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FLASH GENE

Symbol

JAG1

contributors: mct - updated : 03-07-2019

HGNC name	jagged 1
HGNC id	6188

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000214 26 - 5988 NP_000205 - 1218 - 2010 20096396

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon       liver       highly   mouth       highly   pharynx       highly Endocrine pancreas         Hearing/Equilibrium ear inner       Reproductive male system testis       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Reproductive Sertoli 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
	BACE1 can effectively shed the membrane-anchored signaling molecule JAG1 but BACE1 fails to cleave JAG2
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive colon 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 cancer digestive   JAG1-NOTCH1 interference provides therapeutic benefit in a subset of colorectal cancer and FAP syndrome patients cancer angiogenesis   JAG1/NOTCH3 is expected to be a potential target for TNBC neovascularization therapy neuromuscular myopathy   JAG1 may represent a target for DMD therapy in a dystrophin-independent manner cancer brain   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