Insr
entrez
16337
canonical
uniprot
P15208
canonical
ensembl
ENSMUSG00000005534
resolver
ensp
ENSMUSP00000088837
resolver
enst
ENSMUST00000091291
resolver
genesymbol
Insr
resolver
uniprot
F8VPU4
resolver
uniprot
M4TKR7
resolver
uniprot
Q3TPM5
resolver
uniprot_entry
INSR_MOUSE
resolver
uniprot_entry
M4TKR7_MOUSE
resolver
uniprot_entry
Q3TPM5_MOUSE
resolver
uniprot_sec
F8VPU4
resolver
activity_regulation
ACTIVITY REGULATION: Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates (By similarity). Interacts with PTPRF (By similarity). Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P15127}.
uniprot
proteins
amino_acid_sequence
MGFGRGCETTAVPLLVAVAALLVGTAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin (PubMed:38061240). Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). When present in a hybrid receptor with IGF1R, binds IGF1 (By similarity). In adipocytes, inhibits lipolysis (PubMed:27322061). {ECO:0000250, ECO:0000269|PubMed:27322061, ECO:0000269|PubMed:38061240}.
uniprot
proteins
mass_dalton
155610
uniprot
proteins
mutagenesis
MUTAGEN 989; /note="Y->F: Abolishes interaction with IRS1 but not with IRS2."; /evidence="ECO:0000269|PubMed:10207032, ECO:0000269|PubMed:8626379
uniprot
proteins
post_translational_modification
PTM: After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane. {ECO:0000250|UniProtKB:P06213}.; PTM: Autophosphorylated on tyrosine residues in response to insulin (PubMed:38061240). Phosphorylation of Tyr-989 is required for IRS1-, SHC1-, and STAT5B-binding (By similarity). Dephosphorylated by PTPRE on Tyr-989, Tyr-1175, Tyr-1179 and Tyr-1180 residues (By similarity). May also be phosphorylated at Tyr-1175 and Tyr-1180 by mTORC2 (By similarity). Dephosphorylated by PTPRF and PTPN1 (By similarity). Dephosphorylated by PTPN2 and Ptprv; down-regulates insulin-induced signaling (PubMed:12612081, PubMed:20655470). {ECO:0000250|UniProtKB:P06213, ECO:0000269|PubMed:12612081, ECO:0000269|PubMed:20655470, ECO:0000269|PubMed:38061240}.; PTM: S-nitrosylation at Cys-1073 by BLVRB inhibits the receptor tyrosine kinase, thereby inhibiting insulin signaling. {ECO:0000250|UniProtKB:P06213}.; PTM: Ubiquitinated by MARCHF1; leading to degradation thereby reducing surface INSR expression. {ECO:0000250|UniProtKB:P06213}.
uniprot
proteins
protein_family
Insulin receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10207032
uniprot
proteins
pubmed
10821852
uniprot
proteins
pubmed
12612081
uniprot
proteins
pubmed
15169905
uniprot
proteins
pubmed
19122674
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19656770
uniprot
proteins
pubmed
20655470
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
24078630
uniprot
proteins
pubmed
2557333
uniprot
proteins
pubmed
2602374
uniprot
proteins
pubmed
27322061
uniprot
proteins
pubmed
38061240
uniprot
proteins
pubmed
8626379
uniprot
proteins
pubmed
9447983
uniprot
proteins
sequence_length
1372
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27322061}; Single-pass type I membrane protein {ECO:0000305}. Recycling endosome membrane {ECO:0000269|PubMed:27322061}. Late endosome {ECO:0000269|PubMed:27322061}. Lysosome {ECO:0000305|PubMed:27322061}. Note=Binding of insulin to INSR induces internalization and lysosomal degradation of the receptor, a means for down-regulating this signaling pathway after stimulation. In the presence of SORL1, internalized INSR molecules are redirected back to the cell surface, thereby preventing their lysosomal catabolism and strengthening insulin signal reception. {ECO:0000269|PubMed:27322061}.
uniprot
proteins
transmembrane_region
TRANSMEM 947..967; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins