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Q968Y9 (INSR_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-like receptor

Short name=IR
EC=2.7.10.1
Alternative name(s):
Abnormal dauer formation protein 2
Gene names
Name:daf-2
ORF Names:Y55D5A.5
OrganismCaenorhabditis elegans [Reference proteome]
Taxonomic identifier6239 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis

Protein attributes

Sequence length1846 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

An insulin receptor-like protein which regulates metabolism, controls longevity and prevents developmental arrest at the dauer stage. Binding of INS family members may either stimulate, or antagonize, association of the receptor with downstream mediators such as pdk-1 and age-1. Required for the response to environmental stimuli such as food, pheromone, and temperature. Role in immune function and pathogen resistance. Ref.1 Ref.3 Ref.4 Ref.6

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProtKB P06213

Cofactor

Manganese By similarity. UniProtKB P06213

Enzyme regulation

Autophosphorylation activates the kinase activity By similarity. UniProtKB P06213

Subunit structure

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. UniProtKB P06213

Subcellular location

Membrane; Single-pass type I membrane protein By similarity UniProtKB P06213.

Disruption phenotype

Accumulation of fat, pigmented intestine, increased life span, increased dauer formation and increased resistance to pathogens. Severe loss of function mutants display recessive early embryonic lethality. Ref.1 Ref.3 Ref.4 Ref.6 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 3 fibronectin type-III domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCarbohydrate metabolism
Immunity
Innate immunity
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

dauer exit

Inferred from mutant phenotype Ref.3. Source: WormBase

dauer larval development

Inferred from mutant phenotype PubMed 10625546PubMed 11381260Ref.1Ref.3. Source: WormBase

determination of adult lifespan

Inferred from mutant phenotype PubMed 11381260Ref.3. Source: WormBase

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

insulin receptor signaling pathway

Inferred from sequence or structural similarity Ref.1. Source: WormBase

negative regulation of transcription factor import into nucleus

Inferred from mutant phenotype PubMed 18358814. Source: WormBase

positive regulation of multicellular organism growth

Inferred from mutant phenotype PubMed 12571101. Source: WormBase

protein autophosphorylation

Inferred from sequence or structural similarity Ref.1. Source: WormBase

regulation of autophagic vacuole assembly

Inferred from mutant phenotype PubMed 22560223. Source: BHF-UCL

regulation of development, heterochronic

Inferred from genetic interaction PubMed 21471153. Source: WormBase

regulation of response to reactive oxygen species

Inferred from mutant phenotype PubMed 12399591. Source: WormBase

reproduction

Inferred from mutant phenotype PubMed 12399591Ref.3. Source: WormBase

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 24120884. Source: WormBase

cytoplasmic vesicle

Inferred from direct assay PubMed 24120884. Source: WormBase

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 24120884. Source: WormBase

   Molecular_functionATP binding

Inferred from sequence or structural similarity Ref.1. Source: WormBase

SH2 domain binding

Inferred from sequence or structural similarity Ref.1. Source: WormBase

insulin-activated receptor activity

Inferred from sequence or structural similarity Ref.1. Source: WormBase

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptide hormone binding

Inferred from sequence or structural similarity Ref.1. Source: WormBase

protein kinase binding

Inferred from physical interaction PubMed 22672310. Source: WormBase

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform a Ref.1 Ref.2 (identifier: 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.
Isoform b Ref.2 (identifier: Q968Y9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     925-1020: DTMRVRRSIE...PGSWAINVSA → CDIKNDPVGC...HDLMMSVMHD
     1021-1846: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – ? Potential
Chain? – 966Insulin-like receptor subunit alphaPRO_0000386619
Chain970 – 1846877Insulin-like receptor subunit beta
PRO_0000386620

Regions

Topological domain970 – 1183214Extracellular Potential
Transmembrane1184 – 120421Helical; Potential
Topological domain1205 – 1846642Cytoplasmic Potential
Domain775 – 86995Fibronectin type-III 1
Domain969 – 106799Fibronectin type-III 2
Domain1077 – 1179103Fibronectin type-III 3
Domain1246 – 1528283Protein kinase
Nucleotide binding1252 – 12609ATP By similarity UniProtKB P28523

Sites

Active site13881Proton acceptor By similarity UniProtKB P28523
Binding site12821ATP By similarity UniProtKB P28523

Amino acid modifications

Glycosylation1131N-linked (GlcNAc...) Potential
Glycosylation1801N-linked (GlcNAc...) Potential
Glycosylation3641N-linked (GlcNAc...) Ref.5
Glycosylation4531N-linked (GlcNAc...) Ref.5
Glycosylation5181N-linked (GlcNAc...) Potential
Glycosylation6521N-linked (GlcNAc...) Potential
Glycosylation6711N-linked (GlcNAc...) Potential
Glycosylation6961N-linked (GlcNAc...) Ref.5
Glycosylation10171N-linked (GlcNAc...) Ref.5
Glycosylation10471N-linked (GlcNAc...) Potential
Glycosylation10781N-linked (GlcNAc...) Ref.5
Glycosylation10871N-linked (GlcNAc...) Potential
Glycosylation10931N-linked (GlcNAc...) Potential
Disulfide bond371 ↔ 386 By similarity UniProtKB P06213
Disulfide bond393 ↔ 401 By similarity UniProtKB P06213
Disulfide bond397 ↔ 410 By similarity UniProtKB P06213
Disulfide bond413 ↔ 422 By similarity UniProtKB P06213
Disulfide bond426 ↔ 438 By similarity UniProtKB P06213
Disulfide bond469 ↔ 483 By similarity UniProtKB P06213
Disulfide bond486 ↔ 490 By similarity UniProtKB P06213
Disulfide bond615 ↔ 646 By similarity UniProtKB P06213
Disulfide bond706Interchain By similarity UniProtKB P06213

Natural variations

Alternative sequence925 – 102096DTMRV…INVSA → CDIKNDPVGCAMLLLPPEID DSDVGDDDEEPGGGSEQQQR ILRNSEILKRQKRQILGRSL GGIHGIRSIGRKEYEQFADM ILYGNLHDLMMSVMHD in isoform b. Ref.2
VSP_053157
Alternative sequence1021 – 1846826Missing in isoform b. Ref.2
VSP_053158

Experimental info

Mutagenesis1461C → Y: Embronically lethal. Ref.7
Mutagenesis4011C → Y: Dauer formation; when associated with L-470. Ref.1
Mutagenesis4691C → S: Dauer formation above 20 degrees Celsius. Ref.1
Mutagenesis4701P → L: Dauer formation; when associated with Y-401. Ref.1
Mutagenesis5731S → L: Dauer formation above 25 degrees Celsius. Ref.1
Mutagenesis5801A → T: Dauer formation above 26 degrees Celsius. Ref.4
Mutagenesis6481D → N: Dauer formation above 25 degrees Celsius. Ref.1
Mutagenesis13741D → N: Dauer formation above 20 degrees Celsius. Ref.1
Mutagenesis14341P → L: Dauer formation above 20 degrees Celsius. Ref.1
Mutagenesis14651P → S: Extended lifespan. Accumulates fat and undergoes dauer formation above 25 degrees Celsius. Pigmented intestine and increased resistance to bacterial pathogens. Ref.1 Ref.3 Ref.4 Ref.6 Ref.7
Sequence conflict8381H → R in AAC47715. Ref.1
Sequence conflict13131K → Q in AAC47715. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform a [UniParc].

Last modified November 3, 2009. Version 2.
Checksum: 230B28322FF0F126

FASTA1,846207,124
        10         20         30         40         50         60 
MTRMNIVRCR RRHKILENLE EENLGPSCSS TTSTTAATEA LGTTTEDMRL KQQRSSSRAT 

        70         80         90        100        110        120 
EHDIVDGNHH DDEHITMRRL RLVKNSRTRR RTTPDSSMDC YEENPPSQKT SINYSWISKK 

       130        140        150        160        170        180 
SSMTSLMLLL LFAFVQPCAS IVEKRCGPID IRNRPWDIKP QWSKLGDPNE KDLAGQRMVN 

       190        200        210        220        230        240 
CTVVEGSLTI SFVLKHKTKA QEEMHRSLQP RYSQDEFITF PHLREITGTL LVFETEGLVD 

       250        260        270        280        290        300 
LRKIFPNLRV IGGRSLIQHY ALIIYRNPDL EIGLDKLSVI RNGGVRIIDN RKLCYTKTID 

       310        320        330        340        350        360 
WKHLITSSIN DVVVDNAAEY AVTETGLMCP RGACEEDKGE SKCHYLEEKN QEQGVERVQS 

       370        380        390        400        410        420 
CWSNTTCQKS CAYDRLLPTK EIGPGCDANG DRCHDQCVGG CERVNDATAC HACKNVYHKG 

       430        440        450        460        470        480 
KCIEKCDAHL YLLLQRRCVT REQCLQLNPV LSNKTVPIKA TAGLCSDKCP DGYQINPDDH 

       490        500        510        520        530        540 
RECRKCVGKC EIVCEINHVI DTFPKAQAIR LCNIIDGNLT IEIRGKQDSG MASELKDIFA 

       550        560        570        580        590        600 
NIHTITGYLL VRQSSPFISL NMFRNLRRIE AKSLFRNLYA ITVFENPNLK KLFDSTTDLT 

       610        620        630        640        650        660 
LDRGTVSIAN NKMLCFKYIK QLMSKLNIPL DPIDQSEGTN GEKAICEDMA INVSITAVNA 

       670        680        690        700        710        720 
DSVFFSWPSF NITDIDQRKF LGYELFFKEV PRIDENMTIE EDRSACVDSW QSVFKQYYET 

       730        740        750        760        770        780 
SNGEPTPDIF MDIGPRERIR PNTLYAYYVA TQMVLHAGAK NGVSKIGFVR TSYYTPDPPT 

       790        800        810        820        830        840 
LALAQVDSDA IHITWEAPLQ PNGDLTHYTI MWRENEVSPY EEAEKFCTDA STPANRQHTK 

       850        860        870        880        890        900 
DPKETIVADK PVDIPSSRTV APTLLTMMGH EDQQKTCAAT PGCCSCSAIE ESSEQNKKKR 

       910        920        930        940        950        960 
PDPMSAIESS AFENKLLDEV LMPRDTMRVR RSIEDANRVS EELEKAENLG KAPKTLGGKK 

       970        980        990       1000       1010       1020 
PLIHISKKKP SSSSTTSTPA PTIASMYALT RKPTTVPGTR IRLYEIYEPL PGSWAINVSA 

      1030       1040       1050       1060       1070       1080 
LALDNSYVIR NLKHYTLYAI SLSACQNMTV PGASCSISHR AGALKRTKHI TDIDKVLNET 

      1090       1100       1110       1120       1130       1140 
IEWRFMNNSQ QVNVTWDPPT EVNGGIFGYV VKLKSKVDGS IVMTRCVGAK RGYSTRNQGV 

      1150       1160       1170       1180       1190       1200 
LFQNLADGRY FVSVTATSVH GAGPEAESSD PIVVMTPGFF TVEIILGMLL VFLILMSIAG 

      1210       1220       1230       1240       1250       1260 
CIIYYYIQVR YGKKVKALSD FMQLNPEYCV DNKYNADDWE LRQDDVVLGQ QCGEGSFGKV 

      1270       1280       1290       1300       1310       1320 
YLGTGNNVVS LMGDRFGPCA IKINVDDPAS TENLNYLMEA NIMKNFKTNF IVKLYGVIST 

      1330       1340       1350       1360       1370       1380 
VQPAMVVMEM MDLGNLRDYL RSKREDEVFN ETDCNFFDII PRDKFHEWAA QICDGMAYLE 

      1390       1400       1410       1420       1430       1440 
SLKFCHRDLA ARNCMINRDE TVKIGDFGMA RDLFYHDYYK PSGKRMMPVR WMSPESLKDG 

      1450       1460       1470       1480       1490       1500 
KFDSKSDVWS FGVVLYEMVT LGAQPYIGLS NDEVLNYIGM ARKVIKKPEC CENYWYKVMK 

      1510       1520       1530       1540       1550       1560 
MCWRYSPRDR PTFLQLVHLL AAEASPEFRD LSFVLTDNQM ILDDSEALDL DDIDDTDMND 

      1570       1580       1590       1600       1610       1620 
QVVEVAPDVE NVEVQSDSER RNTDSIPLKQ FKTIPPINAT TSHSTISIDE TPMKAKQREG 

      1630       1640       1650       1660       1670       1680 
SLDEEYALMN HSGGPSDAEV RTYAGDGDYV ERDVRENDVP TRRNTGASTS SYTGGGPYCL 

      1690       1700       1710       1720       1730       1740 
TNRGGSNERG AGFGEAVRLT DGVGSGHLND DDYVEKEISS MDTRRSTGAS SSSYGVPQTN 

      1750       1760       1770       1780       1790       1800 
WSGNRGATYY TSKAQQAATA AAAAAAALQQ QQNGGRGDRL TQLPGTGHLQ STRGGQDGDY 

      1810       1820       1830       1840 
IETEPKNYRN NGSPSRNGNS RDIFNGRSAF GENEHLIEDN EHHPLV 

« Hide

Isoform b [UniParc].

Checksum: 0CAECAF111DF3E2A
Show »

FASTA1,020115,345

References

« Hide 'large scale' references
[1]"daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans."
Kimura K.D., Tissenbaum H.A., Liu Y., Ruvkun G.
Science 277:942-946(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-401; CYS-469; PRO-470; SER-573; ASP-648; ASP-1374; PRO-1434 AND PRO-1465.
Strain: Bristol N2.
[2]"Genome sequence of the nematode C. elegans: a platform for investigating biology."
The C. elegans sequencing consortium
Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
Strain: Bristol N2.
[3]"Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span."
Apfeld J., Kenyon C.
Cell 95:199-210(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF PRO-1465.
[4]"Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family."
Pierce S.B., Costa M., Wisotzkey R., Devadhar S., Homburger S.A., Buchman A.R., Ferguson K.C., Heller J., Platt D.M., Pasquinelli A.A., Liu L.X., Doberstein S.K., Ruvkun G.
Genes Dev. 15:672-686(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF ALA-580 AND PRO-1465.
[5]"Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis elegans and suggests an atypical translocation mechanism for integral membrane proteins."
Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T., Taoka M., Takahashi N., Isobe T.
Mol. Cell. Proteomics 6:2100-2109(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-364; ASN-453; ASN-696; ASN-1017 AND ASN-1078, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: Bristol N2.
[6]"The DAF-2 insulin-like signaling pathway independently regulates aging and immunity in C. elegans."
Evans E.A., Chen W.C., Tan M.-W.
Aging Cell 7:879-893(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF PRO-1465.
[7]"Clustering of genetically defined allele classes in the Caenorhabditis elegans DAF-2 insulin/IGF-1 receptor."
Patel D.S., Garza-Garcia A., Nanji M., McElwee J.J., Ackerman D., Driscoll P.C., Gems D.
Genetics 178:931-946(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-146 AND PRO-1465.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF012437 mRNA. Translation: AAC47715.1.
FO081525 Genomic DNA. Translation: CCD72201.2.
FO081525 Genomic DNA. Translation: CCD72203.2.
PIRT42047.
RefSeqNP_001122734.2. NM_001129262.3.
NP_497650.4. NM_065249.4.
UniGeneCel.8775.

3D structure databases

ProteinModelPortalQ968Y9.
SMRQ968Y9. Positions 143-917, 1026-1596.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid40655. 166 interactions.
STRING6239.Y55D5A.5a.

Proteomic databases

PaxDbQ968Y9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaY55D5A.5a; Y55D5A.5a; Y55D5A.5. [Q968Y9-1]
GeneID175410.
KEGGcel:CELE_Y55D5A.5.

Organism-specific databases

CTD175410.
WormBaseY55D5A.5a; CE27499; WBGene00000898; daf-2.
Y55D5A.5b; CE42198; WBGene00000898; daf-2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000151241.
OMASCVACRN.
OrthoDBEOG73RB9N.
PhylomeDBQ968Y9.

Enzyme and pathway databases

SignaLinkQ968Y9.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
3.80.20.20. 3 hits.
InterProIPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 3 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS50853. FN3. 3 hits.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio888038.

Entry information

Entry nameINSR_CAEEL
AccessionPrimary (citable) accession number: Q968Y9
Secondary accession number(s): B5QS63, O16131
Entry history
Integrated into UniProtKB/Swiss-Prot: November 3, 2009
Last sequence update: November 3, 2009
Last modified: April 16, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Caenorhabditis elegans

Caenorhabditis elegans: entries, gene names and cross-references to WormBase