Alternative titles; symbols
HGNC Approved Gene Symbol: NKRF
Cytogenetic location: Xq24 Genomic coordinates (GRCh38): X:119,588,337-119,606,424 (from NCBI)
NRF interacts with specific negative regulatory elements (NREs) to mediate transcriptional repression of certain nuclear factor kappa-B (NFKB; see 164011)-responsive genes.
Frattini et al. (1997) obtained a partial sequence encoding NKRF, which they called ITBA4. Northern blot analysis detected a 4.2-kb transcript in all human tissues examined, with highest expression in skeletal muscle. Expression was moderate in heart, brain, placenta, liver, and pancreas, and low in kidney and lung. An additional strong band of lower molecular mass was detected in brain. Zoo blot analysis revealed possible orthologs in all mammalian species examined.
By screening a HeLa cell cDNA expression library for NRE-binding proteins, followed by filter hybridization, Nourbakhsh and Hauser (1999) cloned NKRF, which they called NRF. The deduced 388-amino acid protein has a calculated molecular mass of 43.8 kD and contains an N-terminal nuclear localization signal. The C-terminal 92 amino acids of NRF constitute the DNA-binding domain, which has 4 turns and 4 alpha helices, similar to a winged helix-turn-helix DNA-binding motif. Northern blot analysis detected ubiquitous expression of 3.7- and 4.0-kb transcripts that differ in their 3-prime untranslated regions. The longer transcript predominated in most tissues, but the 3.7-kb transcript predominated in brain. Fluorescence-tagged NRF showed nuclear localization, and deletion of the nuclear localization signal resulted in cytoplasmic staining. Endogenous NRF expressed by HeLa cells showed an apparent molecular mass of about 50 kD.
Nourbakhsh and Hauser (1999) showed that NRF abolishes the transcriptional activity of the NFKB-binding sites in the beta-interferon (147640) promoter by a distance-independent mechanism.
Feng et al. (2002) determined that NRF constitutively silences the inducible nitric-oxide synthase gene (NOS2A; 163730) by binding to the cis-acting NRE upstream in the NOS2A promoter. Mutation of the NRE resulted in loss of NRF binding and increased basal, but not cytokine-stimulated, NOS2A transcription.
By genomic sequence analysis, Frattini et al. (1997) mapped the NKRF gene to chromosome Xq24-q25.
Gross (2015) mapped the NKRF gene to chromosome Xq24 based on an alignment of the NKRF sequence (GenBank BC047878) with the genomic sequence (GRCh38).
Feng, X., Guo, Z., Nourbakhsh, M., Hauser, H., Ganster, R., Shao, L., Geller, D. A. Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: the role of NF-kappa-B-repressing factor (NRF) in basal repression of the hiNOS gene. Proc. Nat. Acad. Sci. 99: 14212-14217, 2002. [PubMed: 12381793] [Full Text: https://doi.org/10.1073/pnas.212306199]
Frattini, A., Faranda, S., Bagnasco, L., Patrosso, C., Nulli, P., Zucchi, I., Vezzoni, P. Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25. Gene 192: 291-298, 1997. [PubMed: 9224902] [Full Text: https://doi.org/10.1016/s0378-1119(97)00108-x]
Gross, M. B. Personal Communication. Baltimore, Md. 4/30/2015.
Nourbakhsh, M., Hauser, H. Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappa-B-repressing factor), a nuclear inhibitor of NF-kappa-B. EMBO J. 18: 6415-6425, 1999. [PubMed: 10562553] [Full Text: https://doi.org/10.1093/emboj/18.22.6415]