EGR1

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Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
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RefSeq (mRNA)	n/a	n/a
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Wikidata
View/Edit Human

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

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.

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

Further reading

• Heath RG (Mar 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. doi:10.1097/00005053-197503000-00002. PMID 1090709.
• Silverman ES, Collins T (Mar 1999). "Pathways of Egr-1-mediated gene transcription in vascular biology". The American Journal of Pathology. 154 (3): 665–70. doi:10.1016/S0002-9440(10)65312-6. PMC 1866415. 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. doi:10.1159/000059711. PMID 12065847.
• Blaschke F, Bruemmer D, Law RE (Aug 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 (Nov 2005). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1". Annals of the New York Academy of Sciences. 1059: 33–40. doi:10.1196/annals.1339.018. PMID 16382041.
• Khachigian LM (Feb 2006). "Early growth response-1 in cardiovascular pathobiology". Circulation Research. 98 (2): 186–91. doi:10.1161/01.RES.0000200177.53882.c3. PMID 16456111.

External links

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