daf-2 Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase [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
Primary source: WormBase:WBGene00000898
Locus tag: CELE_Y55D5A.5
See related: AllianceGenome:WB:WBGene00000898
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 PTB domain binding activity; SH2 domain binding activity; and protein kinase binding activity. Involved in several processes, including dauer exit; larval feeding behavior; and regulation of gene expression. Acts upstream of with a negative effect on protein import into nucleus. Located in several cellular components, including axon; neuronal cell body; and non-motile cilium. Is spanning component of plasma membrane. Is expressed in gonad; hypodermis; intestine; and nervous system. Used to study Parkinson's disease. Human ortholog(s) of this gene implicated in several diseases, including dementia (multiple); diabetes mellitus (multiple); kidney cancer (multiple); liver disease (multiple); and reproductive organ cancer (multiple). Orthologous to several human genes including IGF1R (insulin like growth factor 1 receptor). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: III

Exon count:: 18

Sequence:: Chromosome: III; NC_003281.10 (2994514..3040846, 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?

Accumulation of Glycogen and Upregulation of LEA-1 in C. elegans daf-2(e1370) Support Stress Resistance, Not Longevity.
Title: Accumulation of Glycogen and Upregulation of LEA-1 in C. elegans daf-2(e1370) Support Stress Resistance, Not Longevity.
Aging Regulated Through a Stability Model of Insulin/Insulin Growth Factor Receptor Function.
Title: Aging Regulated Through a Stability Model of Insulin/Insulin Growth Factor Receptor Function.
Barley beta-glucan resist oxidative stress of Caenorhabditis elegans via daf-2/daf-16 pathway.
Title: Barley β-glucan resist oxidative stress of Caenorhabditis elegans via daf-2/daf-16 pathway.
A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.
Title: A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.
End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies.
Title: End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies.
Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.
Title: Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.
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.

Submit: New GeneRIF Correction See all GeneRIFs (63)

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

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

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

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

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

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

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

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..3040846 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_065249.7 → 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

A0A0K3AUY1, B5QS63, O16131, 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_001312987.4 → NP_001299916.1 Insulin-like receptor subunit beta [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 receptor protein-tyrosine kinase [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