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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 namesHJ2
Jagged2
HGNC (Hugo) JAG2
LocusID (NCBI) 3714
Atlas_Id 41030
Location 14q32.33  [Link to chromosome band 14q32]
Location_base_pair Starts at 105607318 and ends at 105635161 bp from pter ( according to hg19-Feb_2009)  [Mapping JAG2.png]
Local_order Human Jagged2 (jag2), a ligand for Notch receptor, was mapped in the chromosomal region 14 q32.
Fusion genes
(updated 2016)
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

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
 
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
 
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
 
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
 
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
 
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
 

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) [ 0 ]
  Breast: Ductal carcinoma

External links

Nomenclature
HGNC (Hugo)JAG2   6189
Cards
AtlasJAG2ID41030ch14q32
Entrez_Gene (NCBI)JAG2  3714  jagged 2
AliasesHJ2; SER2
GeneCards (Weizmann)JAG2
Ensembl hg19 (Hinxton)ENSG00000184916 [Gene_View]  chr14:105607318-105635161 [Contig_View]  JAG2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000184916 [Gene_View]  chr14:105607318-105635161 [Contig_View]  JAG2 [Vega]
ICGC DataPortalENSG00000184916
TCGA cBioPortalJAG2
AceView (NCBI)JAG2
Genatlas (Paris)JAG2
WikiGenes3714
SOURCE (Princeton)JAG2
Genomic and cartography
GoldenPath hg19 (UCSC)JAG2  -     chr14:105607318-105635161 -  14q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)JAG2  -     14q32   [Description]    (hg38-Dec_2013)
EnsemblJAG2 - 14q32 [CytoView hg19]  JAG2 - 14q32 [CytoView hg38]
Mapping of homologs : NCBIJAG2 [Mapview hg19]  JAG2 [Mapview hg38]
OMIM602570   
Gene and transcription
Genbank (Entrez)AA775404 AB209370 AF003521 AF020201 AF029778
RefSeq transcript (Entrez)NM_002226 NM_145159
RefSeq genomic (Entrez)NC_000014 NC_018925 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)JAG2
Cluster EST : UnigeneHs.433445 [ NCBI ]
CGAP (NCI)Hs.433445
Alternative Splicing GalleryENSG00000184916
Gene ExpressionJAG2 [ NCBI-GEO ]   JAG2 [ EBI - ARRAY_EXPRESS ]   JAG2 [ SEEK ]   JAG2 [ MEM ]
Gene Expression Viewer (FireBrowse)JAG2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3714
GTEX Portal (Tissue expression)JAG2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y219 (Uniprot)
NextProtQ9Y219  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y219
Splice isoforms : SwissVarQ9Y219 (Swissvar)
PhosPhoSitePlusQ9Y219
Domaine pattern : Prosite (Expaxy)ASX_HYDROXYL (PS00010)    DSL (PS51051)    EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    EGF_CA (PS01187)    VWFC_2 (PS50184)   
Domains : Interpro (EBI)DSL    EGF-like_Ca-bd_dom    EGF-like_CS    EGF-like_dom    EGF-type_Asp/Asn_hydroxyl_site    EGF_Ca-bd_CS    Growth_fac_rcpt_    Jagged/Serrate    Notch_ligand_N    VWF_dom   
Domain families : Pfam (Sanger)DSL (PF01414)    EGF (PF00008)    EGF_CA (PF07645)    hEGF (PF12661)    MNNL (PF07657)   
Domain families : Pfam (NCBI)pfam01414    pfam00008    pfam07645    pfam12661    pfam07657   
Domain families : Smart (EMBL)DSL (SM00051)  EGF (SM00181)  EGF_CA (SM00179)  VWC (SM00214)  
DMDM Disease mutations3714
Blocks (Seattle)JAG2
SuperfamilyQ9Y219
Human Protein AtlasENSG00000184916
Peptide AtlasQ9Y219
HPRD03981
IPIIPI00032416   IPI00221383   IPI00556533   
Protein Interaction databases
DIP (DOE-UCLA)Q9Y219
IntAct (EBI)Q9Y219
FunCoupENSG00000184916
BioGRIDJAG2
STRING (EMBL)JAG2
ZODIACJAG2
Ontologies - Pathways
QuickGOQ9Y219
Ontology : AmiGOskeletal system development  in utero embryonic development  respiratory system process  Notch binding  calcium ion binding  protein binding  plasma membrane  integral component of plasma membrane  cell cycle  Notch signaling pathway  Notch signaling pathway  Notch receptor processing  spermatogenesis  growth factor activity  auditory receptor cell fate commitment  morphogenesis of embryonic epithelium  cell differentiation  regulation of cell adhesion  T cell differentiation  regulation of cell migration  regulation of cell proliferation  odontogenesis of dentin-containing tooth  gamma-delta T cell differentiation  thymic T cell selection  positive regulation of Notch signaling pathway  epithelial cell apoptotic process involved in palatal shelf morphogenesis  
Ontology : EGO-EBIskeletal system development  in utero embryonic development  respiratory system process  Notch binding  calcium ion binding  protein binding  plasma membrane  integral component of plasma membrane  cell cycle  Notch signaling pathway  Notch signaling pathway  Notch receptor processing  spermatogenesis  growth factor activity  auditory receptor cell fate commitment  morphogenesis of embryonic epithelium  cell differentiation  regulation of cell adhesion  T cell differentiation  regulation of cell migration  regulation of cell proliferation  odontogenesis of dentin-containing tooth  gamma-delta T cell differentiation  thymic T cell selection  positive regulation of Notch signaling pathway  epithelial cell apoptotic process involved in palatal shelf morphogenesis  
Pathways : KEGGNotch signaling pathway   
REACTOMEQ9Y219 [protein]
REACTOME PathwaysR-HSA-1980150 Signaling by NOTCH4 [pathway]
REACTOME PathwaysR-HSA-2660826 Constitutive Signaling by NOTCH1 t(7 [pathway]
REACTOME Pathways9)(NOTCH1:M1580_K2555) Translocation Mutant [pathway]
REACTOME PathwaysR-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus [pathway]
REACTOME PathwaysR-HSA-2691232 Constitutive Signaling by NOTCH1 HD Domain Mutants [pathway]
REACTOME PathwaysR-HSA-1980148 Signaling by NOTCH3 [pathway]
REACTOME PathwaysR-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants [pathway]
REACTOME PathwaysR-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants [pathway]
REACTOME PathwaysR-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkJAG2
Wikipedia pathwaysJAG2
Orthology - Evolution
OrthoDB3714
GeneTree (enSembl)ENSG00000184916
Phylogenetic Trees/Animal Genes : TreeFamJAG2
Homologs : HomoloGeneJAG2
Homology/Alignments : Family Browser (UCSC)JAG2
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerJAG2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)JAG2
dbVarJAG2
ClinVarJAG2
1000_GenomesJAG2 
Exome Variant ServerJAG2
ExAC (Exome Aggregation Consortium)JAG2 (select the gene name)
Genetic variants : HAPMAP3714
Genomic Variants (DGV)JAG2 [DGVbeta]
Mutations
ICGC Data PortalJAG2 
TCGA Data PortalJAG2 
Broad Tumor PortalJAG2
OASIS PortalJAG2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICJAG2 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch JAG2
DgiDB (Drug Gene Interaction Database)JAG2
DoCM (Curated mutations)JAG2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)JAG2 (select a term)
intoGenJAG2
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:105607318-105635161  ENSG00000184916
CONAN: Copy Number AnalysisJAG2 
Mutations and Diseases : HGMDJAG2
OMIM602570   
MedgenJAG2
Genetic Testing Registry JAG2
NextProtQ9Y219 [Medical]
TSGene3714
GENETestsJAG2
Huge Navigator JAG2 [HugePedia]
snp3D : Map Gene to Disease3714
BioCentury BCIQJAG2
ClinGenJAG2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3714
Chemical/Pharm GKB GenePA29987
Clinical trialJAG2
Miscellaneous
canSAR (ICR)JAG2 (select the gene name)
Probes
Litterature
PubMed55 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineJAG2
EVEXJAG2
GoPubMedJAG2
iHOPJAG2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Jun 11 13:05:16 CEST 2016

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