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FLASH GENE

Symbol

EGR2

contributors: mct/npt/pgu - updated : 09-04-2015

HGNC name	early growth response 2
HGNC id	3239

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Digestive mouth       highly Endocrine thyroid       predominantly Reproductive male system testis     highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Connective bone     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three tandem zinc finger C2H2 type
	DNA binding domain
	one class 2 flanked by two class 1
	one inhibitory domain

HOMOLOGY

interspecies

homolog to Drosophila Krox-20

intraspecies

homolog to Krüppel 20

Homologene

FAMILY

EGR C2H2-type zinc-finger protein family

CATEGORY

transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	involved in early myelination of the peripheral nervous system
	mediator of the PTEN growth suppressive signaling pathway
	stimutaling adipogenesis via C/EBP beta-dependent and -independent mechanisms
	playing a role in the transactivation of C/EBP beta in a hormonal inducers dependent manner
	its expression in Schwann cells was mediated by AKT1
	EGR1, EGR2, EGR3, are essential for conversion of the mitogenic signal of epidermal growth factor into a proliferative response
	specifically required for Schwann cells to initiate and maintain myelination
	EGR1, EGR2 are novel DNA-binding proteins involved in vertebrate tendon differentiation by regulating type I collagen production
	EGR2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells
	functions as a SUMO ligase for its coregulators--the Nab proteins--and NAB2 sumoylation negatively modulates EGR2 transcriptional activity
	important modulator of TNFSF11-induced osteoclast differentiation, providing the link between TNFSF11, EGR2 and ID proteins in osteoclast-lineage cells
	EGR2 and EGR3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation
	is an essential transcriptional regulator of the T cell anergy program
	EGR2-neurons are a critical component of the respiratory chemoreflex into adulthood
	appears to regulate the expression of immunomodulatory molecules
	EGR2 and EGR3 are the unique regulators for systemic autoimmunity

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

behavioral , development

text	brain development
	peripheral nervous system development, mechanosensory behavior

PATHWAY

metabolism

signaling

calcineurin signaling pathway

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	binding to the MECP2 promoter and MECP2 binding to the enhancer region in EGR2 intron 1
	interaction with ADAM19 (functions as a modulator of juxtacrine signaling from axons that activate the AKT pathway and the EGR2 expression)
	colocalization of EGR2 binding with SOX10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development
	YY1 emerges as an important activator of peripheral myelination that links neuregulin signaling with EGR2 expression
	UBE2I is an interaction partner of the transcription factor EGR2, a key regulator of hindbrain development
	negatively regulates TNFSF11-induced osteoclast differentiation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CMT1D , CMT4E

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in ovarian tumor by hypermethylation in intron 1 constitutional     --over   of EGR1 and EGR2 controls natural killer T lineage differentiation in response to TCR signaling (Pubmed 22306690)

Susceptibility

to Ewing sarcoma

Variant & Polymorphism SNP	rs224278 associated with susceptibility to Ewing sarcoma

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Egr2-null mice die perinatally of respiratory insufficiency characterized by subnormal respiratory rate and severe apneas