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FLASH GENE

Symbol

JAG2

contributors: mct/pgu - updated : 19-05-2021

HGNC name	jagged 2
HGNC id	6189

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	LGMDR27 muscular dystrophy, limb-girdle, autosomal recessive 27
Location	14q32.33      Physical location : 105.608.076 - 105.635.161
Synonym symbol(s)	HJ2, SER2

DNA

TYPE	functioning gene
STRUCTURE	27.09 kb     26 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002226 26 - 5077 NP_002217 - 1238 - 2011 21372153 isoform a NM_145159 25 - 4963 NP_660142 129.3 1200 - 2011 21372153 isoform b

EXPRESSION

Type

widely

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 Cardiovascular heart       highly Homo sapiens Endocrine pancreas       highly Homo sapiens Nervous nerve       highly Reproductive female system breast mammary gland   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Muscular striatum skeletal   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol   digestive

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	highly in embryonic limb buds, first branchial arch, developing cochlea and the organ of Corti, central and peripheral nervous system, retina, tooth buds, thymus, submandilas gland, stomach

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide
	a DSL (Delta, Serrate, Lag2) domain
	16 EGF-like repeats
	a cysteine-rich extracellular region

isoforms

Precursor

HOMOLOGY

interspecies	homolog to rattus Jag2
	homolog to Drosophila serrate Dress30
	homolog to murine

Homologene

FAMILY

Notch ligand family

CATEGORY

signaling

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	overexpression may be an early event in the pathogenesis of multiple myeloma involving IL6 production
	play dual roles as activators of Notch receptor signaling and as receptors that mediate nuclear signaling events via gamma-secretase-generated cytoplasmic domain
	critical role for JAG2-Notch signaling in the maintenance of proliferating neural precursors in a discrete compartment of the neural tube during the continuing growth and development of the vertebrate nervous system
	JAG2-Notch axis plays a crucial role in dendritic cells-mediated NK cell cytotoxicity
	can regulate the expression of cytokines that can promote antitumor immunity
	its expression by dendritic cells is not sufficient or required for Th2 cell differentiation
	IRF6 and the Notch ligand JAG2 function in convergent molecular pathways during oral epithelial differentiation
	like Delta-like ligands, induces T-lineage differentiation and inhibits B-cell and myeloid development
	unexpected functional similarity between JAG2 and the Delta-like ligands
	hypoxic induction of JAG2 in tumor cells mediates a hypoxia-regulated cross-talk between tumor and endothelial cells
	JAG2 is a key regulator of the timely and ordered generation of two of the defining cell types in the spinal cord, motor neurons (MNs) and oligodendrocyte progenitors (OLPs)
	enhances immunomodulatory activity in adipose derived mesenchymal stem cells
	JAG2 implicated in promoting aggressiveness of colorectal cancer (CRC)
	JAG2 is involved in the regulation of migration and invasion of colon cancer cells without affecting cell proliferation
	involved in the regulation of migration and invasion independent of the canonical NoTCH1 signaling pathway

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

text

inner ear

PATHWAY

metabolism

signaling

sensory transduction/hearing

a component

INTERACTION

DNA

RNA

small molecule

protein	ligand for NOTCH1 (acts synergistically with DLL1, to regulate hair cell development in the mammalian inner ear)
	interacting with IRF6 (IRF6 and JAG2 function in convergent molecular pathways during development of the oral ectoderm)
	weaker NOTCH1-activator compared with the Delta-like ligands, revealing a NOTCH1 specific signal strength hierarchy for mammalian NOTCH ligands
	BACE1 can effectively shed the membrane-anchored signaling molecule JAG1 but BACE1 fails to cleave JAG2
	YAP1 activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH1 in a non-cell-autonomous manner

cell & other

REGULATION

activated by

transcriptionally activated by hypoxia in a HIF-1a dependent manner

ASSOCIATED DISORDERS

corresponding disease(s)

LGMDR27

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in malignant plasma cells from multiple myeloma constitutional     --over   significantly increased in the colorectal cancer cell lines compared with that of normal colorectal cell line

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	high JAG2 expression may be useful as additional marker to identify aggressive Medulloblastoma (MB)
Therapy target
	System Type Disorder Pubmed cancer digestive colon therapeutic target for the treatment of colorectal cancer

ANIMAL & CELL MODELS