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Q9WTL4

- INSRR_MOUSE

UniProt

Q9WTL4 - INSRR_MOUSE

Protein

Insulin receptor-related protein

Gene

Insrr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB.1 Publication

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1013 – 10131ATPPROSITE-ProRule annotation
    Active sitei1115 – 11151Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi985 – 9939ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: UniProtKB
    2. cellular response to alkaline pH Source: UniProtKB
    3. male sex determination Source: MGI
    4. peptidyl-tyrosine phosphorylation Source: GOC
    5. protein autophosphorylation Source: UniProtKB
    6. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin receptor-related protein (EC:2.7.10.1)
    Short name:
    IRR
    Alternative name(s):
    IR-related receptor
    Cleaved into the following 2 chains:
    Gene namesi
    Name:Insrr
    Synonyms:Irr
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:1346037. Insrr.

    Subcellular locationi

    Membrane By similarity; Single-pass type I membrane protein By similarity

    GO - Cellular componenti

    1. integral component of plasma membrane Source: InterPro
    2. receptor complex Source: MGI

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Renal function is impaired, with reduced ability of the collecting duct to adapt to alkalosis.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2626Sequence AnalysisAdd
    BLAST
    Chaini27 – 13001274Insulin receptor-related proteinPRO_0000016704Add
    BLAST
    Chaini27 – 742716Insulin receptor-related protein alpha chainCuratedPRO_0000016705Add
    BLAST
    Chaini747 – 1300554Insulin receptor-related protein beta chainCuratedPRO_0000016706Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi47 – 471N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi100 – 1001N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi214 ↔ 222By similarity
    Disulfide bondi216 ↔ 228By similarity
    Disulfide bondi229 ↔ 237By similarity
    Disulfide bondi233 ↔ 246By similarity
    Disulfide bondi249 ↔ 258By similarity
    Disulfide bondi262 ↔ 274By similarity
    Disulfide bondi280 ↔ 300By similarity
    Disulfide bondi304 ↔ 317By similarity
    Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi320 ↔ 324By similarity
    Glycosylationi411 – 4111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi492 – 4921N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi528 – 5281N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi616 – 6161N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi634 – 6341N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi657 ↔ 864Interchain (between alpha and beta chains)Sequence Analysis
    Glycosylationi756 – 7561N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi885 – 8851N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi898 – 8981N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1145 – 11451Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1146 – 11461Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5.

    Keywords - PTMi

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

    Proteomic databases

    PaxDbiQ9WTL4.
    PRIDEiQ9WTL4.

    PTM databases

    PhosphoSiteiQ9WTL4.

    Expressioni

    Tissue specificityi

    Highly expressed in the islets as well as in pancreatic beta-cells.1 Publication

    Gene expression databases

    BgeeiQ9WTL4.
    CleanExiMM_INSRR.
    GenevestigatoriQ9WTL4.

    Interactioni

    Subunit structurei

    Probable tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WTL4.
    SMRiQ9WTL4. Positions 28-911, 913-1262.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini747 – 921175ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini944 – 1300357CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei922 – 94322HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini483 – 603121Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini607 – 707101Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini818 – 91396Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini979 – 1254276Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The extracellular domain is required for sensing alterations in external pH.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.
    InParanoidiB2RQC5.
    KOiK05086.
    OMAiFARTMPH.
    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.
    IPR028792. INSRR.
    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]
    PANTHERiPTHR24416:SF107. PTHR24416:SF107. 1 hit.
    PfamiPF00041. fn3. 1 hit.
    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.

    Q9WTL4-1 [UniParc]FASTAAdd to Basket

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    MAVPALWPWG VHLLMSLLSL GSGLDTLEVC PSLDIRSEVT ELRRLENCSV     50
    VEGHLQILLM FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN 100
    LTVIRGTRLF LGYALIIFEM PHLRDVGLPS LGAVLRGAVR VEKNQELCHL 150
    STIDWGLLQP APGTNHIVGN KLGEECADVC PGVLGAAGEP CSRTTFSGRT 200
    DYRCWTSSHC QKVCPCPRGM ACTAGGDCCH SECLGGCSQP EDPRACVACR 250
    HLYFQGVCLR ACPPGTYQYE SWRCVTAELC AHLREVPGLA TTFGIYEGSC 300
    LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV 350
    EGNLILNLRQ GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK 400
    LIRGDSMVDG NYTLYVLDNQ NLQQLGSWVT AGLTIPVGKI YFAFNPRLCL 450
    EHIYQLEEVT GTRGRQSKAE INPRTNGDRA ACQTRTLRFV FNLTEEDRIL 500
    LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT QSWNLLDVEL 550
    PLSRTQEPGV TLAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLRT 600
    LPAAPTVPQD VISTSNSSSH LLVRWKPPVQ RNGNITYYLV LWQRLAEDGD 650
    LYINDYCHRG LRLPTSSHDT RFDREDPALE AEPEQGCCPC QHSPPGQALP 700
    ALEAQEVTFQ KKFENFLHHA ITIPKAPWKV TSINKNPQRD SERHRREAGL 750
    LRLGKNNSDF EIQEDKVPRE RAILSGLRHF TEYRIDIHAC NHAAHTVGCS 800
    AATFVFARTM PHREADGIPG KVAWKAAGKS SVTLHWLEPP DPNGLILKYE 850
    IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS 900
    WTDGVTFYIT DLEEEDTGGM RIFLTVTPVG FMLLVTLAAL GFFYSRKRNS 950
    TLYTSVNPEY FSASHMYVPD EWEVPREQIA IIRELGQGSF GMVYEGLARG 1000
    LEAGEESTPV ALKTVNELAS ARERVEFLKE ASVMKAFKCH HVVRLLGVVS 1050
    QGQPTLVIME LMTRGDLKSH LRSLRPEAEN NPGLPQPALS DMIQMAGEIA 1100
    DGMAYLAAKK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV YETDYYRKGG 1150
    KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ 1200
    VLKFVMDGGV LEELENCPIQ LQELMRLCWQ HSPRLRPTFV HILDRIQDEL 1250
    RPSFRLCSFY YSPECQRGQA SLLPTEAEPD SPPTLNGASD YSAPNGGPGH 1300
    Length:1,300
    Mass (Da):144,875
    Last modified:July 27, 2011 - v2
    Checksum:i3DE9FC3C53DB96BB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti272 – 2721W → G in BAA77835. (PubMed:10342810)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007135 mRNA. Translation: BAA77835.1.
    CH466547 Genomic DNA. Translation: EDL15346.1.
    BC137855 mRNA. Translation: AAI37856.1.
    CCDSiCCDS17454.1.
    RefSeqiNP_035962.2. NM_011832.2.
    UniGeneiMm.42041.

    Genome annotation databases

    EnsembliENSMUST00000029711; ENSMUSP00000029711; ENSMUSG00000005640.
    ENSMUST00000107582; ENSMUSP00000103208; ENSMUSG00000005640.
    GeneIDi23920.
    KEGGimmu:23920.
    UCSCiuc008psy.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007135 mRNA. Translation: BAA77835.1 .
    CH466547 Genomic DNA. Translation: EDL15346.1 .
    BC137855 mRNA. Translation: AAI37856.1 .
    CCDSi CCDS17454.1.
    RefSeqi NP_035962.2. NM_011832.2.
    UniGenei Mm.42041.

    3D structure databases

    ProteinModelPortali Q9WTL4.
    SMRi Q9WTL4. Positions 28-911, 913-1262.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q9WTL4.

    Proteomic databases

    PaxDbi Q9WTL4.
    PRIDEi Q9WTL4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000029711 ; ENSMUSP00000029711 ; ENSMUSG00000005640 .
    ENSMUST00000107582 ; ENSMUSP00000103208 ; ENSMUSG00000005640 .
    GeneIDi 23920.
    KEGGi mmu:23920.
    UCSCi uc008psy.2. mouse.

    Organism-specific databases

    CTDi 3645.
    MGIi MGI:1346037. Insrr.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117239.
    HOGENOMi HOG000038045.
    HOVERGENi HBG006134.
    InParanoidi B2RQC5.
    KOi K05086.
    OMAi FARTMPH.
    OrthoDBi EOG73RB9N.
    TreeFami TF351636.

    Miscellaneous databases

    NextBioi 303697.
    PROi Q9WTL4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9WTL4.
    CleanExi MM_INSRR.
    Genevestigatori Q9WTL4.

    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.
    IPR028792. INSRR.
    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 ]
    PANTHERi PTHR24416:SF107. PTHR24416:SF107. 1 hit.
    Pfami PF00041. fn3. 1 hit.
    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. "Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and-2."
      Hirayama I., Tamemoto H., Yokota H., Kubo S.-K., Wang J., Kuwano H., Nagamachi Y., Takeuchi T., Izumi T.
      Diabetes 48:1237-1244(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Pancreas.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    4. "Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor."
      Kitamura T., Kido Y., Nef S., Merenmies J., Parada L.F., Accili D.
      Mol. Cell. Biol. 21:5624-5630(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    5. Cited for: DISRUPTION PHENOTYPE, FUNCTION, AUTOPHOSPHORYLATION.

    Entry informationi

    Entry nameiINSRR_MOUSE
    AccessioniPrimary (citable) accession number: Q9WTL4
    Secondary accession number(s): B2RQC5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 126 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

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3