UNC5C

This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq]

Full Name

unc-5 homolog C (C. elegans)

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).

Biological Process

Biological Process anterior/posterior axon guidance Source:Ensembl
Biological Process apoptotic process Source:UniProtKB-KW
Biological Process axon guidance Source:GO_Central1 Publication
Biological Process brain development Source:ProtInc1 Publication
Biological Process chemorepulsion of axon Source:UniProtKB
Biological Process dorsal root ganglion development Source:UniProtKB1 Publication
Biological Process ectopic germ cell programmed cell death Source:Ensembl
Biological Process positive regulation of apoptotic process Source:Ensembl
Biological Process positive regulation of developmental process Source:Ensembl
Biological Process positive regulation of reproductive process Source:Ensembl
Biological Process regulation of neuron migration Source:Ensembl

Cellular Location

Cell membrane
Cell surface
Synapse, synaptosome
Cell projection, axon
Cell projection, dendrite
Cell projection, growth cone
Cell projection, lamellipodium
Cell projection, filopodium

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.

Topology

Extracellular: 41-380
Helical: 381-401
Cytoplasmic: 402-931

PTM

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.