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

Gene ID: 173128, updated on 2-Nov-2024

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_003279.8Genomic Context describing neighboring genes Neighboring gene MSP domain-containing protein Neighboring gene Uncharacterized protein Neighboring gene Uncharacterized protein Neighboring gene DUF4817 domain-containing protein Neighboring gene C-type lectin domain-containing protein

Genomic regions, transcripts, and products

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Genomic Sequence:
NC_003279.8

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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Related articles in PubMed

  1. Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling. Kurup N, et al. Curr Biol, 2015 Jun 15. PMID 26051896, Free PMC Article
  2. Mitochondria Localize to Injured Axons to Support Regeneration. Han SM, et al. Neuron, 2016 Dec 21. PMID 28009276, Free PMC Article
  3. Femtosecond laser microdissection for isolation of regenerating C. elegans neurons for single-cell RNA sequencing. Zhao P, et al. Nat Methods, 2023 Apr. PMID 36928074
  4. Functional Recovery Associated with Dendrite Regeneration in PVD Neuron of Caenorhabditis elegans. Brar HK, et al. eNeuro, 2024 May. PMID 38548333, Free PMC Article
  5. The microtubule minus-end-binding protein patronin/PTRN-1 is required for axon regeneration in C. elegans. Chuang M, et al. Cell Rep, 2014 Nov 6. PMID 25437544, Free PMC Article

See all (79) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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

  1. NC_003279.8 Reference assembly

    Range
    12565800..12572801 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O01700.4

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