Zinc finger, FLYWCH-type (IPR007588)

Short name: Znf_FLYWCH

Overlapping homologous superfamilies


Domain relationships



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 [PMID: 10529348, PMID: 15963892, PMID: 15718139, PMID: 17210253, PMID: 12665246]. 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 [PMID: 11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short beta hairpin and an alpha helix (beta/beta/alpha structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 [PMID: 11361095]. C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes [PMID: 10664601]. Transcription factors usually contain several Znf's (each with a conserved beta/beta/alpha structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short alpha-helix in the Znf, the Znf spanning 3-4 bases of the DNA [PMID: 10940247]. C2H2 Znf's can also bind to RNA and protein targets [PMID: 18253864].

This entry represents a potential FLYWCH Zn-finger domain found in a number of eukaryotic proteins. FLYWCH is a C2H2-type zinc finger characterised by five conserved hydrophobic residues, containing the conserved sequence motif:


where X indicates any amino acid. This domain was first characterised in Drosophila Modifier of mdg4 proteins, Mod(mgd4), putative chromatin modulators involved in higher order chromatin domains. Mod(mdg4) proteins share a common N-terminal BTB/POZ domain, but differ in their C-terminal region, most containing C-terminal FLYWCH zinc finger motifs [PMID: 12723696]. The FLYWCH domain in Mod(mdg4) proteins has a putative role in protein-protein interactions; for example, Mod(mdg4)-67.2 interacts with DNA-binding protein Su(Hw) via its FLYWCH domain.

FLYWCH domains have been described in other proteins as well, including suppressor of killer of prune, Su(Kpn), which contains 4 terminal FLYWCH zinc finger motifs in a tandem array and a C-terminal glutathione SH-transferase (GST) domain [PMID: 16944302].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.