UNC5C
Function
Receptor for netrin required for axon guidance (By similarity). Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (By similarity). NTN1/Netrin-1 binding might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Axon repulsion in growth cones may also be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Might also collaborate with DSCAM in NTN1-mediated axon repulsion independently of DCC (By similarity). Also involved in corticospinal tract axon guidance independently of DCC (By similarity). Involved in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity).
Involvement in disease
Alzheimer disease
AD
Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
None
Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Post-translational modifications
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.
Phosphorylated on different cytoplasmic tyrosine residues. Phosphorylation of Tyr-568 leads to an interaction with PTPN11 phosphatase, suggesting that its activity is regulated by phosphorylation/dephosphorylation. Tyrosine phosphorylation is netrin-dependent.
Sequence Similarities
Belongs to the unc-5 family.
Tissue Specificity
Mainly expressed in brain (PubMed:9782087). Expressed in temporal lobe cortical neurons and in neurons of the hippocampal pyramidal layer (PubMed:25419706). Also expressed in kidney (PubMed:9782087). Not expressed in developing or adult lung (PubMed:9782087).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Cell surface
- Synapse
- Synaptosome
- Cell projection
- Axon
- Cell projection
- Dendrite
- Cell projection
- Growth cone
- Cell projection
- Lamellipodium
- Cell projection
- Filopodium
Alternative names
UNC5H3, UNC5C, Netrin receptor UNC5C, Protein unc-5 homolog 3, Protein unc-5 homolog C