EGR2

EGR2
Identifiers
Aliases	EGR2 , AT591, CMT1D, CMT4E, KROX20, early growth response 2, CHN1
External IDs	OMIM: 129010 MGI: 95296 HomoloGene: 20123 GeneCards: EGR2
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 monocyte gastric mucosa smooth muscle tissue sural nerve skin of abdomen lymph node appendix anterior pituitary Top expressed in neuromere rhombomere lip zone of skin spinal nerve ureter urethra thymus male urethra basal forebrain 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
View/Edit Human View/Edit Mouse

Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene. EGR2 (also termed Krox20) is a transcription regulatory factor, containing three zinc finger DNA-binding sites, and is highly expressed in a population of migrating neural crest cells. ^{[5] [6] [7]} It is later expressed in the neural crest derived cells of the cranial ganglion. The protein encoded by Krox20 contains two cys2his2-type zinc fingers. Krox20 gene expression is restricted to the early hindbrain development. ^{[6] [8]} It is evolutionarily conserved in vertebrates, humans, mice, chicks, and zebra fish. ^[9] In addition, the amino acid sequence and most aspects of the embryonic gene pattern is conserved among vertebrates, further implicating its role in hindbrain development. ^{[7] [10] [11] [12]} When the Krox20 is deleted in mice, the protein coding ability of the Krox20 gene (including the DNA-binding domain of the zinc finger) is diminished. These mice are unable to survive after birth and exhibit major hindbrain defects. ^{[6] [8]} These defects include but are not limited to defects in formation of cranial sensory ganglia, partial fusion of the trigeminal nerve (V) with the facial (VII) and auditory (VII) nerves, the proximal nerve roots coming off of these ganglia were disorganized and intertwined among one another as they entered the brainstem, and there was fusion of the glossopharyngeal (IX) nerve complex. ^{[13] [14] [15]}

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, ^[16] Dejerine–Sottas disease, ^[17] and Congenital Hypomyelinating Neuropathy. ^[18] Two studies have linked EGR2 expression to proliferation of osteoprogenitors ^[19] and cell lines derived from Ewing sarcoma, which is a highly aggressive bone-associated cancer. ^[20]

New research suggests that Krox20 - or the lack of it - is the reason for male baldness. ^[21]

References

1. GRCh38: Ensembl release 89: ENSG00000122877 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000037868 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Chavrier P, Janssen-Timmen U, Mattéi MG, Zerial M, Bravo R, Charnay P (February 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.
6. Swiatek PJ, Gridley T (November 1993). "Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20". Genes & Development. 7 (11): 2071–84. doi: 10.1101/gad.7.11.2071 . PMID   8224839.
7. Wilkinson DG, Bhatt S, Chavrier P, Bravo R, Charnay P (February 1989). "Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse". Nature. 337 (6206): 461–4. Bibcode:1989Natur.337..461W. doi:10.1038/337461a0. PMID   2915691. S2CID   4336310.
8. Bradley LC, Snape A, Bhatt S, Wilkinson DG (January 1993). "The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest". Mechanisms of Development. 40 (1–2): 73–84. doi:10.1016/0925-4773(93)90089-g. PMID   8443108. S2CID   20347966.
9. Bhat RV, Worley PF, Cole AJ, Baraban JM (April 1992). "Activation of the zinc finger encoding gene krox-20 in adult rat brain: comparison with zif268". Brain Research. Molecular Brain Research. 13 (3): 263–6. doi:10.1016/0169-328x(92)90034-9. PMID   1317498.
10. Wilkinson DG, Bhatt S, Cook M, Boncinelli E, Krumlauf R (October 1989). "Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain". Nature. 341 (6241): 405–9. Bibcode:1989Natur.341..405W. doi:10.1038/341405a0. PMID   2571936. S2CID   4324322.
11. Hunt P, Gulisano M, Cook M, Sham MH, Faiella A, Wilkinson D, Boncinelli E, Krumlauf R (October 1991). "A distinct Hox code for the branchial region of the vertebrate head". Nature. 353 (6347): 861–4. Bibcode:1991Natur.353..861H. doi:10.1038/353861a0. PMID   1682814. S2CID   4312466.
12. Oxtoby E, Jowett T (March 1993). "Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development". Nucleic Acids Research. 21 (5): 1087–95. doi:10.1093/nar/21.5.1087. PMC   309267 . PMID   8464695.
13. Frohman MA, Boyle M, Martin GR (October 1990). "Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm". Development. 110 (2): 589–607. doi:10.1242/dev.110.2.589. PMID   1983472.
14. Murphy P, Davidson DR, Hill RE (September 1989). "Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain". Nature. 341 (6238): 156–9. Bibcode:1989Natur.341..156M. doi:10.1038/341156a0. PMID   2571087. S2CID   4371764.
15. Nieto MA, Bradley LC, Wilkinson DG (1991). "Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction". Development. Suppl 2: 59–62. doi:10.1242/dev.113.Supplement_2.59. hdl: 10261/32226 . PMID   1688180.
16. "Entrez Gene: EGR2 early growth response 2 (Krox-20 homolog, Drosophila)".
17. Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (July 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics. 3 (3): 153–7. doi:10.1007/s100480100107. PMID   11523566. S2CID   32746701.
18. Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (April 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. S2CID   25550479.
19. Chandra A, Lan S, Zhu J, Siclari VA, Qin L (July 2013). "Epidermal growth factor receptor (EGFR) signaling promotes proliferation and survival in osteoprogenitors by increasing early growth response 2 (EGR2) expression". The Journal of Biological Chemistry. 288 (28): 20488–98. doi: 10.1074/jbc.M112.447250 . PMC   3711314 . PMID   23720781.
20. Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, et al. (September 2015). "Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite". Nature Genetics. 47 (9): 1073–8. doi:10.1038/ng.3363. PMC   4591073 . PMID   26214589.
21. Le, Lu. "Scientists find skin cells at the root of balding, gray hair". UT Southwestern Medical Center. Retrieved 9 May 2017.

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 (February 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 (October 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. Bibcode:1988PNAS...85.7164J. 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 (October 1994). "Krox-20 controls myelination in the peripheral nervous system". Nature. 371 (6500): 796–9. Bibcode:1994Natur.371..796T. doi:10.1038/371796a0. PMID   7935840. S2CID   4333028.
• Sham MH, Vesque C, Nonchev S, Marshall H, Frain M, Gupta RD, Whiting J, Wilkinson D, Charnay P, Krumlauf R (January 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. S2CID   3205209.
• Levi G, Topilko P, Schneider-Maunoury S, Lasagna M, Mantero S, Pesce B, Ghersi G, Cancedda R, Charnay P (June 1996). "Role of Krox-20 in endochondral bone formation". Annals of the New York Academy of Sciences. 785 (1): 288–91. Bibcode:1996NYASA.785..288L. doi:10.1111/j.1749-6632.1996.tb56286.x. PMID   8702157. S2CID   27761983.
• Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (April 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. S2CID   25550479.
• Warner LE, Svaren J, Milbrandt J, Lupski JR (July 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 (June 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. S2CID   11569651.
• Bellone E, Di Maria E, Soriani S, Varese A, Doria LL, Ajmar F, Mandich P (October 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. S2CID   85039222.
• Pareyson D, Taroni F, Botti S, Morbin M, Baratta S, Lauria G, Ciano C, Sghirlanzoni A (April 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. hdl: 2434/531868 . PMID   10762521. S2CID   28404231.
• Gambardella L, Schneider-Maunoury S, Voiculescu O, Charnay P, Barrandon Y (September 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. S2CID   18000564.
• Yoshihara T, Kanda F, Yamamoto M, Ishihara H, Misu K, Hattori N, Chihara K, Sobue G (March 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. S2CID   19693658.
• Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (July 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics. 3 (3): 153–7. doi:10.1007/s100480100107. PMID   11523566. S2CID   32746701.
• 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 (December 2002). "Frequency of mutations in the early growth response 2 gene associated with peripheral demyelinating neuropathies". Journal of Medical Genetics. 39 (12): 81e–81. doi:10.1136/jmg.39.12.e81. PMC   1757229 . PMID   12471219.
• Musso M, Balestra P, Taroni F, Bellone E, Mandich P (February 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. S2CID   29600641.
• Unoki M, Nakamura Y (April 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 (June 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. S2CID   36723641.

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.