PROSITE documentation PDOC00036

Basic-leucine zipper (bZIP) domain signature and profile

The bZIP superfamily [1,2] of eukaryotic DNA-binding transcription factors groups together proteins that contain a basic region mediating sequence-specific DNA-binding followed by a leucine zipper (see <PDOC00029>) required for dimerization. bZIP domains usually bind a palindromic 6 nucleotide site, but the specificity can be altered by interaction with accessory factor [3].

Several structure of bZIP have been solved (see for example <PDB:1AN2>) [4]. The basic region and the leucine zipper form a contiguous α helice where the four hydrophobic residues of the leucine zipper are oriented on one side. This conformation allows dimerization in parallel and it bends the helices so that the newly functional dimer forms a flexible fork where the basic domains, at the N-terminal open end, can then interact with DNA. The two leucine zipper are therefore oriented perpendicular to the DNA [4,5].

This family is quite large and we only list here some representative members.

• Transcription factor AP-1, which binds selectively to enhancer elements in the cis control regions of SV40 and metallothionein IIA. AP-1, also known as c-jun, is the cellular homolog of the avian sarcoma virus 17 (ASV17) oncogene v-jun.
• Jun-B and jun-D, probable transcription factors which are highly similar to jun/AP-1.
• The fos protein, a proto-oncogene that forms a non-covalent dimer with c-jun.
• The fos-related proteins fra-1, and fos B.
• Mammalian cAMP response element (CRE) binding proteins CREB, CREM, ATF-1, ATF-3, ATF-4, ATF-5, ATF-6 and LRF-1.
• Maize Opaque 2, a trans-acting transcriptional activator involved in the regulation of the production of zein proteins during endosperm.
• Arabidopsis G-box binding factors GBF1 to GBF4, Parsley CPRF-1 to CPRF-3, Tobacco TAF-1 and wheat EMBP-1. All these proteins bind the G-box promoter elements of many plant genes.
• Drosophila protein Giant, which represses the expression of both the kruppel and knirps segmentation gap genes.
• Drosophila Box B binding factor 2 (BBF-2), a transcriptional activator that binds to fat body-specific enhancers of alcohol dehydrogenase and yolk protein genes.
• Drosophila segmentation protein cap'n'collar (gene cnc), which is involved in head morphogenesis.
• Caenorhabditis elegans skn-1, a developmental protein involved in the fate of ventral blastomeres in the early embryo.
• Yeast GCN4 transcription factor, a component of the general control system that regulates the expression of amino acid-synthesizing enzymes in response to amino acid starvation, and the related Neurospora crassa cpc-1 protein.
• Neurospora crassa cys-3 which turns on the expression of structural genes which encode sulfur-catabolic enzymes.
• Yeast MET28, a transcriptional activator of sulfur amino acids metabolism.
• Yeast PDR4 (or YAP1), a transcriptional activator of the genes for some oxygen detoxification enzymes.
• Epstein-Barr virus trans-activator protein BZLF1.

The pattern we developped is directed against the basic region. We also developed a profile that covers the whole domain.