Affinage

JAG2

Protein jagged-2 · UniProt Q9Y219

Length
1238 aa
Mass
133.4 kDa
Annotated
2026-04-28
40 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JAG2 is a transmembrane Notch ligand that activates Notch receptors on neighboring cells to govern binary cell fate decisions across diverse tissues, including inner ear hair cells, oral periderm, sebaceous glands, muscle stem cells, immune cells, and multiple tumor types. JAG2 signals primarily through NOTCH1 to suppress progenitor identity and promote differentiation—exemplified by lateral inhibition of hair cell fate via Math1 repression and HES5 induction in the cochlea (PMID:11545143, PMID:16141228), periderm maturation in oral epithelium (PMID:16607638), and sebocyte differentiation from skin progenitors (PMID:39585329)—and also signals through NOTCH2 and NOTCH3 in context-dependent settings such as nucleus pulposus cell survival (PMID:31619270) and macrophage polarization (PMID:41916520). Its surface abundance is regulated by USP11-mediated deubiquitination (PMID:39904982) and gamma-secretase/GSK3-dependent processing (PMID:35819850), while its transcription is driven by MYC, ΔNp63, Wnt/β-catenin, HIF-1α, and NF-κB depending on cellular context (PMID:20133585, PMID:17626181, PMID:28881809, PMID:21402725, PMID:40032820). Biallelic loss-of-function variants in JAG2 cause limb-girdle muscular dystrophy type R27 (LGMD R27), linked to impaired Notch-dependent muscle stem cell self-renewal and myogenesis (PMID:33861953).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Establishing JAG2 as a cochlear Notch ligand that controls hair cell versus supporting cell fate answered the question of which ligand mediates lateral inhibition in the inner ear, revealing that JAG2-dependent Notch activation suppresses Math1 and induces HES5 in cochlear progenitors.

    Evidence In situ hybridization of Math1 and HES5 in Jag2-deltaDSL mutant versus wild-type cochleae

    PMID:11545143

    Open questions at the time
    • Whether JAG2 acts alone or redundantly with other ligands in the cochlea was not resolved
    • Direct receptor identity was not determined
  2. 2005 High

    Demonstrating synergistic action of JAG2 and DLL1 through NOTCH1 in the cochlea resolved the question of ligand redundancy, showing that the two ligands act cooperatively and that the supernumerary hair cell phenotype arises from a cell fate switch rather than excess proliferation.

    Evidence Double Dll1/Jag2 knockout mice and conditional Notch1 inactivation with cell fate tracing

    PMID:16141228

    Open questions at the time
    • Quantitative contribution of each ligand individually was not fully resolved
    • Whether downstream effectors beyond HES5 differ between JAG2 and DLL1 signaling was not addressed
  3. 2004 Medium

    Identifying JAG2 as overexpressed in myeloma due to promoter hypomethylation and showing that it activates stromal NOTCH1 to induce pro-survival cytokines (IL-6, VEGF, IGF-1) established the first paracrine oncogenic function of JAG2, answering how tumor-stroma Notch signaling supports myeloma growth.

    Evidence Anti-Notch-1 antibody blocking in co-culture, methylation analysis of JAG2 promoter in myeloma cells

    PMID:15292061

    Open questions at the time
    • Whether JAG2 signals to other Notch receptors in the myeloma niche was not tested
    • In vivo relevance in myeloma patients was not demonstrated
  4. 2006 High

    Showing that JAG2 signals through NOTCH1 in oral periderm to prevent premature palatal adhesion established JAG2 as essential for epithelial barrier formation, explaining the cleft palate phenotype of Jag2-null mice.

    Evidence Jag2 knockout mice, activated Notch1 immunostaining, recombinant explant co-culture

    PMID:16607638

    Open questions at the time
    • Whether JAG2 controls periderm differentiation cell-autonomously or via juxtacrine signaling was not fully distinguished
    • Downstream transcriptional targets in periderm were not identified
  5. 2007 Medium

    Placing ΔNp63 upstream of JAG2 transcription in thymic epithelium answered the question of how p63 regulates γδ T cell development, establishing a ΔNp63→JAG2→Notch transcriptional cascade.

    Evidence Genetic complementation of p63-null mice with ΔNp63α transgenes, comparison of p63−/− and Jag2−/− thymic phenotypes

    PMID:17626181

    Open questions at the time
    • Direct p63 binding to the JAG2 promoter was not shown
    • Whether JAG1 compensates for JAG2 loss in this context was not tested
  6. 2009 Medium

    Demonstrating that loss of SMRT/NCoR2 corepressor causes aberrant JAG2 promoter acetylation and overexpression in myeloma provided an epigenetic mechanism for JAG2 deregulation, complementing the earlier promoter hypomethylation finding.

    Evidence Chromatin analysis of JAG2 promoter, SMRT restoration suppressing JAG2 and inducing apoptosis in myeloma cells

    PMID:19417136

    Open questions at the time
    • Relative contribution of methylation versus SMRT loss to JAG2 overexpression was not dissected
    • Whether SMRT directly binds the JAG2 promoter or acts indirectly was not resolved
  7. 2010 High

    Identifying JAG2 as a direct MYC transcriptional target that drives Notch-dependent tumorigenesis in B cells answered how the MYC oncogene co-opts Notch signaling, establishing a MYC→JAG2→Notch pathway relevant to lymphomagenesis.

    Evidence Inducible Myc P493-6 B-cell model, direct Myc ChIP at JAG2 locus, RNAi and gamma-secretase inhibitor treatment in vitro and in vivo

    PMID:20133585

    Open questions at the time
    • Whether JAG2 is the sole mediator of MYC-driven Notch activation was not established
    • Specific Notch receptor engaged downstream was not identified
  8. 2011 Medium

    Showing that HIF-1α transcriptionally induces JAG2 under hypoxia to elevate Notch activity and promote angiogenesis answered how the tumor microenvironment regulates JAG2 expression, linking oxygen sensing to Notch ligand biology.

    Evidence HIF-1α siRNA knockdown, icN1 and HEY1 target gene measurement, co-culture endothelial tube formation assay

    PMID:21402725

    Open questions at the time
    • Direct HIF-1α binding to JAG2 regulatory elements was not mapped
    • Whether JAG2-mediated angiogenesis requires cell contact or is exosome-mediated was not tested
  9. 2017 Medium

    Placing JAG2 downstream of Wnt/β-catenin signaling and upstream of p21-mediated chemoresistance in colorectal cancer answered how JAG2 integrates Wnt and Notch pathways to promote treatment resistance.

    Evidence APC conditional knockout mice, β-catenin knockdown, p21 forced expression rescue of JAG2-knockdown sensitivity

    PMID:28881809

    Open questions at the time
    • Whether JAG2 directly transcriptionally regulates p21 or acts through Notch/HES was not shown
    • Relevance to patient chemotherapy response was not validated
  10. 2021 Medium

    Identifying biallelic JAG2 variants as the cause of LGMD R27 answered whether JAG2 is essential for human skeletal muscle maintenance, establishing that Notch pathway dysfunction in muscle stem cells underlies a progressive muscular dystrophy.

    Evidence Whole-exome sequencing in families, muscle transcriptome showing PAX7 and myogenesis gene misregulation, Jag2 siRNA in murine myoblasts, Drosophila Serrate/Draper genetic interaction

    PMID:33861953

    Open questions at the time
    • Cell-type-specific (MuSC vs. MuEC) contributions of JAG2 to disease were not dissected
    • Whether disease variants are loss-of-function or dominant-negative was not fully resolved
  11. 2022 Medium

    Demonstrating that gamma-secretase and GSK3 regulate full-length JAG2 surface abundance in airway epithelium answered how posttranslational processing controls JAG2-mediated Notch signal strength to determine goblet versus ciliated cell fate.

    Evidence Human air-liquid interface cultures, gamma-secretase inhibitors, neutralizing antibodies, RNA-Seq, biochemical fractionation

    PMID:35819850

    Open questions at the time
    • Specific GSK3 phosphorylation sites on JAG2 were not mapped
    • Whether this processing mechanism operates in non-airway tissues was not tested
  12. 2024 High

    Specific antibody-mediated blockade of JAG2 or NOTCH1 causing reversible loss of mature sebocytes established the JAG2/Notch1 axis as the primary differentiation signal in the sebaceous gland, answering which ligand-receptor pair drives this lineage.

    Evidence Monoclonal antibody inhibition of individual Notch ligands and receptors in mice, histology, cell proliferation assays, reversibility upon withdrawal

    PMID:39585329

    Open questions at the time
    • Downstream transcription factors activated by JAG2/Notch1 in sebocytes were not identified
    • Human sebaceous gland relevance was not directly shown
  13. 2025 Medium

    Discovery that USP11 deubiquitinates JAG2 to maintain its stability answered how JAG2 protein turnover is regulated, revealing that ubiquitin-dependent degradation controls JAG2-mediated Notch signaling in marginal zone B cells.

    Evidence Co-IP and ubiquitination assays in Usp11−/− mice, flow cytometry of B cell subsets

    PMID:39904982

    Open questions at the time
    • Specific ubiquitin chain types on JAG2 were not characterized
    • Whether other deubiquitinases compensate for USP11 was not tested
    • Reciprocal validation (e.g., JAG2 pulldown of USP11) not explicitly described
  14. 2025 Medium

    Showing that tumor-derived JAG2 activates NOTCH3/STAT3/CCL2 on macrophages to create an immunosuppressive niche promoting perineural invasion answered how JAG2 shapes the tumor immune microenvironment beyond direct tumor cell effects.

    Evidence Single-cell transcriptomics, ligand-receptor analysis, STAT3 inhibition, CCL2 neutralization, JAG2 knockdown, xenograft and sciatic nerve invasion models

    PMID:41916520

    Open questions at the time
    • Whether this JAG2-NOTCH3 axis operates in other tumor types was not tested
    • Structural basis for JAG2 selectivity for NOTCH3 versus NOTCH1 was not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural determinants of JAG2 receptor selectivity (NOTCH1 vs. NOTCH2 vs. NOTCH3), the identity of E3 ubiquitin ligases that target JAG2 for degradation (given its insensitivity to NEURL), and whether JAG2's cis-inhibitory and trans-activating functions are structurally separable.
  • No crystal structure of JAG2-Notch complex exists
  • E3 ligase(s) targeting JAG2 for ubiquitination are unknown
  • Relative contribution of cis-inhibition versus trans-activation in muscle stem cell biology requires further dissection

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8 GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 10 R-HSA-162582 Signal Transduction 8 R-HSA-1266738 Developmental Biology 7 R-HSA-168256 Immune System 3
Partners
DLL1NOTCH1NOTCH2NOTCH3PRAF2USP11

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 JAG2 and DLL1 act synergistically as Notch ligands to regulate hair cell differentiation in the cochlea, likely signaling through the NOTCH1 receptor; loss of both ligands causes supernumerary hair cells primarily through a cell fate switch rather than excess proliferation, and the Notch pathway also controls cellular proliferation in the organ of Corti. Genetic double-mutant analysis (Dll1/Jag2 double knockout mice), conditional inactivation of Notch1, in situ hybridization, cell fate tracing Development High 16141228
2000 JAG2 activation of Notch in cochlear progenitor cells acts to suppress Math1 expression, possibly through induction of the downstream Notch target HES5, thereby controlling hair cell vs. supporting cell fate; Jag2 mutant cochleae show expanded Math1 expression and dramatically reduced HES5. In situ hybridization for Math1 and HES5 in wild-type vs. Jag2deltaDSL mutant cochleae Journal of the Association for Research in Otolaryngology Medium 11545143
2004 JAG2 overexpression in malignant plasma cells induces secretion of IL-6, VEGF, and IGF-1 from stromal cells via Notch-1 signaling; this induction is blocked by anti-Notch-1 monoclonal antibodies targeting the JAG2-binding sequence of Notch-1. JAG2 overexpression is caused by hypomethylation of its promoter in myeloma cells. In vitro co-culture assay with anti-Notch-1 antibody blocking, methylation analysis, cytokine measurement Blood Medium 15292061
2006 JAG2 signals through NOTCH1 in oral epithelium to drive periderm differentiation and prevent premature palatal adhesion; Jag2-deficient mice show attenuated Notch1 activation in oral periderm, disrupted periderm ultrastructure, and their tongue fuses to wild-type palatal shelves in recombinant explant culture. Genetic knockout, immunostaining for activated Notch1, ultrastructural analysis, recombinant explant co-culture Developmental Dynamics High 16607638
2007 DeltaNp63 transcriptionally enhances Jag2 expression in thymic epithelial cells; p63-null thymi phenocopy Jag2-null thymi in showing reduced gamma-delta T cell formation, placing DeltaNp63 upstream of Jag2 in thymic development. Genetic complementation of p63-/- mice with TAp63alpha or DeltaNp63alpha transgenes, in vivo gene expression analysis, comparison of p63-/- and Jag2-/- thymic phenotypes PNAS Medium 17626181
2009 Loss of the SMRT/NCoR2 corepressor in multiple myeloma leads to aberrant histone acetylation at the JAG2 promoter, causing JAG2 overexpression; restoration of SMRT function suppresses JAG2 and induces myeloma cell apoptosis. Chromatin analysis of JAG2 promoter acetylation, SMRT expression analysis in cell lines and patient samples, functional SMRT restoration experiments Cancer Research Medium 19417136
2010 JAG2 is a direct transcriptional target of ectopic Myc in human B cells; Myc-driven JAG2 activates Notch signaling and promotes hypoxic cell proliferation and in vivo tumorigenesis; inhibition of JAG2 by RNAi or the gamma-secretase inhibitor DAPT preferentially suppresses the neoplastic state. Inducible Myc P493-6 B-cell model, RNAi knockdown of JAG2, gamma-secretase inhibitor (DAPT) treatment in vitro and in vivo, direct Myc ChIP/induction assay PNAS High 20133585
2011 JAG2 is transcriptionally activated by hypoxia in a HIF-1alpha-dependent manner; hypoxic JAG2 induction elevates Notch activity (increased intracellular Notch1 and HEY1 target gene), and JAG2 expressed by hypoxic tumor cells promotes endothelial cell tube formation in co-culture. siRNA knockdown of HIF-1alpha, Notch target gene measurement (icN1, HEY1), co-culture tube formation assay with JAG2 siRNA Molecular Cancer Research Medium 21402725
2012 JAG2 expression is required for self-renewal (clonogenic colony formation) and in vivo tumor formation of myeloma cells; blocking JAG-NOTCH interactions with NOTCH-Fc chimeric molecules impairs colony formation, and JAG2 silencing blocks both colony and tumor formation. JAG2 siRNA silencing, NOTCH-Fc chimeric molecule blocking, semi-solid colony assay, xenograft tumor formation in immunocompromised mice Blood Cells, Molecules & Diseases Medium 22341562
2013 JAG2 promotes Notch activity, clonogenic growth, motility, and invasion in uveal melanoma cells; overexpression increases soft-agar colony formation and invasion, and shRNA-mediated knockdown suppresses growth and invasion, with a corresponding increase in JAG2 and Hes1 mRNA in invasive cells. JAG2-GFP overexpression constructs, shRNA knockdown, soft-agar colony assay, wound-healing and transwell invasion assays, Hes1 mRNA measurement Investigative Ophthalmology & Visual Science Medium 23211831
2014 JAG2 is identified as a direct MYC transcriptional target in medulloblastoma; MYC-driven transcriptional activation of JAG2 is specific to Group 3 (MYC-amplified) medulloblastoma and links the MYC oncogene to Notch pathway activation in these tumors. Expression analysis in MB cohorts, in vitro MYC activation studies, qPCR for JAG2 in MYC-high vs. low cells Acta Neuropathologica Communications Medium 24708907
2017 JAG2 expression in colorectal cancer is regulated by Wnt/beta-catenin signaling (APC deletion or beta-catenin knockdown modulates JAG2); JAG2 promotes chemoresistance through p21, as forced p21 expression rescues sensitivity of JAG2-knockdown cells and p21-null cells are insensitive to JAG2 knockdown. Pharmacological beta-catenin inhibition, siRNA knockdown, Apc conditional knockout mice, in vivo tumorigenicity assay, p21 forced expression rescue experiment Oncotarget Medium 28881809
2018 JAG2 signaling activates Notch in CD14+ monocytes to drive their differentiation into LCH-like cells (acquiring CD1a and langerin), inducing an LCH gene signature; Notch inhibition suppresses this phenotype. In vitro JAG2 co-culture of monocytes, Notch inhibitor treatment, flow cytometry, gene expression profiling Journal of Leukocyte Biology Medium 30296338
2019 JAG2 activates Notch2/Hes1/Hey2 signaling in nucleus pulposus cells to promote proliferation via cyclin D1 and PI3K/Akt and Wnt/beta-catenin pathways, and inhibits TNF-alpha-induced apoptosis by suppressing formation of the RIP1-FADD-caspase-8 complex; intradiscal injection of JAG2 alleviates disc degeneration in rats. Recombinant JAG2 protein treatment, Notch2/Hes1/Hey2 siRNA, cell cycle analysis, Co-IP for RIP1-FADD-caspase-8 complex, PI3K/Akt and Wnt pathway inhibitors, intradiscal rat injection model Arthritis Research & Therapy Medium 31619270
2019 JAG2 promotes migration and invasion of colorectal cancer cells via a non-canonical Notch, non-EMT pathway involving mutual regulation with PRAF2; JAG2-rich exosomes are released from CRC cells in a PRAF2-dependent manner and regulate metastasis in a paracrine fashion. siRNA knockdown, transcriptome microarray, Co-expression analysis, exosome isolation, paracrine co-culture assay Cancer Cell International Medium 31198409
2021 Biallelic pathogenic variants in JAG2 cause a muscular dystrophy (LGMD R27); Jag2 downregulation in murine myoblasts leads to downregulation of multiple Notch pathway components including Megf10; transcriptome analysis of patient muscle shows misregulation of myogenesis genes including PAX7, implicating Notch pathway dysfunction as the disease mechanism. Whole-exome sequencing, muscle transcriptome analysis, Jag2 siRNA knockdown in murine myoblasts, Drosophila genetic interaction studies (Serrate/Drpr), in silico structural prediction of missense variants American Journal of Human Genetics Medium 33861953
2021 MSC supernatant inhibits IL-6-mediated STAT3 phosphorylation to activate the p63-JAG2 signaling axis in basal lung epithelial cells, promoting p63+ cell proliferation and repair; the IL-6-p-STAT3-p63-JAG2 pathway was identified as the mechanistic link between MSC secretome treatment and attenuation of acute lung injury. Mouse bleomycin-induced ALI model, immunofluorescence, Western blot, flow cytometry, siRNA pathway manipulation Stem Cell Research & Therapy Medium 33781349
2022 JAG1 and JAG2 undergo posttranslational modifications in tracheobronchial epithelium: gamma-secretase complex (GSC) and glycogen synthase kinase 3 generate a JAG1 C-terminal peptide and regulate full-length JAG2 surface abundance; these distinct JAG1/JAG2 assemblies regulate Notch signal strength and determine goblet vs. ciliated cell fate in a WNT-independent manner. Human air-liquid-interface cultures, gamma-secretase inhibitors, neutralizing peptides/antibodies, WNT pathway agonists/antagonists, RNA-Seq, biochemical fractionation JCI Insight Medium 35819850
2024 The JAG2/Notch1 signaling axis is the primary regulator of sebocyte differentiation in mouse skin; specific inhibition of JAG2 ligand or Notch1 receptor with monoclonal antibodies causes loss of mature sebocytes and accumulation of proliferative stem/progenitor cells, a phenotype that is reversible upon lifting Notch inhibition. Monoclonal therapeutic antibody inhibition of individual Notch ligands/receptors in mice, histology, cell proliferation assays eLife High 39585329
2025 Usp11 deubiquitinates JAG2 (and DLL1) to maintain their stability; loss of Usp11 reduces JAG2 ubiquitination, altering Notch signaling in marginal zone B cells and their survival after ionizing radiation. Co-IP and ubiquitination assays in Usp11-/- mice, flow cytometry, histological analysis, single-cell sequencing Cell Death & Disease Medium 39904982
2025 CD146 activates NF-κB signaling to upregulate JAG2, which then activates Notch signaling to promote stemness and chemoresistance in hepatocellular carcinoma; JAG2 overexpression rescues Notch activity and stemness suppressed by CD146 knockdown. CD146 overexpression/knockdown, JAG2 overexpression rescue experiment, Notch signaling reporter, in vitro self-renewal and chemoresistance assays, xenograft Cell Death & Disease Medium 40032820
2025 Tumor-derived JAG2 activates NOTCH3 on macrophages, inducing STAT3 phosphorylation and CCL2 upregulation, driving an immunosuppressive M2-like, neurotrophic macrophage phenotype that promotes perineural invasion; disruption of JAG2-NOTCH3 signaling, STAT3 inhibition, or CCL2 blockade attenuates invasion in vitro and in vivo. Single-cell transcriptomics, ligand-receptor analysis, STAT3 inhibition, CCL2 neutralization, JAG2 knockdown, xenograft and sciatic nerve invasion models International Journal of Biological Macromolecules Medium 41916520
2024 NEURL1 and NEURL2 (Neuralized-like) ubiquitin ligases do not activate JAG2 because JAG2 lacks the NxxN Neuralized binding motif present in DLL1 and JAG1, establishing differential regulation: NEURL proteins selectively activate only DLL1 and JAG1 among mammalian Notch ligands. Humanized Drosophila system, mammalian cell culture Notch activation assays, motif mutagenesis, comparison across all four mammalian Notch ligands bioRxivpreprint Medium bio_10.1101_2024.09.20.614084
2025 JAG2 deficiency and pathogenic JAG2 variants impair Notch signaling and myogenic self-renewal and differentiation in muscle stem cells (MuSCs); MuEC-specific Jag2 knockout reduces MuSC self-renewal (trans-activation), while MuSC-specific Jag2 knockout reduces myogenic differentiation (cis-inhibition); hypomorphic Jag2 mutant mice show depleted MuSCs and impaired muscle regeneration; human reference JAG2 but not pathogenic variants rescues Drosophila Serrate deficiency. Cell-type-specific conditional Jag2 knockout mice, co-culture experiments, Drosophila Serrate rescue with human JAG2 constructs, hypomorphic Jag2 mutant mouse analysis, overexpression of pathogenic variants bioRxivpreprint High bio_10.1101_2025.07.23.665646

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear. Development (Cambridge, England) 228 16141228
2004 Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. Blood 141 15292061
2007 DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proceedings of the National Academy of Sciences of the United States of America 134 17626181
2000 Expression of Math1 and HES5 in the cochleae of wildtype and Jag2 mutant mice. Journal of the Association for Research in Otolaryngology : JARO 124 11545143
2006 Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development. Developmental dynamics : an official publication of the American Association of Anatomists 94 16607638
2011 JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation. Molecular cancer research : MCR 63 21402725
2009 Loss of the SMRT/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma. Cancer research 55 19417136
2010 Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model. Proceedings of the National Academy of Sciences of the United States of America 49 20133585
2019 JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix. Arthritis research & therapy 46 31619270
2021 Lyophilized powder of mesenchymal stem cell supernatant attenuates acute lung injury through the IL-6-p-STAT3-p63-JAG2 pathway. Stem cell research & therapy 40 33781349
2014 β-site amyloid precursor protein cleaving enzyme 1(BACE1) regulates Notch signaling by controlling the cleavage of Jagged 1 (Jag1) and Jagged 2 (Jag2) proteins. The Journal of biological chemistry 33 24907271
2014 NOTCH ligands JAG1 and JAG2 as critical pro-survival factors in childhood medulloblastoma. Acta neuropathologica communications 31 24708907
2014 NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer. Medicina (Kaunas, Lithuania) 31 25060200
2018 MicroRNA-876-3p functions as a tumor suppressor gene and correlates with cell metastasis in pancreatic adenocarcinoma via targeting JAG2. American journal of cancer research 27 29736309
2017 Jagged-2 (JAG2) enhances tumorigenicity and chemoresistance of colorectal cancer cells. Oncotarget 27 28881809
2013 A role for Jag2 in promoting uveal melanoma dissemination and growth. Investigative ophthalmology & visual science 24 23211831
2012 Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells. Blood cells, molecules & diseases 23 22341562
2021 A form of muscular dystrophy associated with pathogenic variants in JAG2. American journal of human genetics 22 33861953
2018 JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells. Journal of leukocyte biology 22 30296338
2015 A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. Oncotarget 19 25576913
2000 Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene. Genomics 16 10662552
2022 Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease. JCI insight 15 35819850
2022 miR-2392 functions as tumour suppressor and inhibits malignant progression of hepatocellular carcinoma via directly targeting JAG2. Liver international : official journal of the International Association for the Study of the Liver 14 35485355
2019 Mutual regulation of JAG2 and PRAF2 promotes migration and invasion of colorectal cancer cells uncoupled from epithelial-mesenchymal transition. Cancer cell international 14 31198409
2018 Long noncoding RNA ENST00000455974 plays an oncogenic role through up-regulating JAG2 in human DNA mismatch repair-proficient colon cancer. Biochemical and biophysical research communications 13 30473216
2025 Immunosuppressive JAG2+ tumor-associated neutrophils hamper PD-1 blockade response in ovarian cancer by mediating the differentiation of effector regulatory T cells. Cancer communications (London, England) 12 40120139
2019 Overexpression of JAG2 is related to poor outcomes in oral squamous cell carcinoma. Clinical and experimental dental research 12 32250571
2015 Combined QTL and selective sweep mappings with coding SNP annotation and cis-eQTL analysis revealed PARK2 and JAG2 as new candidate genes for adiposity regulation. G3 (Bethesda, Md.) 10 25653314
2022 MicroRNA-381 Regulates Proliferation and Differentiation of Caprine Skeletal Muscle Satellite Cells by Targeting PTEN and JAG2. International journal of molecular sciences 9 36362373
2021 An immune-related model based on INHBA, JAG2 and CCL19 to predict the prognoses of colon cancer patients. Cancer cell international 7 34103052
2025 CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling. Cell death & disease 6 40032820
2024 Three novel missense variants in two families with JAG2-associated limb-girdle muscular dystrophy. Neuromuscular disorders : NMD 2 39121631
2024 The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation. eLife 2 39585329
2025 Usp11 maintained the survival of marginal zone B cells under ionizing radiation by deubiquitinating DLL1 and JAG2. Cell death & disease 1 39904982
2024 Case Report: Exploring the clinical spectrum of LGMD R27: insights from a case study with homozygous pathogenic variant in the JAG2 gene. Frontiers in pediatrics 1 39649397
2020 [Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 31922603
2026 Tumor-derived JAG2 programs macrophages via NOTCH3 to drive perineural invasion in colorectal cancer. International journal of biological macromolecules 0 41916520
2025 JAG2 AS A KEY MEDIATOR IN PORPHYROMONAS GINGIVALIS-INDUCED PERIODONTAL INFLAMMATION. Georgian medical news 0 40466700
2025 Low SVEP1 in intrahepatic cholangiocarcinoma mediates phenotype switching-driven metastasis by Jag2/Notch1/Hes5. Cell death & disease 0 41315239
2024 JAG2: A Potential Biomarker for Microtia Identified by Integrated RNA Transcriptome Analysis. Current genomics 0 40433419