EGR2

Early growth response 2
PDB rendering based on 1a1i.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1a1i​, 1a1j​, 1a1k​, 1a1l​, 1aay​, 1jk1​, 1jk2​, 1p47​, 1zaa​
Identifiers
Symbols	EGR2 ; AT591; CMT1D; CMT4E; KROX20
External IDs	OMIM: 129010 MGI: 95296 HomoloGene: 20123 GeneCards: EGR2 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II activating transcription factor binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding • ligase activity • ubiquitin protein ligase binding • transcription regulatory region DNA binding • metal ion binding • HMG box domain binding Cellular component • nucleus • cytoplasm Biological process • transcription from RNA polymerase II promoter • protein export from nucleus • brain development • peripheral nervous system development • learning or memory • rhythmic behavior • motor neuron axon guidance • Schwann cell differentiation • protein sumoylation • facial nerve structural organization • rhombomere 3 formation • rhombomere 5 formation • regulation of ossification • response to insulin • brain segmentation • skeletal muscle cell differentiation • myelination • negative regulation of apoptotic process • fat cell differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • regulation of neuronal synaptic plasticity • cellular response to cAMP • cellular response to gonadotropin stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1959	13654
Ensembl	ENSG00000122877	ENSMUSG00000037868
UniProt	P11161	P08152
RefSeq (mRNA)	NM_000399	NM_010118
RefSeq (protein)	NP_000390	NP_034248
Location (UCSC)	Chr 10: 62.81 – 62.92 Mb	Chr 10: 67.54 – 67.54 Mb
PubMed search

Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene.

Function

The early growth response protein 2 is a transcription factor with three tandem C2H2-type zinc fingers. Mutations in this gene are associated with the autosomal dominant Charcot-Marie-Tooth disease, type 1D,^[1] Dejerine–Sottas disease,^[2] and Congenital Hypomyelinating Neuropathy.^[3] Two studies have linked EGR2 expression to proliferation of osteoprogenitors ^[4] and cell lines derived from Ewing sarcoma, which is a highly aggressive bone-associated cancer. ^[5]

References

1. "Entrez Gene: EGR2 early growth response 2 (Krox-20 homolog, Drosophila)".
2. Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (Jul 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics 3 (3): 153–7. doi:10.1007/s100480100107. PMID 11523566.
3. Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (Apr 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies". Nature Genetics 18 (4): 382–384. doi:10.1038/ng0498-382. PMID 9537424.
4. Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Siclari, Valerie A.; Qin, Ling (2013-07-12). "Epidermal Growth Factor Receptor (EGFR) Signaling Promotes Proliferation and Survival in Osteoprogenitors by Increasing Early Growth Response 2 (EGR2) Expression". Journal of Biological Chemistry 288 (28): 20488–20498. doi:10.1074/jbc.M112.447250. ISSN 0021-9258. PMC 3711314. PMID 23720781.
5. Grünewald, Thomas G P; Bernard, Virginie; Gilardi-Hebenstreit, Pascale; Raynal, Virginie; Surdez, Didier; Aynaud, Marie-Ming; Mirabeau, Olivier; Cidre-Aranaz, Florencia; Tirode, Franck. "Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite". Nature Genetics 47 (9): 1073–1078. doi:10.1038/ng.3363. PMC 4591073. PMID 26214589.

Further reading

• Rangnekar VM, Aplin AC, Sukhatme VP (May 1990). "The serum and TPA responsive promoter and intron-exon structure of EGR2, a human early growth response gene encoding a zinc finger protein". Nucleic Acids Research 18 (9): 2749–57. doi:10.1093/nar/18.9.2749. PMC 330760. PMID 2111009.
• Chavrier P, Janssen-Timmen U, Mattéi MG, Zerial M, Bravo R, Charnay P (Feb 1989). "Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos". Molecular and Cellular Biology 9 (2): 787–97. doi:10.1128/mcb.9.2.787. PMC 362656. PMID 2496302.
• Joseph LJ, Le Beau MM, Jamieson GA, Acharya S, Shows TB, Rowley JD, Sukhatme VP (Oct 1988). "Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure". Proceedings of the National Academy of Sciences of the United States of America 85 (19): 7164–8. doi:10.1073/pnas.85.19.7164. PMC 282144. PMID 3140236.
• Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P (Oct 1994). "Krox-20 controls myelination in the peripheral nervous system". Nature 371 (6500): 796–9. doi:10.1038/371796a0. PMID 7935840.
• Sham MH, Vesque C, Nonchev S, Marshall H, Frain M, Gupta RD, Whiting J, Wilkinson D, Charnay P, Krumlauf R (Jan 1993). "The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation". Cell 72 (2): 183–96. doi:10.1016/0092-8674(93)90659-E. PMID 8093858.
• Levi G, Topilko P, Schneider-Maunoury S, Lasagna M, Mantero S, Pesce B, Ghersi G, Cancedda R, Charnay P (Jun 1996). "Role of Krox-20 in endochondral bone formation". Annals of the New York Academy of Sciences 785: 288–91. doi:10.1111/j.1749-6632.1996.tb56286.x. PMID 8702157.
• Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (Apr 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies". Nature Genetics 18 (4): 382–4. doi:10.1038/ng0498-382. PMID 9537424.
• Warner LE, Svaren J, Milbrandt J, Lupski JR (Jul 1999). "Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies". Human Molecular Genetics 8 (7): 1245–51. doi:10.1093/hmg/8.7.1245. PMID 10369870.
• Timmerman V, De Jonghe P, Ceuterick C, De Vriendt E, Löfgren A, Nelis E, Warner LE, Lupski JR, Martin JJ, Van Broeckhoven C (Jun 1999). "Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype". Neurology 52 (9): 1827–32. doi:10.1212/wnl.52.9.1827. PMID 10371530.
• Bellone E, Di Maria E, Soriani S, Varese A, Doria LL, Ajmar F, Mandich P (Oct 1999). "A novel mutation (D305V) in the early growth response 2 gene is associated with severe Charcot-Marie-Tooth type 1 disease". Human Mutation 14 (4): 353–4. doi:10.1002/(SICI)1098-1004(199910)14:4<353::AID-HUMU17>3.0.CO;2-4. PMID 10502832.
• Pareyson D, Taroni F, Botti S, Morbin M, Baratta S, Lauria G, Ciano C, Sghirlanzoni A (Apr 2000). "Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation". Neurology 54 (8): 1696–8. doi:10.1212/wnl.54.8.1696. PMID 10762521.
• Gambardella L, Schneider-Maunoury S, Voiculescu O, Charnay P, Barrandon Y (Sep 2000). "Pattern of expression of the transcription factor Krox-20 in mouse hair follicle". Mechanisms of Development 96 (2): 215–8. doi:10.1016/S0925-4773(00)00398-1. PMID 10960786.
• Yoshihara T, Kanda F, Yamamoto M, Ishihara H, Misu K, Hattori N, Chihara K, Sobue G (Mar 2001). "A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot--Marie--Tooth disease type 1". Journal of the Neurological Sciences 184 (2): 149–53. doi:10.1016/S0022-510X(00)00504-9. PMID 11239949.
• Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (Jul 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics 3 (3): 153–7. doi:10.1007/s100480100107. PMID 11523566.
• Yang Y, Dong B, Mittelstadt PR, Xiao H, Ashwell JD (May 2002). "HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter". The Journal of Biological Chemistry 277 (22): 19482–7. doi:10.1074/jbc.M201687200. PMID 11909874.
• Vandenberghe N, Upadhyaya M, Gatignol A, Boutrand L, Boucherat M, Chazot G, Vandenberghe A, Latour P (Dec 2002). "Frequency of mutations in the early growth response 2 gene associated with peripheral demyelinating neuropathies". Journal of Medical Genetics 39 (12): e81. doi:10.1136/jmg.39.12.e81. PMC 1757229. PMID 12471219.
• Musso M, Balestra P, Taroni F, Bellone E, Mandich P (Feb 2003). "Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter". Neurobiology of Disease 12 (1): 89–95. doi:10.1016/S0969-9961(02)00018-9. PMID 12609493.
• Unoki M, Nakamura Y (Apr 2003). "EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK". Oncogene 22 (14): 2172–85. doi:10.1038/sj.onc.1206222. PMID 12687019.
• Numakura C, Shirahata E, Yamashita S, Kanai M, Kijima K, Matsuki T, Hayasaka K (Jun 2003). "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1". Journal of the Neurological Sciences 210 (1-2): 61–4. doi:10.1016/S0022-510X(03)00028-5. PMID 12736090.

External links

• GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 1
• GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 4
• EGR2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.