P15127 · INSR_RAT
- ProteinInsulin receptor
- GeneInsr
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1383 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. 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 (By similarity).
In adipocytes, inhibits lipolysis (By similarity).
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
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).
Features
Showing features for site, binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 65 | Insulin-binding | ||||
Sequence: F | ||||||
Binding site | 1034 | ATP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1058 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 1105-1111 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ELMAHGD | ||||||
Active site | 1160 | Proton donor/acceptor | ||||
Sequence: D | ||||||
Binding site | 1164-1165 | ATP (UniProtKB | ChEBI) | ||||
Sequence: RN | ||||||
Binding site | 1178 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameInsulin receptor
- EC number
- Short namesIR
- Cleaved into 2 chains
- CD Antigen Name
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP15127
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
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.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 27-759 | Extracellular | ||||
Sequence: HLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDYVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHYKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWNKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGNGAEDTRPS | ||||||
Topological domain | 764-957 | Extracellular | ||||
Sequence: SLEEVGNVTATTPTLPDFPNISSTIAPTSHEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPEERSGVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAK | ||||||
Transmembrane | 958-978 | Helical | ||||
Sequence: IIIGPLIFVFLFSVVIGSIYL | ||||||
Topological domain | 979-1383 | Cytoplasmic | ||||
Sequence: FLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEVETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGCREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MGSGRGCETTAVPLLMAVAVAGGTAG | ||||||
Chain | PRO_0000016696 | 27-759 | Insulin receptor subunit alpha | |||
Sequence: HLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDYVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHYKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWNKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGNGAEDTRPS | ||||||
Disulfide bond | 34↔52 | |||||
Sequence: CPGMDIRNNLTRLHELENC | ||||||
Glycosylation | 42 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 51 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 104 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 137 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 152↔181 | |||||
Sequence: CYLATIDWSRILDYVEDNYIVLNKDDNEEC | ||||||
Disulfide bond | 185↔208 | |||||
Sequence: CPGTAKGKTNCPATVINGQFVERC | ||||||
Disulfide bond | 195↔214 | |||||
Sequence: CPATVINGQFVERCWTHSHC | ||||||
Disulfide bond | 218↔227 | |||||
Sequence: CPTICKSHGC | ||||||
Disulfide bond | 222↔233 | |||||
Sequence: CKSHGCTAEGLC | ||||||
Disulfide bond | 234↔242 | |||||
Sequence: CHKECLGNC | ||||||
Disulfide bond | 238↔251 | |||||
Sequence: CLGNCSEPDDPTKC | ||||||
Glycosylation | 241 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 254↔263 | |||||
Sequence: CRNFYLDGQC | ||||||
Disulfide bond | 267↔279 | |||||
Sequence: CPPPYYHFQDWRC | ||||||
Glycosylation | 281 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 285↔310 | |||||
Sequence: CQDLHYKCRNSRKPGCHQYVIHNNKC | ||||||
Disulfide bond | 292↔300 | |||||
Sequence: CRNSRKPGC | ||||||
Disulfide bond | 314↔327 | |||||
Sequence: CPSGYTMNSSNLMC | ||||||
Glycosylation | 321 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 330↔334 | |||||
Sequence: CLGPC | ||||||
Disulfide bond | 338↔359 | |||||
Sequence: CQILEGEKTIDSVTSAQELRGC | ||||||
Glycosylation | 363 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 399 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 400 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 406 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 423 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 444 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 461↔494 | |||||
Sequence: CLSEIHKMEEVSGTKGRQERNDIALKTNGDQASC | ||||||
Glycosylation | 540 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 550 | Interchain | ||||
Sequence: C | ||||||
Glycosylation | 634 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 652 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 675↔900 | |||||
Sequence: CLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGNGAEDTRPSRKRRSLEEVGNVTATTPTLPDFPNISSTIAPTSHEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPEERSGVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLC | ||||||
Glycosylation | 699 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000016698 | 764-1383 | Insulin receptor subunit beta | |||
Sequence: SLEEVGNVTATTPTLPDFPNISSTIAPTSHEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPEERSGVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEVETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGCREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS | ||||||
Glycosylation | 770 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 783 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 921 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 934 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 1000 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 1084 | S-nitrosocysteine | ||||
Sequence: C | ||||||
Modified residue | 1186 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 1190 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 1191 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 1356 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 1362 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y |
Post-translational modification
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.
Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-1000 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-1000, Tyr-1186, Tyr-1190 and Tyr-1191. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.
S-nitrosylation at Cys-1084 by BLVRB inhibits the receptor tyrosine kinase, thereby inhibiting insulin signaling.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-1000) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-1000), with SOCS3. Interacts (via the phosphorylated Tyr-1186, Tyr-1190, Tyr-1191) with SOCS1. Interacts with ARRB2 (By similarity).
Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with PDPK1. Interacts (via Tyr-1191) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-1000, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1186, Tyr-1190 and Tyr-1191 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF (By similarity).
Interacts with GRB7. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2. 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 (PubMed:25687571).
Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception (By similarity).
Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the Insr C-terminal region (PubMed:25187647).
Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV (PubMed:25187647).
Interacts with LMBRD1 (By similarity).
Interacts (in response to insulin stimulation) with NCK1; this interaction may recruit PTPN1 to mediate INSR dephosphorylation (By similarity).
Interacts with CD248; this interaction diminishes INSR autophosphorylation (By similarity).
Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with PDPK1. Interacts (via Tyr-1191) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-1000, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1186, Tyr-1190 and Tyr-1191 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF (By similarity).
Interacts with GRB7. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2. 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 (PubMed:25687571).
Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception (By similarity).
Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the Insr C-terminal region (PubMed:25187647).
Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV (PubMed:25187647).
Interacts with LMBRD1 (By similarity).
Interacts (in response to insulin stimulation) with NCK1; this interaction may recruit PTPN1 to mediate INSR dephosphorylation (By similarity).
Interacts with CD248; this interaction diminishes INSR autophosphorylation (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P15127 | Jak2 Q62689 | 2 | EBI-7472166, EBI-8656708 | |
BINARY | PRO_0000016698 | Atic O35567 | 3 | EBI-10768746, EBI-10768817 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 625-727 | Fibronectin type-III 1 | ||||
Sequence: VPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEES | ||||||
Region | 687-709 | Disordered | ||||
Sequence: SPPFESDDSQKHNQSEYDDSASE | ||||||
Region | 734-742 | Insulin-binding | ||||
Sequence: EDYLHNVVF | ||||||
Region | 747-783 | Disordered | ||||
Sequence: TSSGNGAEDTRPSRKRRSLEEVGNVTATTPTLPDFPN | ||||||
Domain | 754-848 | Fibronectin type-III 2 | ||||
Sequence: EDTRPSRKRRSLEEVGNVTATTPTLPDFPNISSTIAPTSHEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPEERSGVAAYVSARTMPE | ||||||
Compositional bias | 768-783 | Polar residues | ||||
Sequence: VGNVTATTPTLPDFPN | ||||||
Domain | 854-948 | Fibronectin type-III 3 | ||||
Sequence: IVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDY | ||||||
Region | 997-1000 | Important for interaction with IRS1, SHC1 and STAT5B | ||||
Sequence: NPEY | ||||||
Domain | 1024-1299 | Protein kinase | ||||
Sequence: ITLLRELGQGSFGMVYEGNAKDIIKGEVETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSF | ||||||
Region | 1361-1383 | Disordered | ||||
Sequence: PYTHMNGGKKNGRVLTLPRSNPS | ||||||
Region | 1362-1365 | PIK3R1 binding | ||||
Sequence: YTHM |
Domain
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 (By similarity).
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P15127-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameLong
- SynonymsRIR-B
- Length1,383
- Mass (Da)156,757
- Last updated1990-04-01 v1
- Checksum4B919566902A944A
P15127-2
- NameShort
- SynonymsRIR-A
- Differences from canonical
- 746-757: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
T2CB11 | T2CB11_RAT | Insr | 1384 | ||
A0A8J8Y5N6 | A0A8J8Y5N6_RAT | Insr | 1384 | ||
A0A8I5ZMZ8 | A0A8I5ZMZ8_RAT | Insr | 1372 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_036680 | 746-757 | in isoform Short | |||
Sequence: Missing | ||||||
Compositional bias | 768-783 | Polar residues | ||||
Sequence: VGNVTATTPTLPDFPN |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M29014 EMBL· GenBank· DDBJ | AAA41441.1 EMBL· GenBank· DDBJ | mRNA | ||
AF005776 EMBL· GenBank· DDBJ | AAB61414.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF005777 EMBL· GenBank· DDBJ | AAB61415.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AH004882 EMBL· GenBank· DDBJ | AAB38967.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AH004883 EMBL· GenBank· DDBJ | AAB38968.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U80633 EMBL· GenBank· DDBJ | AAB38746.1 EMBL· GenBank· DDBJ | Genomic DNA |