ID INSR_AEDAE Reviewed; 1393 AA.
AC Q93105; Q17IL5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 27-MAR-2024, entry version 166.
DE RecName: Full=Insulin-like receptor;
DE Short=MIR;
DE EC=2.7.10.1;
DE Contains:
DE RecName: Full=Insulin-like receptor alpha chain;
DE Contains:
DE RecName: Full=Insulin-like receptor beta chain;
DE Flags: Precursor;
GN Name=InR; ORFNames=AAEL002317;
OS Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Culicinae; Aedini; Aedes; Stegomyia.
OX NCBI_TaxID=7159;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=UGAL; TISSUE=Ovary;
RX PubMed=9099579; DOI=10.1111/j.1365-2583.1997.tb00083.x;
RA Graf R., Neuenschwander S., Brown M.R., Ackermann U.;
RT "Insulin-mediated secretion of ecdysteroids from mosquito ovaries and
RT molecular cloning of the insulin receptor homologue from ovaries of
RT bloodfed Aedes aegypti.";
RL Insect Mol. Biol. 6:151-163(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LVPib12;
RX PubMed=17510324; DOI=10.1126/science.1138878;
RA Nene V., Wortman J.R., Lawson D., Haas B.J., Kodira C.D., Tu Z.J.,
RA Loftus B.J., Xi Z., Megy K., Grabherr M., Ren Q., Zdobnov E.M., Lobo N.F.,
RA Campbell K.S., Brown S.E., Bonaldo M.F., Zhu J., Sinkins S.P.,
RA Hogenkamp D.G., Amedeo P., Arensburger P., Atkinson P.W., Bidwell S.L.,
RA Biedler J., Birney E., Bruggner R.V., Costas J., Coy M.R., Crabtree J.,
RA Crawford M., DeBruyn B., DeCaprio D., Eiglmeier K., Eisenstadt E.,
RA El-Dorry H., Gelbart W.M., Gomes S.L., Hammond M., Hannick L.I.,
RA Hogan J.R., Holmes M.H., Jaffe D., Johnston S.J., Kennedy R.C., Koo H.,
RA Kravitz S., Kriventseva E.V., Kulp D., Labutti K., Lee E., Li S.,
RA Lovin D.D., Mao C., Mauceli E., Menck C.F., Miller J.R., Montgomery P.,
RA Mori A., Nascimento A.L., Naveira H.F., Nusbaum C., O'Leary S.B., Orvis J.,
RA Pertea M., Quesneville H., Reidenbach K.R., Rogers Y.-H.C., Roth C.W.,
RA Schneider J.R., Schatz M., Shumway M., Stanke M., Stinson E.O.,
RA Tubio J.M.C., Vanzee J.P., Verjovski-Almeida S., Werner D., White O.R.,
RA Wyder S., Zeng Q., Zhao Q., Zhao Y., Hill C.A., Raikhel A.S., Soares M.B.,
RA Knudson D.L., Lee N.H., Galagan J., Salzberg S.L., Paulsen I.T.,
RA Dimopoulos G., Collins F.H., Bruce B., Fraser-Liggett C.M., Severson D.W.;
RT "Genome sequence of Aedes aegypti, a major arbovirus vector.";
RL Science 316:1718-1723(2007).
CC -!- FUNCTION: Has a ligand-stimulated tyrosine-protein kinase activity.
CC Regulates cell number and cell size during development by regulating
CC cell growth and survival, affecting body size and organ size, including
CC ovaries and imaginal disks. Plays a role in life-span determination.
CC May be involved in regulation of other neuroendocrine signaling
CC pathways. Involved in the development of the embryonic nervous system.
CC Functions upstream of dock/dreadlocks for photoreceptor (R cell) axon
CC guidance and targeting in the visual system.
CC {ECO:0000250|UniProtKB:P09208}.
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: Activated in response to insulin.
CC Autophosphorylation activates the kinase activity.
CC {ECO:0000250|UniProtKB:P09208}.
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 (By
CC similarity). Interacts (via C-terminal cytoplasmic region) with
CC dock/dreadlocks (via SH2 and SH3 domains); when autophosphorylated (By
CC similarity). Interacts (via beta subunit) with chico; this interaction
CC leads to tyrosine phosphorylation of the insulin receptor substrate
CC chico (By similarity). {ECO:0000250|UniProtKB:P06213,
CC ECO:0000250|UniProtKB:P09208}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and ovary.
CC {ECO:0000269|PubMed:9099579}.
CC -!- PTM: Autophosphorylated on tyrosine residues, including Tyr-1549 and
CC Tyr-1550, in response to exogenous insulin (By similarity). Tyr-1549
CC and Tyr-1550 are dephosphorylated by Ptp61F recruited by the
CC dock/dreadlocks adapter protein (By similarity).
CC {ECO:0000250|UniProtKB:P09208}.
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=EAT46545.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; U72939; AAB17094.1; -; mRNA.
DR EMBL; CH477238; EAT46545.1; ALT_SEQ; Genomic_DNA.
DR PIR; T30346; T30346.
DR RefSeq; XP_001661260.1; XM_001661210.1.
DR AlphaFoldDB; Q93105; -.
DR SMR; Q93105; -.
DR DIP; DIP-29908N; -.
DR IntAct; Q93105; 1.
DR STRING; 7159.Q93105; -.
DR GlyCosmos; Q93105; 16 sites, No reported glycans.
DR PaxDb; 7159-AAEL002317-PA; -.
DR VEuPathDB; VectorBase:AAEL002317; -.
DR eggNOG; KOG4258; Eukaryota.
DR HOGENOM; CLU_000288_166_1_1; -.
DR InParanoid; Q93105; -.
DR BRENDA; 2.7.10.1; 149.
DR Proteomes; UP000008820; Unassembled WGS sequence.
DR Proteomes; UP000682892; Unassembled WGS sequence.
DR GO; GO:0071944; C:cell periphery; IEA:UniProt.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043559; F:insulin binding; ISS:UniProtKB.
DR GO; GO:0005009; F:insulin receptor activity; ISS:UniProtKB.
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:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IEA:UniProt.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0000003; P:reproduction; IEA:UniProt.
DR CDD; cd00063; FN3; 2.
DR CDD; cd00064; FU; 1.
DR CDD; cd05032; PTKc_InsR_like; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR Gene3D; 3.80.20.20; Receptor L-domain; 2.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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; IPR016246; Tyr_kinase_insulin-like_rcpt.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF525; INSULIN-LIKE RECEPTOR; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000620; Insulin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00261; FU; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 3.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF52058; L domain-like; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50853; FN3; 3.
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 2: Evidence at transcript level;
KW ATP-binding; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Kinase; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..753
FT /note="Insulin-like receptor alpha chain"
FT /evidence="ECO:0000255"
FT /id="PRO_0000016719"
FT CHAIN 758..1393
FT /note="Insulin-like receptor beta chain"
FT /evidence="ECO:0000255"
FT /id="PRO_0000016721"
FT TOPO_DOM 758..966
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 967..987
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 988..1393
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 240..287
FT /note="FU"
FT DOMAIN 507..623
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 624..729
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 860..961
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1025..1302
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 754..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1328..1365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1374..1393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1349..1363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1163
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1031..1039
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1059
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1189
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1193
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1194
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 457
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 772
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 793
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 796
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 871
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 919
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 933
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 38
FT /note="S -> T (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 110..111
FT /note="IR -> YP (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="L -> V (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="L -> P (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="C -> W (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 1126..1132
FT /note="NGEDPSP -> MRRSIR (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 1151..1153
FT /note="MAY -> IGV (in Ref. 1; AAB17094)"
FT /evidence="ECO:0000305"
FT CONFLICT 1380..1393
FT /note="GPMATIRSPHSPLR -> ARWPRSVRHTRH (in Ref. 1;
FT AAB17094)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1393 AA; 156728 MW; BD75381D755CEC60 CRC64;
MVSLLLFSIL VVPVAVVQGD EMKAGQVGPV PKGGVCGSVD VRNSPAHLDR LKDCVVVEGF
VHILLIDKYI DSSFENYSFP LLTEITEYLL LFRVNGLKSL RRLFPNLAVI RGDALVGDYA
MVIYELMHIE EIGLISLMDI TRGGVRIEKN PKLCFANTID WKAMTVPGTN NYIKDNQKDN
VCPICPAEST AVMLPNGSKQ KCPAAPVRGG NKDHKRTLCW NANHCQTICP PECPKACSKT
GVCCDAESCL GGCNLPNTSS CSVCRHLSID PAGKRQCVAK CPPNTFKYHT RCVTRDECYA
MKKPISLDSN PDLPDQPFIP HNGSCLMECP LDHELITELN KTRWCRKCSG TCPKRCEGSN
IDNIQSAQLL KGCEIIDGSL EIQLRSRGGE NIVKELENFL SSITEIKGYL KVVRSYPLLS
LGFLKKLKII HGKGNKVSNS SLYVVENQNL QELFDHNVTI GEGKLFFFNN PMLCTDRIKA
VKKYNPGIEI ENESQLESNN GDRAACSITE LETSLKSIGS ETAIIQWAPF TELSDARMLL
GYVIYYIEAP YANVTFFDGR DACNTEGWRL DDISDFNMDK ETTKILTQLK PYTQYAYYVK
TYTLGSEGLG GQSKIKYFTT APGTPSVVRD VEVSVNKNML TVKWLPPLKM NGRLKEYEVF
IELNADDNEQ LMLRDYCEDD KLRDIVPETP TSAPPPKTSI CTADQCRNYC KAPTSGGSTG
TIDVTDKENQ ITFEDQLHNY VYIKNPLLRD KTTRRKRSTN LLFPNNTENK KNDTTDRRTE
KVKDEPYYQY IFNATNETSI TFPLSYFNHY SLYVFKIRAC RHPGDPPAPS VRLVDVELAC
GNEVFENFRT PKKEGADDIP PESILIEEQS NNTQRQIRVQ WKEPSKPNGP IVKFVVKYQR
VDLESVSSTD ICIRYSSFNQ TRGALLTKLE PGNYSIRVMA TTIAGDGAPS AARYVLIAKD
DSMGTTLIWL GTLIVIFLCS VGFVAFYWYK YRYMSKQIRM YPEVNPDYAG VQYKVDDWEV
ERNHIIQLEE LGQGSFGMVY KGILTQLRGE KCNQPCAIKT VNESATAREK DSFLLEASVM
KQFNTHHVVR LLGVVSQGDP TLVIMELMAN GDLKSYLRRH RPDYENGEDP SPQPPTLRQI
IQMAIEIADG MAYLSAKKFV HRDLAARNCM VADDMTVKIG DFGMTRDIYE TDYYRKGTKG
FLPVRWMAPE SLKDGIFSSS SDVFSYGVVL WEMATLASQP YQGLTNDQVL RYVIDGGVME
RPENCPDNLY NLMRRCWQHR PTARPTFMEI ISELLPDASP HFQDVAFYNS QDALDMLRGQ
HQTVIIDEAT TPLRPGDDHD EEPGEDDDLV GHGEGHIGDV GTDDEFSMEM TNSHLVRNNG
PMATIRSPHS PLR
//
