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Reviewed, UniProtKB/Swiss-Prot P15127 (INSR_RAT)

Last modified February 9, 2010. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Insulin receptor
      Short name=IR
    EC=2.7.10.1
Alternative name(s):
    CD_antigen=CD220
Cleaved into the following 2 chains:
    1- Recommended name:
            Insulin receptor subunit alpha
    2- Recommended name:
            Insulin receptor subunit beta
Gene names
Name: Insr
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length1383 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

This receptor binds insulin and has a tyrosine-protein kinase activity. Isoform Short has a higher affinity for insulin. Mediates the metabolic functions of insulin. Binding to insulin stimulates association of the receptor with downstream mediators including IRS1 and phosphatidylinositol 3'-kinase (PI3K). Ref.3

Catalytic activity

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

Cofactor

Manganese By similarity.

Enzyme regulation

Autophosphorylation activates the kinase activity.

Subunit structure

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. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Interacts with IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. The sequences surrounding the phosphorylated NPEY motif contribute differentially to either IRS1 or SHC1 recognition. 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. 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 CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27' phosphorylation of CAV2. Interacts with ARRB2 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Post-translational modification

Autophosphorylated on tyrosine residues in response to insulin By similarity.

Phosphorylation of Tyr-1000 is required for IRS1- and SHC1-binding By similarity.

Dephosphorylated by PTPRE on Tyr-1000, Tyr-1186, Tyr-1190 and Tyr-1191 residues By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 3 fibronectin type-III domains.

Contains 1 protein kinase domain.

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Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
   LigandATP-binding
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Cleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Gene Ontology (GO)
   Biological processfat cell differentiation

Inferred from expression pattern. Source: RGD

glucose homeostasis

Inferred from direct assay. Source: RGD

insulin receptor signaling pathway

Inferred from direct assay. Source: RGD

negative regulation of gene expression

Inferred from mutant phenotype. Source: RGD

negative regulation of protein amino acid phosphorylation

Inferred from mutant phenotype. Source: RGD

negative regulation of transporter activity

Inferred from mutant phenotype. Source: RGD

peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype. Source: RGD

positive regulation of glycoprotein biosynthetic process

Inferred from mutant phenotype. Source: RGD

protein amino acid autophosphorylation

Inferred from direct assay. Source: RGD

protein heterotetramerization

Inferred from direct assay. Source: RGD

regulation of hydrogen peroxide metabolic process

Inferred from direct assay. Source: RGD

response to activity

Inferred from expression pattern. Source: RGD

response to estradiol stimulus

Inferred from expression pattern. Source: RGD

response to ethanol

Inferred from expression pattern. Source: RGD

response to glucocorticoid stimulus

Inferred from expression pattern. Source: RGD

response to manganese ion

Inferred from expression pattern. Source: RGD

response to protein stimulus

Inferred from expression pattern. Source: RGD

response to testosterone stimulus

Inferred from expression pattern. Source: RGD

response to tumor necrosis factor

Inferred from mutant phenotype. Source: RGD

response to vitamin D

Inferred from expression pattern. Source: RGD

   Cellular componentcytosol

Inferred from direct assay. Source: RGD

endosome

Inferred from direct assay. Source: RGD

microsome

Inferred from direct assay. Source: RGD

nucleus

Inferred from direct assay. Source: RGD

soluble fraction

Inferred from direct assay. Source: RGD

synapse

Inferred from direct assay. Source: RGD

   Molecular function3-phosphoinositide-dependent protein kinase binding

Inferred from direct assay. Source: RGD

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

insulin binding

Inferred from direct assay. Source: RGD

insulin receptor activity

Inferred from direct assay. Source: RGD

insulin receptor substrate binding

Inferred from mutant phenotype. Source: RGD

lipoic acid binding

Inferred from physical interaction. Source: RGD

manganese ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein complex binding

Inferred from direct assay. Source: RGD

protein phosphatase binding

Inferred from mutant phenotype. Source: RGD

Complete GO annotation...

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P15127-1)

Also known as: RIR-B;

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.
Isoform Short (identifier: P15127-2)

Also known as: RIR-A;

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626
Chain27 – 759733Insulin receptor subunit alpha
PRO_0000016696
Chain764 – 1383620Insulin receptor subunit beta
PRO_0000016698

Regions

Topological domain764 – 957194Extracellular Potential
Transmembrane958 – 97821 Potential
Topological domain979 – 1383405Cytoplasmic Potential
Domain623 – 69674Fibronectin type-III 1
Domain758 – 84588Fibronectin type-III 2
Domain851 – 94797Fibronectin type-III 3
Domain1024 – 1299276Protein kinase
Nucleotide binding1030 – 10389ATP By similarity
Region997 – 10004IRS1 and SHC binding By similarity
Region1362 – 13654PIK3R1 binding By similarity

Sites

Active site11601Proton acceptor By similarity
Binding site10581ATP
Site10001Important for biological activity

Amino acid modifications

Modified residue3991Phosphoserine By similarity
Modified residue4001Phosphotyrosine By similarity
Modified residue4061Phosphoserine By similarity
Modified residue10001Phosphotyrosine; by autocatalysis By similarity
Modified residue10651Phosphoserine By similarity
Modified residue11131N6-acetyllysine By similarity
Modified residue11861Phosphotyrosine; by autocatalysis By similarity
Modified residue11901Phosphotyrosine; by autocatalysis By similarity
Modified residue11911Phosphotyrosine; by autocatalysis By similarity
Modified residue13491Phosphoserine By similarity
Modified residue13561Phosphotyrosine; by autocatalysis By similarity
Modified residue13621Phosphotyrosine; by autocatalysis By similarity
Modified residue13801Phosphoserine By similarity
Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation511N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation2411N-linked (GlcNAc...) Potential
Glycosylation2811N-linked (GlcNAc...) Potential
Glycosylation3211N-linked (GlcNAc...) Potential
Glycosylation3631N-linked (GlcNAc...) Potential
Glycosylation4231N-linked (GlcNAc...) Potential
Glycosylation4441N-linked (GlcNAc...) Potential
Glycosylation5401N-linked (GlcNAc...) Potential
Glycosylation6341N-linked (GlcNAc...) Potential
Glycosylation6521N-linked (GlcNAc...) Potential
Glycosylation6991N-linked (GlcNAc...) Potential
Glycosylation7701N-linked (GlcNAc...) Potential
Glycosylation7831N-linked (GlcNAc...) Potential
Glycosylation9211N-linked (GlcNAc...) Potential
Glycosylation9341N-linked (GlcNAc...) Potential
Disulfide bond218 ↔ 227 By similarity
Disulfide bond222 ↔ 233 By similarity
Disulfide bond234 ↔ 242 By similarity
Disulfide bond238 ↔ 251 By similarity
Disulfide bond254 ↔ 263 By similarity
Disulfide bond267 ↔ 279 By similarity
Disulfide bond285 ↔ 292 By similarity
Disulfide bond300 ↔ 310 By similarity
Disulfide bond314 ↔ 327 By similarity
Disulfide bond330 ↔ 334 By similarity
Disulfide bond461 ↔ 494 By similarity
Disulfide bond550Interchain By similarity

Natural variations

Alternative sequence746 – 75712Missing in isoform Short.
VSP_036680

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Sequences

Sequence LengthMass (Da)Tools
Isoform Long (RIR-B) [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 4B919566902A944A

FASTA1,383156,757
        10         20         30         40         50         60 
MGSGRGCETT AVPLLMAVAV AGGTAGHLYP GEVCPGMDIR NNLTRLHELE NCSVIEGHLQ 

        70         80         90        100        110        120 
ILLMFKTRPE DFRDLSFPKL IMITDYLLLF RVYGLESLKD LFPNLTVIRG SRLFFNYALV 

       130        140        150        160        170        180 
IFEMVHLKEL GLYNLMNITR GSVRIEKNNE LCYLATIDWS RILDYVEDNY IVLNKDDNEE 

       190        200        210        220        230        240 
CGDVCPGTAK GKTNCPATVI NGQFVERCWT HSHCQKVCPT ICKSHGCTAE GLCCHKECLG 

       250        260        270        280        290        300 
NCSEPDDPTK CVACRNFYLD GQCVETCPPP YYHFQDWRCV NFSFCQDLHY KCRNSRKPGC 

       310        320        330        340        350        360 
HQYVIHNNKC IPECPSGYTM NSSNLMCTPC LGPCPKVCQI LEGEKTIDSV TSAQELRGCT 

       370        380        390        400        410        420 
VINGSLIINI RGGNNLAAEL EANLGLIEEI SGFLKIRRSY ALVSLSFFRK LHLIRGETLE 

       430        440        450        460        470        480 
IGNYSFYALD NQNLRQLWDW NKHNLTITQG KLFFHYNPKL CLSEIHKMEE VSGTKGRQER 

       490        500        510        520        530        540 
NDIALKTNGD QASCENELLK FSFIRTSFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN 

       550        560        570        580        590        600 
VTEFDGQDAC GSNSWTVVDI DPPQRSNDPK SQTPSHPGWL MRGLKPWTQY AIFVKTLVTF 

       610        620        630        640        650        660 
SDERRTYGAK SDIIYVQTDA TNPSVPLDPI SVSNSSSQII LKWKPPSDPN GNITHYLVYW 

       670        680        690        700        710        720 
ERQAEDSELF ELDYCLKGLK LPSRTWSPPF ESDDSQKHNQ SEYDDSASEC CSCPKTDSQI 

       730        740        750        760        770        780 
LKELEESSFR KTFEDYLHNV VFVPRKTSSG NGAEDTRPSR KRRSLEEVGN VTATTPTLPD 

       790        800        810        820        830        840 
FPNISSTIAP TSHEEHRPFE KVVNKESLVI SGLRHFTGYR IELQACNQDS PEERSGVAAY 

       850        860        870        880        890        900 
VSARTMPEAK ADDIVGPVTH EIFENNVVHL MWQEPKEPNG LIVLYEVSYR RYGDEELHLC 

       910        920        930        940        950        960 
VSRKHFALER GCRLRGLSPG NYSVRVRATS LAGNGSWTEP TYFYVTDYLD VPSNIAKIII 

       970        980        990       1000       1010       1020 
GPLIFVFLFS VVIGSIYLFL RKRQPDGPMG PLYASSNPEY LSASDVFPSS VYVPDEWEVP 

      1030       1040       1050       1060       1070       1080 
REKITLLREL GQGSFGMVYE GNAKDIIKGE VETRVAVKTV NESASLRERI EFLNEASVMK 

      1090       1100       1110       1120       1130       1140 
GFTCHHVVRL LGVVSKGQPT LVVMELMAHG DLKSHLRSLR PDAENNPGRP PPTLQEMIQM 

      1150       1160       1170       1180       1190       1200 
TAEIADGMAY LNAKKFVHRD LAARNCMVAH DFTVKIGDFG MTRDIYETDY YRKGGKGLLP 

      1210       1220       1230       1240       1250       1260 
VRWMSPESLK DGVFTASSDM WSFGVVLWEI TSLAEQPYQG LSNEQVLKFV MDGGYLDPPD 

      1270       1280       1290       1300       1310       1320 
NCPERLTDLM RMCWQFNPKM RPTFLEIVNL LKDDLHPSFP EVSFFYSEEN KAPESEELEM 

      1330       1340       1350       1360       1370       1380 
EFEDMENVPL DRSSHCQREE AGCREGGSSL SIKRTYDEHI PYTHMNGGKK NGRVLTLPRS 


NPS

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Isoform Short (RIR-A).

Checksum: 146D5FFDA1EF415D
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FASTA1,371155,553

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References

[1]"The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing."
Goldstein B.J., Dudley A.L.
Mol. Endocrinol. 4:235-244(1990) [PubMed: 2330003] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), ALTERNATIVE SPLICING (ISOFORM SHORT).
[2]Liu Y., Tam J.W.O.
Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 731-756; 758-819; 969-994 AND 1119-1177.
Strain: Sprague-Dawley.
[3]"Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells."
Johansson G.S., Arnqvist H.J.
Am. J. Physiol. 291:E1124-E1130(2006) [PubMed: 16803852] [Abstract]
Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
[4]"Identification of pY19-caveolin-2 as a positive regulator of insulin-stimulated actin cytoskeleton-dependent mitogenesis."
Kwon H., Jeong K., Pak Y.
J. Cell. Mol. Med. 13:1549-1564(2009) [PubMed: 19778377] [Abstract]
Cited for: INTERACTION WITH CAV2.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M29014 mRNA. Translation: AAA41441.1.
AF005776 Genomic DNA. Translation: AAB61414.1.
AF005777 Genomic DNA. Translation: AAB61415.1.
U80630, U80629 Genomic DNA. Translation: AAB38967.1.
U80632, U80631 Genomic DNA. Translation: AAB38968.1.
U80633 Genomic DNA. Translation: AAB38746.1.
IPIIPI00393267.
IPI00563042.
PIRA36080.
RefSeqNP_058767.1.
UniGeneRn.9876

3D structure databases

SMRP15127. Positions 30-949, 1009-1311.
ModBaseSearch...

Protein-protein interaction databases

STRINGP15127.

PTM databases

PhosphoSiteP15127.

Proteomic databases

PRIDEP15127.

Genome annotation databases

EnsemblENSRNOT00000050646; ENSRNOP00000046668; ENSRNOG00000029986; Rattus norvegicus. [Genome view]
GeneID24954.
KEGGrno:24954.
UCSCNM_017071. rat.

Organism-specific databases

CTD24954.
RGD2917. Insr.

Phylogenomic databases

eggNOGmaNOG04664.
HOVERGENP15127.
InParanoidP15127.

Enzyme and pathway databases

BRENDA2.7.10.1. 248.

Gene expression databases

GenevestigatorP15127.
GermOnlineENSRNOG00000029986. Rattus norvegicus.

Family and domain databases

InterProIPR000494. EGF_rcpt_L.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR020710. Tyr_kinase_insulin_rcpt.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR002011. Tyr_prot_kinase_rcpt_2_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
PANTHERPTHR23256:SF176. Tyr_kinase_insulin_rcpt. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.
PfamPF00041. fn3. 2 hits.
PF00757. Furin-like. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000620. Insulin_receptor. 1 hit.
SMARTSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS50853. 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]
ProtoNetSearch...

Other Resources

NextBio604981.

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Entry information

Entry nameINSR_RAT
AccessionPrimary (citable) accession number: P15127
Secondary accession number(s): P97681
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: February 9, 2010
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents