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JAG2 (Human Jagged2)

Written2007-02Pushpankur Ghoshal, Lionel J Coignet
Roswell Park Cancer Institute, Dept of Cancer Genetics, Buffalo, NY - USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasHJ2
Jagged2
LocusID (NCBI) 3714
Atlas_Id 41030
Location 14q32.33  [Link to chromosome band 14q32]
Location_base_pair Starts at and ends at bp from pter
Local_order Human Jagged2 (jag2), a ligand for Notch receptor, was mapped in the chromosomal region 14 q32.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
FNIP2 (4q32.1) / JAG2 (14q32.33)NSMF (9q34.3) / JAG2 (14q32.33)

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 1,238-amino acid long. It has several recognizable motifs, including a signal peptide, 16 EGF-like repeats, a transmembrane domain, and a short cytoplasmic domain.
Expression In human, JAG2 is expressed at high levels in the heart, the skeletal muscle and the pancreas.

Implicated in

Note
  
Entity 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.
 
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.
  

Bibliography

Characterization, chromosomal localization, and the complete 30-kb DNA sequence of the human Jagged2 (JAG2) gene.
Deng Y, Madan A, Banta AB, Friedman C, Trask BJ, Hood L, Li L
Genomics. 2000 ; 63 (1) : 133-138.
PMID 10662552
 
Human ligands of the Notch receptor.
Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S
The American journal of pathology. 1999 ; 154 (3) : 785-794.
PMID 10079256
 
Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines.
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
Blood. 2004 ; 104 (12) : 3697-3704.
PMID 15292061
 
The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent gamma-secretase cleavage.
Ikeuchi T, Sisodia SS
The Journal of biological chemistry. 2003 ; 278 (10) : 7751-7754.
PMID 12551931
 
The Jagged2 gene maps to chromosome 12 and is a candidate for the lgl and sm mutations.
Lan Y, Jiang R, Shawber C, Weinmaster G, Gridley T
Mammalian genome : official journal of the International Mammalian Genome Society. 1997 ; 8 (11) : 875-876.
PMID 9341252
 
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, Fero J, Bartelmez S
Blood. 2000 ; 96 (3) : 950-957.
PMID 10910909
 

Citation

This paper should be referenced as such :
Coignet, LJ ; Ghoshal, P
JAG2 (human jagged2)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):199-200.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/JAG2ID41030ch14q32.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Breast: Ductal carcinoma


External links

Nomenclature
Cards
AtlasJAG2ID41030ch14q32.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)3714
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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