InterPro domain: IPR007529

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ 1 , 2 , 3 , 4 , 5 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ 6 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the HIT-type zinc finger, which contains 7 conserved cysteines and one histidine that can potentially coordinate two zinc atoms. It has been named after the first protein that originally defined the domain: the yeast HIT1 protein ( P46973 ) [ 7 ]. The HIT-type zinc finger displays some sequence similarities to the MYND-type zinc finger. The function of this domain is unknown but it is mainly found in nuclear proteins involved in gene regulation and chromatin remodeling. This domain is also found in the thyroid receptor interacting protein 3 (TRIP-3) Q15649 , that specifically interacts with the ligand binding domain of the thyroid receptor.

1. Zinc finger peptides for the regulation of gene expression. J. Mol. Biol. 293, 215-8
2. Multiple modes of RNA recognition by zinc finger proteins. Curr. Opin. Struct. Biol. 15, 367-73
3. Zinc finger proteins: getting a grip on RNA. Curr. Opin. Struct. Biol. 15, 94-8
4. Sticky fingers: zinc-fingers as protein-recognition motifs. Trends Biochem. Sci. 32, 63-70
5. Zinc fingers--folds for many occasions. IUBMB Life 54, 351-5
6. Zinc finger proteins: new insights into structural and functional diversity. Curr. Opin. Struct. Biol. 11, 39-46
7. Ty element-induced temperature-sensitive mutations of Saccharomyces cerevisiae. Genetics 131, 821-32