NRF1
Encyclopedia
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor
which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA
transcription and replication. The protein has also been associated with the regulation of neurite
outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1
. [provided by RefSeq]
and nuclear genes required for mitochondrial respiration, and mitochondrial
DNA transcription
and replication
. Nrf1, together with Nrf2, mediates the biogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encoded ETC
proteins, and indirectly regulating the three mitochondrial-encoded COX
subunit genes by activating mtTFA
, mtTFB1
, and mtTFB2
. The Nrf proteins are also important for the upregulation of antioxidant
and xenobiotic-metabolizing enzymes during oxidative stress
.
Nrf1 is also involved in heme
biosynthesis through regulation of globin
gene expression.
The protein has also been associated with the regulation of neurite
outgrowth.
Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized.
proteins and the resultant heterodimers bind to the antioxidant response element
(ARE) thereby mediating the transcription of antioxidative and phase 2-metabolizing enzymes.
NRF1 has been shown to interact
with DYNLL1
and PPARGC1A
.
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...
which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
transcription and replication. The protein has also been associated with the regulation of neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1
NFE2L1
Nuclear factor erythroid 2-related factor 1 is a protein that in humans is encoded by the NFE2L1 gene....
. [provided by RefSeq]
Function
Nrf1 functions as a transcription factor that activates the expression of some key metabolic genes regulating cellular growthCell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and nuclear genes required for mitochondrial respiration, and mitochondrial
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
DNA transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
and replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. Nrf1, together with Nrf2, mediates the biogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encoded ETC
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
proteins, and indirectly regulating the three mitochondrial-encoded COX
Cytochrome c oxidase
The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
subunit genes by activating mtTFA
TFAM
Transcription factor A, mitochondrial is a protein that in humans is encoded by the TFAM gene.-Further reading:...
, mtTFB1
TFB1M
Dimethyladenosine transferase 1, mitochondrial is an enzyme that in humans is encoded by the TFB1M gene.-Further reading:...
, and mtTFB2
TFB2M
Dimethyladenosine transferase 2, mitochondrial is an enzyme that in humans is encoded by the TFB2M gene.-Further reading:...
. The Nrf proteins are also important for the upregulation of antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
and xenobiotic-metabolizing enzymes during oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
.
Nrf1 is also involved in heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
biosynthesis through regulation of globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
gene expression.
The protein has also been associated with the regulation of neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
outgrowth.
Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized.
Interactions
Nrf1 heterodimerizes with small MafMAF (gene)
Transcription factor Maf also known as proto-oncogene c-Maf or V-maf musculoaponeurotic fibrosarcoma oncogene homolog is a transcription factor that in humans is encoded by the MAF gene.-Types:...
proteins and the resultant heterodimers bind to the antioxidant response element
Response element
Response elements are short sequences of DNA within a gene promoter region that are able to bind a specific transcription factor and regulate transcription of genes.-Examples:Examples of response elements include:*Hormone response element...
(ARE) thereby mediating the transcription of antioxidative and phase 2-metabolizing enzymes.
NRF1 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 DYNLL1
DYNLL1
Dynein light chain 1, cytoplasmic is a protein that in humans is encoded by the DYNLL1 gene.-Interactions:DYNLL1 has been shown to interact with DLGAP1, MYO5A, DYNC1I1, BCL2L11, NRF1, IκBα, PAK1, DLG4 and TP53BP1.-Further reading:...
and PPARGC1A
PPARGC1A
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha is a protein that in humans is encoded by the PPARGC1A gene....
.