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Egr1

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Title: Egr1  
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Subject: Early growth response proteins, WT1, Vocal learning, NeuroD, EMX homeogene
Collection: Molecular Neuroscience, Transcription Factors, Zinc Proteins
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Egr1

Early growth response 1
Cartoon representation of Zif268 (blue) containing three zinc fingers in complex with DNA (orange). The coordinating amino acid residues of the middle zinc ion (green) are highlighted.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

EGR-1 (Early growth response protein 1) also known as Zif268 (zinc finger protein 225) or NGFI-A (nerve growth factor-induced protein A) is a protein that in humans is encoded by the EGR1 gene.

EGR-1 is a mammalian transcription factor. It was also named Krox-24, TIS8, and ZENK. It was originally discovered in mice.

Contents

  • Function 1
  • Structure 2
  • DNA Binding Specificity 3
  • Interactions 4
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

Function

The protein encoded by this gene belongs to the EGR family of Cys2His2-type zinc finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation and mitogenesis. Studies suggest this is a tumor suppressor gene.[1]

It has a distinct pattern of expression in the brain, and its induction has been shown to be associated with neuronal activity. Several studies suggest it has a role in neuronal plasticity.[2]

EGR-1 has also been found to regulate the expression of VAMP2 (a protein important for synaptic exocytosis).[3]

Structure

The DNA-binding domain of EGR-1 consists of three zinc finger domains of the Cys2His2 type. The amino acid structure of the EGR-1 zinc finger domain is given in this table, using the single letter amino acid code. The fingers 1 to 3 are indicated by f1 - f3. The numbers are in reference to the residues (amino acids) of alpha helix (there is no zero). The residues marked 'x' are not part of the zinc fingers, but rather serve to connect them all together.

-1 1 2 3 4 5 6 7 8 9 x x x x x
f1 M A E E R P Y A C P V E S C D R R F S R S D E L T R H I R I H T G Q K P
f2 F Q C A I - - C M R N F S R S D H L T T H I A T H T G E K P
f3 F A C D I - - C G R K F A R S D E R K R H T K I H L R Q K D

The crystal structure of DNA bound by the zinc finger domain of EGR-1 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.[4]

The human EGR-1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5 kDa, and the gene is located on the chromosome 5.

DNA Binding Specificity

EGR-1 binds the DNA sequence 5'-GCG TGG GCG-3' (and similar ones like 5'-GCG GGG GCG-3').[5][6] The f1 position 6 binds the 5' G (the first base count from the left); the f1 position 3 to the second base (C); f1 position -1 binds to the third position (G); f2 position 6 to the fourth base (T); and so on.

Interactions

EGR-1 has been shown to interact with NAB1,[7] CEBPB,[8] EP300,[9] CREB-binding protein,[9] PSMA3[10] and P53.[11]

See also

References

  1. ^ "Entrez Gene: EGR1 early growth response 1". 
  2. ^ Knapska, E and Kaczmarek, L (2004) "A gene for Neuronal Plasticity in the Mammalian Brain: Zif286/Egr1/NGFI-A/Krox-24/TIS-8/ZENK?" Progress in Neurobiology 74, 2004
  3. ^ Petersohn,D and Thiel. G (1996)"Role of zinc-finger proteins Sp1 and zif268/egr-1 in transcriptional regulation of the human synaptobrevin II gene" European Journal of Biochemistry, 239, 1996
  4. ^ Pavletich, N. P.; Pabo, C. O. (1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A". Science 252 (5007): 809–17.  
  5. ^ Christy B, Nathans D (1989). "DNA binding site of the growth factor-inducible protein Zif268". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8737–41.  
  6. ^ Swirnoff AH, Milbrandt J (1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors". Mol. Cell. Biol. 15 (4): 2275–87.  
  7. ^ Russo, M W; Sevetson B R; Milbrandt J (Jul 1995). "Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription".  
  8. ^ Zhang, Fang; Lin Meihong; Abidi Parveen; Thiel Gerald; Liu Jingwen (Nov 2003). "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". J. Biol. Chem. (United States) 278 (45): 44246–54.  
  9. ^ a b Silverman, E S; Du J; Williams A J; Wadgaonkar R; Drazen J M; Collins T (Nov 1998). "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)". Biochem. J. (ENGLAND) 336 (1): 183–9.  
  10. ^ Bae, Myung-Ho; Jeong Chul-Ho, Kim Se-Hee, Bae Moon-Kyoung, Jeong Joo-Won, Ahn Mee-Young, Bae Soo-Kyung, Kim Nam Deuk, Kim Chul Woo, Kim Kwang-Rok, Kim Kyu-Won (Oct 2002). "Regulation of Egr-1 by association with the proteasome component C8". Biochim. Biophys. Acta (Netherlands) 1592 (2): 163–7.  
  11. ^ Liu, J; Grogan L; Nau M M; Allegra C J; Chu E; Wright J J (Apr 2001). "Physical interaction between p53 and primary response gene Egr-1". Int. J. Oncol. (Greece) 18 (4): 863–70.  

Further reading

  • Heath RG (1975). "Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals". J. Nerv. Ment. Dis. 160 (3): 159–75.  
  • Silverman ES, Collins T (1999). "Pathways of Egr-1-mediated gene transcription in vascular biology". Am. J. Pathol. 154 (3): 665–70.  
  • Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival". Tumour Biol. 23 (2): 93–102.  
  • Blaschke F, Bruemmer D, Law RE (2004). "Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis". Reviews in endocrine & metabolic disorders 5 (3): 249–54.  
  • Abdulkadir SA (2006). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1". Ann. N. Y. Acad. Sci. 1059: 33–40.  
  • Khachigian LM (2006). "Early growth response-1 in cardiovascular pathobiology.". Circ Res. 98 (2): 186–191.  

External links

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