EV MemProt Atlas

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

ENSG00000171105

Entrez Gene Symbol

INSR

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

Molecular Function

Biological Process

KEGG

Reactome

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	PTPRE	P23469	Y	999	dephosphorylation	SIGNOR	SIGNOR:15738637
INSR	PTPRE	P23469	Y	1,185	dephosphorylation	SIGNOR	SIGNOR:15738637
INSR	PTPRE	P23469	Y	1,189	dephosphorylation	SIGNOR	SIGNOR:15738637
INSR	PTPRE	P23469	Y	1,190	dephosphorylation	SIGNOR	SIGNOR:15738637
INSR	PTPRE	P23469	Y	1,189	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:15738637
INSR	PTPRE	P23469	Y	1,190	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:15738637
INSR	PTPRE	P23469	Y	999	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:15738637
INSR	PTPRE	P23469	Y	1,185	phosphorylation	SIGNOR_ProtMapperProtMapper	ProtMapper:15738637
INSR	PTPN9	P43378	Y	1,185	dephosphorylation	SIGNOR	SIGNOR:16679294
INSR	PTPN9	P43378	Y	1,190	dephosphorylation	SIGNOR	SIGNOR:16679294

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Ligand-Receptor Signaling

58 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	CellCall	No	Yes	No	Yes	No
receptor	receptor	iTALK	No	Yes	No	Yes	No
growth_factor	receptor	iTALK	No	Yes	No	Yes	No
receptor	receptor	CellCellInteractions	No	Yes	No	Yes	No
receptor	receptor	EMBRACE	No	Yes	No	Yes	No
tyrosine_kinase	receptor	HGNC	No	Yes	No	Yes	No
receptor	receptor	HGNC	No	Yes	No	Yes	No
transmembrane	transmembrane_predicted	Phobius	No	No	No	Yes	No

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Regulatory Interaction Network

53 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
INSR	P06213	PTN6	P29350	Yes	Yes	No	HPRD_MIMPSIGNORProtMapperPhosphoSite_KEAHPRDKinexus_KEAWangPhosphoSite_ProtMapperNetworKIN_KEAphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEASIGNOR_ProtMapperSparser_ProtMapperAdhesomeHPRD-phos	HPRD:8692915 HPRD-phos:8114715 KEA:8692915 iPTMnet:7512963 HPRD:7512963 Adhesome:7512963 Adhesome:8114715 Adhesome:8692915 HPRD:8114715 ProtMapper:18377662 ProtMapper:8114715 KEA:8114715 Adhesome:12468540 KEA:14699166 ProtMapper:7512963 HPRD-phos:7512963 SIGNOR:7512963 KEA:14757045 KEA:7512963 ProtMapper:16497976 KEA:12468540 HPRD-phos:16497976 HPRD:12468540 KEA:17570479
PTN6	P29350	INSR	P06213	Yes	Yes	Yes	AdhesomeSIGNORProtMapperHPRDSIGNOR_ProtMapper	HPRD:7512963 Adhesome:7512963 HPRD:8692915 Adhesome:12468540 ProtMapper:10734133 Adhesome:8114715 Adhesome:8692915 HPRD:12468540 HPRD:8114715 SIGNOR:10734133
PTPRH	Q9HD43	INSR	P06213	Yes	No	Yes	SIGNOR_ProtMapperSIGNORProtMapper	ProtMapper:10734133 SIGNOR:10734133
INSR	P06213	CALM2	P0DP24	Yes	No	Yes	phosphoELM_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEAphosphoELMSIGNOR_ProtMapperHPRD-phos	SIGNOR:3415247 HPRD-phos:12153558 KEA:8639568 HPRD-phos:18669648 ProtMapper:3415247 HPRD:12153558 KEA:2843348 ProtMapper:17016520 HPRD-phos:18578522 KEA:7925415 HPRD-phos:20068231 KEA:12153558 HPRD-phos:8639568 ProtMapper:12153558 KEA:15592455 ProtMapper:17287340 phosphoELM:8639568 HPRD-phos:19901323 HPRD-phos:18707149 HPRD-phos:17389395 ProtMapper:16497976 HPRD-phos:17287340 HPRD-phos:16497976 phosphoELM:2843348 ProtMapper:18669648 HPRD-phos:17016520
INSR	P06213	FRS2	Q8WU20	Yes	Yes	No	HPRDWangPhosphoPointSIGNOR	SIGNOR:10650943 HPRD:10650943
INSR	P06213	KHDR1	Q07666	Yes	Yes	No	HPRDWangPhosphoPointSIGNOR	HPRD:10437794 SIGNOR:11604231
IGF2	P01344	INSR	P06213	Yes	Yes	No	iTALKSIGNORHINTHPMR_talklrHPRD_LRdbtalklrHPRDRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbHPRD_talklrBaccin2019CellinkerEMBRACECellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb	CellTalkDB:9281335 HPRD:9722981 Cellinker:9722981 Cellinker:9281335 LRdb:9281335LRdb:972HINT:38521788 SIGNOR:9281335 connectomeDB2020:9722981 connectomeDB2020:9281335 Baccin2019:9722981 Baccin2019:9281335 HINT:33961781
INSR	P06213	P85A	P27986	Yes	Yes	No	HPRD_MIMPSIGNORProtMapperHINTPhosphoSite_KEAphosphoELM_KEALi2012DIPLit-BM-17HPRDKinexus_KEAIntActLMPIDWangNetworKIN_KEAPhosphoSite_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_norefPhosphoPointiPTMnetKEABioGRIDHPRD_KEAphosphoELMSIGNOR_ProtMapperPhosphoSiteHPRD-phos	Lit-BM-17:11796522 KEA:17570479 LMPID:7983060 HINT:10500481 HINT:9593725 HPRD:15629149 DIP:7589433 HINT:15735664 Lit-BM-17:9593725 Lit-BM-17:10500481 ProtMapper:8385099 HINT:8567177 ProtMapper:17016520 phosphoELM:8385099 HPRD-phos:20068231 HINT:8603569 HINT:1334490 SIGNOR:8385099 ProtMapper:17389395 HPRD:14729945 HPRD:8276809 HPRD-phos:8385099 HINT:11796522 IntAct:11796522 KEA:14729945 KEA:18083107 ProtMapper:14729945 KEA:15592455 BioGRID:8567177 HINT:7589433 IntAct:10500481 KEA:8385099 PhosphoSite:8385099 HPRD-phos:14729945 HPRD-phos:17389395 Lit-BM-17:7589433 ProtMapper:16497976 ProtMapper:20068231 HPRD-phos:16497976 HPRD:8385099 IntAct:9593725 HPRD-phos:17016520
INSR	P06213	P55G	Q92569	Yes	No	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDKEAKinexus_KEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:7542745 HPRD:9524259 KEA:18083107 ProtMapper:7542745 SIGNOR:7542745
INSR	P06213	IRS4	O14654	Yes	Yes	No	WangSIGNOR	SIGNOR:25905389

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Protein Complex Composition

12 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
SNX complex (SNX1SNX1aSNX2SNX4INSR)	INSR SNX1 SNX2 SNX4	O60749 O95219 P06213 Q13596	1:1:1:1	CompleatCORUM	CORUM:1093Compleat:HC3406	9819414
Sam68-p85 P13K-IRS-1-IR signaling complex	INSR IRS1 KHDRBS1 PIK3R1	P06213 P27986 P35568 Q07666	1:1:1:1	CompleatCORUM	CORUM:2577Compleat:HC1698	11604231
	A6XGL2 INSR	A6XGL2 P06213	4:2	PDB	PDB:6pxwPDB:6pxv
	INS INS-IGF2 INSR	F8WCM5 P01308 P06213	1:1:2	PDB	PDB:7yq5PDB:7yq4PDB:8guyPDB:7yq3
	INS INSR	P01308 P06213	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
	IGF2 INSR	P01344 P06213	4:2	PDB	PDB:8vjbPDB:8vjcPDB:8yszPDB:8u4ePDB:8u4c
	IGF1 INSR	P05019 P06213	2:2	PDB	PDB:8xkmPDB:8x2mPDB:8xjsPDB:8x06PDB:8xk1PDB:8xkr
	INSR	P06213	2	PDB	PDB:9jhsPDB:9jf9PDB:8u4bPDB:4ibmPDB:7yq6PDB:3etaPDB:9jfdPDB:2hr7PDB:7u6d
	INSR PTPN1	P06213 P18031	2:2	PDB	PDB:2b4s
	INSR IRS1	P06213 P35568	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

Acute diabete complication Alzheimer disease Breast cancer Crohn disease Diabetes mellitus Hyper-lipoproteinaemia Hypo-glycaemia Lymphoma Lysosomal disease Multiple myeloma Pain Pancreatic internal secretion disorder Psychotic disorder Type 2 diabetes mellitus Type-1/2 diabete

Biomarker

Approved; Phase 2; Discontinued in Phase 1/2; Phase 1; Terminated; Investigative; Phase 4

Drug Targets

FDA approved drug targets

Drugs

CERITINIB NULL KW-2450 GW441756X CYC-116 INSULIN LISPRO PROTAMINE RECOMBINANT INSULIN ASPART PROTAMINE, HUMAN INSULIN GLULISINE, HUMAN INSULIN TREGOPIL INSULIN ZINC SUSP EXTENDED BEEF INSULIN ZINC SUSP PROMPT BEEF AGT-182 RECOMBINANT HUMAN KALLIKREIN-1 INSULIN, PROTAMINE ZINC GO-6976 INSULIN ZINC SUSP PURIFIED BEEF/PORK FLUOROURACIL INSULIN [INJECTION], BIPHASIC INSULIN, ISOPHANE INSULIN HUMAN, ISOPHANE CENISERTIB INSULIN SUSP PROTAMINE ZINC PURIFIED PORK INSULIN ZINC SUSP EXTENDED PURIFIED BEEF INSULIN SUSP ISOPHANE BEEF/PORK INSULIN ZINC SUSP PURIFIED BEEF INSULIN, REGULAR, HUMAN METHAZOLAMIDE INSULIN, REGULAR, PORK INSULIN ZINC SUSP SEMISYNTHETIC PURIFIED HUMAN EPIRUBICIN NVP-TAE684 INSULIN DETEMIR INSULIN PURIFIED BEEF INSULIN GLARGINE-YFGN INSULIN SUSP PROTAMINE ZINC BEEF/PORK INSULIN SUSP ISOPHANE PURIFIED BEEF INSULIN PEGLISPRO INSULIN SUSP ISOPHANE RECOMBINANT HUMAN SP-600125 DOVITINIB TOPIRAMATE BMS-754807 INSULIN SENSITIZER S-707106 INSULIN DEGLUDEC METFORMIN GLYCINATE ILORASERTIB INSULIN PURIFIED PORK INSULIN ZINC SUSP PURIFIED PORK INSULIN SUSP ISOPHANE SEMISYNTHETIC PURIFIED HUMAN HESPERADIN RG-1530 INSULIN ZINC SUSP PROMPT PURIFIED PORK INSULIN ZINC, EXTENDED TAMATINIB INSULIN ASPART PROTAMINE RECOMBINANT INSULIN LISPRO-AABC INSULIN ZINC, PROMPT INSULIN SUSP PROTAMINE ZINC PURIFIED BEEF PF-562271 LINIFANIB TOZASERTIB INSULIN ZINC SUSP RECOMBINANT HUMAN INSULIN ZINC SUSP BEEF INSULIN SUSP ISOPHANE PURIFIED PORK INSULIN ZINC SUSP EXTENDED RECOMBINANT HUMAN INSULIN SUSP ISOPHANE BEEF CYCLOPHOSPHAMIDE ANHYDROUS AEW-541 TESOFENSINE LINSITINIB MITOGLITAZONE

Antibody

HPA036302 HPA036303

Interaction Protein

ENSG00000027644ENSG00000106070ENSG00000128228ENSG00000140443ENSG00000145675ENSG00000153233ENSG00000160691ENSG00000164109ENSG00000167065ENSG00000168961ENSG00000169047ENSG00000178188ENSG00000179295ENSG00000185950ENSG00000196396ENSG00000197594

Interaction Count

16

Interaction Dataset

intact_biogrid_bioplexintact_biogridbiogrid_bioplex

Protein symbol INSR	UniProt ID P06213	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