P15127 (INSR_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin receptor
Short name=IR
EC=2.7.10.1

Alternative name(s):
CD_antigen=CD220

Cleaved into the following 2 chains:

1. Insulin receptor subunit alpha
2. Insulin receptor subunit beta

Gene names

Name:

Insr

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1383 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different 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. Ref.4
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates By similarity.
Subunit structure	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. Ref.3 Ref.5
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Domain	The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2 By similarity.
Post-translational modification	Autophosphorylated on tyrosine residues in response to insulin By similarity. Phosphorylation of Tyr-1000 is required for binding to IRS1, SHC1, and STAT5B By similarity. Dephosphorylated by PTPRE on Tyr-1000, Tyr-1186, Tyr-1190 and Tyr-1191 residues By similarity. Dephosphorylated by PTPRF and PTPN1 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fat cell differentiation Inferred from expression pattern PubMed 17286602. Source: RGD glucose homeostasis Inferred from direct assay PubMed 18256749. Source: RGD negative regulation of gene expression Inferred from mutant phenotype PubMed 17585961. Source: RGD negative regulation of protein phosphorylation Inferred from mutant phenotype PubMed 17585961. Source: RGD negative regulation of transporter activity Inferred from mutant phenotype PubMed 19049803. Source: RGD peptidyl-tyrosine phosphorylation Inferred from mutant phenotype PubMed 12850498. Source: RGD positive regulation of glycoprotein biosynthetic process Inferred from mutant phenotype PubMed 19049803. Source: RGD positive regulation of phosphorylation Inferred from direct assay PubMed 12435589. Source: BHF-UCL protein autophosphorylation Inferred from direct assay PubMed 12891559PubMed 17919343PubMed 3275643. Source: RGD protein heterotetramerization Inferred from direct assay PubMed 3516142. Source: RGD regulation of hydrogen peroxide metabolic process Inferred from direct assay PubMed 17919343. Source: RGD response to activity Inferred from expression pattern PubMed 17603294. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 17931855. Source: RGD response to ethanol Inferred from expression pattern PubMed 19185210. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern PubMed 18401942. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 12435589. Source: BHF-UCL response to manganese ion Inferred from expression pattern PubMed 6368536. Source: RGD response to testosterone stimulus Inferred from expression pattern PubMed 17673259. Source: RGD response to tumor necrosis factor Inferred from mutant phenotype PubMed 17761893. Source: RGD response to vitamin D Inferred from expression pattern PubMed 18638371. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 15665515. Source: RGD endosome Inferred from direct assay PubMed 15665515. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay PubMed 18798337. Source: RGD plasma membrane Inferred from direct assay PubMed 15665515. Source: RGD synapse Inferred from direct assay PubMed 16978790. Source: RGD
Molecular_function	3-phosphoinositide-dependent protein kinase binding Inferred from direct assay PubMed 16314505. Source: RGD ATP binding Inferred from electronic annotation. Source: UniProtKB-KW insulin binding Inferred from direct assay PubMed 17023527PubMed 3275643. Source: RGD insulin receptor substrate binding Inferred from mutant phenotype PubMed 12850498. Source: RGD insulin-activated receptor activity Inferred from direct assay PubMed 12891559PubMed 17023527PubMed 3275643. Source: RGD lipoic acid binding Inferred from physical interaction PubMed 17274632. Source: RGD protein complex binding Inferred from direct assay PubMed 3516142. Source: RGD protein phosphatase binding Inferred from mutant phenotype PubMed 12850498. Source: RGD
Complete GO annotation...

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26
	Chain	27 – 759	733	Insulin receptor subunit alpha		PRO_0000016696
	Chain	764 – 1383	620	Insulin receptor subunit beta		PRO_0000016698
Regions
	Topological domain	27 – 759	733	Extracellular Probable
	Topological domain	764 – 957	194	Extracellular Probable
	Transmembrane	958 – 978	21	Helical; Potential
	Topological domain	979 – 1383	405	Cytoplasmic Probable
	Domain	623 – 696	74	Fibronectin type-III 1
	Domain	758 – 845	88	Fibronectin type-III 2
	Domain	851 – 947	97	Fibronectin type-III 3
	Domain	1024 – 1299	276	Protein kinase
	Nucleotide binding	1105 – 1111	7	ATP By similarity
	Nucleotide binding	1164 – 1165	2	ATP By similarity
	Region	734 – 742	9	Insulin-binding By similarity
	Region	997 – 1000	4	Important for interaction with IRS1, SHC1 and STAT5B
	Region	1362 – 1365	4	PIK3R1 binding By similarity
	Compositional bias	27 – 173	147	Leu-rich
Sites
	Active site	1160	1	Proton donor/acceptor By similarity
	Binding site	1034	1	ATP By similarity
	Binding site	1058	1	ATP By similarity
	Binding site	1178	1	ATP By similarity
	Site	65	1	Insulin-binding By similarity
Amino acid modifications
	Modified residue	399	1	Phosphoserine By similarity
	Modified residue	400	1	Phosphotyrosine By similarity
	Modified residue	406	1	Phosphoserine By similarity
	Modified residue	1000	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1186	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1190	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1191	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1356	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1362	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Glycosylation	51	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	137	1	N-linked (GlcNAc...) Potential
	Glycosylation	241	1	N-linked (GlcNAc...) Potential
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	321	1	N-linked (GlcNAc...) Potential
	Glycosylation	363	1	N-linked (GlcNAc...) Potential
	Glycosylation	423	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
	Glycosylation	540	1	N-linked (GlcNAc...) Potential
	Glycosylation	634	1	N-linked (GlcNAc...) Potential
	Glycosylation	652	1	N-linked (GlcNAc...) Potential
	Glycosylation	699	1	N-linked (GlcNAc...) Potential
	Glycosylation	770	1	N-linked (GlcNAc...) Potential
	Glycosylation	783	1	N-linked (GlcNAc...) Potential
	Glycosylation	921	1	N-linked (GlcNAc...) Potential
	Glycosylation	934	1	N-linked (GlcNAc...) Potential
	Disulfide bond	34 ↔ 52		By similarity
	Disulfide bond	152 ↔ 181		By similarity
	Disulfide bond	185 ↔ 208		By similarity
	Disulfide bond	195 ↔ 214		By similarity
	Disulfide bond	218 ↔ 227		By similarity
	Disulfide bond	222 ↔ 233		By similarity
	Disulfide bond	234 ↔ 242		By similarity
	Disulfide bond	238 ↔ 251		By similarity
	Disulfide bond	254 ↔ 263		By similarity
	Disulfide bond	267 ↔ 279		By similarity
	Disulfide bond	285 ↔ 310		By similarity
	Disulfide bond	292 ↔ 300		By similarity
	Disulfide bond	314 ↔ 327		By similarity
	Disulfide bond	330 ↔ 334		By similarity
	Disulfide bond	338 ↔ 359		By similarity
	Disulfide bond	461 ↔ 494		By similarity
	Disulfide bond	550		Interchain By similarity
	Disulfide bond	675 ↔ 900		By similarity
Natural variations
	Alternative sequence	746 – 757	12	Missing in isoform Short.		VSP_036680

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (RIR-B) [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 4B919566902A944A	FASTA	1,383	156,757
	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
	Isoform Short (RIR-A) [UniParc]. Checksum: 146D5FFDA1EF415D	FASTA	1,371	155,553
	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 VFVPRPSRKR RSLEEVGNVT ATTPTLPDFP NISSTIAPTS 790 800 810 820 830 840 HEEHRPFEKV VNKESLVISG LRHFTGYRIE LQACNQDSPE ERSGVAAYVS ARTMPEAKAD 850 860 870 880 890 900 DIVGPVTHEI FENNVVHLMW QEPKEPNGLI VLYEVSYRRY GDEELHLCVS RKHFALERGC 910 920 930 940 950 960 RLRGLSPGNY SVRVRATSLA GNGSWTEPTY FYVTDYLDVP SNIAKIIIGP LIFVFLFSVV 970 980 990 1000 1010 1020 IGSIYLFLRK RQPDGPMGPL YASSNPEYLS ASDVFPSSVY VPDEWEVPRE KITLLRELGQ 1030 1040 1050 1060 1070 1080 GSFGMVYEGN AKDIIKGEVE TRVAVKTVNE SASLRERIEF LNEASVMKGF TCHHVVRLLG 1090 1100 1110 1120 1130 1140 VVSKGQPTLV VMELMAHGDL KSHLRSLRPD AENNPGRPPP TLQEMIQMTA EIADGMAYLN 1150 1160 1170 1180 1190 1200 AKKFVHRDLA ARNCMVAHDF TVKIGDFGMT RDIYETDYYR KGGKGLLPVR WMSPESLKDG 1210 1220 1230 1240 1250 1260 VFTASSDMWS FGVVLWEITS LAEQPYQGLS NEQVLKFVMD GGYLDPPDNC PERLTDLMRM 1270 1280 1290 1300 1310 1320 CWQFNPKMRP TFLEIVNLLK DDLHPSFPEV SFFYSEENKA PESEELEMEF EDMENVPLDR 1330 1340 1350 1360 1370 SSHCQREEAG CREGGSSLSI KRTYDEHIPY THMNGGKKNG RVLTLPRSNP S

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] [Europe PMC] [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]	"Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2." Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F. Oncogene 19:2052-2059(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB7.
[4]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
[5]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00393267. IPI00949768.
PIR	A36080.
UniGene	Rn.9876.
3D structure databases
ProteinModelPortal	P15127.
SMR	P15127. Positions 30-949, 1009-1311.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1348005.
PTM databases
PhosphoSite	P15127.
Proteomic databases
PaxDb	P15127.
PRIDE	P15127.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:2917. rat.
Organism-specific databases
RGD	2917. Insr.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000038045.
HOVERGEN	HBG006134.
InParanoid	P15127.
Enzyme and pathway databases
BRENDA	2.7.10.1. 5301.
Gene expression databases
ArrayExpress	P15127.
Genevestigator	P15127.
GermOnline	ENSRNOG00000029986. Rattus norvegicus.
Family and domain databases
Gene3D	2.60.40.10. 4 hits.
InterPro	IPR000494. EGF_rcpt_L. IPR003961. Fibronectin_type3. IPR006211. Furin-like_Cys-rich_dom. IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF00041. fn3. 2 hits. PF00757. Furin-like. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF01030. Recep_L_domain. 2 hits. [Graphical view]
PIRSF	PIRSF000620. Insulin_receptor. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00060. FN3. 3 hits. SM00261. FU. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits. SSF57184. Grow_fac_recept. 1 hit. SSF56112. Kinase_like. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P15127.
ChEMBL	CHEMBL5486.
NextBio	13948910.

Entry information

Entry name

INSR_RAT

Accession

Primary (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:	April 3, 2013
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program