The neuralized homology repeat (NHR) domain is a module of ~160 amino acids, which has been identified as a tandem repeat in drosophila neuralized, a protein involved in development of the central and peripheral nervous system [ (PUBMED:9519875) ]. Several other fly, worm, and mammalian neuralized-like proteins were found to contain between one and six NHR domains associated with other modules, such as RING, SOCS, or SPRY [ (PUBMED:11779830) (PUBMED:11731489) ]. It has been suggested that the NHR domain is required for the localization of neuralized to the plasma membrane [ (PUBMED:11696324) ]. As it has been proposed that NHR domains do partly resemble SPRY domains, it is possible that NHR possess microtubule-binding functions, similar to those proposed for SPRY domains [ (PUBMED:11731489) ].
Family alignment:
There are 5025 NEUZ domains in 1679 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing NEUZ domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with NEUZ domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing NEUZ domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Systematic identification of novel protein domain families associated with nuclear functions.
Genome Res. 2002; 12: 47-56
Display abstract
A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic lineages, but 3 are species specific. For about 500 of the 1200 proteins that contain these new domains, nuclear localization could be inferred, and for 700, additional features could be predicted. For example, we identified a new domain, likely to have a role downstream of the unfolded protein response; a nematode-specific signalling domain; and a widespread domain, likely to be a noncatalytic homolog of ubiquitin-conjugating enzymes.
Novel protein domains and repeats in Drosophila melanogaster: insights into structure, function, and evolution.
Genome Res. 2001; 11: 1996-2008
Display abstract
Sequence database searching methods such as BLAST, are invaluable for predicting molecular function on the basis of sequence similarities among single regions of proteins. Searches of whole databases however, are not optimized to detect multiple homologous regions within a single polypeptide. Here we have used the prospero algorithm to perform self-comparisons of all predicted Drosophila melanogaster gene products. Predicted repeats, and their homologs from all species, were analyzed further to detect hitherto unappreciated evolutionary relationships. Results included the identification of novel tandem repeats in the human X-linked retinitis pigmentosa type-2 gene product, repeated segments in cystinosin, associated with a defect in cystine transport, and 'nested' homologous domains in dysferlin, whose gene is mutated in limb girdle muscular dystrophy. Novel signaling domain families were found that may regulate the microtubule-based cytoskeleton and ubiquitin-mediated proteolysis, respectively. Two families of glycosyl hydrolases were shown to contain internal repetitions that hint at their evolution via a piecemeal, modular approach. In addition, three examples of fruit fly genes were detected with tandem exons that appear to have arisen via internal duplication. These findings demonstrate how completely sequenced genomes can be exploited to further understand the relationships between molecular structure, function, and evolution.
