Nach (Nrf and CNC homology)

Created by: Yiguo Zhang

 The article "Nach Is a Novel Subgroup at  an Early Evolutionary Stage of the CNC-bZIP Subfamily Transcription Factors  from the Marine Bacteria to Humans" has been published in the IJMS. Nachs, a specific group of bZIP proteins is identified, designated Nach (Nrf and CNC homology), because of their strong conservation with all the known CNC and NF-E2 p45 subunit-related factors Nrf1/2. Further experiments have revealed that Nach1/2(Nach1 and Nach2 with the GenBank accession No. WP_062268396 and WP_034835593 ) from the marine bacteria exerts distinctive functions, when compared with human Nrf1/2, in the transcriptional regulation of antioxidant response element (ARE)-battery genes. Collectively, further insights into these Nach/CNC-bZIP subfamily transcription factors provide a better understanding of distinct biological functions of these factors expressed in distinct species from marine bacteria to humans.

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1. Species Distribution and Phylogenetic Analysis of bZIP Transcription Factors (Figure 1)

Here, we found that bZIP transcription factors existed in 14 representative metazoans, 5 typical protozoans, 2 bacteria, and 2 viruses.

2. A Novel Evolutionary Branch of the CNC-bZIP Subfamily from Ancestral Nach Proteins (Figure 2)

 A novel subgroup of Nach1-8, with a high homology with all the known CNC-bZIP proteins, are herein identified to be present in the Echinodermata, Mollusca, Actiniaria, Placozoa, Porifera, and bacteria, respectively.

3. Distinct Subgroups of the Membrane-Bound bZIP Transcription Factors (Figure 3)

We have further predicted by using both the TMpred and TMHMM tools, and also summarized all potential TM-containing bZIP proteins across 23 species, which were classified into 4 major subgroups including CNC-NHB1 (also including Nach3, 5, 6, and 7), XBP1u, OASIS/ATF6, and SREBPs.

4. Expressive Differentiations of Human bZIP Factors within Their Endogenous Interaction Networks (Figure 4)

We have demonstrated that the complex regulatory networks of human bZIP transcription factors, in which the CNC-bZIP factors are closely interactive with sMaf.

5. Nach1 Shares Conserved Domains with Other CNC-bZIP Factors at Differently Regulating Target Genes (Figure 5)

The bacterial Nach1 shares structures features with human NF-E2 p45. Nach1 and Nach2 proteins were over-expressed and changes in the expression of downstream targets followed to some extent, but functions of regulating target genes  are distinct.


Zhu, Y.-P.; Wang, M.; Xiang, Y.; Qiu, L.; Hu, S.; Zhang, Z.; Mattjus, P.; Zhu, X.; Zhang, Y. Nach Is a Novel Subgroup at an Early Evolutionary Stage of the CNC-bZIP Subfamily Transcription Factors from the Marine Bacteria to Humans. Int. J. Mol. Sci. 201819, 2927.