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Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. NTN1/Netrin-1 binding might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion. Axon repulsion in growth cones may also be caused by its association with DCC that may trigger signaling for repulsion. Might also collaborate with DSCAM in NTN1-mediated axon repulsion independently of DCC. Also involved in corticospinal tract axon guidance independently of DCC. Involved in dorsal root ganglion axon projection towards the spinal cord. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.
Gene References into Functions
Promoter Hypermethylation of UNC5C Gene is associated with Colorectal Cancer. PMID: 29801399
The objective of this study is to investigate the influence of UNC5C loci on the neuroimaging of strategic regions of Alzheimer's disease. PMID: 26660111
the results suggest that UNC5C methylation may be an earlier event in the development of colorectal cancer, which was negatively correlated with protein expression. PMID: 28378635
7 of these 8 variants do not cause increased colorectal cancer risk, including UNC5C c.1882_1883delinsAA (p.A628K). PMID: 26852919
Data show that overexpression of wild-type netrin receptor UNC5C (UNC5C) causes low-grade death, which is intensified by an Alzheimer Disease-linked mutation T835M, and mediated by amyloid beta precursor protein (APP). PMID: 27068745
identify the V-2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2 PMID: 26859457
we have identified novel frequent somatic mutations of UNC5C in muscle-invasive bladder cancers. PMID: 25316812
T835M (rs137875858) in the UNC5C was associated with late-onset Alzheimer disease and increased cell death in HEK293 cells. PMID: 25419706
The rare coding variant might not play an important role in AD risk in mainland China. PMID: 24866402
UNC5C mutations are very rare in familial and sporadic colorectal carcinomas. PMID: 24415873
TNM stage 1 hepatocellular carcinoma (HCC) presented UNC5C methylation, indicating that the UNC5C gene has been methylated from the early stages of HCC. PMID: 23178624
knockdown of DSCAM inhibits netrin-induced tyrosine phosphorylation of UNC5C and Fyn as well as the interaction of UNC5C with Fyn. The double knockdown of both receptors abolishes the induction of Fyn tyrosine phosphorylation by netrin-1 PMID: 22685302
Inherited mutations in UNC5C prevent apoptosis and increase risk of colorectal cancer. PMID: 21893118
UNC5C acts as a tumour suppressor in RCC and is down-regulated in RCC. Loss of heterozygosity and DNA methylation contribute to the inactivation of UNC5C in renal cell carcinoma. PMID: 21600761
UNC5C methylation was observed in the course of gastric carcinogenesis and disappeared in highly advanced gastric carcinomas. PMID: 20032384
may represent tumor suppressor that inhibit tumor extension outside the region of netrin-1 availability by inducing apoptosis PMID: 12655055
Netrin binds through multiple domains to both DCC and Unc5c. in Caenorhabditis elegans indicate that both netrin binding and nonbinding domains are necessary for phenotypic rescue of an unc-5 loss of function mutation. PMID: 15574733
Data suggest a model in which netrin stimulates UNC5 tyrosine phosphorylation and signaling in a manner dependent on the co-receptor DCC, through the recruitment of Src and FAK kinases. PMID: 16371650
The loss of UNC5C expression observed in human colorectal cancer is a selective advantage for tumor progression PMID: 17967459
study provides evidence that most colorectal cancers have alterations in both UNC5C and DCC netrin receptors; while UNC5C expression is regulated primarily via epigenetic regulation, DCC defects are mediated through allelic deletions PMID: 18054557
Aberrant methylation of the netrin-1 receptor genes UNC5C and DCC detected in advanced colorectal cancer. PMID: 19242752
UNC5C might act as a tumor suppressor and UNC5C methylation might present a malignant potential in colorectal cancer. PMID: 19331160
Stronger expression of UNC5B and UNC5C receptors in synovial fibroblasts might contribute to the disordered phenotype of rheumatoid arthritis and osteoarthritis. PMID: 19822088
Mainly expressed in brain. Expressed in temporal lobe cortical neurons and in neurons of the hippocampal pyramidal layer. Also expressed in kidney. Not expressed in developing or adult lung.