Nuclear factor (erythroid 2)-like factor 3, also known asNFE2L3 or 'NRF3', is atranscription factor that in humans is encoded by theNfe2l3gene.[5][6]
Nrf3 is a basicleucine zipper (bZIP)transcription factor belonging to the Cap 'n' Collar (CNC) family of proteins.[7] In 1989, the first CNCtranscription factorNFE2L2 was identified. Subsequently, several relatedproteins were identified, includingNFE2L1 and NFE2L3, in different organisms such as humans,mice, andzebrafish.[8] These proteins are specifically encoded in the humans byNfe2l1 andNfe2l3 genes respectively.[9][10]
TheNfe2l3 gene was mapped to the chromosomal location7p15-p14 byfluorescence 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 theHOXA gene cluster, similar to the clustering ofp45 NF-E2,NFE2L1, andNFE2L2 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 humanNfe2l3 gene encodes a 694amino acid residue sequence.[7][9] Frombioinformatic analysis, it has been observed that the NRF3 protein shows a high degree of conservation through itsevolutionary pathway from zebrafish to humans. Keyconserved domains such asN-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 amembrane boundglycoprotein that can be targeted specifically to theendoplasmic reticulum (ER) and thenuclear membrane.[9]Biochemical studies have identified threemigratingendogenous forms of NRF3 protein – A, B, and C – which are constitutively degraded by severalproteolytic mechanisms.[9][12] It is known that the "A" form isglycosylated, 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 ofNFE2L1 due to their structural similarity. It is known that NRF3 canheterodimerize with small musculo-aponeurotic fibro-sarcoma (MAF genes) factors to bindantioxidantresponse 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, et al. (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.
