NRF1

Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a is_associated_with::transcription factor which activates the expression of some key is_associated_with::metabolic genes regulating cellular growth and nuclear genes required for respiration, is_associated_with::heme biosynthesis, and is_associated_with::mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of is_associated_with::neurite outgrowth. Alternate is_associated_with::transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein is_associated_with::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 is_associated_with::NFE2L1.

Function
Nrf1 functions as a transcription factor that activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for mitochondrial respiration, and mitochondrial DNA transcription and replication. Nrf1, together with is_associated_with::Nrf2, mediates the is_associated_with::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 is_associated_with::antioxidant and is_associated_with::xenobiotic-metabolizing enzymes during is_associated_with::oxidative stress.

Nrf1 is also involved in is_associated_with::heme biosynthesis through regulation of is_associated_with::globin gene expression. The protein has also been associated with the regulation of is_associated_with::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.

Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function.

Interactions
Nrf1 is_associated_with::heterodimerizes with small Maf proteins and the resultant is_associated_with::heterodimers bind to the antioxidant is_associated_with::response element (ARE) thereby mediating the transcription of antioxidative and phase 2-metabolizing enzymes.

NRF1 has been shown to interact with is_associated_with::DYNLL1 and is_associated_with::PPARGC1A.