JAG1 (Jagged-1) is a single-pass type I transmembrane Notch ligand of the Serrate/Jagged subclass of the DSL family. Its extracellular region comprises an N-terminal MNNL domain, the DSL domain, 16 EGF-like repeats (the second atypical) and a cysteine-rich region; the DSL-EGF3 region forms the Notch-binding face used for both trans-activation and cis-inhibition. JAG1 binds NOTCH1, NOTCH2 and NOTCH3 in a calcium-dependent manner, and its cytoplasmic tail, which carries a C-terminal PDZ-binding motif, is recognised at two sites by the E3 ligase MIB1; ubiquitination and endocytosis of the ligand provide the mechanical pull required for Notch activation. Fringe-mediated glycosylation of NOTCH1 reduces its responsiveness to JAG1. JAG1 also binds the complement regulator CD46 on T cells. JAG1-Notch signaling is required for cardiovascular (outflow tract, pulmonary artery, valve), bile duct, inner ear, kidney and eye development; heterozygous loss of function causes Alagille syndrome, and JAG1 variants also cause tetralogy of Fallot and an axonal Charcot-Marie-Tooth neuropathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | NAS PMID:8955070 An antisense oligonucleotide to the notch ligand jagged enha... | KEEP AS NON CORE | Summary: Antisense JAG1 enhances FGF-induced endothelial invasion and tube formation in vitro. Reason: Supports a (negative) regulatory role in FGF-driven angiogenesis in vitro; retained as a non-core, context-specific process. Supporting Evidence: PMID:8955070 the addition of an antisense Jagged oligomer to bovine microvascular endothelial cells grown on a collagen gel resulted in a marked increase in invasion and tube formation in the underlying gel in response to fibroblast growth factor. |
| GO:0001709 cell fate determination | NAS PMID:9207788 Alagille syndrome is caused by mutations in human Jagged1, w... | KEEP AS NON CORE | Summary: Cell fate determination via Notch. Reason: General consequence of Notch ligand function; non-core. Supporting Evidence: PMID:9207787 Within this region we identified JAG1, the human homologue of rat Jagged1, which encodes a ligand for the Notch receptor. |
| GO:0001953 negative regulation of cell-matrix adhesion | IDA PMID:11549580 Members of the Jagged/Notch gene families are expressed in i... | MARK AS OVER ANNOTATED | Summary: Adhesion/migration phenotypes from NIH3T3 cells expressing a secreted JAG1 ectodomain. Reason: The effect comes from an engineered soluble fragment that antagonises endogenous JAG1-Notch signaling (PMID:11427524), so it does not reflect a function of native transmembrane JAG1. Supporting Evidence: PMID:11549580 we studied an in vitro model of NIH3T3 cells transfected with a secreted form of the extracellular domain of Jagged1. PMID:11549580 We report that the soluble Jagged1 protein caused decreased cell-matrix adhesion and cell migration defects. PMID:11427524 may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. |
| GO:0002456 T cell mediated immunity | IMP PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | KEEP AS NON CORE | Summary: Alagille patients' CD4+ T cells fail to mount TH1 responses; JAG1-CD46 crosstalk. Reason: Specific immunological role supported by patient data; non-core relative to Notch ligand function. Supporting Evidence: PMID:23086448 CD4(+) T cells from CD46-deficient patients and patients with hypomorphic mutations in the gene encoding Jagged1 (Alagille syndrome) failed to mount appropriate T(H)1 responses in vitro and in vivo |
| GO:0003180 aortic valve morphogenesis | NAS PMID:20951801 NOTCH1 missense alleles associated with left ventricular out... | KEEP AS NON CORE | Summary: Aortic valve morphogenesis cited from a NOTCH1 LVOT study. Reason: JAG1-NOTCH1 signaling drives endocardial EMT in outflow tract development; the annotation is plausible as a tissue-level role but non-core. Supporting Evidence: PMID:20951801 we investigated their effect on epithelial-to-mesenchymal transition (EMT), a critical process for development of the outflow tract. |
| GO:0003184 pulmonary valve morphogenesis | IMP PMID:20437614 Jagged1 (JAG1) mutations in patients with tetralogy of Fallo... | KEEP AS NON CORE | Summary: Right-sided outflow (pulmonary valve/artery) defects in patients with JAG1 mutations. Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: PMID:9207787 We conclude that AGS is caused by haploinsufficiency of JAG1. PMID:20437614 The four missense mutations were assayed for their effect on protein localization, posttranslational modification, and ability to activate Notch signaling. |
| GO:0003184 pulmonary valve morphogenesis | IMP PMID:9207787 Mutations in the human Jagged1 gene are responsible for Alag... | KEEP AS NON CORE | Summary: Right-sided outflow (pulmonary valve/artery) defects in patients with JAG1 mutations. Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: PMID:9207787 We conclude that AGS is caused by haploinsufficiency of JAG1. PMID:20437614 The four missense mutations were assayed for their effect on protein localization, posttranslational modification, and ability to activate Notch signaling. |
| GO:0003215 cardiac right ventricle morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0003215 cardiac right ventricle morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0005112 Notch binding | IBA GO_REF:0000033 | ACCEPT | Summary: Notch binding inherited from the ancestral DSL ligand node (PTN002371879). Reason: JAG1 binds NOTCH1, NOTCH2 and NOTCH3; the IBA placement across Delta/Serrate ligands is sound. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005112 Notch binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic Notch binding, consistent with experimental data. Reason: Core molecular function. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Interacts with NOTCH1 (in the presence of calcium ions) |
| GO:0005112 Notch binding | IPI PMID:11006133 Physical interaction of Delta1, Jagged1, and Jagged2 with No... | ACCEPT | Summary: Direct Ca2+-dependent binding of Jagged1 to NOTCH1/NOTCH3 ectodomains. Reason: Primary experimental evidence for the core MF. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. PMID:11006133 All interactions between the DSL proteins and soluble Notch proteins were dependent on Ca(2+). |
| GO:0005112 Notch binding | NAS PMID:9268641 Identification and cloning of the human homolog (JAG1) of th... | ACCEPT | Summary: JAG1 identified as the human homolog of the rat Notch ligand Jagged1. Reason: Consistent with direct binding evidence. Supporting Evidence: PMID:9268641 We have isolated the human homolog of the rat Jagged1 gene, JAG1 file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0005198 structural molecule activity | NAS PMID:10679295 A non-transmembrane form of Jagged-1 regulates the formation... | REMOVE | Summary: Structural molecule activity assigned from a study of a secreted JAG1 fragment in NIH3T3 cells. Reason: Nothing in the study indicates that JAG1 contributes to structural integrity of a complex or assembly; the observed chord-like phenotype is a signaling consequence of an engineered soluble form. JAG1 is a signaling ligand. Supporting Evidence: PMID:10679295 we stably transfected NIH 3T3 cells with a truncated form of Jagged(J)-1, which results in the secretion of a soluble(s) form of the protein. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Calcium ion binding by calcium-binding EGF-like repeats. Reason: JAG1-Notch binding is Ca2+-dependent; structural MF, non-core. Supporting Evidence: PMID:11006133 All interactions between the DSL proteins and soluble Notch proteins were dependent on Ca(2+). file:human/JAG1/JAG1-uniprot.txt Interacts with NOTCH1 (in the presence of calcium ions) |
| GO:0005515 protein binding | IPI PMID:18660822 A conserved face of the Jagged/Serrate DSL domain is involve... | MODIFY | Summary: Structural/NMR evidence of Jagged-1 DSL-EGF3 binding NOTCH1. Reason: Generic protein binding; the interaction is Notch binding. Proposed replacements: Notch binding Supporting Evidence: PMID:18660822 We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. |
| GO:0005515 protein binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | MODIFY | Summary: JAG1 binds the complement regulator CD46 (via CCP1-2) as a physiological ligand. Reason: Generic protein binding; CD46 is a cell-surface receptor for which Jagged1 is described as a ligand, so signaling receptor binding is more informative. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:23086448 Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. |
| GO:0005515 protein binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | MODIFY | Summary: JAG1-NOTCH1 interaction in T-cell study. Reason: Generic protein binding; the partner is NOTCH1, so Notch binding is the informative MF. Proposed replacements: Notch binding Supporting Evidence: PMID:23086448 Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. |
| GO:0005515 protein binding | IPI PMID:29713059 Inactivation of the serine protease HTRA1 inhibits tumor gro... | REMOVE | Summary: HTRA1 protease binds and cleaves JAG1 in its intracellular domain. Reason: Generic protein binding; JAG1 is a substrate of HTRA1 and no specific JAG1 MF is implied. The interaction itself is not disputed. Supporting Evidence: PMID:29713059 HTRA1 physically interacted with JAG1 and cleaved it within the intracellular domain, leading to protein degradation. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: JAG1 binds the complement regulator CD46 (via CCP1-2) as a physiological ligand. Reason: Generic protein binding; CD46 is a cell-surface receptor for which Jagged1 is described as a ligand, so signaling receptor binding is more informative. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:23086448 Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | REMOVE | Summary: High-throughput surface interactome hit with VASN. Reason: Generic protein binding with no functional characterization; uninformative. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PDZ-binding motif affinity survey including the JAG1 C-terminal motif. Reason: Generic protein binding; the assay measures PDZ domain binding to the JAG1 C-terminal PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region PMID:22465068 a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif |
| GO:0005543 phospholipid binding | IMP PMID:22465068 Flexibility of the PDZ-binding motif in the micelle-bound fo... | KEEP AS NON CORE | Summary: The JAG1 intracellular region binds negatively charged phospholipid micelles/vesicles (NMR, SPR). Reason: Real biophysical property of the cytoplasmic tail that may regulate PDZ-motif accessibility; not a core function. Supporting Evidence: PMID:22465068 Binding of J1_tmic to negatively charged, but not to zwitterionic vesicles, was confirmed by surface plasmon resonance. |
| GO:0005576 extracellular region | NAS PMID:11427524 Soluble Jagged 1 represses the function of its transmembrane... | MARK AS OVER ANNOTATED | Summary: Extracellular region based on an engineered soluble JAG1 ectodomain. Reason: Native JAG1 is transmembrane; the soluble form studied acts as an antagonist of endogenous JAG1 signaling. Supporting Evidence: PMID:11427524 may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. |
| GO:0005886 plasma membrane | IDA PMID:20437614 Jagged1 (JAG1) mutations in patients with tetralogy of Fallo... | ACCEPT | Summary: Cell-surface localization of JAG1 shown by surface trypsinization / biotinylation of wild-type vs mutant protein. Reason: Core location of the transmembrane ligand. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. PMID:32065591 the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. |
| GO:0005886 plasma membrane | IDA PMID:32065591 Dominant mutations of the Notch ligand Jagged1 cause periphe... | ACCEPT | Summary: Cell-surface localization of JAG1 shown by surface trypsinization / biotinylation of wild-type vs mutant protein. Reason: Core location of the transmembrane ligand. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. PMID:32065591 the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | NAS PMID:11427524 Soluble Jagged 1 represses the function of its transmembrane... | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220944 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220976 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2660822 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2691226 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2730752 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2737728 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2768999 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2769007 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2900743 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2900765 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8878212 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9013284 | ACCEPT | Summary: Plasma membrane localization of transmembrane JAG1. Reason: Consistent with experimental data. Supporting Evidence: PMID:20437614 JAG1 is a cell surface protein that interacts with the human Notch receptors. |
| GO:0005912 adherens junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Junctional/apical localization transferred from rodent Jag1. Reason: Plausible polarized-epithelium localization; not directly shown for human JAG1. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005912 adherens junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Junctional/apical localization transferred from rodent Jag1. Reason: Plausible polarized-epithelium localization; not directly shown for human JAG1. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0007154 cell communication | IEA GO_REF:0000002 | ACCEPT | Summary: Cell communication from the DSL domain. Reason: Correct but general; JAG1 mediates juxtacrine signaling. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: JAG1 is a canonical ligand initiating Notch signaling. Reason: Core process. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0007219 Notch signaling pathway | IMP PMID:19682396 Notch signaling is required for maintaining stem-cell featur... | ACCEPT | Summary: Notch signaling in hESC-derived neuroepithelial spheres expressing JAG1. Reason: Perturbation was pathway-wide (gamma-secretase inhibitor), but JAG1's role in Notch signaling is well established. Supporting Evidence: PMID:19682396 Notch signaling pathway proteins such as JAG1 and DLL1 and NICD and the target gene products HES1 and HES5 were abundant in hESC-derived NESs PMID:19682396 Inhibition of the Notch signaling by a gamma-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs |
| GO:0007219 Notch signaling pathway | IMP PMID:20437614 Jagged1 (JAG1) mutations in patients with tetralogy of Fallo... | ACCEPT | Summary: TOF/PS-associated JAG1 missense variants show reduced ability to activate a CBF1/RBPJ reporter in co-culture. Reason: Direct evidence that JAG1 triggers Notch signaling. Supporting Evidence: PMID:20437614 The four missense mutations were assayed for their effect on protein localization, posttranslational modification, and ability to activate Notch signaling. PMID:20437614 We assayed the variant proteins for Notch signaling ability via a CBF-dependent luciferase assay. |
| GO:0007219 Notch signaling pathway | IMP PMID:9207787 Mutations in the human Jagged1 gene are responsible for Alag... | ACCEPT | Summary: Alagille syndrome caused by JAG1 haploinsufficiency. Reason: Genetic evidence consistent with JAG1 functioning as a Notch ligand; curator judgment deferred to. Supporting Evidence: PMID:9207787 Within this region we identified JAG1, the human homologue of rat Jagged1, which encodes a ligand for the Notch receptor. PMID:9207787 We conclude that AGS is caused by haploinsufficiency of JAG1. |
| GO:0007219 Notch signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: JAG1 is a canonical ligand initiating Notch signaling. Reason: Core process. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0007219 Notch signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: JAG1 is a canonical ligand initiating Notch signaling. Reason: Core process. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0007219 Notch signaling pathway | NAS PMID:9268641 Identification and cloning of the human homolog (JAG1) of th... | ACCEPT | Summary: JAG1 is a canonical ligand initiating Notch signaling. Reason: Core process. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0007399 nervous system development | NAS PMID:8923452 Expression patterns of Jagged, Delta1, Notch1, Notch2, and N... | KEEP AS NON CORE | Summary: Expression in developing rat nervous system consistent with lateral inhibition. Reason: Broad, expression-based; non-core. Supporting Evidence: PMID:8923452 The punctate expression patterns we detected for Jagged and Delta 1 are consistent with their role in mediating lateral inhibition, a process proposed to regulate neural determination. |
| GO:0008083 growth factor activity | NAS PMID:11067884 The notch ligand jagged-1 represents a novel growth factor o... | MODIFY | Summary: Soluble JAG1 described as a 'growth factor' for human hematopoietic stem cells. Reason: JAG1 acts by engaging Notch receptors; the appropriate MF is receptor ligand activity / Notch binding rather than growth factor activity. Proposed replacements: receptor ligand activity Supporting Evidence: PMID:11067884 intravenous transplantation of cultured cells into immunodeficient mice revealed that human (h)Jagged-1 induces the survival and expansion of human stem cells capable of pluripotent repopulating capacity. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Regulation of gene expression (ARBA). Reason: Indirect consequence of Notch signaling in the receiving cell. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: JAG1 is a single-pass type I membrane protein. Reason: Correct though less specific than plasma membrane. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0016020 membrane | IMP PMID:22465068 Flexibility of the PDZ-binding motif in the micelle-bound fo... | ACCEPT | Summary: JAG1 is a single-pass type I membrane protein. Reason: Correct though less specific than plasma membrane. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0016020 membrane | TAS PMID:9268641 Identification and cloning of the human homolog (JAG1) of th... | ACCEPT | Summary: JAG1 is a single-pass type I membrane protein. Reason: Correct though less specific than plasma membrane. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Junctional/apical localization transferred from rodent Jag1. Reason: Plausible polarized-epithelium localization; not directly shown for human JAG1. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0016324 apical plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Junctional/apical localization transferred from rodent Jag1. Reason: Plausible polarized-epithelium localization; not directly shown for human JAG1. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0022408 negative regulation of cell-cell adhesion | IDA PMID:11549580 Members of the Jagged/Notch gene families are expressed in i... | MARK AS OVER ANNOTATED | Summary: Adhesion/migration phenotypes from NIH3T3 cells expressing a secreted JAG1 ectodomain. Reason: The effect comes from an engineered soluble fragment that antagonises endogenous JAG1-Notch signaling (PMID:11427524), so it does not reflect a function of native transmembrane JAG1. Supporting Evidence: PMID:11549580 we studied an in vitro model of NIH3T3 cells transfected with a secreted form of the extracellular domain of Jagged1. PMID:11549580 We report that the soluble Jagged1 protein caused decreased cell-matrix adhesion and cell migration defects. PMID:11427524 may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. |
| GO:0030097 hemopoiesis | NAS PMID:10329626 Rel/NF-kappaB can trigger the Notch signaling pathway by ind... | KEEP AS NON CORE | Summary: Hemopoiesis: JAG1 expressed in B cells/stroma and triggers Notch in lymphocytes. Reason: Supported but broad. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt May be involved in cell-fate decisions during hematopoiesis PMID:10329626 Cell surface expression of Jagged1 in c-Rel-expressing cell monolayers led to a functional interaction with lymphocytes expressing the Notch1/TAN-1 receptor. |
| GO:0030216 keratinocyte differentiation | NAS PMID:12107827 Jagged-1 mediated activation of notch signaling induces comp... | KEEP AS NON CORE | Summary: A JAG1 peptide induces keratinocyte/epidermal maturation. Reason: Supported in human epidermal equivalents; non-core. Supporting Evidence: PMID:12107827 Addition of JAG-1 peptide to submerged EEs was sufficient to induce epidermal maturation. |
| GO:0030336 negative regulation of cell migration | IDA PMID:11549580 Members of the Jagged/Notch gene families are expressed in i... | MARK AS OVER ANNOTATED | Summary: Adhesion/migration phenotypes from NIH3T3 cells expressing a secreted JAG1 ectodomain. Reason: The effect comes from an engineered soluble fragment that antagonises endogenous JAG1-Notch signaling (PMID:11427524), so it does not reflect a function of native transmembrane JAG1. Supporting Evidence: PMID:11549580 we studied an in vitro model of NIH3T3 cells transfected with a secreted form of the extracellular domain of Jagged1. PMID:11549580 We report that the soluble Jagged1 protein caused decreased cell-matrix adhesion and cell migration defects. PMID:11427524 may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. |
| GO:0031625 ubiquitin protein ligase binding | EXP PMID:25747658 A tail of two sites: a bipartite mechanism for recognition o... | KEEP AS NON CORE | Summary: The JAG1 cytoplasmic tail is bound by two substrate-recognition domains of the E3 ligase MIB1. Reason: JAG1 is the substrate of MIB1; binding the ligase is required for ligand ubiquitination and signaling. Well supported by structures and cell assays, but describes the ligand as substrate rather than its signaling activity; non-core. Supporting Evidence: PMID:25747658 Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. PMID:25747658 both interactions are needed for normal stimulation of Notch signal transduction. |
| GO:0031625 ubiquitin protein ligase binding | IMP PMID:25747658 A tail of two sites: a bipartite mechanism for recognition o... | KEEP AS NON CORE | Summary: The JAG1 cytoplasmic tail is bound by two substrate-recognition domains of the E3 ligase MIB1. Reason: JAG1 is the substrate of MIB1; binding the ligase is required for ligand ubiquitination and signaling. Well supported by structures and cell assays, but describes the ligand as substrate rather than its signaling activity; non-core. Supporting Evidence: PMID:25747658 Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. PMID:25747658 both interactions are needed for normal stimulation of Notch signal transduction. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:25747658 A tail of two sites: a bipartite mechanism for recognition o... | KEEP AS NON CORE | Summary: The JAG1 cytoplasmic tail is bound by two substrate-recognition domains of the E3 ligase MIB1. Reason: JAG1 is the substrate of MIB1; binding the ligase is required for ligand ubiquitination and signaling. Well supported by structures and cell assays, but describes the ligand as substrate rather than its signaling activity; non-core. Supporting Evidence: PMID:25747658 Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. PMID:25747658 both interactions are needed for normal stimulation of Notch signal transduction. |
| GO:0032495 response to muramyl dipeptide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to muramyl dipeptide (mouse, Ensembl Compara). Reason: Expression-response annotation with no mechanistic link to JAG1 function. |
| GO:0035909 aorta morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0035909 aorta morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0042127 regulation of cell population proliferation | NAS PMID:10329626 Rel/NF-kappaB can trigger the Notch signaling pathway by ind... | MARK AS OVER ANNOTATED | Summary: Regulation of proliferation from introductory statement. Reason: Generic downstream consequence of Notch signaling. Supporting Evidence: PMID:10329626 Jagged1 belongs to the DSL family of ligands for Notch receptors that control the proliferation and differentiation of various cell lineages. |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Junctional/apical localization transferred from rodent Jag1. Reason: Plausible polarized-epithelium localization; not directly shown for human JAG1. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0045445 myoblast differentiation | NAS PMID:10329626 Rel/NF-kappaB can trigger the Notch signaling pathway by ind... | KEEP AS NON CORE | Summary: Myoblast differentiation (JAG1 inhibits myoblast differentiation in rodent cells). Reason: Non-core developmental role. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Inhibits myoblast differentiation (By similarity). |
| GO:0045446 endothelial cell differentiation | NAS PMID:10329626 Rel/NF-kappaB can trigger the Notch signaling pathway by ind... | KEEP AS NON CORE | Summary: Endothelial cell differentiation. Reason: JAG1-Notch signaling regulates endothelial behaviour; non-core. Supporting Evidence: PMID:8955070 the addition of an antisense Jagged oligomer to bovine microvascular endothelial cells grown on a collagen gel resulted in a marked increase in invasion and tube formation in the underlying gel in response to fibroblast growth factor. |
| GO:0045596 negative regulation of cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Negative regulation of cell differentiation (ARBA). Reason: General Notch-ligand outcome; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Inhibits myoblast differentiation (By similarity). |
| GO:0045602 negative regulation of endothelial cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endothelial cell differentiation. Reason: JAG1-Notch signaling regulates endothelial behaviour; non-core. Supporting Evidence: PMID:8955070 the addition of an antisense Jagged oligomer to bovine microvascular endothelial cells grown on a collagen gel resulted in a marked increase in invasion and tube formation in the underlying gel in response to fibroblast growth factor. |
| GO:0045747 positive regulation of Notch signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of Notch signaling (rodent). Reason: As ligand, JAG1 is part of the pathway itself; the regulation term is partly redundant with GO:0007219 but not wrong. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0045747 positive regulation of Notch signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of Notch signaling (rodent). Reason: As ligand, JAG1 is part of the pathway itself; the regulation term is partly redundant with GO:0007219 but not wrong. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Ligand for multiple Notch receptors and involved in the mediation of Notch signaling |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of RNA polymerase II transcription based on Notch reporter activation. Reason: Transcription of Notch targets is executed by NICD-RBPJ-MAML in the receiving cell; for the ligand this is indirect. The reporter data are captured by Notch signaling pathway. Supporting Evidence: PMID:20437614 We assayed the variant proteins for Notch signaling ability via a CBF-dependent luciferase assay. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:20437614 Jagged1 (JAG1) mutations in patients with tetralogy of Fallo... | MARK AS OVER ANNOTATED | Summary: Positive regulation of RNA polymerase II transcription based on Notch reporter activation. Reason: Transcription of Notch targets is executed by NICD-RBPJ-MAML in the receiving cell; for the ligand this is indirect. The reporter data are captured by Notch signaling pathway. Supporting Evidence: PMID:20437614 We assayed the variant proteins for Notch signaling ability via a CBF-dependent luciferase assay. |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad organ/system development (ARBA). Reason: True but very general; multi-organ developmental role of JAG1 is evident from Alagille syndrome. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. |
| GO:0048731 system development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad organ/system development (ARBA). Reason: True but very general; multi-organ developmental role of JAG1 is evident from Alagille syndrome. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. |
| GO:0048839 inner ear development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inner ear development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. JAG1 variants cause hearing loss (DCHE). Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt mild to severe combined hearing loss, congenital heart defects, and posterior embryotoxon |
| GO:0060411 cardiac septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0060411 cardiac septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0061156 pulmonary artery morphogenesis | IMP PMID:9207787 Mutations in the human Jagged1 gene are responsible for Alag... | KEEP AS NON CORE | Summary: Right-sided outflow (pulmonary valve/artery) defects in patients with JAG1 mutations. Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: PMID:9207787 We conclude that AGS is caused by haploinsufficiency of JAG1. PMID:20437614 The four missense mutations were assayed for their effect on protein localization, posttranslational modification, and ability to activate Notch signaling. |
| GO:0061309 cardiac neural crest cell development involved in outflow tract morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0061309 cardiac neural crest cell development involved in outflow tract morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0061444 endocardial cushion cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0061444 endocardial cushion cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiovascular morphogenesis (rodent Jag1 orthology). Reason: JAG1 haploinsufficiency causes Alagille syndrome and tetralogy of Fallot with right-sided outflow tract, pulmonary artery and valve defects. Cardiovascular morphogenesis is a real, well-supported but tissue-specific consequence of JAG1-Notch signaling; non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Seems to be involved in early and late stages of mammalian cardiovascular development. file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072006 nephron development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072006 nephron development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072015 podocyte development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072015 podocyte development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072017 distal tubule development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0072070 loop of Henle development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron/podocyte/tubule development (mouse Jag1). Reason: Developmental role transferred from rodent Jag1 by orthology. JAG1 contributes as the Notch ligand of the signal-sending cell; this tissue-level outcome is consistent with human JAG1 disease phenotypes but is not the core molecular role, so it is kept as non-core. Supporting Evidence: file:human/JAG1/JAG1-uniprot.txt Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas |
| GO:0097150 neuronal stem cell population maintenance | IEP PMID:19682396 Notch signaling is required for maintaining stem-cell featur... | KEEP AS NON CORE | Summary: JAG1 expression in NESCs where Notch maintains stemness. Reason: Expression-pattern evidence; non-core. Supporting Evidence: PMID:19682396 Notch signaling pathway proteins such as JAG1 and DLL1 and NICD and the target gene products HES1 and HES5 were abundant in hESC-derived NESs |
| GO:2000737 negative regulation of stem cell differentiation | IMP PMID:19682396 Notch signaling is required for maintaining stem-cell featur... | KEEP AS NON CORE | Summary: Notch inhibition triggers neuronal differentiation of hESC-derived NESCs. Reason: Pathway-wide inhibitor; JAG1-specific role inferred. Non-core. Supporting Evidence: PMID:19682396 Inhibition of the Notch signaling by a gamma-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs |
| GO:0048018 receptor ligand activity | IMP PMID:20437614 Jagged1 (JAG1) mutations in patients with tetralogy of Fallo... | NEW | Summary: JAG1 activates Notch receptors on adjacent cells; loss-of-function missense variants lose signaling ability. Reason: Receptor ligand activity is the appropriate MF for JAG1 alongside Notch binding (DLL1 already carries it). Comparator: DLL1, DLL4 and JAG2 are Notch ligands in the same role. Supporting Evidence: PMID:20437614 The four missense mutations were assayed for their effect on protein localization, posttranslational modification, and ability to activate Notch signaling. PMID:20437614 We assayed the variant proteins for Notch signaling ability via a CBF-dependent luciferase assay. |
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Download this section (compressed HTML)Q: Does JAG1 binding to CD46 transmit a signal into T cells independent of Notch, and should it be annotated as a distinct receptor-binding activity?
Q: How much of JAG1's in vivo activity is cis-inhibition versus trans-activation in tissues co-expressing Fringe-modified NOTCH1?
Experiment: Quantify trans-activation of NOTCH1 vs NOTCH2 by JAG1 in the presence and absence of LFNG to define Fringe sensitivity of each receptor in human cells.
Experiment: Test Alagille missense variants for loss of MIB1 recognition versus loss of Notch binding using the two-epitope MIB1 binding assay.
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