InterPro domain: IPR000967

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 a domain presumed to be a zinc binding domain. The following pattern describes the zinc finger:

C-X(1-6)-H-X-C-X3-C(H/C)-X(3-4)-(H/C)-X(1-10)-C

where X can be any amino acid, and numbers in brackets indicate the number of residues. The two position can be either His or Cys. This central cysteine-rich portion encodes the DNA-binding domain which is highly conserved in eukaryotes [ 7 ]. The NFX1 family of proteins may have additional roles mediated by protein-protein interactions regarding the reiterated RING finger motifs in this central domain which strongly suggest that NFX1 is a probable E3 ubiquitin protein ligase [ 8 ]. This domain is found in the human transcriptional repressor NK-X1, a repressor of HLA-DRA transcription [ 9 ]; the Drosophila shuttle craft protein, which plays an essential role during the late stages of embryonic neurogenesis and has been shown to be a DNA- or RNA-binding protein [ 10 ]; and the yeast FKBP12-associated protein 1 (FAP1) [ 11 ].

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. NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. J Virol 81, 3786-96
8. Murine NFX.1: isolation and characterization of its messenger RNA, mapping of its chromosomal location and assessment of its developmental expression. Immunology 106, 173-81
9. A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor. J. Exp. Med. 180, 1763-74
10. A homolog of human transcription factor NF-X1 encoded by the Drosophila shuttle craft gene is required in the embryonic central nervous system. Mol. Cell. Biol. 16, 192-201
11. FAP1, a homologue of human transcription factor NF-X1, competes with rapamycin for binding to FKBP12 in yeast. Mol. Microbiol. 37, 1480-93