daf-2 Insulin-like receptor subunit beta;Protein kinase domain-containing protein;Receptor protein-tyrosine kinase;hypothetical protein [Caenorhabditis elegans] - Gene

Summary

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Gene symbol: daf-2
Gene description: Insulin-like receptor subunit beta;Protein kinase domain-containing protein;Receptor protein-tyrosine kinase;hypothetical protein
Primary source: WormBase:WBGene00000898
Locus tag: CELE_Y55D5A.5
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
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Genomic context

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See daf-2 in Genome Data Viewer

Location:: chromosome: III

Exon count:: 18

Sequence:: Chromosome: III; NC_003281.10 (2994514..3040860, complement)

Chromosome III - NC_003281.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003281.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DAF-2 acts independently of the FOXO transcription factor, DAF-16, to mediate the protective effects of fasting. These results suggest a non-canonical role for the insulin/IGF-like signaling pathway in coordinating the effects of hypoxia and nutritional state on proteostasis.
Title: Fasting prevents hypoxia-induced defects of proteostasis in C. elegans.
Daf-2 is required to regulate neuromuscular junction response to oxidative stress. Daf-2 functions downstream of Skn-1.
Title: A Receptor Tyrosine Kinase Network Regulates Neuromuscular Function in Response to Oxidative Stress in Caenorhabditis elegans.
DAF-2 and its downstream signaling molecules, including the DAF-16 FOXO transcription factor, act in the ascr#3-sensing ADL neurons to regulate synaptic transmission to downstream target neurons, including the AVA command interneurons.
Title: Feeding state regulates pheromone-mediated avoidance behavior via the insulin signaling pathway in Caenorhabditis elegans.
This study demonstrated that reducing daf-2, insulin/IGF signaling (IIS) prolongs life and ameliorates aspects of motor dysfunction in C. elegans models of Spinal Muscular Atrophy.
Title: Enhancing GABAergic Transmission Improves Locomotion in a Caenorhabditis elegans Model of Spinal Muscular Atrophy.
our results indicate that Methyl 3,4-dihydroxybenzoate (MDHB) at least partially acts as a modulator of the daf-2/daf-16 pathway to extend the lifespan of C. elegans, and MDHB might be a promising therapeutic agent for age-related diseases
Title: Methyl 3,4-Dihydroxybenzoate Enhances Resistance to Oxidative Stressors and Lifespan in C. elegans Partially via daf-2/daf-16.
neuron-class-specific alternative splicing determined by the combinatorial action of RBFOX proteins (ASD-1 and FOX-1), UNC-75/CELF and PTB-1/PTB
Title: Splicing factors control C. elegans behavioural learning in a single neuron by producing DAF-2c receptor.
Suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.
Title: The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.
Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2 CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue
Title: Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies.
Cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16, and cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16.
Title: Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.
this study shows that heat shock increases the life span of wild type Caenorhabditis elegans upon pathogenic encounter; similar increase in resistance towards pathogenesis observed in long-lived C. elegans daf-2 mutants
Title: External induction of heat shock stimulates the immune response and longevity of Caenorhabditis elegans towards pathogen exposure.

Submit: New GeneRIF Correction See all GeneRIFs (57)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Y55D5A_391.b (e-PCR)
- UniSTS:323122

Y55D5A_392.a (e-PCR)
- UniSTS:323124

Homology

Homologs of the daf-2 gene: The daf-2 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ATP binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
PTB domain binding	IPI Inferred from Physical Interaction more info	PubMed
SH2 domain binding	IPI Inferred from Physical Interaction more info	PubMed
insulin receptor substrate binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
insulin-activated receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
insulin-activated receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
kinase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
peptide hormone binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	IEA Inferred from Electronic Annotation more info
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
transferase activity	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane receptor protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
cellular response to salt	IGI Inferred from Genetic Interaction more info	PubMed
cellular response to salt	IMP Inferred from Mutant Phenotype more info	PubMed
dauer exit	IMP Inferred from Mutant Phenotype more info	PubMed
dauer larval development	IMP Inferred from Mutant Phenotype more info	PubMed
determination of adult lifespan	IGI Inferred from Genetic Interaction more info	PubMed
determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
heat acclimation	IGI Inferred from Genetic Interaction more info	PubMed
heat acclimation	IMP Inferred from Mutant Phenotype more info	PubMed
immune system process	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
larval feeding behavior	IGI Inferred from Genetic Interaction more info	PubMed
larval feeding behavior	IMP Inferred from Mutant Phenotype more info	PubMed
multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
multicellular organism development	IEA Inferred from Electronic Annotation more info
negative regulation of dauer entry	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of lipid storage	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of neuromuscular synaptic transmission	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of protein kinase B signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of synaptic growth at neuromuscular junction	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
protein import into nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	IEA Inferred from Electronic Annotation more info
regulation of autophagosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of dauer entry	IGI Inferred from Genetic Interaction more info	PubMed
regulation of dauer larval development	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of development, heterochronic	IGI Inferred from Genetic Interaction more info	PubMed
regulation of eating behavior	IGI Inferred from Genetic Interaction more info	PubMed
regulation of eating behavior	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
regulation of lipid storage	IGI Inferred from Genetic Interaction more info	PubMed
regulation of response to reactive oxygen species	IMP Inferred from Mutant Phenotype more info	PubMed
reproduction	IMP Inferred from Mutant Phenotype more info	PubMed
response to UV	IGI Inferred from Genetic Interaction more info	PubMed
response to UV	IMP Inferred from Mutant Phenotype more info	PubMed
response to oxidative stress	IGI Inferred from Genetic Interaction more info	PubMed
response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
axon	IBA Inferred from Biological aspect of Ancestor more info	PubMed
axon	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
insulin receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of membrane	IEA Inferred from Electronic Annotation more info
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
non-motile cilium	IDA Inferred from Direct Assay more info	PubMed
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
spanning component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: Insulin-like receptor subunit beta;Protein kinase domain-containing protein;Receptor protein-tyrosine kinase;hypothetical protein

NP_001299916.1

Confirmed by transcript evidence

NP_001299917.1

Confirmed by transcript evidence

NP_001299918.1

Confirmed by transcript evidence

NP_001299919.1

Confirmed by transcript evidence

NP_001299920.1

Confirmed by transcript evidence

NP_497650.4

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_003281.10 Reference assembly

Range

2994514..3040860 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_065249.6 → NP_497650.4 Insulin-like receptor subunit beta [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_497650.4

Status: REVIEWED

UniProtKB/Swiss-Prot

Q968Y9

Conserved Domains (5) summary

cd05032
Location:1239 → 1522

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases

smart00221
Location:1246 → 1520

STYKc; Protein kinase; unclassified specificity

cd00063
Location:1087 → 1173

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam00757
Location:360 → 490

Furin-like; Furin-like cysteine rich region

pfam01030
Location:512 → 627

Recep_L_domain; Receptor L domain
NM_001312987.3 → NP_001299916.1 Receptor protein-tyrosine kinase [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A0K3AUY1

Conserved Domains (5) summary

cd05032
Location:1321 → 1604

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases

smart00221
Location:1328 → 1602

STYKc; Protein kinase; unclassified specificity

cd00063
Location:1169 → 1255

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam00757
Location:360 → 490

Furin-like; Furin-like cysteine rich region

pfam01030
Location:512 → 627

Recep_L_domain; Receptor L domain
NM_001312988.3 → NP_001299917.1 Receptor protein-tyrosine kinase [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A0K3AXA0

Conserved Domains (5) summary

cd05032
Location:1192 → 1475

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases

smart00221
Location:1199 → 1473

STYKc; Protein kinase; unclassified specificity

cd00063
Location:1040 → 1126

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam00757
Location:313 → 443

Furin-like; Furin-like cysteine rich region

pfam01030
Location:465 → 580

Recep_L_domain; Receptor L domain
NM_001312989.3 → NP_001299918.1 Receptor protein-tyrosine kinase [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A0K3ARZ1

Conserved Domains (5) summary

cd05032
Location:1163 → 1446

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases

smart00221
Location:1170 → 1444

STYKc; Protein kinase; unclassified specificity

cd00063
Location:1011 → 1097

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam00757
Location:284 → 414

Furin-like; Furin-like cysteine rich region

pfam01030
Location:436 → 551

Recep_L_domain; Receptor L domain
NM_001312990.3 → NP_001299919.1 Uncharacterized protein CELE_Y55D5A.5 [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A0K3AUA1

Conserved Domains (3) summary

cd05032
Location:429 → 712

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases

smart00221
Location:436 → 710

STYKc; Protein kinase; unclassified specificity

cd00063
Location:277 → 363

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
NM_001312991.3 → NP_001299920.1 Protein kinase domain-containing protein [Caenorhabditis elegans]

Status: REVIEWED

UniProtKB/TrEMBL

A0A0K3ARE8

Conserved Domains (1) summary

cd05032
Location:65 → 348

PTKc_InsR_like; Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases