EGR1

Last updated
EGR1
Zinc finger DNA complex.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EGR1 , AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268, ZNF225, early growth response 1
External IDs OMIM: 128990 MGI: 95295 HomoloGene: 56394 GeneCards: EGR1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001964

NM_007913

RefSeq (protein)

NP_001955

NP_031939

Location (UCSC) Chr 5: 138.47 – 138.47 Mb Chr 18: 34.99 – 35 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

Contents

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. [5]

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.

-1123456789xxxxx
f1MAEERPYACPVESCDRRFSRSDELTRHIRIHTGQKP
f2FQCRI--CMRNFSRSDHLTTHIRTHTGEKP
f3FACDI--CGRKFARSDERKRHTKIHLRQKD

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 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'). [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 interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">Zinc finger</span> Small structural protein motif found mostly in transcriptional proteins

A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (Xenopus laevis) transcription factor IIIA. However, it has been found to encompass a wide variety of differing protein structures in eukaryotic cells. Xenopus laevis TFIIIA was originally demonstrated to contain zinc and require the metal for function in 1983, the first such reported zinc requirement for a gene regulatory protein followed soon thereafter by the Krüppel factor in Drosophila. It often appears as a metal-binding domain in multi-domain proteins.

A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.

Immediate early genes (IEGs) are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized. IEGs are distinct from "late response" genes, which can only be activated later, following the synthesis of early response gene products. Thus IEGs have been called the "gateway to the genomic response". The term can describe viral regulatory proteins that are synthesized following viral infection of a host cell, or cellular proteins that are made immediately following stimulation of a resting cell by extracellular signals.

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA. Some DNA-binding domains may also include nucleic acids in their folded structure.

<span class="mw-page-title-main">GLI1</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells.

In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of eukaryotic C2H2 zinc finger DNA-binding proteins that regulate gene expression. This family has been expanded to also include the Sp transcription factor and related proteins, forming the Sp/KLF family.

<span class="mw-page-title-main">Artificial transcription factor</span>

Artificial transcription factors (ATFs) are engineered individual or multi molecule transcription factors that either activate or repress gene transcription (biology).

<span class="mw-page-title-main">EGR2</span> Protein-coding gene in the species Homo sapiens

Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene. EGR2 is a transcription regulatory factor, containing three zinc finger DNA-binding sites, and is highly expressed in a population of migrating neural crest cells. It is later expressed in the neural crest derived cells of the cranial ganglion. The protein encoded by Krox20 contains two cys2his2-type zinc fingers. Krox20 gene expression is restricted to the early hindbrain development. It is evolutionarily conserved in vertebrates, humans, mice, chicks, and zebra fish. In addition, the amino acid sequence and most aspects of the embryonic gene pattern is conserved among vertebrates, further implicating its role in hindbrain development. When the Krox20 is deleted in mice, the protein coding ability of the Krox20 gene is diminished. These mice are unable to survive after birth and exhibit major hindbrain defects. These defects include but are not limited to defects in formation of cranial sensory ganglia, partial fusion of the trigeminal nerve (V) with the facial (VII) and auditory (VII) nerves, the proximal nerve roots coming off of these ganglia were disorganized and intertwined among one another as they entered the brainstem, and there was fusion of the glossopharyngeal (IX) nerve complex.

<span class="mw-page-title-main">NAB2</span>

NGFI-A-binding protein 2 also known as EGR-1-binding protein 2 or melanoma-associated delayed early response protein (MADER) is a protein that in humans is encoded by the NAB2 gene.

<span class="mw-page-title-main">NAB1</span>

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

Zinc finger protein chimera are chimeric proteins composed of a DNA-binding zinc finger protein domain and another domain through which the protein exerts its effect. The effector domain may be a transcriptional activator (A) or repressor (R), a methylation domain (M) or a nuclease (N).

<span class="mw-page-title-main">ZBTB7B</span> Protein-coding gene in the species Homo sapiens

Zinc finger and BTB domain-containing protein 7B is a protein that in humans is encoded by the ZBTB7B gene. ZFP67 is an early growth response gene that encodes a zinc finger-containing transcription factor that binds to the promoter regions of type I collagen genes and has a role in development.[supplied by OMIM]

<span class="mw-page-title-main">ZNF423</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 423 is a protein that in humans is encoded by the ZNF423 gene.

<span class="mw-page-title-main">Zinc finger protein 804A</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 804A is a protein that in humans is encoded by the ZNF804A gene. The human gene maps to chromosome 2 q32.1 and consists of 4 exons that code for a protein of 1210 amino acids.

<span class="mw-page-title-main">Activity-regulated cytoskeleton-associated protein</span> Protein-coding gene in the species Homo sapiens

Activity-regulated cytoskeleton-associated protein is a plasticity protein that in humans is encoded by the ARC gene. It was first characterized in 1995. ARC is a member of the immediate-early gene (IEG) family, a rapidly activated class of genes functionally defined by their ability to be transcribed in the presence of protein synthesis inhibitors. ARC mRNA is localized to activated synaptic sites in an NMDA receptor-dependent manner, where the newly translated protein is believed to play a critical role in learning and memory-related molecular processes. Arc protein is widely considered to be important in neurobiology because of its activity regulation, localization, and utility as a marker for plastic changes in the brain. Dysfunction in the production of Arc protein has been implicated as an important factor in understanding various neurological conditions, including amnesia, Alzheimer's disease, Autism spectrum disorders, and Fragile X syndrome. Along with other IEGs such as ZNF268 and HOMER1, ARC is also a significant tool for systems neuroscience as illustrated by the development of the cellular compartment analysis of temporal activity by fluorescence in situ hybridization, or catFISH technique.

<span class="mw-page-title-main">Squamosa promoter binding protein</span> InterPro Family

The SQUAMOSA promoter binding protein-like family of transcription factors are defined by a plant-specific DNA-binding domain. The founding member of the family was identified based on its specific in vitro binding to the promoter of the snapdragon SQUAMOSA gene. SBP proteins are thought to be transcriptional activators.

<span class="mw-page-title-main">EGR4</span> Protein-coding gene in the species Homo sapiens

Early growth response protein 4 (EGR-4), also known as AT133, is a protein that in humans is encoded by the EGR4 gene.

In molecular biology, a GC box, also known as a GSG box, is a distinct pattern of nucleotides found in the promoter region of some eukaryotic genes. The GC box is upstream of the TATA box, and approximately 110 bases upstream from the transcription initiation site. It has a consensus sequence GGGCGG which is position-dependent and orientation-independent. The GC elements are bound by transcription factors and have similar functions to enhancers. Some known GC box-binding proteins include Sp1, Krox/Egr, Wilms' tumor, MIGI, and CREA.

<span class="mw-page-title-main">WRKY protein domain</span> Protein domain

The WRKY domain is found in the WRKY transcription factor family, a class of transcription factors. The WRKY domain is found almost exclusively in plants although WRKY genes appear present in some diplomonads, social amoebae and other amoebozoa, and fungi incertae sedis. They appear absent in other non-plant species. WRKY transcription factors have been a significant area of plant research for the past 20 years. The WRKY DNA-binding domain recognizes the W-box (T)TGAC(C/T) cis-regulatory element.

References

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Further reading