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Entry version 193 (16 Oct 2019)
Sequence version 1 (01 Apr 1990)
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Protein

Insulin receptor

Gene

Insr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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).By similarity1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei65Insulin-bindingBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei1034ATPPROSITE-ProRule annotation1
Binding sitei1058ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei1160Proton donor/acceptorBy similarity1
Binding sitei1178ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi1105 – 1111ATPPROSITE-ProRule annotation7
Nucleotide bindingi1164 – 1165ATPPROSITE-ProRule annotation2

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
2.7.10.1 5301

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-RNO-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-RNO-74713 IRS activation
R-RNO-74749 Signal attenuation
R-RNO-74751 Insulin receptor signalling cascade
R-RNO-74752 Signaling by Insulin receptor
R-RNO-77387 Insulin receptor recycling

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Insulin receptor (EC:2.7.10.1)
Short name:
IR
Alternative name(s):
CD_antigen: CD220
Cleaved into the following 2 chains:
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Insr
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiRattus norvegicus (Rat)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10116 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000002494 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unplaced

Organism-specific databases

Rat genome database

More...
RGDi
2917 Insr

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini27 – 759ExtracellularCuratedAdd BLAST733
Topological domaini764 – 957ExtracellularCuratedAdd BLAST194
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei958 – 978HelicalSequence analysisAdd BLAST21
Topological domaini979 – 1383CytoplasmicCuratedAdd BLAST405

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL5486

DrugCentral

More...
DrugCentrali
P15127

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 26Add BLAST26
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001669627 – 759Insulin receptor subunit alphaAdd BLAST733
ChainiPRO_0000016698764 – 1383Insulin receptor subunit betaAdd BLAST620

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi34 ↔ 52By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi42N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi51N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi137N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi152 ↔ 181By similarity
Disulfide bondi185 ↔ 208By similarity
Disulfide bondi195 ↔ 214By similarity
Disulfide bondi218 ↔ 227By similarity
Disulfide bondi222 ↔ 233By similarity
Disulfide bondi234 ↔ 242By similarity
Disulfide bondi238 ↔ 251By similarity
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi254 ↔ 263By similarity
Disulfide bondi267 ↔ 279By similarity
Glycosylationi281N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi285 ↔ 310By similarity
Disulfide bondi292 ↔ 300By similarity
Disulfide bondi314 ↔ 327By similarity
Glycosylationi321N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi330 ↔ 334By similarity
Disulfide bondi338 ↔ 359By similarity
Glycosylationi363N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei399PhosphoserineBy similarity1
Modified residuei400PhosphotyrosineBy similarity1
Modified residuei406PhosphoserineBy similarity1
Glycosylationi423N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi444N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi461 ↔ 494By similarity
Glycosylationi540N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi550InterchainBy similarity
Glycosylationi634N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi652N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi675 ↔ 900By similarity
Glycosylationi699N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi770N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi783N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi921N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi934N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1000Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1186Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1190Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1191Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1356Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1362Phosphotyrosine; by autocatalysisBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-1000 is required for binding to IRS1, SHC1, and STAT5B. Dephosphorylated by PTPRE on Tyr-1000, Tyr-1186, Tyr-1190 and Tyr-1191 residues. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P15127

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P15127

PeptideAtlas

More...
PeptideAtlasi
P15127

PRoteomics IDEntifications database

More...
PRIDEi
P15127

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P15127

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P15127

UniCarbKB; an annotated and curated database of glycan structures

More...
UniCarbKBi
P15127

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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).

By similarity3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

Database of interacting proteins

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DIPi
DIP-42209N

Protein interaction database and analysis system

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IntActi
P15127, 460 interactors

Molecular INTeraction database

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MINTi
P15127

STRING: functional protein association networks

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STRINGi
10116.ENSRNOP00000060141

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P15127

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11383
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P15127

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini625 – 727Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST103
Domaini754 – 848Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST95
Domaini854 – 948Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST95
Domaini1024 – 1299Protein kinasePROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni734 – 742Insulin-bindingBy similarity9
Regioni997 – 1000Important for interaction with IRS1, SHC1 and STAT5B4
Regioni1362 – 1365PIK3R1 bindingBy similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi27 – 173Leu-richAdd BLAST147

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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).By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4258 Eukaryota
COG0515 LUCA

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000038045

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P15127

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P15127

Family and domain databases

Conserved Domains Database

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CDDi
cd00063 FN3, 2 hits
cd00064 FU, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.10, 2 hits
3.80.20.20, 2 hits

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR040969 Insulin_TMD
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016246 Tyr_kinase_insulin-like_rcpt
IPR002011 Tyr_kinase_rcpt_2_CS

Pfam protein domain database

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Pfami
View protein in Pfam
PF00041 fn3, 1 hit
PF00757 Furin-like, 1 hit
PF17870 Insulin_TMD, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF000620 Insulin_receptor, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00109 TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00060 FN3, 3 hits
SM00261 FU, 1 hit
SM00219 TyrKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF49265 SSF49265, 3 hits
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50853 FN3, 3 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00239 RECEPTOR_TYR_KIN_II, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: P15127-1) [UniParc]FASTAAdd to basket
Also known as: RIR-B

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGSGRGCETT AVPLLMAVAV AGGTAGHLYP GEVCPGMDIR NNLTRLHELE
60 70 80 90 100
NCSVIEGHLQ ILLMFKTRPE DFRDLSFPKL IMITDYLLLF RVYGLESLKD
110 120 130 140 150
LFPNLTVIRG SRLFFNYALV IFEMVHLKEL GLYNLMNITR GSVRIEKNNE
160 170 180 190 200
LCYLATIDWS RILDYVEDNY IVLNKDDNEE CGDVCPGTAK GKTNCPATVI
210 220 230 240 250
NGQFVERCWT HSHCQKVCPT ICKSHGCTAE GLCCHKECLG NCSEPDDPTK
260 270 280 290 300
CVACRNFYLD GQCVETCPPP YYHFQDWRCV NFSFCQDLHY KCRNSRKPGC
310 320 330 340 350
HQYVIHNNKC IPECPSGYTM NSSNLMCTPC LGPCPKVCQI LEGEKTIDSV
360 370 380 390 400
TSAQELRGCT VINGSLIINI RGGNNLAAEL EANLGLIEEI SGFLKIRRSY
410 420 430 440 450
ALVSLSFFRK LHLIRGETLE IGNYSFYALD NQNLRQLWDW NKHNLTITQG
460 470 480 490 500
KLFFHYNPKL CLSEIHKMEE VSGTKGRQER NDIALKTNGD QASCENELLK
510 520 530 540 550
FSFIRTSFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN VTEFDGQDAC
560 570 580 590 600
GSNSWTVVDI DPPQRSNDPK SQTPSHPGWL MRGLKPWTQY AIFVKTLVTF
610 620 630 640 650
SDERRTYGAK SDIIYVQTDA TNPSVPLDPI SVSNSSSQII LKWKPPSDPN
660 670 680 690 700
GNITHYLVYW ERQAEDSELF ELDYCLKGLK LPSRTWSPPF ESDDSQKHNQ
710 720 730 740 750
SEYDDSASEC CSCPKTDSQI LKELEESSFR KTFEDYLHNV VFVPRKTSSG
760 770 780 790 800
NGAEDTRPSR KRRSLEEVGN VTATTPTLPD FPNISSTIAP TSHEEHRPFE
810 820 830 840 850
KVVNKESLVI SGLRHFTGYR IELQACNQDS PEERSGVAAY VSARTMPEAK
860 870 880 890 900
ADDIVGPVTH EIFENNVVHL MWQEPKEPNG LIVLYEVSYR RYGDEELHLC
910 920 930 940 950
VSRKHFALER GCRLRGLSPG NYSVRVRATS LAGNGSWTEP TYFYVTDYLD
960 970 980 990 1000
VPSNIAKIII GPLIFVFLFS VVIGSIYLFL RKRQPDGPMG PLYASSNPEY
1010 1020 1030 1040 1050
LSASDVFPSS VYVPDEWEVP REKITLLREL GQGSFGMVYE GNAKDIIKGE
1060 1070 1080 1090 1100
VETRVAVKTV NESASLRERI EFLNEASVMK GFTCHHVVRL LGVVSKGQPT
1110 1120 1130 1140 1150
LVVMELMAHG DLKSHLRSLR PDAENNPGRP PPTLQEMIQM TAEIADGMAY
1160 1170 1180 1190 1200
LNAKKFVHRD LAARNCMVAH DFTVKIGDFG MTRDIYETDY YRKGGKGLLP
1210 1220 1230 1240 1250
VRWMSPESLK DGVFTASSDM WSFGVVLWEI TSLAEQPYQG LSNEQVLKFV
1260 1270 1280 1290 1300
MDGGYLDPPD NCPERLTDLM RMCWQFNPKM RPTFLEIVNL LKDDLHPSFP
1310 1320 1330 1340 1350
EVSFFYSEEN KAPESEELEM EFEDMENVPL DRSSHCQREE AGCREGGSSL
1360 1370 1380
SIKRTYDEHI PYTHMNGGKK NGRVLTLPRS NPS
Length:1,383
Mass (Da):156,757
Last modified:April 1, 1990 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4B919566902A944A
GO
Isoform Short (identifier: P15127-2) [UniParc]FASTAAdd to basket
Also known as: RIR-A

The sequence of this isoform differs from the canonical sequence as follows:
     746-757: Missing.

Show »
Length:1,371
Mass (Da):155,553
Checksum:i146D5FFDA1EF415D
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
T2CB11T2CB11_RAT
Tyrosine-protein kinase receptor
Insr rCG_58966
1,384Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F1LPL6F1LPL6_RAT
Tyrosine-protein kinase receptor
Insr
1,383Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_036680746 – 757Missing in isoform Short. CuratedAdd BLAST12

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
M29014 mRNA Translation: AAA41441.1
AF005776 Genomic DNA Translation: AAB61414.1
AF005777 Genomic DNA Translation: AAB61415.1
AH004882 Genomic DNA Translation: AAB38967.1
AH004883 Genomic DNA Translation: AAB38968.1
U80633 Genomic DNA Translation: AAB38746.1

Protein sequence database of the Protein Information Resource

More...
PIRi
A36080

Genome annotation databases

UCSC genome browser

More...
UCSCi
RGD:2917 rat [P15127-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29014 mRNA Translation: AAA41441.1
AF005776 Genomic DNA Translation: AAB61414.1
AF005777 Genomic DNA Translation: AAB61415.1
AH004882 Genomic DNA Translation: AAB38967.1
AH004883 Genomic DNA Translation: AAB38968.1
U80633 Genomic DNA Translation: AAB38746.1
PIRiA36080

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4XSTX-ray3.00F726-748[»]
5TQ1X-ray1.49B1008-1018[»]
SMRiP15127
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

DIPiDIP-42209N
IntActiP15127, 460 interactors
MINTiP15127
STRINGi10116.ENSRNOP00000060141

Chemistry databases

BindingDBiP15127
ChEMBLiCHEMBL5486
DrugCentraliP15127

PTM databases

iPTMnetiP15127
PhosphoSitePlusiP15127
UniCarbKBiP15127

Proteomic databases

jPOSTiP15127
PaxDbiP15127
PeptideAtlasiP15127
PRIDEiP15127

Genome annotation databases

UCSCiRGD:2917 rat [P15127-1]

Organism-specific databases

RGDi2917 Insr

Phylogenomic databases

eggNOGiKOG4258 Eukaryota
COG0515 LUCA
HOGENOMiHOG000038045
InParanoidiP15127
PhylomeDBiP15127

Enzyme and pathway databases

BRENDAi2.7.10.1 5301
ReactomeiR-RNO-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-RNO-74713 IRS activation
R-RNO-74749 Signal attenuation
R-RNO-74751 Insulin receptor signalling cascade
R-RNO-74752 Signaling by Insulin receptor
R-RNO-77387 Insulin receptor recycling

Miscellaneous databases

Protein Ontology

More...
PROi
PR:P15127

Family and domain databases

CDDicd00063 FN3, 2 hits
cd00064 FU, 1 hit
Gene3Di2.60.40.10, 2 hits
3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR040969 Insulin_TMD
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016246 Tyr_kinase_insulin-like_rcpt
IPR002011 Tyr_kinase_rcpt_2_CS
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF00757 Furin-like, 1 hit
PF17870 Insulin_TMD, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PIRSFiPIRSF000620 Insulin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 3 hits
SM00261 FU, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49265 SSF49265, 3 hits
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 3 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00239 RECEPTOR_TYR_KIN_II, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiINSR_RAT
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P15127
Secondary accession number(s): P97681
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 16, 2019
This is version 193 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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