Unc5c unc-5 netrin receptor C [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Unc5cprovided by MGI
Official Full Name: unc-5 netrin receptor Cprovided by MGI
Primary source: MGI:MGI:1095412
See related: Ensembl:ENSMUSG00000059921 AllianceGenome:MGI:1095412
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: rcm; Unc5h3; B130051O18Rik
Summary: Enables netrin receptor activity involved in chemorepulsion and tubulin binding activity. Involved in chemorepulsion of axon and netrin-activated signaling pathway. Acts upstream of or within nervous system development; positive regulation of apoptotic process; and regulation of cell migration. Located in several cellular components, including filopodium; growth cone; and lamellipodium. Is expressed in several structures, including brain; embryo mesenchyme; ovary; sensory organ; and skeleton. Orthologous to human UNC5C (unc-5 netrin receptor C). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cerebellum adult (RPKM 4.5), limb E14.5 (RPKM 4.2) and 11 other tissues See more
Orthologs: human all
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Genomic context

Location:: 3 H1; 3 65.57 cM

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	3	NC_000069.7 (141171360..141540685)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	3	NC_000069.6 (141465564..141834924)

Chromosome 3 - NC_000069.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Netrin-1 receptor UNC5C cleavage by active delta-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.
Title: Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.
The netrin-1 receptor UNC5C contributes to the homeostasis of undifferentiated spermatogonia in adult mice.
Title: The netrin-1 receptor UNC5C contributes to the homeostasis of undifferentiated spermatogonia in adult mice.
Here, we report that dissociation of UNC5C and polymerized TUBB3, the highly dynamic beta-tubulin isoform in neurons, is essential for netrin-1/UNC5C-promoted axon repulsion. These results not only provide a working model of direct modulation of MTs by guidance cues in growth cone navigation but also help us to understand molecular mechanisms underlying developmental brain disorders associated with TUBB3 mutations.
Title: Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates Netrin-1 Repulsion.
UNC5C expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos. Repression of UNC5C in the anterior nucleus stage inhibited development to the blastocyst stage.
Title: Molecular Effects of Polymorphism in the 3'UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins.
UNC5c expression is enriched in CA3 hippocampal neurons, but UNC5c is not expressed in microglia or perpheral blood mononuclear cells.
Title: A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death.
Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation.
Title: Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation.
unc5c haploinsufficiency results in diminished amphetamine-induced locomotion in male and female mice. This phenotype is identical to that produced by dcc haploinsufficiency and is observed after adolescence.
Title: unc5c haploinsufficient phenotype: striking similarities with the dcc haploinsufficiency model.
this study suggested that Unc5c plays a broad role in dorsal guidance of axons in the developing hindbrain.
Title: The UNC5C netrin receptor regulates dorsal guidance of mouse hindbrain axons.
repression of Unc5c expression by Rhox5 may, in part, mediate the pro-survival function of Rhox5 in the testis
Title: The RHOX5 homeodomain protein mediates transcriptional repression of the netrin-1 receptor gene Unc5c.
The netrin-1 receptor UNC5c, a proapoptotic molecule that is inhibited by RHOX5, was also regulated in vivo, and is thus a candidate to be downstream of RHOX5 in a prosurvival germ-cell pathway.
Title: Regulation and function of the Rhox5 homeobox gene.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1)
Transgenic (2) 1 citation
Targeted (1)
Endonuclease-mediated (6)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3Mit368 (e-PCR), detects polymorphism
- UniSTS:129803

Unc5c (e-PCR), detects polymorphism
- UniSTS:526928

D3Mit196 (e-PCR), detects polymorphism
- UniSTS:129618

Unc5c (e-PCR), detects polymorphism
- UniSTS:526931

RH135837 (e-PCR)
- UniSTS:209835

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables netrin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables netrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables netrin receptor activity involved in chemorepulsion	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables tubulin binding	IPI Inferred from Physical Interaction more info	PubMed
enables tubulin binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within anterior/posterior axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within brain development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chemorepulsion of axon	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal root ganglion development	ISO Inferred from Sequence Orthology more info
acts_upstream_of ectopic germ cell programmed cell death	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in netrin-activated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of developmental process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of reproductive process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of neuron migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in filopodium	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuron projection	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: netrin receptor UNC5C

Names: UNC-5 homolog 3; rostral cerebellar malformation protein; unc-5 homolog C; unc5 homolog 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001293561.2 → NP_001280490.1 netrin receptor UNC5C isoform 1 precursor

See identical proteins and their annotated locations for NP_001280490.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC157492, AC158552, AC170085

Consensus CDS

CCDS80034.1

UniProtKB/TrEMBL

Q3UQ08, Q3URW2

Related

ENSMUSP00000074758.4, ENSMUST00000075282.10

Conserved Domains (5) summary

smart00218
Location:547 → 650

ZU5; Domain present in ZO-1 and Unc5-like netrin receptors

smart00209
Location:263 → 314

TSP1; Thrombospondin type 1 repeats

pfam07679
Location:169 → 257

I-set; Immunoglobulin I-set domain

cd08799
Location:863 → 945

Death_UNC5C; Death domain found in Uncoordinated-5C

cl11960
Location:171 → 257

Ig; Immunoglobulin domain
NM_009472.5 → NP_033498.1 netrin receptor UNC5C isoform 2 precursor

See identical proteins and their annotated locations for NP_033498.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC157492, AC158552, AC170085

Consensus CDS

CCDS17873.1

UniProtKB/Swiss-Prot

O08747, Q8CD16

UniProtKB/TrEMBL

Q3URW2

Related

ENSMUSP00000101843.3, ENSMUST00000106236.9

Conserved Domains (5) summary

smart00218
Location:528 → 631

ZU5; Domain present in ZO-1 and Unc5-like netrin receptors

smart00209
Location:263 → 314

TSP1; Thrombospondin type 1 repeats

pfam07679
Location:169 → 257

I-set; Immunoglobulin I-set domain

cd08799
Location:844 → 926

Death_UNC5C; Death domain found in Uncoordinated-5C

cl11960
Location:171 → 257

Ig; Immunoglobulin domain