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FLASH GENE
Symbol JAG1 contributors: mct - updated : 03-07-2019
HGNC name jagged 1
HGNC id 6188
Corresponding disease
ALGS Alagille syndrome
ICHD isolated congenital heart defects
Location 20p12.2      Physical location : 10.618.331 - 10.654.694
Synonym name CD339 antigen
Synonym symbol(s) HJ1, JAGL1, AHD, AWS, JAGL1, SER1, CD339, AGS, MGC104644
DNA
TYPE functioning gene
STRUCTURE 36.36 kb     26 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map see AGS
Physical map
pFUSIP1 20p12.3 FUSIP1 pseudogene HAO1 20p12.3 hydroxyacid oxidase (glycolate oxidase) 1 DJ971N18.2 20p12 hypothetical protein DJ971N18.2 PHKBP1 20p12.3-20p12.2 phosphorylase kinase, beta pseudogene 1 PLCB1 20p12 phospholipase C, beta 1 (phosphoinositide-specific) PLCB4 20p12 phospholipase C, beta 4 C20orf103 20p12 chromosome 20 open reading frame 103 PAK7 20p12 p21(CDKN1A)-activated kinase 7 ANKRD5 20pter-q11.23 ankyrin repeat domain 5 SNAP25 20p12-p11.2 synaptosomal-associated protein, 25kDa RPL23AP6 20p12.2 ribosomal protein L23a pseudogene 6 LOC284773 20p12.2 similar to hypothetical protein FLJ10498 MKKS 20p12 McKusick-Kaufman syndrome LOC128710 20p12.2 similar to RIKEN cDNA 2210009G21 JAG1 20p12.1-p11.23 jagged 1 (Alagille syndrome) FAT1P1 20 FAT tumor suppressor homolog 1 (Drosophila) pseudogene 1 RPS11P1 20p12.1 ribosomal protein S11, pseudogene 1 PGAM3P 20p12.1 phosphoglycerate mutase 3, pseudogene BTBD3 20p12.1 BTB (POZ) domain containing 3 PA2G4P2 20p12.1 proliferation-associated 2G4 pseudogene 2 C20orf38 20p12.1 chromosome 20 open reading frame 38 C20orf82 20p12.1 chromosome 20 open reading frame 82 C20orf13 20p12.1 chromosome 20 open reading frame 13 GAPDP2 20p12 glyceraldehyde-3-phosphate dehydrogenase pseudogene 2 MRPS36P6 20p12.1 mitochondrial ribosomal protein S36 pseudogene C20orf6 20p12.1 chromosome 20 open reading frame 6 C20orf7 20p12.1 chromosome 20 open reading frame 7 C20orf50 20p12.1 chromosome 20 open reading frame 50 C20orf133 20p12.1 chromosome 20 open reading frame 133 RPS3P1 20p12 ribosomal protein S3 pseudogene 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
26 - 5988 - 1218 - 2010 20096396
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon  
 liver   highly
 mouth   highly
 pharynx   highly
Endocrinepancreas    
Hearing/Equilibriumearinner   
Reproductivemale systemtestis    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsecretoryglandularendocrine 
cells
SystemCellPubmedSpeciesStageRna symbol
ReproductiveSertoli cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text heart at early and late stages of cardiovascular development, liver, distal cardiac outflow tract, major arteries, portal vein, optic vesicles, otocyst, branchial arches, metanephros, pancreas, mesocardium, neural tube
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal DSL (Delta, Serrate lag2) domain
  • fifteen tandemly repeated EGF-like domain
  • a transmembrane cysteine rich region
  • transmembrane domain
  • intracellular domain, having a role in bi-directional signaling
  • VWF type C domain
  • HOMOLOGY
    interspecies homolog to rattus Jagged 1
    homolog to Drosophila serrate
    homolog to Drosophila jagged receptor notch
    Homologene
    FAMILY
  • Delta, Serrate, Lag-2 (DSL) family of single-pass transmembrane ligands that activate the Notch receptors
  • CATEGORY regulatory , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,adherens
    basic FUNCTION
  • NOTCH1 ligand playing a pivotal role in the development of the organ of Corti and specification of some vestibular sensory epithelia
  • functioning as WNT-dependent Notch signaling activator, and key molecule maintaining the homeostasis of stem and progenitor cells
  • JAG1 expression decreased hair cells, JAG1 suppression increased hair cells
  • undergoing a metalloprotease-dependent cleavage resulting in the shedding of its extracellular domain and this domain seems able to fulfill a biological function, probably by antagonizing Notch signaling
  • playing an essential role for vascular remodeling, and its primary role is to potentiate the development of neighboring vascular smooth muscle
  • involved in endothelial-pericyte interactions
  • DLL4 and Jagged1 have opposing effects on angiogenesis
  • unique role for JAG1 in preventing the induction of T-lineage differentiation in hematopoietic stem cells
  • crucial role for JAG1 in valve morphogenesis
  • in addition to its role in early heart development, JAG1 signaling is required postnatally to prevent valve calcification
  • crucial role for JAG1 in the endocardium during heart development
  • JAG1-regulated angiogenesis
  • JAG1-mediated NOTCH1 signaling regulates multiple cell fate decisions as well as differentiation in the respiratory system to coordinate lung development and to maintain a balance of airway cell types in adult life
  • is necessary for postnatal and adult neurogenesis in the dentate gyrus
  • JAG1 intracellular domain-mediated inhibition of NOTCH1 signalling regulates cardiac homeostasis in the postnatal heart
  • JAG1 signaling within the osteoblast lineage regulates bone metabolism in a compartment-dependent manner
  • critical role of osteolineage JAG1 in bone homeostasis, where JAG1 maintains the transition of osteoprogenitor (OP) to maturing osteoblasts
  • DLL4 and JAG1 promote tumour growth by modulating tumour angiogenesis via different mechanisms
  • JAG1/NOTCH3 signaling pathway plays a key role in angiogenesis of breast cancer
  • both NOTCH1 and its ligands DLL1 and JAG1 in B cells promote antibody production
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text required for inner ear sensory development
    PATHWAY
    metabolism
    signaling signal transduction
  • ligand in the Notch signaling pathway
  • JAG1 signaling within the osteoblast lineage regulates bone metabolism in a compartment-dependent manner
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • JAG2
  • interacting with PAX9 (acting downstream of GLI)3 in vertebrate limb development
  • binding of JAG1 intracellular region to the PDZ domain of afadin couples Notch signaling with the adhesion system and the cytoskeleton
  • shed by ADAM17 in a lipid-raft-independent manner, and that the cytosolic domain of the former protein is not a pre-requisite for either constitutive or regulated shedding
  • repression of SOX9 by JAG1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells
  • DLL1 and JAG1 function redundantly and are necessary to maintain the centroacinar cells as an environmental niche in the developing pancreas
  • JAG1-mediated NOTCH1 signaling regulates differentiation of Basal cells (BC) into secretory cells
  • JAG1 Regulates GDNF Expression in Sertoli cells
  • JAG1 and NOTCH2 play a key role in kidney fibrosis development by regulating TFAM expression and metabolic reprogramming
  • DLL4 and JAG1 mediated NR4A1-induced angiogenic responses and signaling molecules, but not the expression of integrins
  • cell & other
    REGULATION
    activated by Rel/NFKB responsive gene
    ASSOCIATED DISORDERS
    corresponding disease(s) ALGS , ICHD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in proliferating hemangiomas
    constitutional germinal mutation     loss of function
    silencing mutations in JAG1 gene may play crucial roles in the pathogenesis of Tetralogy of Fallot
    tumoral     --over  
    significant over-expression of ligand JAG1 in the vast majority of Medulloblastoma (MB)
    Susceptibility
    Variant & Polymorphism
    Candidate gene candidate for BMD regulation in different ethnic groups, and it is a potential key factor for fracture pathogenesis
    Marker
  • JAG1/NOTCH3 is expected to be an important signaling pathway for TNBC (Triple-negative breast cancer) progression
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    inhibitors for Jagged1-mediated Notch activation [i.e., inhibitors of glycosil-transferases that modulate Notch/Notch-ligand interaction would be a new promising strategy for Colorectal cancer therapy
    osteoarticular  
    transient NOTCH1 inhibition by soluble JAG1 could be used to enhance Placenta-derived mesenchymal stromal cells (PMSCs) survival and chondrogenic differentiation, thereby increasing the therapeutic potential of PMSCs for cartilage regeneration
    cancerdigestive 
    JAG1-NOTCH1 interference provides therapeutic benefit in a subset of colorectal cancer and FAP syndrome patients
    cancerangiogenesis 
    JAG1/NOTCH3 is expected to be a potential target for TNBC neovascularization therapy
    neuromuscularmyopathy 
    JAG1 may represent a target for DMD therapy in a dystrophin-independent manner
    cancerbrain 
    JAG1 mediates pro-proliferative signals via activation of NOTCH2 receptor and induction of HES1 expression, thus representing an attractive therapeutic targetin medulloblastomas
    ANIMAL & CELL MODELS
  • endothelial-specific deletion of Jag1 leads to cardiovascular defects in both embryonic and adult mice that are reminiscent of those in Alagille syndrome