| Description: |
This entry represents the RING-type zinc finger domain of E3 ubiquitin-protein ligase ZNRF3 (Zinc/RING finger protein 3), a transmembrane enzyme () homologue of Ring finger protein 43 (RNF43). It is predominantly found in vertebrates.In humans, ZNRF3 acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6 [, , ]. ZNRF3 also functions as a tumour suppressor in the intestinal stem cell zone by restricting the size of the intestinal stem cell zone []. In frogs (Xenopus), ZNRF3 and RNF43 were seen to play a key role in limb specification, constituting a master switch along with RSPO2, which may have implications for regenerative medicine []. 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 [, , , , ]. 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 []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. |
