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JAG2 (human jagged2)
Pushpankur Ghoshal, Lionel J Coignet
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263,
USA
Published in Atlas Database: February 2007
Online updated version: http://AtlasGeneticsOncology.org/Genes/JAG2ID41030ch14q32.html
DOI: 10.4267/2042/38440
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Expression
Identity
In human, JAG2 is expressed at high levels in the heart,
the skeletal muscle and the pancreas.
Hugo: JAG2
Other names: HJ2; Jagged2
Location: Human Jagged2 (jag2), a ligand for Notch
receptor, was mapped in the chromosomal region
14q32.
Implicated in
Multiple Myeloma
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.
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.
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.
Protein
Description
The predicted JAG2 protein is approximately 1,238amino acid long. It has several recognizable motifs,
including a signal peptide, 16 EGF-like repeats, a
transmembrane domain, and a short cytoplasmic
domain.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3)
199
JAG2 (human jagged2)
Ghoshal P, Coignet LJ
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.
and promotes the survival and proliferation of hematopoietic
progenitors by direct cell-to-cell contact. Blood 2000;96:950957.
References
Lan Y, Jiang R, Shawber C, Weinmaster G, Gridley T. The
Jagged2 gene maps to chromosome 12 and is a candidate for
the lgl and sm mutations. Mammalian Genome 1997;8:875876.
Ikeuchi T, Sisodia SS. The notch ligands, delta-1 and jagged-2,
are substrates for presenilin-dependent gamma-secretase
cleavage. J. Biol. Chem 2003;278:7751-7754.
Houde C, Li Y, Song L, Barton K, Zhang Q, Godwin J, Nand S,
Toor A, Alkan S, Smadja NV, Avet-Loiseau H, Lima CS, Miele
L, Coignet LJ. Overexpression of the NOTCH ligand JAG2 in
malignant plasma cells from multiple myeloma patients and cell
lines. Blood 2004;104:(12), 3697-3704.
Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML,
Banks A, Leiman J, Ward D, Ish-Horowitz D, ArtavanisTsakonas S. Human ligands of the Notch receptor. Am. J. Path
1999;154:785-794.
Deng Y, Madan A, Banta AB, Friedman C, Trask BJ, Hood L,
Li L. Characterization, chromosomal localization, and the
complete 30-kb DNA sequence of the human Jagged2 (JAG2)
gene. Genomics 2000;63:133-138.
This article should be referenced as such:
Ghoshal P, Coignet LJ. JAG2 (human jagged2). Atlas Genet
Cytogenet Oncol Haematol.2007;11(3):199-200.
Tsai S, Fero J, Bartelmez S. Mouse Jagged2 is differentially
expressed in hematopoietic progenitors and endothelial cells
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3)
200