NuBaID, N-terminal domain (NuBaID_N)
Type: Domain

This entry represents the N-terminal zinc finger domain (formerly ZnF-C3HC) of Zinc finger C3HC-type protein 1 (ZC3HC1, also known as Nuclear-interacting partner of ALK (NIPA)), pre-mRNA leakage protein 39 (Pml39), mRNA export factor Rsm1 and related eukaryotic proteins. Pml39 and Rsm1 are ZC3HC1 homologues from S. cerevisiae and S. pombe, respectively . This domain contains three highly conserved cysteine residues, two of which evolutionarily invariant, followed by an invariant pair of histidine and cysteine residues . This zinc finger domain is often found repeated and the second repeat domain (

) can harbour a large insert located after the first three cysteine residues. Both domains coordinate zinc ion via two cysteines and the histidine-cysteine pair, in a mode similar to the presumably related BIR domains (

) .

Rsm1 protein (

), containing this domain, is involved in mRNA export from the nucleus . Recently, Pml39 was found to be required for the retention of unspliced mRNA . ZC3HC1 was formerly described as Nuclear-interacting partner of ALK (NIPA), with a proposed role in cell cycle regulation as a component of an SCF complex specifically targeting cyclin B1 . These findings were recently refuted . In contrast, ZC3HC1 was identified as a nuclear envelope-associated protein residing at the NPC-attached nuclear basket (NB) of Xenopus laevis oocytes and cultured human cells . It was shown that ZC3HC1 is a constituent structural component of the NB essential for recruitment, positioning and linkage of a subpopulation of the NB scaffold protein TPR . Furthermore, it was demonstrated that the Pml39 is a functional homologue of ZC3HC1 and, similarly, is capable of interconnecting Mlp1 polypeptide, the corresponding homologue of TPR in S. cerevisiae . Both N- (this entry) and C-terminal [

] zinc finger domains were found to be essential for binding TPR/Mlp1 and therefore denoted as the nuclear basket-interaction domain (NuBaID), representing an evolutionary conserved integral functional unit .

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.