unc-6 Netrin unc-6 [Caenorhabditis elegans] - Gene

Summary

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Gene symbol: unc-6
Gene description: Netrin unc-6
Primary source: WormBase:WBGene00006746
Locus tag: CELE_F41C6.1
See related: AllianceGenome:WB:WBGene00006746
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Caenorhabditis elegans (strain: Bristol N2)
Lineage: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
Summary: Predicted to enable signaling receptor binding activity. Involved in several processes, including axon guidance; establishment or maintenance of actin cytoskeleton polarity; and regulation of axon guidance. Acts upstream of or within dendrite morphogenesis. Located in axon; basement membrane; and cytoplasm. Is expressed in several structures, including P1; P10; accessory cell; muscle cell; and neurons. Human ortholog(s) of this gene implicated in congenital mirror movement disorder. Orthologous to several human genes including NTN1 (netrin 1). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: X

Exon count:: 13

Sequence:: Chromosome: X; NC_003284.9 (6889674..6897147)

Chromosome X - NC_003284.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003284.9

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans.
Title: TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans.
Regulation of UNC-40/DCC and UNC-6/Netrin by DAF-16 promotes functional rewiring of the injured axon.
Title: Regulation of UNC-40/DCC and UNC-6/Netrin by DAF-16 promotes functional rewiring of the injured axon.
Genetic interactions are consistent with RHO-1 and RHGF-1 acting with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin
Title: RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegans.
Our results also show that dendrite length is determined by the antagonistic effects on the actin cytoskeleton of separate sets of effectors for retraction mediated by UNC-6(Netrin) versus outgrowth promoted by the DMA-1 receptor.
Title: Actin assembly and non-muscle myosin activity drive dendrite retraction in an UNC-6/Netrin dependent self-avoidance response.
C. elegans Netrin ortholog UNC-6, signaling through its cognate receptor UNC-40/DCC and the CED-5/DOCK180 guanine nucleotide exchange factor, is both required and sufficient for male-specific synaptic maintenance. The dimorphism of unc-6 activity is brought about by sex-specific regulation of unc-6 transcription.
Title: Sexually Dimorphic unc-6/Netrin Expression Controls Sex-Specific Maintenance of Synaptic Connectivity.
rom these studies we conclude that FMO-1, FMO-4, FMO-5, and EHBP-1 represent new players downstream of UNC-6/Netrin receptors and Rac GTPases that inhibit growth cone filopodial protrusion in repulsive axon guidance
Title: Flavin monooxygenases regulate Caenorhabditis elegans axon guidance and growth cone protrusion with UNC-6/Netrin signaling and Rac GTPases.
the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway.
Title: The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans.
We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/beta-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants. On the other hand, the UNC-6/Netrin pathway intersects orthogonally with Wnt-PCP signaling to guide PLM branch growth along the dorsal-ventral axis.
Title: A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling.
LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration.
Title: Glypican Is a Modulator of Netrin-Mediated Axon Guidance.
Ire-1/xbp-1 pathway of the unfolded protein response is crucial for establishing positional information of UNC-6/Netrin.
Title: IRE-1/XBP-1 pathway of the unfolded protein response is required for properly localizing neuronal UNC-6/Netrin for axon guidance in C. elegans.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

F41C6.1 (e-PCR)
- UniSTS:310247

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
enables signaling receptor binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in animal organ morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal/ventral axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in dorsal/ventral axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment or maintenance of actin cytoskeleton polarity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in gonad morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in gonad morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interneuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in interneuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesodermal cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in motor neuron axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in motor neuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in motor neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of microtubule polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nematode male tail tip morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in netrin-activated signaling pathway	IC Inferred by Curator more info	PubMed
involved_in netrin-activated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in netrin-activated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of anterior/posterior axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of anterior/posterior axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of locomotion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synapse assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of dorsal/ventral axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of dorsal/ventral axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of motor neuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of sensory neuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in sensory neuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in sensory neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tissue development	IBA Inferred from Biological aspect of Ancestor more info
involved_in ventral cord development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in ventral cord development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
is_active_in basement membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basement membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basement membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: Netrin unc-6

NP_509165.1

Confirmed by transcript evidence

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_003284.9 Reference assembly

Range

6889674..6897147

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_076764.5 → NP_509165.1 Netrin unc-6 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_509165.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P34710

Conserved Domains (4) summary

smart00136
Location:41 → 289

LamNT; Laminin N-terminal domain (domain VI)

cd00055
Location:290 → 333

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd03579
Location:490 → 604

NTR_netrin-1_like; NTR domain, Netrin-1-like subfamily; The C-terminal NTR domain of netrins is also called domain C in the context of C. elegans netrin UNC-6. Netrins are secreted proteins that function as tropic cues in the direction of axon growth and cell migration ...

pfam00053
Location:410 → 453

Laminin_EGF; Laminin EGF domain