morc3 knock-out results in de-repression and increased chromatin accessibility of specific ERV families (LTR retrotransposons) in mouse ESCs, with only minor losses of H3K9me3. Proteomic analyses reveal that Morc3 mutant proteins (ATPase-dead and SUMOylation-deficient) fail to interact with the histone H3.3 chaperone Daxx. This interaction depends on Morc3 SUMOylation and Daxx SUMO-binding. Loss of Morc3 results in strongly reduced H3.3 at Morc3 binding sites, demonstrating Morc3 enables Daxx-mediated H3.3 incorporation for ERV silencing. sgRNA genome-wide screen, Morc3 KO, ChIP-seq (H3K9me3, H3.3), ATAC-seq, proteomics (MS), Morc3 ATPase and SUMOylation mutants Nature communications High 34650047
2021 Morc3 is identified as a novel interacting partner of MIWI2 in mouse embryonic male germ cells. MORC3 functions as a nuclear effector of retrotransposon silencing via piRNA-dependent de novo DNA methylation in embryonic testis, and is also important for transcription of piRNA precursors and subsequent piRNA production. Co-immunoprecipitation (MIWI2-MORC3), Morc3 loss-of-function, DNA methylation analysis, piRNA sequencing Scientific reports Medium 34650118
2021 Loss of Morc3 in mouse ESCs upregulates transposable elements, specifically LTR-class ERVs. ChIP-seq shows MORC3 binds directly to ERV loci in addition to H3K4me3 promoters. Loss of Morc3 increases chromatin accessibility at ERVs (ATAC-seq) with only minor H3K9me3 changes, suggesting MORC3 acts downstream of or in parallel with TRIM28/SETDB1 at the level of chromatin compaction. Morc3 mutant mESCs (MommeD screen), RNA-seq, ChIP-seq, ATAC-seq Epigenetics & chromatin Medium 34706774
2022 MORC3 restricts HCMV replication by suppressing the major immediate-early promoter (MIEP) activity and consequent IE1 gene expression with the assistance of PML. HCMV induces transient MORC3 protein reduction via the ubiquitin-proteasome pathway during immediate-early to early stages; MORC3 transcription is later upregulated and protein recovers. Knockdown or knockout of MORC3 augments IE1 expression and viral replication; overexpression inhibits replication. siRNA knockdown, CRISPR-Cas9 KO, overexpression, MIEP-based reporter assays, ubiquitin-proteasome pathway inhibitors Journal of medical virology High 35879101
2023 MORC3 is recruited to the HCMV major immediate-early promoter (MIEP) and forms MORC3 nuclear bodies that co-localize with viral genomes during HCMV latency in myeloid cells. THP1 cells devoid of MORC3 fail to establish latency. The viral latency-associated LUNA protein deSUMOylates MORC3 (via its deSUMOylase activity), likely preventing untimely HCMV reactivation. MORC3 is induced during latent infection. CRISPR-Cas9 sub-genomic epigenetic library screen, MORC3 KO, GFP-MIEP reporter, immunofluorescence, LUNA protein deSUMOylase mutant analysis Journal of medical virology High 38009611
2024 MORC3 knockdown in head and neck cancer cells significantly upregulates PD-L1 and STAT1 expression, as well as multiple IFN-associated genes, and promotes cancer cell proliferation. MORC3 knockdown also upregulates the immune-related lncRNA LINC00880, and silencing LINC00880 attenuates PD-L1 expression, placing LINC00880 downstream of MORC3 in PD-L1 regulation. RNAi knockdown, RNA-seq, qRT-PCR, LINC00880 silencing epistasis Frontiers in cell and developmental biology Low 39329063
2026 MORC3 restricts chromatin accessibility at tandem repeat elements harboring homotypic transcription factor motif clusters (including 45 PU.1 binding sites). Upon MORC3 loss, one such element becomes a potent IFNB1 enhancer. PU.1 recruits MORC3 to repress this enhancer by also recruiting DAXX and enabling H3.3 incorporation. Upon MORC3 loss, PU.1 drives IRF3/7-independent IFN induction via this tandem repeat enhancer. ATAC-seq, ChIP-seq, CRISPR deletion of tandem repeat, transcription factor motif analysis, DAXX interaction, H3.3 incorporation assays The EMBO journal High 42249047
2025 MORC3 is expressed in the thymus and its loss of function causes a severe arrest in T cell development at the DN1 stage, with expansion of NK and myeloid cells. MORC3 function in the thymus requires both its ATPase activity and H3K4me3-binding CW domain. Altered chromatin accessibility at regulatory elements of key T cell transcription factors (including TCF1) is observed in DN1 cells; re-expressing TCF1 in MORC3-deficient progenitors rescues T cell development. Morc3 loss-of-function mouse model, flow cytometry, ATAC-seq, TCF1 rescue experiment, ATPase and CW domain mutants bioRxivpreprint Medium bio_10.1101_2025.03.05.641591

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ. Arthritis and rheumatism 296 24037894
2006 NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proceedings of the National Academy of Sciences of the United States of America 95 16567619
2007 Dynamic regulation of p53 subnuclear localization and senescence by MORC3. Molecular biology of the cell 80 17332504
2021 Self-guarding of MORC3 enables virulence factor-triggered immunity. Nature 64 34759314
2010 Two-step colocalization of MORC3 with PML nuclear bodies. Journal of cell science 58 20501696
2002 The newly identified human nuclear protein NXP-2 possesses three distinct domains, the nuclear matrix-binding, RNA-binding, and coiled-coil domains. The Journal of biological chemistry 53 11927593
2016 MORC3, a Component of PML Nuclear Bodies, Has a Role in Restricting Herpes Simplex Virus 1 and Human Cytomegalovirus. Journal of virology 48 27440897
2021 Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation. Nature communications 45 34650047
2016 Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin. Proceedings of the National Academy of Sciences of the United States of America 45 27528681
2016 Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase. Cell reports 41 27653685
2015 The Cellular Factor NXP2/MORC3 Is a Positive Regulator of Influenza Virus Multiplication. Journal of virology 38 26202233
2016 Morc3 mutant mice exhibit reduced cortical area and thickness, accompanied by altered haematopoietic stem cells niche and bone cell differentiation. Scientific reports 31 27188231
2019 Mechanism for autoinhibition and activation of the MORC3 ATPase. Proceedings of the National Academy of Sciences of the United States of America 29 30850548
2019 MORC3 Forms Nuclear Condensates through Phase Separation. iScience 25 31284181
2021 The role of MORC3 in silencing transposable elements in mouse embryonic stem cells. Epigenetics & chromatin 21 34706774
2021 Clinical characteristics and poor predictors of anti-NXP2 antibody-associated Chinese JDM children. Pediatric rheumatology online journal 20 33407621
2021 Association of anti-NXP2 antibody with clinical characteristics and outcomes in adult dermatomyositis: results from clinical applications based on a myositis-specific antibody. Clinical rheumatology 18 33712891
2022 An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations. Clinical reviews in allergy & immunology 17 35092577
2021 Gastrointestinal perforation in anti-NXP2 antibody-associated juvenile dermatomyositis: case reports and a review of the literature. Pediatric rheumatology online journal 17 33407602
2022 Selenium Deficiency Promotes the Expression of LncRNA-MORC3, Activating NLRP3-Caspase-1/IL-1β Signaling to Induce Inflammatory Damage and Disrupt Tight Junctions in Piglets. Biological trace element research 16 35759081
2024 Severe gastrointestinal involvements in patients with adult dermatomyositis with anti-NXP2 antibody. RMD open 15 38199847
2019 MORC3 Is a Target of the Influenza A Viral Protein NS1. Structure (London, England : 1993) 15 31006586
2023 circMORC3-encoded novel protein negatively regulates antiviral immunity through synergizing with host gene MORC3. PLoS pathogens 14 38150467
2021 MORC3, a novel MIWI2 association partner, as an epigenetic regulator of piRNA dependent transposon silencing in male germ cells. Scientific reports 10 34650118
2017 NXP-2 Positive Dermatomyositis: A Unique Clinical Presentation. Case reports in rheumatology 9 28695037
2015 Interstitial lung disease in an adult patient with dermatomyositis and anti-NXP2 autoantibody. European respiratory review : an official journal of the European Respiratory Society 8 26028648
2025 Circulating cell-free DNA promotes inflammation in dermatomyositis patients with anti-NXP2 antibodies  via the cGAS/STING pathway. Rheumatology (Oxford, England) 7 39110532
2023 MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies. Journal of medical virology 6 38009611
2022 Interstitial lung disease in adult patients with anti-NXP2 antibody positivity: a multicentre 18-month follow-up study. Clinical and experimental rheumatology 6 35819809
2022 MORC3 restricts human cytomegalovirus infection by suppressing the major immediate-early promoter activity. Journal of medical virology 6 35879101
2021 Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis: A case report. Medicine 5 33725895
2019 A Viral Protein Mimics Histone to Hijack Host MORC3. Structure (London, England : 1993) 4 31167123
2018 Anti-NXP2-antibody-positive immune-mediated necrotizing myopathy associated with acute myeloid leukemia: A case report. Medicine 4 29995816
2025 Monoclonal antibody targeting IFNβ for the treatment of NXP2-positive ulcerative juvenile dermatomyositis. Pediatrics 3 40112879
2023 Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy. Internal medicine (Tokyo, Japan) 3 37926535
2021 A rare case of NXP-2 positive dermatomyositis. Archive of clinical cases 2 34754931
2025 The feature and significance of lower limb MRI in adult myositis patients with anti-NXP2 antibody: a retrospective cohort study in China. Frontiers in medicine 1 40927189
2024 Genome-wide analysis reveals the MORC3-mediated repression of PD-L1 expression in head and neck cancer. Frontiers in cell and developmental biology 1 39329063
2022 Inflammatory Myositis in a Child due to Anti-NXP2 Antibody, First Case Report from India. Neurology India 1 35864663
2026 Association of NXP2 autoantibodies with a more severe clinical phenotype of juvenile dermatomyositis. Clinical and experimental rheumatology 0 41537529
2026 Parallel course of calcinosis and cancer in a patient with anti-NXP2-positive dermatomyositis: A case report. Modern rheumatology case reports 0 41786612
2026 Beyond Hypothyroid Myopathy: Signal Recognition Particle (SRP)-Negative Necrotizing Dermatomyositis Unmasked by Anti-nuclear Matrix Protein 2 (Anti-NXP2) Positivity in a 60-Year-Old Woman With Hashimoto's Thyroiditis. Cureus 0 42037978
2026 A Rare Coexistence of Anti-CN1A and Anti-NXP2 Myositis-Specific Antibodies in a 63-Year-Old Female From the Philippines With Chronic Progressive Myopathy: A Case Report. Cureus 0 42058360
2026 Reversibility of calcinosis in anti-NXP2-positive refractory dermatomyositis treated with TNF-α blockade: a brief report. Frontiers in medicine 0 42180689
2026 MORC3 represses a tandem repeat enhancer to regulate interferon. The EMBO journal 0 42249047
2025 Progressive course of anti-nuclear matrix protein-2 (NXP-2) positive-interstitial lung disease. Respiratory medicine and research 0 40250199
2024 Possible correlation between serum interleukin-8 levels and the activity of myositis in anti-NXP2 antibody-positive dermatomyositis. Immunological medicine 0 38174692
2024 [Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report]. Rinsho shinkeigaku = Clinical neurology 0 38797685
2022 Rapidly progressive interstitial pneumonia associated with anti-NXP2 antibody secondary to malignancy. Respiratory medicine case reports 0 36324337

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