INSR_DROME
ID INSR_DROME Reviewed; 2144 AA.
AC P09208; B7Z0N6; Q24023; Q24089; Q9VD94;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Insulin-like receptor;
DE Short=dIR;
DE Short=dInr;
DE EC=2.7.10.1;
DE AltName: Full=dIRH;
DE Contains:
DE RecName: Full=Insulin-like receptor subunit alpha;
DE Contains:
DE RecName: Full=Insulin-like receptor subunit beta 1;
DE Contains:
DE RecName: Full=Insulin-like receptor subunit beta 2;
DE Flags: Precursor;
GN Name=InR; Synonyms=dinr, Dir-a, Inr-a; ORFNames=CG18402;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND PROTEOLYTIC
RP PROCESSING.
RX PubMed=7628438; DOI=10.1002/j.1460-2075.1995.tb07343.x;
RA Fernandez R., Tabarini D., Azpiazu N., Frasch M., Schlessinger J.;
RT "The Drosophila insulin receptor homolog: a gene essential for embryonic
RT development encodes two receptor isoforms with different signaling
RT potential.";
RL EMBO J. 14:3373-3384(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7876183; DOI=10.1074/jbc.270.9.4236;
RA Ruan Y., Chen C., Cao Y., Garofalo R.S.;
RT "The Drosophila insulin receptor contains a novel carboxyl-terminal
RT extension likely to play an important role in signal transduction.";
RL J. Biol. Chem. 270:4236-4243(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 652-1851.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=3099787; DOI=10.1016/s0006-291x(86)80197-8;
RA Nishida Y., Hata M., Nishizuka Y., Rutter W.J., Ebina Y.;
RT "Cloning of a Drosophila cDNA encoding a polypeptide similar to the human
RT insulin receptor precursor.";
RL Biochem. Biophys. Res. Commun. 141:474-481(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1300-1598, DEVELOPMENTAL STAGE, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=3014506; DOI=10.1073/pnas.83.13.4710;
RA Petruzzelli L., Herrera R., Arenas-Garcia R., Fernandez R., Birnbaum M.J.,
RA Rosen O.M.;
RT "Isolation of a Drosophila genomic sequence homologous to the kinase domain
RT of the human insulin receptor and detection of the phosphorylated
RT Drosophila receptor with an anti-peptide antibody.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:4710-4714(1986).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=2454394; DOI=10.1128/mcb.8.4.1638-1647.1988;
RA Garofalo R.S., Rosen O.M.;
RT "Tissue localization of Drosophila melanogaster insulin receptor
RT transcripts during development.";
RL Mol. Cell. Biol. 8:1638-1647(1988).
RN [8]
RP FUNCTION, AND AUTOPHOSPHORYLATION.
RX PubMed=8603594; DOI=10.1210/endo.137.3.8603594;
RA Chen C., Jack J., Garofalo R.S.;
RT "The Drosophila insulin receptor is required for normal growth.";
RL Endocrinology 137:846-856(1996).
RN [9]
RP FUNCTION, AND INTERACTION WITH CHICO.
RX PubMed=10455177; DOI=10.1074/jbc.274.35.24987;
RA Marin-Hincapie M., Garofalo R.S.;
RT "The carboxyl terminal extension of the Drosophila insulin receptor
RT homologue binds IRS-1 and influences cell survival.";
RL J. Biol. Chem. 274:24987-24994(1999).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ARG-1467; GLY-1539 AND GLY-1599.
RX PubMed=11250149; DOI=10.1016/s0960-9822(01)00068-9;
RA Brogiolo W., Stocker H., Ikeya T., Rintelen F., Fernandez R., Hafen E.;
RT "An evolutionarily conserved function of the Drosophila insulin receptor
RT and insulin-like peptides in growth control.";
RL Curr. Biol. 11:213-221(2001).
RN [11]
RP FUNCTION.
RX PubMed=11292875; DOI=10.1126/science.1057987;
RA Tatar M., Kopelman A., Epstein D., Tu M.P., Yin C.M., Garofalo R.S.;
RT "A mutant Drosophila insulin receptor homolog that extends life-span and
RT impairs neuroendocrine function.";
RL Science 292:107-110(2001).
RN [12]
RP FUNCTION, AND INTERACTION WITH DOCK.
RX PubMed=12702880; DOI=10.1126/science.1081203;
RA Song J., Wu L., Chen Z., Kohanski R.A., Pick L.;
RT "Axons guided by insulin receptor in Drosophila visual system.";
RL Science 300:502-505(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1816, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-824; ASN-839; ASN-864; ASN-898;
RP ASN-1147 AND ASN-1218, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
CC -!- FUNCTION: Has a ligand-stimulated tyrosine-protein kinase activity.
CC Required for cell survival. Regulates body size and organ size by
CC altering cell number and cell size in a cell-autonomous manner.
CC Involved in the development of the embryonic nervous system, and is
CC necessary for axon guidance and targeting in the visual system. Also
CC plays a role in life-span determination. {ECO:0000269|PubMed:10455177,
CC ECO:0000269|PubMed:11250149, ECO:0000269|PubMed:11292875,
CC ECO:0000269|PubMed:12702880, ECO:0000269|PubMed:7628438,
CC ECO:0000269|PubMed:8603594}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Autophosphorylation activates the kinase activity.
CC -!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide
CC bonds. The alpha chains contribute to the formation of the ligand-
CC binding domain, while the beta chains carry the kinase domain. When
CC autophosphorylated, the beta-subunit binds the SH2 and SH3 domains of
CC the adapter protein Dock. The beta subunit also binds and tyrosine
CC phosphorylates the insulin receptor substrate Chico.
CC -!- INTERACTION:
CC P09208; Q9XTN2: chico; NbExp=3; IntAct=EBI-92063, EBI-176370;
CC P09208; P09208: InR; NbExp=2; IntAct=EBI-92063, EBI-92063;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Widely distributed throughout the embryo. Expressed
CC at high levels in the embryonic nervous system. Larval expression is
CC limited to the nervous system and all imaginal disks. Expressed at high
CC levels in the adult nervous system and ovaries.
CC {ECO:0000269|PubMed:2454394, ECO:0000269|PubMed:7628438}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development. Embryonic
CC expression is most prominent 8 to 12 hours after egg laying.
CC {ECO:0000269|PubMed:2454394, ECO:0000269|PubMed:3014506}.
CC -!- PTM: The 280 kDa proreceptor is proteolytically processed to form a 120
CC kDa alpha subunit and a 170 kDa beta subunit. The beta subunit
CC undergoes cell-specific cleavage to generate a 90 kDa beta subunit and
CC a free 60 kDa C-terminal subunit. Both the 90 kDa and the 170 kDa beta
CC subunits can assemble with the alpha subunits to form mature receptors.
CC {ECO:0000269|PubMed:7628438}.
CC -!- PTM: Autophosphorylated on tyrosine residues in response to exogenous
CC insulin. {ECO:0000269|PubMed:18327897}.
CC -!- PTM: Phosphorylation of Tyr-1354 is required for Chico-binding.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28644.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA68953.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U28136; AAA68953.1; ALT_FRAME; mRNA.
DR EMBL; U18351; AAC47458.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF55903.2; -; Genomic_DNA.
DR EMBL; AE014297; ACL83549.1; -; Genomic_DNA.
DR EMBL; AE014297; ACL83550.1; -; Genomic_DNA.
DR EMBL; AE014297; ACL83551.1; -; Genomic_DNA.
DR EMBL; M14778; AAA28644.1; ALT_FRAME; mRNA.
DR EMBL; M13568; AAA28645.1; -; Genomic_DNA.
DR PIR; A56081; A56081.
DR PIR; S57245; S57245.
DR RefSeq; NP_001138093.1; NM_001144621.3.
DR RefSeq; NP_001138094.1; NM_001144622.2.
DR RefSeq; NP_001138095.1; NM_001144623.2.
DR RefSeq; NP_524436.2; NM_079712.6.
DR AlphaFoldDB; P09208; -.
DR SMR; P09208; -.
DR BioGRID; 67515; 82.
DR IntAct; P09208; 5.
DR STRING; 7227.FBpp0288669; -.
DR GlyGen; P09208; 21 sites.
DR iPTMnet; P09208; -.
DR PaxDb; P09208; -.
DR PRIDE; P09208; -.
DR EnsemblMetazoa; FBtr0084121; FBpp0083519; FBgn0283499.
DR EnsemblMetazoa; FBtr0290230; FBpp0288669; FBgn0283499.
DR EnsemblMetazoa; FBtr0290231; FBpp0288670; FBgn0283499.
DR EnsemblMetazoa; FBtr0290232; FBpp0288671; FBgn0283499.
DR GeneID; 42549; -.
DR KEGG; dme:Dmel_CG18402; -.
DR CTD; 42549; -.
DR FlyBase; FBgn0283499; InR.
DR VEuPathDB; VectorBase:FBgn0283499; -.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000168802; -.
DR HOGENOM; CLU_000288_166_2_1; -.
DR InParanoid; P09208; -.
DR OMA; QYIPDDW; -.
DR OrthoDB; 223327at2759; -.
DR PhylomeDB; P09208; -.
DR BRENDA; 2.7.10.1; 1994.
DR Reactome; R-DME-110478; Insulin signaling pathway.
DR Reactome; R-DME-77387; Insulin receptor recycling.
DR Reactome; R-DME-9009391; Extra-nuclear estrogen signaling.
DR SignaLink; P09208; -.
DR BioGRID-ORCS; 42549; 0 hits in 3 CRISPR screens.
DR ChiTaRS; InR; fly.
DR GenomeRNAi; 42549; -.
DR PRO; PR:P09208; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0283499; Expressed in visceral mesoderm and 27 other tissues.
DR ExpressionAtlas; P09208; baseline and differential.
DR Genevisible; P09208; DM.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005899; C:insulin receptor complex; IDA:FlyBase.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043559; F:insulin binding; IPI:FlyBase.
DR GO; GO:0005009; F:insulin receptor activity; IDA:FlyBase.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IMP:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR GO; GO:0033500; P:carbohydrate homeostasis; IMP:FlyBase.
DR GO; GO:0009267; P:cellular response to starvation; IMP:FlyBase.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IMP:FlyBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEP:UniProtKB.
DR GO; GO:0001700; P:embryonic development via the syncytial blastoderm; IEP:FlyBase.
DR GO; GO:0048132; P:female germ-line stem cell asymmetric division; IMP:FlyBase.
DR GO; GO:0036099; P:female germ-line stem cell population maintenance; IMP:FlyBase.
DR GO; GO:0008585; P:female gonad development; IMP:FlyBase.
DR GO; GO:0060180; P:female mating behavior; IMP:FlyBase.
DR GO; GO:0007390; P:germ-band shortening; IGI:FlyBase.
DR GO; GO:0042078; P:germ-line stem cell division; IMP:FlyBase.
DR GO; GO:0060250; P:germ-line stem-cell niche homeostasis; IMP:FlyBase.
DR GO; GO:0042593; P:glucose homeostasis; IMP:FlyBase.
DR GO; GO:0007446; P:imaginal disc growth; IMP:FlyBase.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:FlyBase.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; IGI:FlyBase.
DR GO; GO:0055088; P:lipid homeostasis; IMP:FlyBase.
DR GO; GO:0007626; P:locomotory behavior; IMP:FlyBase.
DR GO; GO:0048542; P:lymph gland development; IMP:FlyBase.
DR GO; GO:0048133; P:male germ-line stem cell asymmetric division; IMP:FlyBase.
DR GO; GO:0035264; P:multicellular organism growth; IMP:FlyBase.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:FlyBase.
DR GO; GO:0042321; P:negative regulation of circadian sleep/wake cycle, sleep; IMP:FlyBase.
DR GO; GO:0061964; P:negative regulation of entry into reproductive diapause; IMP:FlyBase.
DR GO; GO:2000252; P:negative regulation of feeding behavior; IMP:FlyBase.
DR GO; GO:0090278; P:negative regulation of peptide hormone secretion; IMP:FlyBase.
DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB.
DR GO; GO:0007424; P:open tracheal system development; HMP:FlyBase.
DR GO; GO:0030707; P:ovarian follicle cell development; IMP:FlyBase.
DR GO; GO:1903688; P:positive regulation of border follicle cell migration; IMP:FlyBase.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:FlyBase.
DR GO; GO:0070346; P:positive regulation of fat cell proliferation; IMP:FlyBase.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:FlyBase.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IGI:FlyBase.
DR GO; GO:1904801; P:positive regulation of neuron remodeling; IMP:FlyBase.
DR GO; GO:0046622; P:positive regulation of organ growth; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:FlyBase.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:FlyBase.
DR GO; GO:0007285; P:primary spermatocyte growth; IMP:FlyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:FlyBase.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:FlyBase.
DR GO; GO:0046620; P:regulation of organ growth; IMP:FlyBase.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:FlyBase.
DR GO; GO:0034059; P:response to anoxia; IDA:FlyBase.
DR GO; GO:0042220; P:response to cocaine; IGI:FlyBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:FlyBase.
DR CDD; cd00063; FN3; 1.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.60.40.10; -; 4.
DR Gene3D; 3.80.20.20; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00261; FU; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cleavage on pair of basic residues; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Growth regulation; Kinase;
KW Manganese; Membrane; Metal-binding; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; SH3-binding; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT CHAIN 651..1081
FT /note="Insulin-like receptor subunit alpha"
FT /id="PRO_0000016715"
FT CHAIN 1086..2144
FT /note="Insulin-like receptor subunit beta 1"
FT /id="PRO_0000016716"
FT CHAIN 1086..?
FT /note="Insulin-like receptor subunit beta 2"
FT /id="PRO_0000016717"
FT CHAIN ?..2144
FT /note="Insulin-like receptor"
FT /id="PRO_0000016718"
FT TOPO_DOM 1086..1310
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1311..1331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1332..2144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 825..927
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 928..1026
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1210..1305
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1371..1659
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 174..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1053..1084
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1351..1354
FT /note="Chico-binding"
FT /evidence="ECO:0000250"
FT REGION 1690..1724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1788..1871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1886..1962
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2020..2144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..196
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1708..1724
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1828..1867
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1887..1957
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2020..2041
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2044..2061
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2080..2124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1519
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1377..1385
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1405
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1354
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1545
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1549
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1550
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1816
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 509
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 751
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 824
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 839
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 864
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 898
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 946
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1053
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 1218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 1265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 531..539
FT /evidence="ECO:0000250"
FT DISULFID 535..545
FT /evidence="ECO:0000250"
FT DISULFID 546..554
FT /evidence="ECO:0000250"
FT DISULFID 550..564
FT /evidence="ECO:0000250"
FT DISULFID 567..576
FT /evidence="ECO:0000250"
FT DISULFID 580..591
FT /evidence="ECO:0000250"
FT DISULFID 597..618
FT /evidence="ECO:0000250"
FT DISULFID 635..638
FT /evidence="ECO:0000250"
FT MUTAGEN 1467
FT /note="R->C: In allele 353; reduction in head size."
FT /evidence="ECO:0000269|PubMed:11250149"
FT MUTAGEN 1539
FT /note="G->E: In allele 339; strong reduction in head size."
FT /evidence="ECO:0000269|PubMed:11250149"
FT MUTAGEN 1599
FT /note="G->R: In allele 211; reduction in head size."
FT /evidence="ECO:0000269|PubMed:11250149"
FT CONFLICT 29
FT /note="T -> ATTAK (in Ref. 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="V -> D (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="Q -> H (in Ref. 1; AAA68953 and 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="F -> C (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="H -> L (in Ref. 1; AAA68953 and 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="S -> T (in Ref. 1; AAA68953 and 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="T -> P (in Ref. 1; AAA68953 and 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="T -> S (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="R -> S (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="T -> N (in Ref. 1; AAA68953 and 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 653..660
FT /note="DSLERARE -> PPPPPPPL (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 679..681
FT /note="RES -> GER (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 723..727
FT /note="ISGDP -> LAAI (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 793
FT /note="V -> E (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 822
FT /note="M -> S (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 864..877
FT /note="NSTKSSDDPCDDRW -> TQLKAVTIHAMIAG (in Ref. 5;
FT AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 933..935
FT /note="Missing (in Ref. 1; AAA68953 and 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 954..958
FT /note="KPYGV -> NLMA (in Ref. 1; AAA68953 and 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1161
FT /note="Missing (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1187..1192
FT /note="LCSDYD -> SAAIIH (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1224..1232
FT /note="VRVRWTPPV -> ATFSLGRHQL (in Ref. 1; AAA68953 and 5;
FT AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1263..1282
FT /note="DFNQTAGYLIKLNEGLYSFR -> RLQPDCRLFNKAQRGPLQLQ (in
FT Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1300..1303
FT /note="IKVE -> LIQQ (in Ref. 2; AAA28645)"
FT /evidence="ECO:0000305"
FT CONFLICT 1457..1458
FT /note="GD -> VE (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1469..1484
FT /note="EERDEAMMTYLNRIGV -> RSGMRPDDVSLIAWM (in Ref. 5;
FT AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1473..1479
FT /note="EAMMTYL -> DGHDDVS (in Ref. 2; AAA28645)"
FT /evidence="ECO:0000305"
FT CONFLICT 1499
FT /note="M -> V (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1519..1520
FT /note="DL -> PF (in Ref. 2; AAA28645)"
FT /evidence="ECO:0000305"
FT CONFLICT 1569..1578
FT /note="RDGVYSSASD -> QAWCLLLVPVT (in Ref. 2; AAA28645)"
FT /evidence="ECO:0000305"
FT CONFLICT 1591..1598
FT /note="TLAAQPYQ -> ILSLWRSP (in Ref. 2; AAA28645)"
FT /evidence="ECO:0000305"
FT CONFLICT 1682
FT /note="N -> H (in Ref. 2; AAC47458 and 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1706
FT /note="T -> S (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1715
FT /note="Q -> E (in Ref. 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 1792..1799
FT /note="IYDPSPKC -> STIPVRNG (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1828
FT /note="Q -> K (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1850..1851
FT /note="TA -> GI (in Ref. 5; AAA28644)"
FT /evidence="ECO:0000305"
FT CONFLICT 1852..1854
FT /note="SAG -> FTT (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
FT CONFLICT 1854
FT /note="G -> A (in Ref. 2; AAC47458)"
FT /evidence="ECO:0000305"
FT CONFLICT 1887
FT /note="F -> Y (in Ref. 1; AAA68953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2144 AA; 239776 MW; C4A8ECB08C70523A CRC64;
MFNMPRGVTK SKSKRGKIKM ENDMAAAATT TACTLGHICV LCRQEMLLDT CCCRQAVEAV
DSPASSEEAY SSSNSSSCQA SSEISAEEVW FLSHDDIVLC RRPKFDEVET TGKKRDVKCS
GHQCSNECDD GSTKNNRQQR ENFNIFSNCH NILRTLQSLL LLMFNCGIFN KRRRRQHQQQ
HHHHYQHHHQ QHHQQHHQRQ QANVSYTKFL LLLQTLAAAT TRLSLSPKNY KQQQQLQHNQ
QLPRATPQQK QQEKDRHKCF HYKHNYSYSP GISLLLFILL ANTLAIQAVV LPAHQQHLLH
NDIADGLDKT ALSVSGTQSR WTRSESNPTM RLSQNVKPCK SMDIRNMVSH FNQLENCTVI
EGFLLIDLIN DASPLNRSFP KLTEVTDYII IYRVTGLHSL SKIFPNLSVI RGNKLFDGYA
LVVYSNFDLM DLGLHKLRSI TRGGVRIEKN HKLCYDRTID WLEILAENET QLVVLTENGK
EKECRLSKCP GEIRIEEGHD TTAIEGELNA SCQLHNNRRL CWNSKLCQTK CPEKCRNNCI
DEHTCCSQDC LGGCVIDKNG NESCISCRNV SFNNICMDSC PKGYYQFDSR CVTANECITL
TKFETNSVYS GIPYNGQCIT HCPTGYQKSE NKRMCEPCPG GKCDKECSSG LIDSLERARE
FHGCTIITGT EPLTISIKRE SGAHVMDELK YGLAAVHKIQ SSLMVHLTYG LKSLKFFQSL
TEISGDPPMD ADKYALYVLD NRDLDELWGP NQTVFIRKGG VFFHFNPKLC VSTINQLLPM
LASKPKFFEK SDVGADSNGN RGSCGTAVLN VTLQSVGANS AMLNVTTKVE IGEPQKPSNA
TIVFKDPRAF IGFVFYHMID PYGNSTKSSD DPCDDRWKVS SPEKSGVMVL SNLIPYTNYS
YYVRTMAISS ELTNAESDVK NFRTNPGRPS KVTEVVATAI SDSKINVTWS YLDKPYGVLT
RYFIKAKLIN RPTRNNNRDY CTEPLVKAME NDLPATTPTK KISDPLAGDC KCVEGSKKTS
SQEYDDRKVQ AGMEFENALQ NFIFVPNIRK SKNGSSDKSD GAEGAALDSN AIPNGGATNP
SRRRRDVALE PELDDVEGSV LLRHVRSITD DTDAFFEKDD ENTYKDEEDL SSNKQFYEVF
AKELPPNQTH FVFEKLRHFT RYAIFVVACR EEIPSEKLRD TSFKKSLCSD YDTVFQTTKR
KKFADIVMDL KVDLEHANNT ESPVRVRWTP PVDPNGEIVT YEVAYKLQKP DQVEEKKCIP
AADFNQTAGY LIKLNEGLYS FRVRANSIAG YGDFTEVEHI KVEPPPSYAK VFFWLLGIGL
AFLIVSLFGY VCYLHKRKVP SNDLHMNTEV NPFYASMQYI PDDWEVLREN IIQLAPLGQG
SFGMVYEGIL KSFPPNGVDR ECAIKTVNEN ATDRERTNFL SEASVMKEFD TYHVVRLLGV
CSRGQPALVV MELMKKGDLK SYLRAHRPEE RDEAMMTYLN RIGVTGNVQP PTYGRIYQMA
IEIADGMAYL AAKKFVHRDL AARNCMVADD LTVKIGDFGM TRDIYETDYY RKGTKGLLPV
RWMPPESLRD GVYSSASDVF SFGVVLWEMA TLAAQPYQGL SNEQVLRYVI DGGVMERPEN
CPDFLHKLMQ RCWHHRSSAR PSFLDIIAYL EPQCPNSQFK EVSFYHSEAG LQHREKERKE
RNQLDAFAAV PLDQDLQDRE QQEDATTPLR MGDYQQNSSL DQPPESPIAM VDDQGSHLPF
SLPSGFIASS TPDGQTVMAT AFQNIPAAQG DISATYVVPD ADALDGDRGY EIYDPSPKCA
ELPTSRSGST GGGKLSGEQH LLPRKGRQPT IMSSSMPDDV IGGSSLQPST ASAGSSNASS
HTGRPSLKKT VADSVRNKAN FINRHLFNHK RTGSNASHKS NASNAPSTSS NTNLTSHPVA
MGNLGTIESG GSGSAGSYTG TPRFYTPSAT PGGGSGMAIS DNPNYRLLDE SIASEQATIL
TTSSPNPNYE MMHPPTSLVS TNPNYMPMNE TPVQMAGVTI SHNPNYQPMQ APLNARQSQS
SSDEDNEQEE DDEDEDDDVD DEHVEHIKME RMPLSRPRQR ALPSKTQPPR SRSVSQTRKS
PTNPNSGIGA TGAGNRSNLL KENWLRPAST PRPPPPNGFI GREA
