EGR1
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| Location (UCSC) | Chr 5: 138.47 – 138.47 Mb | Chr 18: 34.99 – 35 Mb | |||||||
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EGR-1 (Early growth response protein 1) also known as ZNF268 (zinc finger protein 268) 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.
Function
The protein encoded by this gene belongs to the
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.[6]
EGR-1 is an important transcription factor in memory formation. It has an essential role in brain neuron epigenetic reprogramming. EGR-1 recruits the TET1 protein that initiates a pathway of DNA demethylation.[7] Removing DNA methylation marks allows the activation of downstream genes. EGR-1, together with TET1, is employed in programming the distribution of methylation sites on brain DNA during brain development, in learning and in long-term neuronal plasticity. EGR-1 has also been found to regulate the expression of VAMP2 (a protein important for synaptic exocytosis).[8]
Beside its function in the nervous system, there is significant evidence that EGR-1 along with its paralog EGR-2 is induced in fibrotic diseases has key functions in fibrinogenesis and is necessary for experimentally induced fibrosis in mice.[9]
It may also be involved in ovarian function [10]
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 | R | I | - | - | C | M | R | N | F | S | R | S | D | H | L | T | T | H | I | R | 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 |
Amino acid key: Alanine (Ala, A), Arginine (Arg, R), Asparagine (Asn, N), Aspartic acid (Asp, D), Cysteine (Cys, C), Glutamic acid (Glu, E), Glutamine (Gln, Q), Glycine (Gly, G), Histidine (His, H), Isoleucine (Ile, I), Leucine (Leu, L), Lysine (Lys, K), Methionine (Met, M), Phenylalanine (Phe, F), Proline (Pro, P), Serine (Ser, S), Threonine (Thr, T), Tryptophan (Trp, W), Tyrosine (Tyr, Y), Valine (Val, V)
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.[11]
The human EGR-1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5
DNA binding specificity
EGR-1 binds the DNA sequence 5'-GCG TGG GCG-3' (and similar ones like 5'-GCG GGG GCG-3').[12][13] 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
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000120738 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038418 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: EGR1 early growth response 1".
- S2CID 39251786.
- ^ Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L, Zhu J, Chen J, Morozov A, Pickrell AM, Theus MH, Xie H. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nat Commun. 2019 Aug 29;10(1):3892. doi: 10.1038/s41467-019-11905-3. PMID 31467272
- PMID 8774732.
- PMID 21511034.
- PMID 28733346.
- S2CID 38000717.
- PMID 2510170.
- PMID 7891721.
- PMID 12947119.
- ^ PMID 9806899.
- PMID 7624335.
- PMID 11251186.
- PMID 12379479.
Further reading
- Heath RG (March 1975). "Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals". The Journal of Nervous and Mental Disease. 160 (3): 159–75. S2CID 23024944.
- Silverman ES, Collins T (March 1999). "Pathways of Egr-1-mediated gene transcription in vascular biology". The American Journal of Pathology. 154 (3): 665–70. PMID 10079243.
- Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival". Tumour Biology. 23 (2): 93–102. S2CID 46795197.
- Blaschke F, Bruemmer D, Law RE (August 2004). "Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis". Reviews in Endocrine & Metabolic Disorders. 5 (3): 249–54. S2CID 11968305.
- Abdulkadir SA (November 2005). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1". Annals of the New York Academy of Sciences. 1059 (1): 33–40. S2CID 6774788.
- Khachigian LM (February 2006). "Early growth response-1 in cardiovascular pathobiology". Circulation Research. 98 (2): 186–91. PMID 16456111.
External links
- Zif+268+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook Egr-1
- Overview of all the structural information available in the PDB for UniProt: P18146 (Human Early growth response protein 1) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: P08046 (Mouse Early growth response protein 1) at the PDBe-KB.
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