JAG2 (Human Jagged2)

2007-02-01   Pushpankur Ghoshal  , Lionel J Coignet  

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

Identity

HGNC
JAG2
LOCATION
14q32.33
LOCUSID
3714
ALIAS
HJ2,SER2
FUSION GENES
Show Gene Fusions

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
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.
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.
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 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

Variants:

dbSNP: 3714
ClinVar: 3714
TCGA: ENSG00000184916
COSMIC: JAG2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184916ENST00000331782Q9Y219
ENSG00000184916ENST00000347004Q9Y219

Expression (GTEx)

0
10
20
30
40
50
60
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Notch signaling pathwayKEGGko04330
Notch signaling pathwayKEGGhsa04330
DiseaseREACTOMER-HSA-1643685
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
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
379664902024Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.0
383957622024miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.0
384850332024ZEB2 alleviates Hirschsprung's-associated enterocolitis by promoting the proliferation and differentiation of enteric neural precursor cells via the Notch-1/Jagged-2 pathway.1
385755762024Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells.0
379664902024Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.0
383957622024miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.0
384850332024ZEB2 alleviates Hirschsprung's-associated enterocolitis by promoting the proliferation and differentiation of enteric neural precursor cells via the Notch-1/Jagged-2 pathway.1
385755762024Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells.0
338619532021A form of muscular dystrophy associated with pathogenic variants in JAG2.6
338619532021A form of muscular dystrophy associated with pathogenic variants in JAG2.6
319226032020[Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population].0
322505712020Overexpression of JAG2 is related to poor outcomes in oral squamous cell carcinoma.8
327928622020Jagged2 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
319226032020[Association between the JAG2 gene polymorphism and the occurrence of nonsyndromic cleft lip with or without cleft palate in northwest Chinese population].0
322505712020Overexpression 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-(human-jagged2)