JAG2 (Human Jagged2)
2007-02-01 Pushpankur Ghoshal , Lionel J Coignet AffiliationRoswell Park Cancer Institute, Dept of Cancer Genetics, Buffalo, NY - USA
DNA/RNA
Description
Human Jagged2 gene contains approximately 5,077 bps including 26 exons and a putative promoter region. In addition to a TATA box and a CAC binding site, the promoter region also contains several transcription factor binding sites like NF-kappaB, E47, E12, E2F etc. JAG2 gene has a structural similarity (overall 62% at nucleotide level) with JAG1, though JAG1 is located at chromosomal region 20p12.
Proteins
Expression
In human, JAG2 is expressed at high levels in the heart, the skeletal muscle and the pancreas.
Implicated in
Entity name
Disease
The NOTCH ligand, JAG2, has been found to be overexpressed in malignant plasma cells from multiple myeloma (MM) patients and cell lines but not in nonmalignant plasma cells from tonsils, bone marrow from healthy individuals, or patients with other malignancies. Since MM cells have been shown to induce IL-6 expression in stromal cells in a largely cell contact-dependent manner, it has been concluded that MM cells induce production of IL-6 in stromal cells through overexpression of JAG2. Once secreted, IL-6 enhances proliferation of myeloma cells in a paracrine fashion.
Schematic representation of the physiological activation of NOTCH, with Cell 1 (MM plasma cell) expressing JAG2 and Cell 2 (Stromal cell) NOTCH.
A: JAG2 binds NOTCH via cell-to-cell contact.
B: Binding of JAG2 induces a proteolytic cleavage of the intracellular part of NOTCH (NOTCH-IC).
C: Once cleaved, NOTCH-IC is translocated into the nucleus.
D: Once in the nucleus, NOTCH-IC will be able to bind to downstream effectors such as CBF1, to activate, for example, the IL-6 gene transcription.
Oncogenesis
The induction of IL-6 secretion has been blocked in vitro by interference with anti-Notch-1 monoclonal antibodies raised against the binding sequence of Notch-1 with JAG2. Taken together, these results indicate that JAG2 over expression may be an early event in the pathogenesis of multiple myeloma involving IL-6 production.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10662552 | 2000 | Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene. | Deng Y et al |
| 10079256 | 1999 | Human ligands of the Notch receptor. | Gray GE et al |
| 15292061 | 2004 | Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. | Houde C et al |
| 12551931 | 2003 | The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage. | Ikeuchi T et al |
| 9341252 | 1997 | The Jagged2 gene maps to chromosome 12 and is a candidate for the lgl and sm mutations. | Lan Y et al |
| 10910909 | 2000 | Mouse Jagged2 is differentially expressed in hematopoietic progenitors and endothelial cells and promotes the survival and proliferation of hematopoietic progenitors by direct cell-to-cell contact. | Tsai S et al |
Other Information
Locus ID:
NCBI: 3714
MIM: 602570
HGNC: 6189
Ensembl: ENSG00000184916
Variants:
dbSNP: 3714
ClinVar: 3714
TCGA: ENSG00000184916
COSMIC: JAG2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000184916 | ENST00000331782 | Q9Y219 |
| ENSG00000184916 | ENST00000347004 | Q9Y219 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37966490 | 2024 | Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis. | 0 |
| 38395762 | 2024 | miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells. | 0 |
| 38485033 | 2024 | ZEB2 alleviates Hirschsprung's-associated enterocolitis by promoting the proliferation and differentiation of enteric neural precursor cells via the Notch-1/Jagged-2 pathway. | 1 |
| 38575576 | 2024 | Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells. | 0 |
| 37966490 | 2024 | Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis. | 0 |
| 38395762 | 2024 | miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells. | 0 |
| 38485033 | 2024 | ZEB2 alleviates Hirschsprung's-associated enterocolitis by promoting the proliferation and differentiation of enteric neural precursor cells via the Notch-1/Jagged-2 pathway. | 1 |
| 38575576 | 2024 | Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells. | 0 |
| 33861953 | 2021 | A form of muscular dystrophy associated with pathogenic variants in JAG2. | 6 |
| 33861953 | 2021 | A form of muscular dystrophy associated with pathogenic variants in JAG2. | 6 |
| 31922603 | 2020 | [Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population]. | 0 |
| 32250571 | 2020 | Overexpression of JAG2 is related to poor outcomes in oral squamous cell carcinoma. | 8 |
| 32792862 | 2020 | Jagged2 progressively increased expression from Stage I to III of Bladder Cancer and Melatonin-mediated downregulation of Notch/Jagged2 suppresses the Bladder Tumorigenesis via inhibiting PI3K/AKT/mTOR/MMPs signaling. | 11 |
| 31922603 | 2020 | [Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population]. | 0 |
| 32250571 | 2020 | Overexpression of JAG2 is related to poor outcomes in oral squamous cell carcinoma. | 8 |
Citation
Pushpankur Ghoshal ; Lionel J Coignet
JAG2 (Human Jagged2)
Atlas Genet Cytogenet Oncol Haematol. 2007-02-01
Online version: http://atlasgeneticsoncology.org/gene/41030/jag2
