dlk-1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans] - Gene

Summary

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Official Symbol: dlk-1
Official Full Name: Mitogen-activated protein kinase kinase kinase dlk-1
Primary source: WormBase:WBGene00001008
Locus tag: CELE_F33E2.2
See related: AllianceGenome:WB:WBGene00001008
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: Enables ubiquitin protein ligase binding activity. Involved in several processes, including p38MAPK cascade; regulation of axon extension; and sprouting of injured axon. Located in neuronal cell body and synapse. Is expressed in neurons and pharynx. Orthologous to several human genes including MAP3K12 (mitogen-activated protein kinase kinase kinase 12). [provided by Alliance of Genome Resources, Nov 2024]
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Genomic context

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See dlk-1 in Genome Data Viewer

Location:: chromosome: I

Exon count:: 11

Sequence:: Chromosome: I; NC_003279.8 (12565800..12572801, complement)

Chromosome I - NC_003279.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003279.8

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.
Title: An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.
UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.
Title: UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.
Complete morphological regeneration depends on DLK-1 but neuronal sprouting and outgrowth is DLK-1 independent. We show that touch receptor neuron(TRN) regeneration is fully functional since animals regain their ability to respond to mechanical stimulation.
Title: Diapause induces functional axonal regeneration after necrotic insult in C. elegans.
Mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase 1 (DLK-1), a conserved regulator of axon regeneration.
Title: Mitochondria Localize to Injured Axons to Support Regeneration.
DLK-1, SEK-3 and PMK-3 have roles in C. elegans adaptation to disruption of the mitochondrial electron transport chain, and in extended lifespan
Title: DLK-1, SEK-3 and PMK-3 Are Required for the Life Extension Induced by Mitochondrial Bioenergetic Disruption in C. elegans.
These findings explain how DLK specifically mediates nerve injury responses and reveal a novel cellular mechanism that ensures the specificity of neuronal kinase signaling.
Title: Palmitoylation controls DLK localization, interactions and activity to ensure effective axonal injury signaling.
Independent of myosin light chain activation, RHGF-1 acts via Rho-dependent kinase LET-502/ROCK and activates a conserved, retrograde DLK-1 MAPK pathway, triggering synaptic branch retraction and overgrowth of the PLM neurite in a dose-dependent manner.
Title: RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly.
Genetic, transgenic, and biochemical studies indicated that PPM-2 functions coordinately with the ubiquitin ligase activity of RPM-1 and the F-box protein FSN-1 to negatively regulate DLK-1
Title: RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development.
DLK-1 is activated by calcium-mediated dissociation from an inhibitory isoform.
Title: Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform.
These findings reveal the relationship between Ca(2+)/cAMP signaling and the DLK-1 MAPK (mitogen-activated protein kinase) cascade in regeneration.
Title: Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase.

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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

F33E2.2 (e-PCR)
- UniSTS:312584

STS1-6 (e-PCR)
- UniSTS:241759

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon extension involved in regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon regeneration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in formation of growth cone in injured axon	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microtubule polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in p38MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of axon extension	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of axon extension involved in regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of 3'-UTR-mediated mRNA stabilization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of axon extension involved in axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of synapse organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to stimulus	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in cilium	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: Mitogen-activated protein kinase kinase kinase dlk-1

NP_001021443.1

Confirmed by transcript evidence

NP_001021444.1

Confirmed by transcript evidence

NP_001021445.1

Confirmed by transcript evidence

NP_001129769.1

Confirmed by transcript evidence

NP_001251937.1

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_003279.8 Reference assembly

Range

12565800..12572801 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001026273.7 → NP_001021444.1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021444.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O01700

Conserved Domains (2) summary

smart00220
Location:141 → 374

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:141 → 377

PKc_like; Protein Kinases, catalytic domain
NM_001026272.5 → NP_001021443.1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021443.1

Status: REVIEWED

UniProtKB/Swiss-Prot

B3KYB4, O01700, Q7JKE7, Q7JKE9

Conserved Domains (2) summary

smart00220
Location:141 → 374

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:141 → 377

PKc_like; Protein Kinases, catalytic domain
NM_001136297.4 → NP_001129769.1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001129769.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O01700

Conserved Domains (2) summary

smart00220
Location:68 → 301

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:68 → 304

PKc_like; Protein Kinases, catalytic domain
NM_001265008.3 → NP_001251937.1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001251937.1

Status: REVIEWED

UniProtKB/TrEMBL

D6VPA3
NM_001026274.5 → NP_001021445.1 Mitogen-activated protein kinase kinase kinase dlk-1 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_001021445.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O01700

Conserved Domains (2) summary

smart00220
Location:141 → 374

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:141 → 377

PKc_like; Protein Kinases, catalytic domain