ZU5Domain present in ZO-1 and Unc5-like netrin receptors
|SMART accession number:||SM00218|
|Description:||Domain of unknown function.|
|Interpro abstract (IPR000906):||This is a domain of unknown function, present in ZO-1 and Unc5-like netrin receptors. It is also found in different variants of ankyrin, which are responsible for attaching integral membrane proteins to cytoskeletal elements.|
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing ZU5 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with ZU5 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing ZU5 domain in the selected taxonomic class.
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Ackerman SL, Kozak LP, Przyborski SA, Rund LA, Boyer BB, Knowles BB
- The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein.
- Nature. 1997; 386: 838-42
- Display abstract
Migration of neurons from proliferative zones to their functional sites is fundamental to the normal development of the central nervous system. Mice homozygous for the spontaneous rostral cerebellar malformation mutation (rcm(s)) or a newly identified transgenic insertion allele (rcm(tg)) exhibit cerebellar and midbrain defects, apparently as a result of abnormal neuronal migration. Laminar structure abnormalities in lateral regions of the rostral cerebellar cortex have been described in homozygous rcm(s) mice. We now demonstrate that the cerebellum of both rcm(s) and rcm(tg) homozygotes is smaller and has fewer folia than in the wild-type, ectopic cerebellar cells are present in midbrain regions by three days after birth, and there are abnormalities in postnatal cerebellar neuronal migration. We have cloned the rcm complementary DNA, which encodes a transmembrane receptor of the immunoglobulin superfamily. The sequence of the rcm protein (Rcm) is highly similar to that of UNC-5, a Caenorhabditis elegans protein that is essential for dorsal guidance of pioneer axons and for the movement of cells away from the netrin ligand, which is encoded by the unc-6 gene. As Rcm is a member of a newly described family of vertebrate homologues of UNC-5 which are netrin-binding proteins, our results indicate that UNC-5-like proteins may have a conserved function in mediating netrin-guided migration.
- Leonardo ED, Hinck L, Masu M, Keino-Masu K, Ackerman SL, Tessier-Lavigne M
- Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors.
- Nature. 1997; 386: 833-8
- Display abstract
In the developing nervous system, migrating cells and axons are guided to their targets by cues in the extracellular environment. The netrins are a family of phylogenetically conserved guidance cues that can function as diffusible attractants and repellents for different classes of cells and axons. In vertebrates, insects and nematodes, members of the DCC subfamily of the immunoglobulin superfamily have been implicated as receptors that are involved in migration towards netrin sources. The mechanisms that direct migration away from netrin sources (presumed repulsions) are less well understood. In Caenorhabditis elegans, the transmembrane protein UNC-5 (ref. 14) has been implicated in these responses, as loss of unc-5 function causes migration defects and ectopic expression of unc-5 in some neurons can redirect their axons away from a netrin source. Whether UNC-5 is a netrin receptor or simply an accessory to such a receptor has not, however, been defined. We now report the identification of two vertebrate homologues of UNC-5 which, with UNC-5 and the product of the mouse rostral cerebellar malformation gene (rcm), define a new subfamily of the immunoglobulin superfamily, and whose messenger RNAs show prominent expression in various classes of differentiating neurons. We provide evidence that these two UNC-5 homologues, as well as the rcm gene product, are netrin-binding proteins, supporting the hypothesis that UNC-5 and its relatives are netrin receptors.
- Leung-Hagesteijn C et al.
- UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migrations in C. elegans.
- Cell. 1992; 71: 289-99
- Display abstract
The unc-5 gene is required for guiding pioneering axons and migrating cells along the body wall in C. elegans. In mutants, dorsal migrations are disrupted, but ventral and longitudinal movements are largely unaffected. The gene was tagged for molecular cloning by transposon insertions. Based on genomic and cDNA sequencing, the gene encodes UNC-5, a transmembrane protein of 919 aa. The predicted extracellular N-terminus comprises two immunoglobulin and two thrombospondin type 1 domains. Except for an SH3-like motif, the large intracellular C-terminus is novel. Mosaic analysis shows that unc-5 acts in migrating cells and pioneering neurons. We propose that UNC-5 is a transmembrane receptor expressed on the surface of motile cells and growth cones to guide dorsal movements.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 40.00 map04360 Axon guidance 15.00 map04520 Adherens junction 15.00 map05120 Epithelial cell signaling in Helicobacter pylori infection 15.00 map04540 Gap junction 15.00 map04530 Tight junction
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with ZU5 domain which could be assigned to a KEGG orthologous group, and not all proteins containing ZU5 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of ZU5 domains in PDB
PDB code Main view Title 2kxr ZO1 ZU5 domain MC/AA mutation 2kxs ZO1 ZU5 domain in complex with GRINL1A peptide 3f59 Crystal structure of ZU5-ANK, the spectrin binding region of human erythroid ankyrin 3g5b The structure of UNC5b cytoplasmic domain 3kbt Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK) 3kbu Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK), EMTS derivative 3ud1 Crystal structure of ZU5A-ZU5B domains of human erythrocyte ankyrin 3ud2 Crystal structure of Selenomethionine ZU5A-ZU5B protein domains of human erythrocyte ankyrin 4d8o Crystal Structure of the ankyrin-B ZU5-ZU5-UPA-DD tandem
- Links (links to other resources describing this domain)
PFAM ZU5 INTERPRO IPR000906