EGR2

The protein encoded by this gene is a transcription factor with three tandem C2H2-type zinc fingers. Defects in this gene are associated with Charcot-Marie-Tooth disease type 1D (CMT1D), Charcot-Marie-Tooth disease type 4E (CMT4E), and with Dejerine-Sottas syndrome (DSS). Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq]

early growth response 2 (Krox-20 homolog, Drosophila)

Sequence-specific DNA-binding transcription factor (PubMed:17717711).

Plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes and in Schwann cell myelination by regulating the expression of genes involved in the formation and maintenance of myelin (By similarity).

Binds to two EGR2-consensus sites EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3') in the HOXB3 enhancer and promotes HOXB3 transcriptional activation (By similarity).

Binds to specific DNA sites located in the promoter region of HOXA4, HOXB2 and ERBB2 (By similarity).

Regulates hindbrain segmentation by controlling the expression of Hox genes, such as HOXA4, HOXB3 and HOXB2, and thereby specifying odd and even rhombomeres (By similarity).

Promotes the expression of HOXB3 in the rhombomere r5 in the hindbrain (By similarity).

Regulates myelination in the peripheral nervous system after birth, possibly by regulating the expression of myelin proteins, such as MPZ, and by promoting the differentiation of Schwann cells (By similarity).

Involved in the development of the jaw openener musculature, probably by playing a role in its innervation through trigeminal motor neurons (By similarity).

May play a role in adipogenesis, possibly by regulating the expression of CEBPB (By similarity).

E3 SUMO-protein ligase helping SUMO1 conjugation to its coregulators NAB1 and NAB2, whose sumoylation down-regulates EGR2 transcriptional activity.

Brain development Source: ProtInc
Brain segmentation Source: Ensembl
Cellular response to organic substance Source: Ensembl
Facial nerve structural organization Source: UniProtKB
Fat cell differentiation Source: BHF-UCL
Gene expression Source: Ensembl
Learning or memory Source: Ensembl
Motor neuron axon guidance Source: Ensembl
Myelination Source: Ensembl
Peripheral nervous system development Source: ProtInc
Positive regulation of myelination Source: UniProtKB
Positive regulation of Schwann cell differentiation Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Protein export from nucleus Source: UniProtKB
Protein sumoylation Source: ARUK-UCL
Regulation of neuronal synaptic plasticity Source: Ensembl
Regulation of ossification Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to insulin Source: Ensembl
Rhombomere 3 formation Source: Ensembl
Rhombomere 3 structural organization Source: UniProtKB
Rhombomere 5 formation Source: Ensembl
Rhombomere 5 structural organization Source: UniProtKB
Rhythmic behavior Source: Ensembl
Schwann cell differentiation Source: UniProtKB
Skeletal muscle cell differentiation Source: UniProtKB

Nucleus

Neuropathy, congenital hypomyelinating, 1, autosomal recessive (CHN1):
The disease is caused by variants affecting the gene represented in this entry. Patients affected by the amyelinating form carry a causative, homozygous deletion encompassing a myelin-specific enhancer of EGR2 (PubMed:22522483). A severe degenerating neuropathy that results from a congenital impairment in myelin formation. It is clinically characterized by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (as low as 3m/s). Some patients manifest nearly complete absence of spontaneous limb movements, respiratory distress at birth, and complete absence of myelin shown by electron microscopy of peripheral nerves.
Charcot-Marie-Tooth disease 1D (CMT1D):
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
Dejerine-Sottas syndrome (DSS)Z:
A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome.

Ubiquitinated by WWP2 leading to proteasomal degradation.
Acetylated at Lys-247. May be deacetylated by HDAC6, HDAC10 or SIRT1.