Protein detail
INSR
Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
Protein symbol INSR | UniProt ID | EVMP score 0.63 |
Frequency 6 | Transmembrane count 1 | Protein classification CD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
Protein Class
CD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Endocrine and metabolic diseases:Diabetes
- Human disease related genes:Congenital disorders of metabolism:Other congenital disorders of metabolism
- ENZYME proteins:Transferases
- CD markers
- RAS pathway related proteins
- Human disease related genes:Endocrine and metabolic diseases:Other endocrine and metabolic diseases
- Enzymes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- FDA approved drug targets:Biotech drugs
Transmembrane
957..979; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
CD220
Gene Description
Insulin receptor
Chromosome
19
Position
7112255-7294414
Frequency
6
EVMP Score
0.63
Fluorescence & Localization
Tissue Specificbone marrowCell SpecificEnterocytesSingle-Nuclei Brain SpecificfibroblastBlood Cell Specificclassical monocyteBlood Lineage Specificdendritic cellsSecretome LocationIntracellular and membraneSecretome FunctionEnzyme
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Endocrine and metabolic diseases:Diabetes
- Human disease related genes:Congenital disorders of metabolism:Other congenital disorders of metabolism
- ENZYME proteins:Transferases
- CD markers
- RAS pathway related proteins
- Human disease related genes:Endocrine and metabolic diseases:Other endocrine and metabolic diseases
- Enzymes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- FDA approved drug targets:Biotech drugs
Cellular Component
- GO:0005635 nuclear envelope
- GO:0005764 lysosome
- GO:0005770 late endosome
- GO:0005886 plasma membrane
- GO:0005899 insulin receptor complex
- GO:0005901 caveola
- GO:0009897 external side of plasma membrane
- GO:0010008 endosome membrane
- GO:0016020 membrane
- GO:0030424 axon
- GO:0030425 dendrite
- GO:0031981 nuclear lumen
- GO:0032590 dendrite membrane
- GO:0032809 neuronal cell body membrane
- GO:0043025 neuronal cell body
- GO:0043235 receptor complex
- GO:0044297 cell body
- GO:0070062 extracellular exosome
Molecular Function
- GO:0001540 amyloid-beta binding
- GO:0004713 protein tyrosine kinase activity
- GO:0005009 insulin receptor activity
- GO:0005159 insulin-like growth factor receptor binding
- GO:0005198 structural molecule activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0005525 GTP binding
- GO:0019904 protein domain specific binding
- GO:0030295 protein kinase activator activity
- GO:0031994 insulin-like growth factor I binding
- GO:0031995 insulin-like growth factor II binding
- GO:0038024 cargo receptor activity
- GO:0042802 identical protein binding
- GO:0043548 phosphatidylinositol 3-kinase binding
- GO:0043559 insulin binding
- GO:0043560 insulin receptor substrate binding
- GO:0044877 protein-containing complex binding
- GO:0051425 PTB domain binding
Biological Process
KEGG
- hsa04010 MAPK signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04022 cGMP-PKG signaling pathway
- KEGG:hsa04066 HIF-1 signaling pathway
- KEGG:hsa04068 FoxO signaling pathway
- KEGG:hsa04072 Phospholipase D signaling pathway
- KEGG:hsa04081 Hormone signaling
- KEGG:hsa04150 mTOR signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04152 AMPK signaling pathway
- KEGG:hsa04211 Longevity regulating pathway
- KEGG:hsa04213 Longevity regulating pathway - multiple species
- KEGG:hsa04520 Adherens junction
- KEGG:hsa04910 Insulin signaling pathway
- KEGG:hsa04913 Ovarian steroidogenesis
- KEGG:hsa04923 Regulation of lipolysis in adipocytes
- KEGG:hsa04930 Type II diabetes mellitus
- KEGG:hsa04931 Insulin resistance
- KEGG:hsa04932 Non-alcoholic fatty liver disease
- KEGG:hsa04960 Aldosterone-regulated sodium reabsorption
- KEGG:hsa05010 Alzheimer disease
- KEGG:hsa05415 Diabetic cardiomyopathy
Reactome
- R-hsa-77387 insulin receptor recycling
- R-hsa-74751 insulin receptor signalling cascade
- R-hsa-9006925 intracellular signaling by second messengers
- R-hsa-74713 irs activation
- R-hsa-199418 negative regulation of the pi3k akt network
- R-hsa-74752 signaling by insulin receptor
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-74749 signal attenuation
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
143 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| INSR | TNF | P01375 | Y | 999 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:24966659 |
| INSR | MAPKAP1 | Q9BPZ7 | S | 473 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:27273879 |
| INSR | IRS1 | P35568 | S | 473 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:15718410ProtMapper:25365322 |
| INSR | HGF | P14210 | Y | 1,189 | phosphorylation | REACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:30197476 |
| INSR | HGF | P14210 | Y | 1,185 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:30197476 |
| INSR | HGF | P14210 | Y | 1,190 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:30197476 |
| INSR | TBK1 | Q9UHD2 | S | 994 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:30223576 |
| INSR | IGF1R | P08069 | Y | 1,185 | phosphorylation | KEA | KEA:17570479 |
| INSR | IGF1R | P08069 | Y | 1,189 | phosphorylation | KEA | KEA:17570479 |
| INSR | IGF1R | P08069 | Y | 1,190 | phosphorylation | KEA | KEA:17570479 |
Ligand-Receptor Signaling
58 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| transmembrane | transmembrane | UniProt_keyword | No | No | No | Yes | No |
| transmembrane | transmembrane | GO_Intercell | No | No | No | Yes | No |
| transmembrane | transmembrane | CellPhoneDB | No | No | No | Yes | No |
| transmembrane | transmembrane | TopDB | No | No | No | Yes | No |
| transmembrane | transmembrane | LOCATE | No | No | No | Yes | No |
| transmembrane | transmembrane | Ramilowski_location | No | No | No | Yes | No |
| transmembrane | transmembrane | OmniPath | No | No | No | Yes | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | Yes | No |
| plasma_membrane | plasma_membrane | Cellinker | No | No | No | Yes | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | Yes | No |
Regulatory Interaction Network
53 records.
Protein Complex Composition
12 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| SNX complex (SNX1SNX1aSNX2SNX4INSR) | INSRSNX1SNX2SNX4 | O60749O95219P06213Q13596 | 1:1:1:1 | CompleatCORUM | CORUM:1093Compleat:HC3406 | 9819414 |
| Sam68-p85 P13K-IRS-1-IR signaling complex | INSRIRS1KHDRBS1PIK3R1 | P06213P27986P35568Q07666 | 1:1:1:1 | CompleatCORUM | CORUM:2577Compleat:HC1698 | 11604231 |
| A6XGL2INSR | A6XGL2P06213 | 4:2 | PDB | PDB:6pxwPDB:6pxv | ||
| INSINS-IGF2INSR | F8WCM5P01308P06213 | 1:1:2 | PDB | PDB:7yq5PDB:7yq4PDB:8guyPDB:7yq3 | ||
| INSINSR | P01308P06213 | 2:2 | PDB | PDB:6sofPDB:7mqoPDB:7u6ePDB:7pg2PDB:7pg4PDB:7kd6PDB:7bw7PDB:3w11PDB:7qidPDB:3w13PDB:6vepPDB:7bw8PDB:7mqsPDB:7bwaPDB:7md5PDB:7md4PDB:7mqrPDB:8yysPDB:3w12PDB:4ogaPDB:7pg3PDB:7pg0 | ||
| IGF2INSR | P01344P06213 | 4:2 | PDB | PDB:8vjbPDB:8vjcPDB:8yszPDB:8u4ePDB:8u4c | ||
| IGF1INSR | P05019P06213 | 2:2 | PDB | PDB:8xkmPDB:8x2mPDB:8xjsPDB:8x06PDB:8xk1PDB:8xkr | ||
| INSR | P06213 | 2 | PDB | PDB:9jhsPDB:9jf9PDB:8u4bPDB:4ibmPDB:7yq6PDB:3etaPDB:9jfdPDB:2hr7PDB:7u6d | ||
| INSRPTPN1 | P06213P18031 | 2:2 | PDB | PDB:2b4s | ||
| INSRIRS1 | P06213P35568 | 1:1 | PDB | PDB:5u1mPDB:2z8c |
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Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | NA | 1 | 37505422 |
Sequence, Structure & Domains
Sequences
Length
1,382
Mass
156,333
Sequence
MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=Long; Synonyms=HIR-B; IsoId=P06213-1; Sequence=Displayed; Name=Short; Synonyms=HIR-A; IsoId=P06213-2; Sequence=VSP_002898
Alternative Sequence
745..756; Missing (in isoform Short)
3D Structural Models
Turn
73..75; 100..102; 187..192; 276..278; 323..325; 356..359; 422..424; 441..443; 476..478; 481..483; 1003..1005; 1185..1187; 1236..1239; 1303..1305
Helix
45..50; 70..72; 160..162; 167..169; 176..178; 221..223; 283..295; 351..355; 377..385; 463..472; 524..526; 666..669; 732..740; 902..908; 953..979; 1009..1011; 1014..1016; 1020..1022; 1065..1078; 1111..1117; 1133..1152; 1162..1164; 1200..1202; 1205..1210; 1215..1230; 1242..1250; 1263..1272; 1277..1279; 1283..1290; 1291..1293; 1298..1301; 1307..1309
Beta Strand
33..42; 53..65; 83..86; 88..93; 103..105; 115..117; 118..124; 141..149; 155..158; 171..175; 199..201; 204..206; 209..211; 224..226; 230..232; 243..247; 251..260; 263..267; 273..275; 279..281; 298..300; 305..307; 310..314; 319..321; 327..330; 332..334; 338..348; 361..369; 373..375; 390..393; 395..399; 404..406; 414..416; 425..430; 437..439; 447..450; 452..458; 486..490; 498..500; 504..507; 512..515; 527..536; 538..540; 552..554; 557..561; 570..573; 577..580; 588..597; 601..603; 608..610; 613..616; 626..631; 633..636; 638..643; 654..658; 798..803; 805..809; 817..827; 838..843; 858..861; 867..870; 881..890; 896..901; 910..913; 918..931; 940..944; 992..995; 1023..1031; 1033..1043; 1046..1048; 1050..1057; 1089..1093; 1095..1098; 1100..1104; 1119..1121; 1154..1156; 1165..1167; 1173..1175; 1181..1183; 1190..1192; 1194..1198
3D Structure
Electron microscopy (40); NMR spectroscopy (2); X-ray crystallography (34)
Domain & Motif Annotations
Domain (CC)
The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2..
Domain (FT)
624..726; Fibronectin type-III 1; 757..842; Fibronectin type-III 2; 853..947; Fibronectin type-III 3; 1023..1298; Protein kinase
Region
686..708; Disordered; 733..741; Insulin-binding; 746..766; Disordered; 999; Important for interaction with IRS1, SHC1 and STAT5B; 1360..1382; Disordered; 1361..1364; PIK3R1-binding
Protein Families
- Protein kinase superfamily
- Tyr protein kinase family
- Insulin receptor subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Clinical Relevance
Disease Involvement
Diabetes mellitusDisease variantFDA approved drug targets
Related Diseases
Biomarker
Approved; Phase 2; Discontinued in Phase 1/2; Phase 1; Terminated; Investigative; Phase 4
Drug Targets
FDA approved drug targets
Drugs
CERITINIBNULLKW-2450GW441756XCYC-116INSULIN LISPRO PROTAMINE RECOMBINANTINSULIN ASPART PROTAMINE, HUMANINSULIN GLULISINE, HUMANINSULIN TREGOPILINSULIN ZINC SUSP EXTENDED BEEFINSULIN ZINC SUSP PROMPT BEEFAGT-182RECOMBINANT HUMAN KALLIKREIN-1INSULIN, PROTAMINE ZINCGO-6976INSULIN ZINC SUSP PURIFIED BEEF/PORKFLUOROURACILINSULIN [INJECTION], BIPHASICINSULIN, ISOPHANEINSULIN HUMAN, ISOPHANECENISERTIBINSULIN SUSP PROTAMINE ZINC PURIFIED PORKINSULIN ZINC SUSP EXTENDED PURIFIED BEEFINSULIN SUSP ISOPHANE BEEF/PORKINSULIN ZINC SUSP PURIFIED BEEFINSULIN, REGULAR, HUMANMETHAZOLAMIDEINSULIN, REGULAR, PORKINSULIN ZINC SUSP SEMISYNTHETIC PURIFIED HUMANEPIRUBICINNVP-TAE684INSULIN DETEMIRINSULIN PURIFIED BEEFINSULIN GLARGINE-YFGNINSULIN SUSP PROTAMINE ZINC BEEF/PORKINSULIN SUSP ISOPHANE PURIFIED BEEFINSULIN PEGLISPROINSULIN SUSP ISOPHANE RECOMBINANT HUMANSP-600125DOVITINIBTOPIRAMATEBMS-754807INSULIN SENSITIZER S-707106INSULIN DEGLUDECMETFORMIN GLYCINATEILORASERTIBINSULIN PURIFIED PORKINSULIN ZINC SUSP PURIFIED PORKINSULIN SUSP ISOPHANE SEMISYNTHETIC PURIFIED HUMANHESPERADINRG-1530INSULIN ZINC SUSP PROMPT PURIFIED PORKINSULIN ZINC, EXTENDEDTAMATINIBINSULIN ASPART PROTAMINE RECOMBINANTINSULIN LISPRO-AABCINSULIN ZINC, PROMPTINSULIN SUSP PROTAMINE ZINC PURIFIED BEEFPF-562271LINIFANIBTOZASERTIBINSULIN ZINC SUSP RECOMBINANT HUMANINSULIN ZINC SUSP BEEFINSULIN SUSP ISOPHANE PURIFIED PORKINSULIN ZINC SUSP EXTENDED RECOMBINANT HUMANINSULIN SUSP ISOPHANE BEEFCYCLOPHOSPHAMIDE ANHYDROUSAEW-541TESOFENSINELINSITINIBMITOGLITAZONE
Interaction Protein
ENSG00000027644ENSG00000106070ENSG00000128228ENSG00000140443ENSG00000145675ENSG00000153233ENSG00000160691ENSG00000164109ENSG00000167065ENSG00000168961ENSG00000169047ENSG00000178188ENSG00000179295ENSG00000185950ENSG00000196396ENSG00000197594
Interaction Count
16
Interaction Dataset
intact_biogrid_bioplexintact_biogridbiogrid_bioplex