Q968Y9 · INSR_CAEEL

  • Protein
    Insulin-like receptor
  • Gene
    daf-2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Insulin receptor-like tyrosine kinase which regulates metabolism, controls longevity and prevents developmental arrest at the dauer stage (PubMed:11743719, PubMed:21334311, PubMed:22916022, PubMed:24332851, PubMed:24385923, PubMed:28853436, PubMed:29500338, PubMed:9252323, PubMed:9790527).
Binding of INS family members may either stimulate, or antagonize, association of the receptor with downstream mediators such as pdk-1 and age-1 (PubMed:11274053).
Required for germline progenitor proliferation during larval development (PubMed:22278922).
Plays a role in maintaining gonad integrity in a daf-16/FOXO-dependent manner (PubMed:22916022).
Required for the response to environmental stimuli such as light, food, pheromone, and temperature (PubMed:24332851, PubMed:29500338).
Negatively regulates resistance to UV and oxidative stress (PubMed:24332851).
In a daf-16/FOXO-dependent manner, plays a role in regulating the response to white light (PubMed:29500338).
Role in immune function and pathogen resistance (PubMed:18782349).
Negatively regulates autophagy (PubMed:22560223).
Regulates daf-18/PTEN protein levels (PubMed:23995781).
Plays a role in controlling seam cell development during the larval stages (PubMed:21471153).

Isoform a

Required for taste avoidance learning in the cell body of ASER gustatory neurons.

Isoform c

Required for taste avoidance learning in axons of ASER gustatory neurons.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Activity regulation

Autophosphorylation activates the kinase activity (By similarity).
Interaction with shc-1 may inhibit its activity (PubMed:18832074).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site1252-1260ATP (UniProtKB | ChEBI)
Binding site1282ATP (UniProtKB | ChEBI)
Active site1388Proton acceptor

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcytoplasm
Cellular Componentcytoplasmic vesicle
Cellular Componentinsulin receptor complex
Cellular Componentneuronal cell body
Cellular Componentnon-motile cilium
Cellular Componentplasma membrane
Molecular FunctionATP binding
Molecular Functioninsulin receptor activity
Molecular Functioninsulin receptor substrate binding
Molecular Functionmetal ion binding
Molecular Functionpeptide hormone binding
Molecular Functionprotein kinase binding
Molecular FunctionPTB domain binding
Molecular FunctionSH2 domain binding
Biological Processcell adhesion
Biological Processcellular response to salt
Biological Processdauer exit
Biological Processdauer larval development
Biological Processdefense response to Gram-negative bacterium
Biological Processdetermination of adult lifespan
Biological Processglucose homeostasis
Biological Processheat acclimation
Biological Processinnate immune response
Biological Processinsulin receptor signaling pathway
Biological Processlarval feeding behavior
Biological Processnegative regulation of dauer entry
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of lipid storage
Biological Processnegative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Processnegative regulation of protein localization to nucleus
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of multicellular organism growth
Biological Processpositive regulation of neuromuscular synaptic transmission
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of synaptic assembly at neuromuscular junction
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processprotein import into nucleus
Biological Processregulation of autophagosome assembly
Biological Processregulation of dauer entry
Biological Processregulation of dauer larval development
Biological Processregulation of development, heterochronic
Biological Processregulation of eating behavior
Biological Processregulation of gene expression
Biological Processregulation of lipid storage
Biological Processregulation of response to reactive oxygen species
Biological Processreproductive process
Biological Processresponse to oxidative stress
Biological Processresponse to UV

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

Gene names

    • Name
      daf-2
    • ORF names
      Y55D5A.5

Organism names

  • Taxonomic identifier
  • Strain
    • Bristol N2
  • Taxonomic lineage
    Eukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis

Accessions

  • Primary accession
    Q968Y9
  • Secondary accessions
    • A0A0K3AUY1
    • B5QS63
    • O16131

Proteomes

Organism-specific databases

Subcellular Location

Membrane
; Single-pass type I membrane protein

Isoform c

Cell projection, axon
Note: Localizes to the synapse-rich neurite that extends axons. Casy-1 is required for axonal localization.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain970-1183Extracellular
Transmembrane1184-1204Helical
Topological domain1205-1846Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Accumulation of fat, pigmented intestine, increased lifespan, increased dauer formation and increased resistance to pathogens. Severe loss of function mutants display recessive early embryonic lethality (PubMed:11274053, PubMed:18245374, PubMed:18782349, PubMed:9252323, PubMed:9790527).
RNAi-mediated knockdown in germline, hypodermis, intestine or in muscles causes increased lifespan (PubMed:24332851, PubMed:28853436).
RNAi-mediated knockdown in a ncl-1 mutant (e1942) background reduces the increased longevity of the daf-2 single mutant, and reduces the increased ribosomal protein synthesis in the ncl-1 single mutant (e1942) (PubMed:28853436).
RNAi-mediated knockdown in adults causes an increase in lgg-1 positive autophagic vesicles (PubMed:22560223).
RNAi-mediated knockdown results in an increase in the number of muscle arm extensions (PubMed:18436204).
RNAi-mediated knockdown together with tatn-1 RNAi extends the lifespan of the single daf-2 RNAi mutant (PubMed:24385923).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis146Embronically lethal.
Mutagenesis383In m41; temperature-sensitive. No visible change in dauer formation and adult lifepspan at 15 degrees Celsius, but undergoes dauer formation at 25 degrees Celsius and has increased lifespan. Slight decrease in NaCl avoidance behavior after exposure to NaCl under starvation conditions. Normal number of muscle membrane extensions.
Mutagenesis401Dauer formation; when associated with L-470.
Mutagenesis469Dauer formation above 20 degrees Celsius.
Mutagenesis470Dauer formation; when associated with Y-401.
Mutagenesis547In m596; increases the number of muscle membrane extensions during larval development.
Mutagenesis573In e1368; dauer formation above 25 degrees Celsius. Enhances dauer formation in a tatn-1 RNAi mutant background.
Mutagenesis580Dauer formation above 26 degrees Celsius.
Mutagenesis648Dauer formation above 25 degrees Celsius.
Mutagenesis1045In m577; normal number of muscle membrane extensions.
Mutagenesis1374In sa219; dauer formation above 20 degrees Celsius. Normal NaCl avoidance behavior after exposure to NaCl under starvation conditions.
Mutagenesis1434In e1391; dauer formation above 20 degrees Celsius and increased lifespan. Increases the number of muscle membrane extensions during larval development.
Mutagenesis1465In e1370; extended lifespan. Accumulates fat and undergoes dauer formation with a developmentally arrested germline at 25 degrees Celsius and above. Pigmented intestine and increased resistance to bacterial pathogens, UV, high temperature and paraquat treatment. At 22 degrees Celsius, under constant darkness conditions only 41% of animals enter the dauer diapause phase, while under constant white light exposure, 100% of animals enter the dauer diapause phase and lifepan increases. Under standard day light conditions 87% of animals lived longer as compared to wild-type. Reduced number of germline progenitors during larval development and proliferation of germline stem cells. Fails to avoid NaCl after exposure to NaCl under starvation conditions. Increases the number of muscle membrane extensions during larval development. Overextension of PML neuron axons. Reduces nucleoli size in hypodermal and pharyngeal muscle cells. Enhances the defective seam cell development and delayed terminal differentiation phenotype of the sea-2 bp283 mutant.

PTM/Processing

Features

Showing features for chain, signal, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_0000386619?-966Insulin-like receptor subunit alpha
Signal1-?
Glycosylation113N-linked (GlcNAc...) asparagine
Glycosylation180N-linked (GlcNAc...) asparagine
Glycosylation364N-linked (GlcNAc...) asparagine
Disulfide bond371↔386
Disulfide bond393↔401
Disulfide bond397↔410
Disulfide bond413↔422
Disulfide bond426↔438
Glycosylation453N-linked (GlcNAc...) asparagine
Disulfide bond469↔483
Disulfide bond486↔490
Glycosylation518N-linked (GlcNAc...) asparagine
Disulfide bond615↔646
Glycosylation652N-linked (GlcNAc...) asparagine
Glycosylation671N-linked (GlcNAc...) asparagine
Glycosylation696N-linked (GlcNAc...) asparagine
Disulfide bond706Interchain
ChainPRO_0000386620970-1846Insulin-like receptor subunit beta
Glycosylation1017N-linked (GlcNAc...) asparagine
Glycosylation1047N-linked (GlcNAc...) asparagine
Glycosylation1078N-linked (GlcNAc...) asparagine
Glycosylation1087N-linked (GlcNAc...) asparagine
Glycosylation1093N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain (By similarity).
Interacts (via cytoplasmic domain) with shc-1 (PID domain) (PubMed:18832074).
Interacts (via kinase domain) with daf-18 (via C-terminus) (PubMed:23995781).

Isoform c

Interacts with casy-1; promoting axonal localization.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias.

TypeIDPosition(s)Description
Domain775-869Fibronectin type-III 1
Region944-980Disordered
Domain969-1067Fibronectin type-III 2
Domain1077-1179Fibronectin type-III 3
Domain1246-1528Protein kinase
Region1718-1742Disordered
Compositional bias1723-1742Polar residues
Compositional bias1769-1797Polar residues
Region1769-1826Disordered
Compositional bias1806-1826Polar residues

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 2 isoforms produced by Alternative splicing.

Q968Y9-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    1,846
  • Mass (Da)
    207,124
  • Last updated
    2009-11-03 v2
  • Checksum
    230B28322FF0F126
MTRMNIVRCRRRHKILENLEEENLGPSCSSTTSTTAATEALGTTTEDMRLKQQRSSSRATEHDIVDGNHHDDEHITMRRLRLVKNSRTRRRTTPDSSMDCYEENPPSQKTSINYSWISKKSSMTSLMLLLLFAFVQPCASIVEKRCGPIDIRNRPWDIKPQWSKLGDPNEKDLAGQRMVNCTVVEGSLTISFVLKHKTKAQEEMHRSLQPRYSQDEFITFPHLREITGTLLVFETEGLVDLRKIFPNLRVIGGRSLIQHYALIIYRNPDLEIGLDKLSVIRNGGVRIIDNRKLCYTKTIDWKHLITSSINDVVVDNAAEYAVTETGLMCPRGACEEDKGESKCHYLEEKNQEQGVERVQSCWSNTTCQKSCAYDRLLPTKEIGPGCDANGDRCHDQCVGGCERVNDATACHACKNVYHKGKCIEKCDAHLYLLLQRRCVTREQCLQLNPVLSNKTVPIKATAGLCSDKCPDGYQINPDDHRECRKCVGKCEIVCEINHVIDTFPKAQAIRLCNIIDGNLTIEIRGKQDSGMASELKDIFANIHTITGYLLVRQSSPFISLNMFRNLRRIEAKSLFRNLYAITVFENPNLKKLFDSTTDLTLDRGTVSIANNKMLCFKYIKQLMSKLNIPLDPIDQSEGTNGEKAICEDMAINVSITAVNADSVFFSWPSFNITDIDQRKFLGYELFFKEVPRIDENMTIEEDRSACVDSWQSVFKQYYETSNGEPTPDIFMDIGPRERIRPNTLYAYYVATQMVLHAGAKNGVSKIGFVRTSYYTPDPPTLALAQVDSDAIHITWEAPLQPNGDLTHYTIMWRENEVSPYEEAEKFCTDASTPANRQHTKDPKETIVADKPVDIPSSRTVAPTLLTMMGHEDQQKTCAATPGCCSCSAIEESSEQNKKKRPDPMSAIESSAFENKLLDEVLMPRDTMRVRRSIEDANRVSEELEKAENLGKAPKTLGGKKPLIHISKKKPSSSSTTSTPAPTIASMYALTRKPTTVPGTRIRLYEIYEPLPGSWAINVSALALDNSYVIRNLKHYTLYAISLSACQNMTVPGASCSISHRAGALKRTKHITDIDKVLNETIEWRFMNNSQQVNVTWDPPTEVNGGIFGYVVKLKSKVDGSIVMTRCVGAKRGYSTRNQGVLFQNLADGRYFVSVTATSVHGAGPEAESSDPIVVMTPGFFTVEIILGMLLVFLILMSIAGCIIYYYIQVRYGKKVKALSDFMQLNPEYCVDNKYNADDWELRQDDVVLGQQCGEGSFGKVYLGTGNNVVSLMGDRFGPCAIKINVDDPASTENLNYLMEANIMKNFKTNFIVKLYGVISTVQPAMVVMEMMDLGNLRDYLRSKREDEVFNETDCNFFDIIPRDKFHEWAAQICDGMAYLESLKFCHRDLAARNCMINRDETVKIGDFGMARDLFYHDYYKPSGKRMMPVRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGLSNDEVLNYIGMARKVIKKPECCENYWYKVMKMCWRYSPRDRPTFLQLVHLLAAEASPEFRDLSFVLTDNQMILDDSEALDLDDIDDTDMNDQVVEVAPDVENVEVQSDSERRNTDSIPLKQFKTIPPINATTSHSTISIDETPMKAKQREGSLDEEYALMNHSGGPSDAEVRTYAGDGDYVERDVRENDVPTRRNTGASTSSYTGGGPYCLTNRGGSNERGAGFGEAVRLTDGVGSGHLNDDDYVEKEISSMDTRRSTGASSSSYGVPQTNWSGNRGATYYTSKAQQAATAAAAAAAALQQQQNGGRGDRLTQLPGTGHLQSTRGGQDGDYIETEPKNYRNNGSPSRNGNSRDIFNGRSAFGENEHLIEDNEHHPLV

Q968Y9-3

  • Name
    c
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 924-924: R → RCDIKNDPVGCAMLLLPPEIDDSDVGDDDEEPGGGSEQQQRILRNSEILKRQKRQILGRSLGGIHGIRSIGRKEYEQFADMIL

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0K3ARE8A0A0K3ARE8_CAEELdaf-2672
A0A0K3ARZ1A0A0K3ARZ1_CAEELdaf-21770
A0A0K3AUA1A0A0K3AUA1_CAEELdaf-21036
A0A0K3AXA0A0A0K3AXA0_CAEELdaf-21799

Features

Showing features for sequence conflict, alternative sequence, compositional bias.

TypeIDPosition(s)Description
Sequence conflict838in Ref. 1; AAC47715
Alternative sequenceVSP_061883924in isoform c
Sequence conflict1313in Ref. 1; AAC47715
Compositional bias1723-1742Polar residues
Compositional bias1769-1797Polar residues
Compositional bias1806-1826Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF012437
EMBL· GenBank· DDBJ
AAC47715.1
EMBL· GenBank· DDBJ
mRNA
BX284603
EMBL· GenBank· DDBJ
CCD72201.2
EMBL· GenBank· DDBJ
Genomic DNA
BX284603
EMBL· GenBank· DDBJ
CTQ86616.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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