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 List of PDB id codes 4R2A, 4R2C, 4R2D, 4X9J
Identifiers
Symbols	EGR1 ; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225
External IDs	OMIM: 128990 MGI: 95295 HomoloGene: 56394 GeneCards: EGR1 Gene
Gene ontology Molecular function • transcription regulatory region sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding • transcription factor binding • histone acetyltransferase binding • sequence-specific DNA binding • metal ion binding Cellular component • nucleus • nucleoplasm • cytoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • response to amphetamine • transcription from RNA polymerase II promoter • learning or memory • circadian rhythm • response to glucose • cytokine-mediated signaling pathway • T cell differentiation • BMP signaling pathway • response to nutrient levels • cellular response to insulin stimulus • regulation of protein sumoylation • response to carbon monoxide • cellular response to drug • skeletal muscle cell differentiation • response to cocaine • positive regulation of neuron apoptotic process • response to ethanol • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • regulation of long-term neuronal synaptic plasticity • oligodendrocyte differentiation • response to electrical stimulus • long-term synaptic potentiation • type I interferon signaling pathway • regulation of transcription from RNA polymerase II promoter in response to hypoxia • interleukin-1-mediated signaling pathway • cellular response to antibiotic • cellular response to mechanical stimulus • cellular response to isoquinoline alkaloid • cellular response to cAMP • cellular response to follicle-stimulating hormone stimulus • cellular response to steroid hormone stimulus • cellular response to hyperoxia • cellular response to gamma radiation • cellular response to heparin • cellular response to mycophenolic acid • response to norepinephrine • glomerular mesangial cell proliferation • positive regulation of glomerular metanephric mesangial cell proliferation • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE EGR1 201694 s at tn.png
File:PBB GE EGR1 201693 s at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1958	13653
Ensembl	ENSG00000120738	ENSMUSG00000038418
UniProt	P18146	P08046
RefSeq (mRNA)	NM_001964	NM_007913
RefSeq (protein)	NP_001955	NP_031939
Location (UCSC)	Chr 5: 138.47 – 138.47 Mb	Chr 18: 34.86 – 34.86 Mb
PubMed search	[1]	[2]

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.

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.

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.

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

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.

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'). 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:

• CEBPB,
• CREB-binding protein,
• EP300,
• NAB1,
• P53, and
• PSMA3

See also

• Zinc finger

External links

• Zif 268 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook Egr-1