Zif268
From Wikipedia, the free encyclopedia
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| 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. | |
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early growth response 1
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| Identifiers | |
| Symbol | EGR1 |
| HUGO | 3238 |
| Entrez | 1958 |
| OMIM | 128990 |
| RefSeq | NM_001964 |
| UniProt | P18146 |
| Other data | |
| Locus | Chr. 5 q31.1 |
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.
[edit] 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.[1]
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.
[edit] Function
Zif268 binds the DNA sequence 5'-GC[G/T]GGGCG-3.[2][3]
It has a distinct pattern of expression in the brain, and its induction has been shown to be assiociated with neuronal activity. Several studies suggest it has a role in neuronal plasticity.[4]
Zif268 has also been found to regulate the expression of synaptobrevin II (a protein important for synaptic exocytosis).[5]
[edit] References
- ^ 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.
- ^ Christy, B. and D. Nathans (1989). "DNA binding site of the growth factor-inducible protein Zif268." Proc Natl Acad Sci U S An 86(22): 8737-41.
- ^ Swirnoff, A. H. and J. Milbrandt (1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors." Mol Cell Biol 15(4): 2275-87.
- ^ 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
- ^ 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
