Q968Y9 · INSR_CAEEL
- ProteinInsulin-like receptor
- Genedaf-2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1846 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Cofactor
Activity regulation
Autophosphorylation activates the kinase activity (By similarity).
Interaction with shc-1 may inhibit its activity (PubMed:18832074).
Interaction with shc-1 may inhibit its activity (PubMed:18832074).
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameInsulin-like receptor
- EC number
- Short namesIR
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionQ968Y9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Isoform c
Note: Localizes to the synapse-rich neurite that extends axons. Casy-1 is required for axonal localization.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 970-1183 | Extracellular | ||||
Sequence: PSSSSTTSTPAPTIASMYALTRKPTTVPGTRIRLYEIYEPLPGSWAINVSALALDNSYVIRNLKHYTLYAISLSACQNMTVPGASCSISHRAGALKRTKHITDIDKVLNETIEWRFMNNSQQVNVTWDPPTEVNGGIFGYVVKLKSKVDGSIVMTRCVGAKRGYSTRNQGVLFQNLADGRYFVSVTATSVHGAGPEAESSDPIVVMTPGFFTVE | ||||||
Transmembrane | 1184-1204 | Helical | ||||
Sequence: IILGMLLVFLILMSIAGCIIY | ||||||
Topological domain | 1205-1846 | Cytoplasmic | ||||
Sequence: YYIQVRYGKKVKALSDFMQLNPEYCVDNKYNADDWELRQDDVVLGQQCGEGSFGKVYLGTGNNVVSLMGDRFGPCAIKINVDDPASTENLNYLMEANIMKNFKTNFIVKLYGVISTVQPAMVVMEMMDLGNLRDYLRSKREDEVFNETDCNFFDIIPRDKFHEWAAQICDGMAYLESLKFCHRDLAARNCMINRDETVKIGDFGMARDLFYHDYYKPSGKRMMPVRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGLSNDEVLNYIGMARKVIKKPECCENYWYKVMKMCWRYSPRDRPTFLQLVHLLAAEASPEFRDLSFVLTDNQMILDDSEALDLDDIDDTDMNDQVVEVAPDVENVEVQSDSERRNTDSIPLKQFKTIPPINATTSHSTISIDETPMKAKQREGSLDEEYALMNHSGGPSDAEVRTYAGDGDYVERDVRENDVPTRRNTGASTSSYTGGGPYCLTNRGGSNERGAGFGEAVRLTDGVGSGHLNDDDYVEKEISSMDTRRSTGASSSSYGVPQTNWSGNRGATYYTSKAQQAATAAAAAAAALQQQQNGGRGDRLTQLPGTGHLQSTRGGQDGDYIETEPKNYRNNGSPSRNGNSRDIFNGRSAFGENEHLIEDNEHHPLV |
Keywords
- Cellular component
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 146 | Embronically lethal. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 383 | In 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. | ||||
Sequence: G → E | ||||||
Mutagenesis | 401 | Dauer formation; when associated with L-470. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 469 | Dauer formation above 20 degrees Celsius. | ||||
Sequence: C → S | ||||||
Mutagenesis | 470 | Dauer formation; when associated with Y-401. | ||||
Sequence: P → L | ||||||
Mutagenesis | 547 | In m596; increases the number of muscle membrane extensions during larval development. | ||||
Sequence: G → S | ||||||
Mutagenesis | 573 | In e1368; dauer formation above 25 degrees Celsius. Enhances dauer formation in a tatn-1 RNAi mutant background. | ||||
Sequence: S → L | ||||||
Mutagenesis | 580 | Dauer formation above 26 degrees Celsius. | ||||
Sequence: A → T | ||||||
Mutagenesis | 648 | Dauer formation above 25 degrees Celsius. | ||||
Sequence: D → N | ||||||
Mutagenesis | 1045 | In m577; normal number of muscle membrane extensions. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 1374 | In sa219; dauer formation above 20 degrees Celsius. Normal NaCl avoidance behavior after exposure to NaCl under starvation conditions. | ||||
Sequence: D → N | ||||||
Mutagenesis | 1434 | In e1391; dauer formation above 20 degrees Celsius and increased lifespan. Increases the number of muscle membrane extensions during larval development. | ||||
Sequence: P → L | ||||||
Mutagenesis | 1465 | In 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. | ||||
Sequence: P → S |
PTM/Processing
Features
Showing features for chain, signal, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000386619 | ?-966 | Insulin-like receptor subunit alpha | |||
Sequence: MTRMNIVRCRRRHKILENLEEENLGPSCSSTTSTTAATEALGTTTEDMRLKQQRSSSRATEHDIVDGNHHDDEHITMRRLRLVKNSRTRRRTTPDSSMDCYEENPPSQKTSINYSWISKKSSMTSLMLLLLFAFVQPCASIVEKRCGPIDIRNRPWDIKPQWSKLGDPNEKDLAGQRMVNCTVVEGSLTISFVLKHKTKAQEEMHRSLQPRYSQDEFITFPHLREITGTLLVFETEGLVDLRKIFPNLRVIGGRSLIQHYALIIYRNPDLEIGLDKLSVIRNGGVRIIDNRKLCYTKTIDWKHLITSSINDVVVDNAAEYAVTETGLMCPRGACEEDKGESKCHYLEEKNQEQGVERVQSCWSNTTCQKSCAYDRLLPTKEIGPGCDANGDRCHDQCVGGCERVNDATACHACKNVYHKGKCIEKCDAHLYLLLQRRCVTREQCLQLNPVLSNKTVPIKATAGLCSDKCPDGYQINPDDHRECRKCVGKCEIVCEINHVIDTFPKAQAIRLCNIIDGNLTIEIRGKQDSGMASELKDIFANIHTITGYLLVRQSSPFISLNMFRNLRRIEAKSLFRNLYAITVFENPNLKKLFDSTTDLTLDRGTVSIANNKMLCFKYIKQLMSKLNIPLDPIDQSEGTNGEKAICEDMAINVSITAVNADSVFFSWPSFNITDIDQRKFLGYELFFKEVPRIDENMTIEEDRSACVDSWQSVFKQYYETSNGEPTPDIFMDIGPRERIRPNTLYAYYVATQMVLHAGAKNGVSKIGFVRTSYYTPDPPTLALAQVDSDAIHITWEAPLQPNGDLTHYTIMWRENEVSPYEEAEKFCTDASTPANRQHTKDPKETIVADKPVDIPSSRTVAPTLLTMMGHEDQQKTCAATPGCCSCSAIEESSEQNKKKRPDPMSAIESSAFENKLLDEVLMPRDTMRVRRSIEDANRVSEELEKAENLGKAPKTLGGKKPLIHIS | ||||||
Signal | 1-? | |||||
Glycosylation | 113 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 180 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 364 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 371↔386 | |||||
Sequence: CAYDRLLPTKEIGPGC | ||||||
Disulfide bond | 393↔401 | |||||
Sequence: CHDQCVGGC | ||||||
Disulfide bond | 397↔410 | |||||
Sequence: CVGGCERVNDATAC | ||||||
Disulfide bond | 413↔422 | |||||
Sequence: CKNVYHKGKC | ||||||
Disulfide bond | 426↔438 | |||||
Sequence: CDAHLYLLLQRRC | ||||||
Glycosylation | 453 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 469↔483 | |||||
Sequence: CPDGYQINPDDHREC | ||||||
Disulfide bond | 486↔490 | |||||
Sequence: CVGKC | ||||||
Glycosylation | 518 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 615↔646 | |||||
Sequence: CFKYIKQLMSKLNIPLDPIDQSEGTNGEKAIC | ||||||
Glycosylation | 652 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 671 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 696 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 706 | Interchain | ||||
Sequence: C | ||||||
Chain | PRO_0000386620 | 970-1846 | Insulin-like receptor subunit beta | |||
Sequence: PSSSSTTSTPAPTIASMYALTRKPTTVPGTRIRLYEIYEPLPGSWAINVSALALDNSYVIRNLKHYTLYAISLSACQNMTVPGASCSISHRAGALKRTKHITDIDKVLNETIEWRFMNNSQQVNVTWDPPTEVNGGIFGYVVKLKSKVDGSIVMTRCVGAKRGYSTRNQGVLFQNLADGRYFVSVTATSVHGAGPEAESSDPIVVMTPGFFTVEIILGMLLVFLILMSIAGCIIYYYIQVRYGKKVKALSDFMQLNPEYCVDNKYNADDWELRQDDVVLGQQCGEGSFGKVYLGTGNNVVSLMGDRFGPCAIKINVDDPASTENLNYLMEANIMKNFKTNFIVKLYGVISTVQPAMVVMEMMDLGNLRDYLRSKREDEVFNETDCNFFDIIPRDKFHEWAAQICDGMAYLESLKFCHRDLAARNCMINRDETVKIGDFGMARDLFYHDYYKPSGKRMMPVRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGLSNDEVLNYIGMARKVIKKPECCENYWYKVMKMCWRYSPRDRPTFLQLVHLLAAEASPEFRDLSFVLTDNQMILDDSEALDLDDIDDTDMNDQVVEVAPDVENVEVQSDSERRNTDSIPLKQFKTIPPINATTSHSTISIDETPMKAKQREGSLDEEYALMNHSGGPSDAEVRTYAGDGDYVERDVRENDVPTRRNTGASTSSYTGGGPYCLTNRGGSNERGAGFGEAVRLTDGVGSGHLNDDDYVEKEISSMDTRRSTGASSSSYGVPQTNWSGNRGATYYTSKAQQAATAAAAAAAALQQQQNGGRGDRLTQLPGTGHLQSTRGGQDGDYIETEPKNYRNNGSPSRNGNSRDIFNGRSAFGENEHLIEDNEHHPLV | ||||||
Glycosylation | 1017 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1047 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1078 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1087 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1093 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 775-869 | Fibronectin type-III 1 | ||||
Sequence: TPDPPTLALAQVDSDAIHITWEAPLQPNGDLTHYTIMWRENEVSPYEEAEKFCTDASTPANRQHTKDPKETIVADKPVDIPSSRTVAPTLLTMMG | ||||||
Region | 944-980 | Disordered | ||||
Sequence: EKAENLGKAPKTLGGKKPLIHISKKKPSSSSTTSTPA | ||||||
Domain | 969-1067 | Fibronectin type-III 2 | ||||
Sequence: KPSSSSTTSTPAPTIASMYALTRKPTTVPGTRIRLYEIYEPLPGSWAINVSALALDNSYVIRNLKHYTLYAISLSACQNMTVPGASCSISHRAGALKRT | ||||||
Domain | 1077-1179 | Fibronectin type-III 3 | ||||
Sequence: LNETIEWRFMNNSQQVNVTWDPPTEVNGGIFGYVVKLKSKVDGSIVMTRCVGAKRGYSTRNQGVLFQNLADGRYFVSVTATSVHGAGPEAESSDPIVVMTPGF | ||||||
Domain | 1246-1528 | Protein kinase | ||||
Sequence: VVLGQQCGEGSFGKVYLGTGNNVVSLMGDRFGPCAIKINVDDPASTENLNYLMEANIMKNFKTNFIVKLYGVISTVQPAMVVMEMMDLGNLRDYLRSKREDEVFNETDCNFFDIIPRDKFHEWAAQICDGMAYLESLKFCHRDLAARNCMINRDETVKIGDFGMARDLFYHDYYKPSGKRMMPVRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGLSNDEVLNYIGMARKVIKKPECCENYWYKVMKMCWRYSPRDRPTFLQLVHLLAAEASPEF | ||||||
Region | 1718-1742 | Disordered | ||||
Sequence: ISSMDTRRSTGASSSSYGVPQTNWS | ||||||
Compositional bias | 1723-1742 | Polar residues | ||||
Sequence: TRRSTGASSSSYGVPQTNWS | ||||||
Compositional bias | 1769-1797 | Polar residues | ||||
Sequence: QQQQNGGRGDRLTQLPGTGHLQSTRGGQD | ||||||
Region | 1769-1826 | Disordered | ||||
Sequence: QQQQNGGRGDRLTQLPGTGHLQSTRGGQDGDYIETEPKNYRNNGSPSRNGNSRDIFNG | ||||||
Compositional bias | 1806-1826 | Polar residues | ||||
Sequence: KNYRNNGSPSRNGNSRDIFNG |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe 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.
- Namea
- Length1,846
- Mass (Da)207,124
- Last updated2009-11-03 v2
- Checksum230B28322FF0F126
Q968Y9-3
- Namec
- Differences from canonical
- 924-924: R → RCDIKNDPVGCAMLLLPPEIDDSDVGDDDEEPGGGSEQQQRILRNSEILKRQKRQILGRSLGGIHGIRSIGRKEYEQFADMIL
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0K3ARE8 | A0A0K3ARE8_CAEEL | daf-2 | 672 | ||
A0A0K3ARZ1 | A0A0K3ARZ1_CAEEL | daf-2 | 1770 | ||
A0A0K3AUA1 | A0A0K3AUA1_CAEEL | daf-2 | 1036 | ||
A0A0K3AXA0 | A0A0K3AXA0_CAEEL | daf-2 | 1799 |
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 838 | in Ref. 1; AAC47715 | ||||
Sequence: H → R | ||||||
Alternative sequence | VSP_061883 | 924 | in isoform c | |||
Sequence: R → RCDIKNDPVGCAMLLLPPEIDDSDVGDDDEEPGGGSEQQQRILRNSEILKRQKRQILGRSLGGIHGIRSIGRKEYEQFADMIL | ||||||
Sequence conflict | 1313 | in Ref. 1; AAC47715 | ||||
Sequence: K → Q | ||||||
Compositional bias | 1723-1742 | Polar residues | ||||
Sequence: TRRSTGASSSSYGVPQTNWS | ||||||
Compositional bias | 1769-1797 | Polar residues | ||||
Sequence: QQQQNGGRGDRLTQLPGTGHLQSTRGGQD | ||||||
Compositional bias | 1806-1826 | Polar residues | ||||
Sequence: KNYRNNGSPSRNGNSRDIFNG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |