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P15208

- INSR_MOUSE

UniProt

P15208 - INSR_MOUSE

Protein

Insulin receptor

Gene

Insr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 165 (01 Oct 2014)
      Sequence version 2 (03 Oct 2012)
      Previous versions | rss
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    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 phosphotyrosines 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.By similarity

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
    Sitei66 – 661Insulin-bindingBy similarity
    Binding sitei1023 – 10231ATPPROSITE-ProRule annotation
    Binding sitei1047 – 10471ATP
    Active sitei1149 – 11491Proton donor/acceptorBy similarity
    Binding sitei1167 – 11671ATPPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1094 – 11007ATPPROSITE-ProRule annotation
    Nucleotide bindingi1153 – 11542ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. GTP binding Source: Ensembl
    3. insulin-activated receptor activity Source: UniProtKB
    4. insulin binding Source: UniProtKB
    5. insulin receptor substrate binding Source: UniProtKB
    6. phosphatidylinositol 3-kinase binding Source: UniProtKB
    7. protein binding Source: UniProtKB
    8. PTB domain binding Source: UniProtKB
    9. receptor signaling protein tyrosine kinase activity Source: Ensembl

    GO - Biological processi

    1. activation of MAPK activity Source: Ensembl
    2. activation of protein kinase B activity Source: Ensembl
    3. cellular response to growth factor stimulus Source: MGI
    4. epidermis development Source: MGI
    5. exocrine pancreas development Source: MGI
    6. glucose homeostasis Source: Ensembl
    7. G-protein coupled receptor signaling pathway Source: Ensembl
    8. heart morphogenesis Source: Ensembl
    9. insulin receptor signaling pathway Source: MGI
    10. male sex determination Source: MGI
    11. organ morphogenesis Source: MGI
    12. peptidyl-tyrosine autophosphorylation Source: MGI
    13. positive regulation of cell migration Source: Ensembl
    14. positive regulation of developmental growth Source: Ensembl
    15. positive regulation of DNA replication Source: Ensembl
    16. positive regulation of glycogen biosynthetic process Source: BHF-UCL
    17. positive regulation of glycolytic process Source: Ensembl
    18. positive regulation of mitosis Source: MGI
    19. positive regulation of nitric oxide biosynthetic process Source: Ensembl
    20. positive regulation of protein kinase B signaling Source: Ensembl
    21. positive regulation of respiratory burst Source: Ensembl
    22. protein autophosphorylation Source: UniProtKB
    23. protein heterotetramerization Source: UniProtKB
    24. regulation of embryonic development Source: Ensembl
    25. regulation of transcription, DNA-templated Source: Ensembl
    26. transformation of host cell by virus Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 3474.

    Names & Taxonomyi

    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:
    Gene namesi
    Name:Insr
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:96575. Insr.

    Subcellular locationi

    GO - Cellular componenti

    1. caveola Source: MGI
    2. insulin receptor complex Source: Ensembl
    3. membrane Source: BHF-UCL
    4. plasma membrane Source: MGI
    5. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi989 – 9891Y → F: Abolishes interaction with IRS1 but not with IRS2. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Add
    BLAST
    Chaini28 – 748721Insulin receptor subunit alphaPRO_0000016693Add
    BLAST
    Chaini753 – 1372620Insulin receptor subunit betaPRO_0000016695Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi35 ↔ 53By similarity
    Glycosylationi43 – 431N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi52 – 521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi105 – 1051N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi138 – 1381N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi153 ↔ 182By similarity
    Disulfide bondi186 ↔ 209By similarity
    Disulfide bondi196 ↔ 215By similarity
    Disulfide bondi219 ↔ 228By similarity
    Disulfide bondi223 ↔ 234By similarity
    Disulfide bondi235 ↔ 243By similarity
    Disulfide bondi239 ↔ 252By similarity
    Glycosylationi242 – 2421N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi255 ↔ 264By similarity
    Disulfide bondi268 ↔ 280By similarity
    Glycosylationi282 – 2821N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi286 ↔ 311By similarity
    Disulfide bondi293 ↔ 301By similarity
    Disulfide bondi315 ↔ 328By similarity
    Glycosylationi322 – 3221N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi331 ↔ 335By similarity
    Disulfide bondi339 ↔ 360By similarity
    Glycosylationi364 – 3641N-linked (GlcNAc...)Sequence Analysis
    Modified residuei400 – 4001PhosphoserineBy similarity
    Modified residuei401 – 4011PhosphotyrosineBy similarity
    Modified residuei407 – 4071PhosphoserineBy similarity
    Glycosylationi424 – 4241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi445 – 4451N-linked (GlcNAc...)2 Publications
    Disulfide bondi462 ↔ 495By similarity
    Glycosylationi541 – 5411N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi551 – 551InterchainBy similarity
    Glycosylationi635 – 6351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi653 – 6531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi676 ↔ 889By similarity
    Glycosylationi700 – 7001N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi759 – 7591N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi772 – 7721N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi815 ↔ 824By similarity
    Glycosylationi910 – 9101N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi923 – 9231N-linked (GlcNAc...)Sequence Analysis
    Modified residuei989 – 9891Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1175 – 11751Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1179 – 11791Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1180 – 11801Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1345 – 13451Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1351 – 13511Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    Autophosphorylated on tyrosine residues in response to insulin By similarity. 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. Dephosphorylated by PTPRF and PTPN1 By similarity. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.By similarity1 Publication

    Keywords - PTMi

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

    Proteomic databases

    MaxQBiP15208.
    PaxDbiP15208.
    PRIDEiP15208.

    PTM databases

    PhosphoSiteiP15208.

    Expressioni

    Gene expression databases

    ArrayExpressiP15208.
    CleanExiMM_INSR.
    GenevestigatoriP15208.

    Interactioni

    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 By similarity. Activated form of INSR interacts (via Tyr-989) 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 By similarity. Interacts (via the phosphorylated Tyr-989), with SOCS3. Interacts (via the phosphorylated Tyr-1175, Tyr-1179, Tyr-1180) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 By similarity. Interacts with ARRB2. 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 By similarity. Interacts with GRB7 By similarity. Interacts with PDPK1 By similarity. Interacts (via Tyr-1180) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-989, this results in decreased interaction with, and phosphorylation of, IRS1 By similarity. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation By similarity. Interacts with PTPRE; this interaction is dependent of Tyr-1175, Tyr-1179 and Tyr-1180 of the INSR By similarity. Interacts with STAT5B (via SH2 domain) By similarity. Interacts with PTPRF By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Grb10Q607606EBI-6999015,EBI-861810

    Protein-protein interaction databases

    BioGridi200774. 13 interactions.
    DIPiDIP-41452N.
    IntActiP15208. 4 interactions.
    MINTiMINT-1516207.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LK2X-ray1.35P423-430[»]
    ProteinModelPortaliP15208.
    SMRiP15208. Positions 31-938, 998-1300.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP15208.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini28 – 748721ExtracellularCuratedAdd
    BLAST
    Topological domaini753 – 946194ExtracellularCuratedAdd
    BLAST
    Topological domaini968 – 1372405CytoplasmicCuratedAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei947 – 96721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini626 – 728103Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini744 – 83895Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini843 – 93795Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini1013 – 1288276Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni735 – 7439Insulin-bindingBy similarity
    Regioni986 – 9894Important for interaction with IRS1, SHC1 and STAT5BBy similarity
    Regioni1351 – 13544PIK3R1 bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi28 – 174147Leu-richAdd
    BLAST

    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

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
    Contains 3 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117239.
    HOGENOMiHOG000038045.
    HOVERGENiHBG006134.
    InParanoidiP15208.
    KOiK04527.
    OMAiCPERVTD.
    OrthoDBiEOG73RB9N.
    TreeFamiTF351636.

    Family and domain databases

    Gene3Di2.60.40.10. 4 hits.
    3.80.20.20. 2 hits.
    InterProiIPR000494. EGF_rcpt_L.
    IPR003961. Fibronectin_type3.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    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.
    [Graphical view]
    PfamiPF00041. fn3. 2 hits.
    PF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view]
    PIRSFiPIRSF000620. Insulin_receptor. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00060. FN3. 3 hits.
    SM00261. FU. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 4 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 1 hit.
    PROSITEiPS50853. 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.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P15208-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGFGRGCETT AVPLLVAVAA LLVGTAGHLY PGEVCPGMDI RNNLTRLHEL     50
    ENCSVIEGHL QILLMFKTRP EDFRDLSFPK LIMITDYLLL FRVYGLESLK 100
    DLFPNLTVIR GSRLFFNYAL VIFEMVHLKE LGLYNLMNIT RGSVRIEKNN 150
    ELCYLATIDW SRILDSVEDN YIVLNKDDNE ECGDVCPGTA KGKTNCPATV 200
    INGQFVERCW THSHCQKVCP TICKSHGCTA EGLCCHKECL GNCSEPDDPT 250
    KCVACRNFYL DGQCVETCPP PYYHFQDWRC VNFSFCQDLH FKCRNSRKPG 300
    CHQYVIHNNK CIPECPSGYT MNSSNLMCTP CLGPCPKVCQ ILEGEKTIDS 350
    VTSAQELRGC TVINGSLIIN IRGGNNLAAE LEANLGLIEE ISGFLKIRRS 400
    YALVSLSFFR KLHLIRGETL EIGNYSFYAL DNQNLRQLWD WSKHNLTITQ 450
    GKLFFHYNPK LCLSEIHKME EVSGTKGRQE RNDIALKTNG DQASCENELL 500
    KFSFIRTSFD KILLRWEPYW PPDFRDLLGF MLFYKEAPYQ NVTEFDGQDA 550
    CGSNSWTVVD IDPPQRSNDP KSQTPSHPGW LMRGLKPWTQ YAIFVKTLVT 600
    FSDERRTYGA KSDIIYVQTD ATNPSVPLDP ISVSNSSSQI ILKWKPPSDP 650
    NGNITHYLVY WERQAEDSEL FELDYCLKGL KLPSRTWSPP FESDDSQKHN 700
    QSEYDDSASE CCSCPKTDSQ ILKELEESSF RKTFEDYLHN VVFVPRPSRK 750
    RRSLEEVGNV TATTLTLPDF PNVSSTIVPT SQEEHRPFEK VVNKESLVIS 800
    GLRHFTGYRI ELQACNQDSP DERCSVAAYV SARTMPEAKA DDIVGPVTHE 850
    IFENNVVHLM WQEPKEPNGL IVLYEVSYRR YGDEELHLCV SRKHFALERG 900
    CRLRGLSPGN YSVRVRATSL AGNGSWTEPT YFYVTDYLDV PSNIAKIIIG 950
    PLIFVFLFSV VIGSIYLFLR KRQPDGPMGP LYASSNPEYL SASDVFPSSV 1000
    YVPDEWEVPR EKITLLRELG QGSFGMVYEG NAKDIIKGEA ETRVAVKTVN 1050
    ESASLRERIE FLNEASVMKG FTCHHVVRLL GVVSKGQPTL VVMELMAHGD 1100
    LKSHLRSLRP DAENNPGRPP PTLQEMIQMT AEIADGMAYL NAKKFVHRDL 1150
    AARNCMVAHD FTVKIGDFGM TRDIYETDYY RKGGKGLLPV RWMSPESLKD 1200
    GVFTASSDMW SFGVVLWEIT SLAEQPYQGL SNEQVLKFVM DGGYLDPPDN 1250
    CPERLTDLMR MCWQFNPKMR PTFLEIVNLL KDDLHPSFPE VSFFYSEENK 1300
    APESEELEME FEDMENVPLD RSSHCQREEA GGREGGSSLS IKRTYDEHIP 1350
    YTHMNGGKKN GRVLTLPRSN PS 1372
    Length:1,372
    Mass (Da):155,610
    Last modified:October 3, 2012 - v2
    Checksum:iB0FA7DBD2AD4646A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1089 – 10891T → M in AAA39318. (PubMed:2557333)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05149 mRNA. Translation: AAA39318.1.
    AC168068 Genomic DNA. No translation available.
    M28869 Genomic DNA. Translation: AAA39319.1.
    CCDSiCCDS22059.1.
    PIRiA34157.
    RefSeqiNP_034698.2. NM_010568.2.
    UniGeneiMm.268003.

    Genome annotation databases

    EnsembliENSMUST00000091291; ENSMUSP00000088837; ENSMUSG00000005534.
    GeneIDi16337.
    KEGGimmu:16337.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05149 mRNA. Translation: AAA39318.1 .
    AC168068 Genomic DNA. No translation available.
    M28869 Genomic DNA. Translation: AAA39319.1 .
    CCDSi CCDS22059.1.
    PIRi A34157.
    RefSeqi NP_034698.2. NM_010568.2.
    UniGenei Mm.268003.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1LK2 X-ray 1.35 P 423-430 [» ]
    ProteinModelPortali P15208.
    SMRi P15208. Positions 31-938, 998-1300.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200774. 13 interactions.
    DIPi DIP-41452N.
    IntActi P15208. 4 interactions.
    MINTi MINT-1516207.

    Chemistry

    BindingDBi P15208.
    ChEMBLi CHEMBL3187.

    PTM databases

    PhosphoSitei P15208.

    Proteomic databases

    MaxQBi P15208.
    PaxDbi P15208.
    PRIDEi P15208.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000091291 ; ENSMUSP00000088837 ; ENSMUSG00000005534 .
    GeneIDi 16337.
    KEGGi mmu:16337.

    Organism-specific databases

    CTDi 3643.
    MGIi MGI:96575. Insr.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117239.
    HOGENOMi HOG000038045.
    HOVERGENi HBG006134.
    InParanoidi P15208.
    KOi K04527.
    OMAi CPERVTD.
    OrthoDBi EOG73RB9N.
    TreeFami TF351636.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 3474.

    Miscellaneous databases

    ChiTaRSi INSR. mouse.
    EvolutionaryTracei P15208.
    NextBioi 289438.
    PROi P15208.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P15208.
    CleanExi MM_INSR.
    Genevestigatori P15208.

    Family and domain databases

    Gene3Di 2.60.40.10. 4 hits.
    3.80.20.20. 2 hits.
    InterProi IPR000494. EGF_rcpt_L.
    IPR003961. Fibronectin_type3.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    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.
    [Graphical view ]
    Pfami PF00041. fn3. 2 hits.
    PF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000620. Insulin_receptor. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00060. FN3. 3 hits.
    SM00261. FU. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 4 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 1 hit.
    PROSITEi 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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Substrate phosphorylation catalyzed by the insulin receptor tyrosine kinase. Kinetic correlation to autophosphorylation of specific sites in the beta subunit."
      Flores-Riveros J.R., Sibley E., Kastelic T., Lane M.D.
      J. Biol. Chem. 264:21557-21572(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "Characterization of the mouse insulin receptor gene promoter."
      Sibley E., Kastelic T., Kelly T.J., Lane M.D.
      Proc. Natl. Acad. Sci. U.S.A. 86:9732-9736(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
    4. "Insulin receptor substrate-2 binds to the insulin receptor through its phosphotyrosine-binding domain and through a newly identified domain comprising amino acids 591-786."
      Sawka-Verhelle D., Tartare-Deckert S., White M.F., Van Obberghen E.
      J. Biol. Chem. 271:5980-5983(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS1 AND IRS2, MUTAGENESIS OF TYR-989.
    5. "A novel, multifunctional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes."
      Ribon V., Printen J.A., Hoffman N.G., Kay B.K., Saltiel A.R.
      Mol. Cell. Biol. 18:872-879(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SORBS1.
    6. "Mutation of tyrosine 960 within the insulin receptor juxtamembrane domain impairs glucose transport but does not inhibit ligand-mediated phosphorylation of insulin receptor substrate-2 in 3T3-L1 adipocytes."
      Chaika O.V., Chaika N., Volle D.J., Hayashi H., Ebina Y., Wang L.M., Pierce J.H., Lewis R.E.
      J. Biol. Chem. 274:12075-12080(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF TYR-989.
    7. "SOCS-3 is an insulin-induced negative regulator of insulin signaling."
      Emanuelli B., Peraldi P., Filloux C., Sawka-Verhelle D., Hilton D., Van Obberghen E.
      J. Biol. Chem. 275:15985-15991(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SOCS3.
    8. "Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP."
      Galic S., Klingler-Hoffmann M., Fodero-Tavoletti M.T., Puryer M.A., Meng T.C., Tonks N.K., Tiganis T.
      Mol. Cell. Biol. 23:2096-2108(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2.
    9. "Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms."
      Ueki K., Kondo T., Kahn C.R.
      Mol. Cell. Biol. 24:5434-5446(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SOCS1 AND SOCS3.
    10. "The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation."
      Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.
      Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-445.
      Tissue: Myoblast.
    11. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
      Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
      Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-445.
    12. "Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance."
      Luan B., Zhao J., Wu H., Duan B., Shu G., Wang X., Li D., Jia W., Kang J., Pei G.
      Nature 457:1146-1149(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2.

    Entry informationi

    Entry nameiINSR_MOUSE
    AccessioniPrimary (citable) accession number: P15208
    Secondary accession number(s): F8VPU4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 165 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3