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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
1a1f, 1a1g, 1a1h, 1a1i, 1a1j, 1a1k, 1a1l, 1aay, 1f2i, 1jk1, 1jk2, 1p47, 1zaa
Identifiers
Symbols EGR1; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225
External IDs OMIM128990 MGI95295 HomoloGene56394 GeneCards: EGR1 Gene
RNA expression pattern
PBB GE EGR1 201694 s at tn.png
PBB GE EGR1 201693 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1958 13653
Ensembl ENSG00000120738 ENSMUSG00000038418
UniProt P18146 Q3UM09
RefSeq (mRNA) NM_001964 NM_007913
RefSeq (protein) NP_001955 NP_031939
Location (UCSC) Chr 5:
137.83 - 137.83 Mb
Chr 18:
34.99 - 34.99 Mb
PubMed search [1] [2]

Zif268 is a mammalian transcription factor that is now officially known as Egr1 (Early Growth Response Protein 1). It was also named Krox-24, NGFI-A, TIS8, and ZENK. It was originally discovered in mouse.

The protein encoded by this gene belongs to the EGR family of C2H2-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]

Contents

Structure

The DNA binding domain of Zif268 consists of three zinc finger domains of the Cys2His2 type. The amino acid structure of the Zif268 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 '0'). 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 O 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 Zif268 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.[2]

The human Zif268/EGR1 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.

Function

Zif268 binds the DNA sequence 5'-GCG[G/T]GGGCG-3'.[3][4]

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.[5]

Zif268 has also been found to regulate the expression of synaptobrevin II (a protein important for synaptic exocytosis).[6]

Interactions

Zif268 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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1958.  
  2. ^ Pavletich, N. P. and C. O. Pabo (1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A." Science 252(5007): 809-17.
  3. ^ 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. doi:10.1073/pnas.86.22.8737. PMID 2510170. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2510170.  
  4. ^ Swirnoff AH, Milbrandt J (1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors". Mol. Cell. Biol. 15 (4): 2275–87. PMID 7891721. http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=7891721.  
  5. ^ 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
  6. ^ 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
  7. ^ Russo, M W; Sevetson B R, Milbrandt J (Jul. 1995). "Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 92 (15): 6873–7. ISSN 0027-8424. PMID 7624335.  
  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. doi:10.1074/jbc.M305564200. ISSN 0021-9258. PMID 12947119.  
  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 ( Pt 1): 183–9. ISSN 0264-6021. PMID 9806899.  
  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. ISSN 0006-3002. PMID 12379479.  
  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. ISSN 1019-6439. PMID 11251186.  

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. PMID 1090709.  
  • Silverman ES, Collins T (1999). "Pathways of Egr-1-mediated gene transcription in vascular biology". Am. J. Pathol. 154 (3): 665–70. PMID 10079243.  
  • Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival". Tumour Biol. 23 (2): 93–102. doi:10.1159/000059711. PMID 12065847.  
  • 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. doi:10.1023/B:REMD.0000032413.88756.ee. PMID 15211096.  
  • Abdulkadir SA (2006). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1". Ann. N. Y. Acad. Sci. 1059: 33–40. doi:10.1196/annals.1339.018. PMID 16382041.  
  • Khachigian LM (2006). "Early growth response-1 in cardiovascular pathobiology.". Circ Res. 98 (2): 186–191. doi:10.1161/01.RES.0000200177.53882.c3. PMID 16456111.  

External links








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