UniProt Accession

 IGF1R_HUMAN; P08069; B1B5Y2; Q14CV2; Q9UCC0 

Genbank Protein ID

 X04434; AB425196; AY332722; AC055807; AC069029; AC118658; AC118660; BC113610; BC113612; M69229 

Genbank Nucleotide ID

 CAA28030.1; BAG11657.1; AAP81165.1; AAI13611.1; AAI13613.1; AAB59399.1 

Protein Name

 Insulin-like growth factor 1 receptor 

Protein Synonyms/Alias

 Insulin-like growth factor I receptor; IGF-I receptor; CD221; Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain 

Gene Name

 IGF1R 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
1033	PETRVAIKTVNEAAS	ubiquitination	[1, 2, 3, 4, 5]
1055	LNEASVMKEFNCHHV	sumoylation	[6]
1130	MAYLNANKFVHRDLA	sumoylation	[6]
1150	VAEDFTVKIGDFGMT	sumoylation	[6]
1168	YETDYYRKGGKGLLP	ubiquitination	[4]
1171	DYYRKGGKGLLPVRW	ubiquitination	[2, 4]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor.
 Sehat B, Tofigh A, Lin Y, Trocmé E, Liljedahl U, Lagergren J, Larsson O.
 Sci Signal. 2010 Feb 9;3(108):ra10. [PMID: 20145208] 

Functional Description

 Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K- driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R. 

Sequence Annotation

 DOMAIN 488 606 Fibronectin type-III 1.
 DOMAIN 611 689 Fibronectin type-III 2.
 DOMAIN 831 926 Fibronectin type-III 3.
 DOMAIN 999 1274 Protein kinase.
 NP_BIND 1005 1013 ATP (By similarity).
 MOTIF 977 980 IRS1- and SHC1-binding.
 ACT_SITE 1135 1135 Proton acceptor (By similarity).
 BINDING 1033 1033 ATP.
 MOD_RES 980 980 Phosphotyrosine.
 MOD_RES 1161 1161 Phosphotyrosine; by autocatalysis.
 MOD_RES 1165 1165 Phosphotyrosine; by autocatalysis.
 MOD_RES 1166 1166 Phosphotyrosine; by autocatalysis.
 CARBOHYD 51 51 N-linked (GlcNAc...).
 CARBOHYD 102 102 N-linked (GlcNAc...) (Potential).
 CARBOHYD 135 135 N-linked (GlcNAc...).
 CARBOHYD 244 244 N-linked (GlcNAc...).
 CARBOHYD 314 314 N-linked (GlcNAc...).
 CARBOHYD 417 417 N-linked (GlcNAc...) (Potential).
 CARBOHYD 438 438 N-linked (GlcNAc...) (Potential).
 CARBOHYD 534 534 N-linked (GlcNAc...) (Potential).
 CARBOHYD 607 607 N-linked (GlcNAc...) (Potential).
 CARBOHYD 622 622 N-linked (GlcNAc...) (Potential).
 CARBOHYD 640 640 N-linked (GlcNAc...) (Potential).
 CARBOHYD 747 747 N-linked (GlcNAc...) (Potential).
 CARBOHYD 756 756 N-linked (GlcNAc...) (Potential).
 CARBOHYD 764 764 N-linked (GlcNAc...) (Potential).
 CARBOHYD 900 900 N-linked (GlcNAc...) (Potential).
 CARBOHYD 913 913 N-linked (GlcNAc...) (Potential).
 DISULFID 33 52
 DISULFID 150 178
 DISULFID 182 205
 DISULFID 192 211
 DISULFID 215 224
 DISULFID 219 230
 DISULFID 231 239
 DISULFID 235 248
 DISULFID 251 260
 DISULFID 264 276
 DISULFID 282 303
 DISULFID 307 321
 DISULFID 324 328
 DISULFID 332 353
 DISULFID 455 488
 CROSSLNK 1168 1168 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 1171 1171 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; ATP-binding; Cleavage on pair of basic residues; Complete proteome; Direct protein sequencing; Disease mutation; Disulfide bond; Glycoprotein; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1367 AA 

Protein Sequence

Gene Ontology

 GO:0005901; C:caveola; IEA:Compara.
 GO:0005887; C:integral to plasma membrane; IC:UniProtKB.
 GO:0043231; C:intracellular membrane-bounded organelle; IDA:BHF-UCL.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043559; F:insulin binding; IPI:BHF-UCL.
 GO:0005158; F:insulin receptor binding; IDA:BHF-UCL.
 GO:0005520; F:insulin-like growth factor binding; IDA:UniProtKB.
 GO:0005010; F:insulin-like growth factor-activated receptor activity; IDA:UniProtKB.
 GO:0007409; P:axonogenesis; IEA:Compara.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0030010; P:establishment of cell polarity; IEA:Compara.
 GO:0031017; P:exocrine pancreas development; IEA:Compara.
 GO:0006955; P:immune response; IMP:BHF-UCL.
 GO:0051389; P:inactivation of MAPKK activity; IDA:UniProtKB.
 GO:0008286; P:insulin receptor signaling pathway; TAS:ProtInc.
 GO:0030238; P:male sex determination; IEA:Compara.
 GO:0030879; P:mammary gland development; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IEA:Compara.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IC:BHF-UCL.
 GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
 GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
 GO:0032467; P:positive regulation of cytokinesis; IEA:Compara.
 GO:0045740; P:positive regulation of DNA replication; IMP:BHF-UCL.
 GO:0043410; P:positive regulation of MAPK cascade; IEA:Compara.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Compara.
 GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IEA:Compara.
 GO:0060740; P:prostate gland epithelium morphogenesis; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051262; P:protein tetramerization; IDA:UniProtKB.
 GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
 GO:0033197; P:response to vitamin E; IEA:Compara. 

Interpro

 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_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. 

Pfam

 PF00041; fn3
 PF00757; Furin-like
 PF07714; Pkinase_Tyr
 PF01030; Recep_L_domain 

SMART

 SM00060; FN3
 SM00261; FU
 SM00219; TyrKc 

PROSITE

 PS50853; FN3
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00239; RECEPTOR_TYR_KIN_II 

PRINTS

 PR00109; TYRKINASE.