JAG2 (Human Jagged2)

2007-02-01   Pushpankur Ghoshal , Lionel J Coignet 

Roswell Park Cancer Institute, Dept of Cancer Genetics, Buffalo, NY - USA





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.



In human, JAG2 is expressed at high levels in the heart, the skeletal muscle and the pancreas.

Implicated in

Entity name
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.
Atlas Image
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.
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.


Pubmed IDLast YearTitleAuthors
106625522000Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene.Deng Y et al
100792561999Human ligands of the Notch receptor.Gray GE et al
152920612004Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines.Houde C et al
125519312003The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage.Ikeuchi T et al
93412521997The Jagged2 gene maps to chromosome 12 and is a candidate for the lgl and sm mutations.Lan Y et al
109109092000Mouse 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


dbSNP: 3714
ClinVar: 3714
TCGA: ENSG00000184916


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Notch signaling pathwayKEGGko04330
Notch signaling pathwayKEGGhsa04330
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by NOTCH1 in CancerREACTOMER-HSA-2644603
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation MutantREACTOMER-HSA-2660825
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation MutantREACTOMER-HSA-2660826
Signaling by NOTCH1 HD Domain Mutants in CancerREACTOMER-HSA-2691230
Constitutive Signaling by NOTCH1 HD Domain MutantsREACTOMER-HSA-2691232
Signaling by NOTCH1 PEST Domain Mutants in CancerREACTOMER-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain MutantsREACTOMER-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in CancerREACTOMER-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain MutantsREACTOMER-HSA-2894862
Signal TransductionREACTOMER-HSA-162582
Signaling by NOTCHREACTOMER-HSA-157118
Signaling by NOTCH1REACTOMER-HSA-1980143
Activated NOTCH1 Transmits Signal to the NucleusREACTOMER-HSA-2122948
Signaling by NOTCH2REACTOMER-HSA-1980145
NOTCH2 Activation and Transmission of Signal to the NucleusREACTOMER-HSA-2979096
Signaling by NOTCH3REACTOMER-HSA-1980148
Signaling by NOTCH4REACTOMER-HSA-1980150
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
214993082011Hypoxia-induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells.77
163278842005Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.70
152920612004Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines.57
216025252011Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells.38
201335852010Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model.31
214027252011JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation.28
117008652001Requirement of Notch 1 and its ligand jagged 2 expressions for spermatogenesis in rat and human testes.27
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27
213721532011Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions.25
226910422012Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression.25


Pushpankur Ghoshal ; Lionel J Coignet

JAG2 (Human Jagged2)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/gene/41030/jag2-(human-jagged2)