background:
The UNC5H family of proteins act as transmembrane receptors for netrin-1 and play a crucial role in axon guidance and migration of neural cells. Additionally, when cleaved by a caspase to produce an intracellular fragment containing a death domain,UNC5H receptors induce apoptosis. This activity is blocked by the binding of netrin-1. In the absence of netrin-1, UNC5H receptors act as tumor suppressors by inhibiting anchorage-independent growth and invasion, but mutation of these receptors provides a potential mechanism for tumorigenicity. The expression of UNC5H receptors is downregulated in multiple carcinomas, including colorectal, breast, ovary, uterus, stomach, lung and kidney cancers. UNC5H1, also known as UNC5HA (unc-5 homolog A), is a member of the UNC5H family of proteins and is localized to the cell membrane. Three isoforms of UNC5H1 exist due to alternative splicing events.
Function:
Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.
Subunit:
Interacts with the cytoplasmic part of DCC. Interacts with MAGED1. Interacts with PRKCABP, possibly mediating some interaction with PKC
Subcellular Location:
Cell membrane. The interaction with PRKCABP regulates its surface expression and leads to its removal from surface of neurons and growth cones.
Post-translational modifications:
Phosphorylated on cytoplasmic tyrosine residues. Phosphorylated by PKC in vitro.
Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.
Similarity:
Belongs to the unc-5 family.
Contains 1 death domain.
Contains 1 Ig-like (immunoglobulin-like) domain.
Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
Contains 1 TSP type-1 domain.
Contains 1 ZU5 domain.
Database links:
Entrez Gene: 90249 Human
Entrez Gene: 107448 Mouse
Entrez Gene: 60629 Rat
Omim: 607869 Human
SwissProt: Q6ZN44 Human
SwissProt: Q8K1S4 Mouse
SwissProt: O08721 Rat
Unigene: 33191 Human
Unigene: 23573 Mouse
Unigene: 44433 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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