EGR2

Early growth response protein 2 (EGR2), also known as Krox20, is a transcription factor encoded by the EGR2 gene in humans. It is highly expressed in migrating neural crest cells and later in neural crest-derived cells of the cranial ganglia.^[5][6][7] Expression of EGR2 is restricted to early hindbrain development,^[6][8] and the gene is evolutionarily conserved among vertebrates, including humans, mice, chicks, and zebrafish.^[9] The conservation of its amino acid sequence and embryonic expression pattern underscores its essential role in hindbrain segmentation and neural differentiation.^{[7][10][11][12]}

EGR2
Identifiers
Aliases	EGR2, AT591, CMT1D, CMT4E, KROX20, early growth response 2, CHN1
External IDs	OMIM: 129010; MGI: 95296; HomoloGene: 20123; GeneCards: EGR2; OMA:EGR2 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q21.3 Start 62,811,996 bp[1] End 62,819,167 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B5.1|10 34.96 cM Start 67,535,475 bp[2] End 67,542,188 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gallbladder tibial nerve granulocyte testicle monocyte gastric mucosa smooth muscle tissue sural nerve skin of abdomen lymph node Top expressed in neural ectoderm neuromere rhombomere lip zone of skin spinal nerve ureter urethra thymus male urethra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding DNA-binding transcription factor activity HMG box domain binding DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding metal ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding nucleic acid binding ubiquitin protein ligase binding transferase activity DNA-binding transcription factor activity, RNA polymerase II-specific SUMO ligase activity Cellular component cytoplasm nucleus nucleoplasm intracellular membrane-bounded organelle Biological process cellular response to organic substance rhythmic behavior peripheral nervous system development regulation of transcription, DNA-templated rhombomere 3 development brain segmentation transcription by RNA polymerase II protein sumoylation rhombomere 3 formation transcription, DNA-templated response to insulin positive regulation of transcription, DNA-templated brain development rhombomere 5 formation protein export from nucleus learning or memory skeletal muscle cell differentiation Schwann cell differentiation regulation of neuronal synaptic plasticity myelination facial nerve structural organization regulation of ossification motor neuron axon guidance fat cell differentiation positive regulation of transcription by RNA polymerase II regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1959 13654 Ensembl ENSG00000122877 ENSMUSG00000037868 UniProt P11161 P08152 RefSeq (mRNA) NM_000399 NM_001136177 NM_001136178 NM_001136179 NM_001321037 NM_010118 NM_001347458 RefSeq (protein) NP_000390 NP_001129649 NP_001129650 NP_001129651 NP_001307966 NP_001334387 NP_034248 NP_001360912 NP_001360914 NP_001360915 NP_001360916 Location (UCSC) Chr 10: 62.81 – 62.82 Mb Chr 10: 67.54 – 67.54 Mb PubMed search [3] [4]
Wikidata
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Structure

The EGR2 protein contains three tandem C2H2-type zinc finger domains that mediate specific DNA binding.^[6][8] These zinc fingers enable EGR2 to function as a transcriptional regulator of genes involved in neural development and myelination.

Function

EGR2 acts as a transcription factor that regulates gene expression during neural development and peripheral nerve myelination. It binds to specific DNA sequences via its zinc finger motifs to control target genes essential for Schwann cell differentiation and myelin sheath formation.^[13] It is also expressed in osteoprogenitor cells and has been implicated in the proliferation of Ewing sarcoma–derived cell lines, suggesting a role in both bone biology and tumorigenesis.^[14][15]

Clinical significance

Mutations in EGR2 are associated with several hereditary demyelinating neuropathies, including Charcot–Marie–Tooth disease type 1D,^[13] Dejerine–Sottas disease,^[16] and congenital hypomyelinating neuropathy.^[17] Recent studies have also suggested that EGR2 expression in hair follicle stem cells may influence hair maintenance and pigmentation, with loss of Krox20-expressing cells contributing to male-pattern baldness and graying hair.^[18]

Deletion of Egr2 in mice results in loss of protein-coding capacity, including the DNA-binding domain, leading to perinatal lethality and severe hindbrain malformations.^[6][8] These defects include aberrant formation of cranial sensory ganglia, fusion of the trigeminal (V), facial (VII), and auditory (VIII) nerves, and disorganization of their proximal roots as they enter the brainstem.^[19][20][21]