SMART: ZU5 domain annotation

ZU5 Domain 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.
Family alignment:	View or

There are 293 ZU5 domains in 293 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with ZU5 domain is also avaliable.

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Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes
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)

Structure (3D structures containing this domain)
3D Structures of ZU5 domains in PDB
PDB code Main view Title
3f59 Crystal structure of zu5-ank, the spectrin binding region of human erythroid ankyrin

3g5b The structure of unc5b cytoplasmic domain
Links (links to other resources describing this domain)
PFAM ZU5
INTERPRO IPR000906

PDB code	Main view	Title
3f59		Crystal structure of zu5-ank, the spectrin binding region of human erythroid ankyrin
3g5b		The structure of unc5b cytoplasmic domain

PFAM	ZU5
INTERPRO	IPR000906

ZU5

3D Structures of ZU5 domains in PDB