EGR-1 also known as Zif268 (zinc finger protein 225) or NGFI-A (nerve growth factor-induced protein A) is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the EGR1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

EGR-1 is a mammalian transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

. It was also named Krox-24, TIS8, and ZENK. It was originally discovered in mice

House mouse

The house mouse is a small rodent, a mouse, one of the most numerous species of the genus Mus.As a wild animal the house mouse mainly lives associated with humans, causing damage to crops and stored food....

.

Function

The protein encoded by this gene belongs to the EGR family

Early growth response proteins

Early growth response proteins are a family of zinc finger transcription factors.Members of the family include:* EGR1, EGR2, EGR3 and EGR4...

 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

Tumor suppressor gene

A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

.

Structure

The DNA-binding domain of Zif268 consists of three zinc finger

Zinc finger

Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...

 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

Alpha helix

A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...

 (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

Crystal structure

In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...

 of DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 bound by the zinc finger domain of Zif268 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.

The human Zif268/EGR1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5 kDa

KDA

KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...

, and the gene is located on the chromosome 5.

Function

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

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

Synaptic plasticity

In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...

.

Zif268 has also been found to regulate the expression of synaptobrevin II (a protein important for synaptic

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

 exocytosis

Exocytosis

Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

).

Interactions

Zif268 has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with NAB1

NAB1

NGFI-A-binding protein 1 is a protein that in humans is encoded by the NAB1 gene.-Further reading:...

, CEBPB

CEBPB

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.- Function :The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins...

, EP300

EP300

E1A binding protein p300 also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body...

, CREB-binding protein, PSMA3

PSMA3

Proteasome subunit alpha type-3 is a protein that in humans is encoded by the PSMA3 gene.-Interactions:PSMA3 has been shown to interact with PSMA6, PLK1, Zif268 and CRYAB.-Further reading:...

 and P53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

.