Nuclear factor (erythroid 2)-like factor 3, also known as NFE2L3 or 'NRF3', is a transcription factor that in humans is encoded by the Nfe2l3gene.[5][6]
Nrf3 is a basic leucine zipper (bZIP) transcription factor belonging to the Cap ‘n’ Collar (CNC) family of proteins.[7] In 1989, the first CNC transcription factorNFE2L2 was identified. Subsequently, several related proteins were identified, including NFE2L1 and NFE2L3, in different organisms such as humans, mice, and zebrafish.[8] These proteins are specifically encoded in the humans by Nfe2l1 and Nfe2l3 genes respectively.[9][10]
The Nfe2l3 gene was mapped to the chromosomal location 7p15-p14byfluorescence in situ hybridization (FISH).[9] It covers 34.93 kB from base 26191830 to 26226754 on the direct DNA strand with an exon count of 4. The gene is found near the HOXA gene cluster, similar to the clustering of p45 NF-E2, NFE2L1, and NFE2L2 near HOXC, HOXB, and HOXD genes respectively.[7][9] This implies that all four genes were likely derived from a single ancestral gene which was duplicated alongside the ancestral HOX cluster, diverging to give rise to four closely related transcription factors.[9]
The human Nfe2l3 gene encodes a 694 amino acid residue sequence.[7][9] From bioinformatic analysis, it has been observed that the NRF3 protein shows a high degree of conservation through its evolutionary pathway from zebrafish to humans. Key conserved domains such as N-terminal homology box 1 (NHB1), N-terminal homology box 2 (NHB2), and the CNC domain allude to the conserved functional properties of this transcription factor.[11]
NRF3 is a membrane bound glycoprotein that can be targeted specifically to the endoplasmic reticulum (ER) and the nuclear membrane.[9]Biochemical studies have identified three migratingendogenous forms of NRF3 protein – A, B, and C – which are constitutively degraded by several proteolytic mechanisms.[9][12] It is known that the "A" form is glycosylated, whereas "B" is unglycosylated, and "C" is generated by cleavage of "B."[7][9] In total, seven potential sites of N-linked glycosylation [7] has been observed in the center portion of the NRF3 protein. However, further details of the three forms' location, regulation, and function in each cellular compartment remain unknown.
The specific functions of the NRF3 protein are still unknown, but some putative functional properties have been inferred from those of NFE2L1 due to their structural similarity. It is known that NRF3 can heterodimerize with small musculo-aponeurotic fibro-sarcoma (MAF genes) factors to bind antioxidantresponse elements in target genes.[17]
^Blank V, Andrews NC (November 1997). "The Maf transcription factors: regulators of differentiation". Trends in Biochemical Sciences. 22 (11): 437–41. doi:10.1016/s0968-0004(97)01105-5. PMID9397686.
^Willenbrock K, Küppers R, Renné C, Brune V, Eckerle S, Weidmann E, Bräuninger A, Hansmann ML (May 2006). "Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma". Haematologica. 91 (5): 596–604. PMID16670065.
^Hayes JD, McMahon M (December 2001). "Molecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention". Cancer Letters. 174 (2): 103–13. doi:10.1016/s0304-3835(01)00695-4. PMID11689285.
