CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014248
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
1034PETRVAIKTVNEAASubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 (By similarity). When present in a hybrid receptor with INSR, binds IGF1 (By similarity). 
Sequence Annotation
 DOMAIN 489 607 Fibronectin type-III 1.
 DOMAIN 612 690 Fibronectin type-III 2.
 DOMAIN 832 927 Fibronectin type-III 3.
 DOMAIN 1000 1276 Protein kinase.
 NP_BIND 1006 1014 ATP (By similarity).
 MOTIF 978 981 IRS1- and SHC1-binding (By similarity).
 ACT_SITE 1137 1137 Proton acceptor (By similarity).
 BINDING 1034 1034 ATP (By similarity).
 MOD_RES 981 981 Phosphotyrosine (By similarity).
 MOD_RES 1163 1163 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1167 1167 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1168 1168 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 51 51 N-linked (GlcNAc...) (Potential).
 CARBOHYD 102 102 N-linked (GlcNAc...) (Potential).
 CARBOHYD 135 135 N-linked (GlcNAc...) (Potential).
 CARBOHYD 245 245 N-linked (GlcNAc...) (Potential).
 CARBOHYD 314 314 N-linked (GlcNAc...) (Potential).
 CARBOHYD 418 418 N-linked (GlcNAc...) (Potential).
 CARBOHYD 439 439 N-linked (GlcNAc...) (Potential).
 CARBOHYD 535 535 N-linked (GlcNAc...) (Potential).
 CARBOHYD 608 608 N-linked (GlcNAc...) (Potential).
 CARBOHYD 623 623 N-linked (GlcNAc...) (Potential).
 CARBOHYD 639 639 N-linked (GlcNAc...); atypical.
 CARBOHYD 641 641 N-linked (GlcNAc...).
 CARBOHYD 748 748 N-linked (GlcNAc...).
 CARBOHYD 757 757 N-linked (GlcNAc...).
 CARBOHYD 765 765 N-linked (GlcNAc...).
 CARBOHYD 901 901 N-linked (GlcNAc...).
 CARBOHYD 914 914 N-linked (GlcNAc...) (Potential).
 DISULFID 33 52 By similarity.
 DISULFID 150 178 By similarity.
 DISULFID 182 205 By similarity.
 DISULFID 192 211 By similarity.
 DISULFID 215 224 By similarity.
 DISULFID 219 230 By similarity.
 DISULFID 231 239 By similarity.
 DISULFID 235 248 By similarity.
 DISULFID 251 260 By similarity.
 DISULFID 264 276 By similarity.
 DISULFID 282 303 By similarity.
 DISULFID 307 321 By similarity.
 DISULFID 324 328 By similarity.
 DISULFID 332 354 By similarity.
 DISULFID 456 489 By similarity.
 CROSSLNK 1170 1170 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 1173 1173 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 ATP-binding; Cleavage on pair of basic residues; Complete proteome; Disulfide bond; Glycoprotein; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1373 AA 
Protein Sequence
MKSGSGGGSP TSLWGLVFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGFLH 60
ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF 120
EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTIDWSLI LDAVSNNYIV GNKPPKECGD 180
LCPGTLEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSVCG KRACTENNEC CHPECLGSCH 240
TPDDNTTCVA CRHYYYKGVC VPACPPGTYR FEGWRCVDRD FCANIPNAES SDSDGFVIHD 300
DECMQECPSG FIRNSTQSMY CIPCEGPCPK VCGDEEKKTK TIDSVTSAQM LQGCTILKGN 360
LLINIRRGNN IASELENFMG LIEVVTGYVK IRHSHALVSL SFLKNLRLIL GEEQLEGNYS 420
FYVLDNQNLQ QLWDWNHRNL TVRSGKMYFA FNPKLCVSEI YRMEEVTGTK GRQSKGDINT 480
RNNGERASCE SDVLRFTSTT TWKNRIIITW HRYRPPDYRD LISFTVYYKE APFKNVTEYD 540
GQDACGSNSW NMVDVDLPPN KEGEPGILLH GLKPWTQYAV YVKAVTLTMV ENDHIRGAKS 600
EILYIRTNAS VPSIPLDVLS ASNSSSQLIV KWNPPTLPNG NLSYYIVRWQ RQPQDGYLYR 660
HNYCSKDKIP IRKYADGTID VEEVTENPKT EVCGGDKGPC CACPKTEAEK QAEKEEAEYR 720
KVFENFLHNS IFVPRPERRR RDVMQVANTT MSSRSRNTTV ADTYNITDPE EFETEYPFFE 780
SRVDNKERTV ISNLRPFTLY RIDIHSCNHE AEKLGCSASN FVFARTMPAE GADDIPGPVT 840
WEPRPENSIF LKWPEPENPN GLILMYEIKY GSQVEDQREC VSRQEYRKYG GAKLNRLNPG 900
NYTARIQATS LSGNGSWTDP VFFYVPAKTT YENFMHLIIA LPVAILLIVG GLVIMLYVFH 960
RKRNNSRLGN GVLYASVNPE YFSAADVYVP DEWEVAREKI TMNRELGQGS FGMVYEGVAK 1020
GVVKDEPETR VAIKTVNEAA SMRERIEFLN EASVMKEFNC HHVVRLLGVV SQGQPTLVIM 1080
ELMTRGDLKS YLRSLRPEVE QNNLVLIPPS LSKMIQMAGE IADGMAYLNA NKFVHRDLAA 1140
RNCMVAEDFT VKIGDFGMTR DIYETDYYRK GGKGLLPVRW MSPESLKDGV FTTHSDVWSF 1200
GVVLWEIATL AEQPYQGLSN EQVLRFVMEG GLLDKPDNCP DMLFELMRMC WQYNPKMRPS 1260
FLEIIGSIKD EMEPSFQEVS FYYSEENKPP EPEELEMELE MEPENMESVP LDPSASSASL 1320
PLPERHSGHK AENGPGPGVL VLRASFDERQ PYAHMNGGRA NERALPLPQS STC 1373 
Gene Ontology
 GO:0005901; C:caveola; IEA:Compara.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0043231; C:intracellular membrane-bounded organelle; IEA:Compara.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0005886; C:plasma membrane; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043559; F:insulin binding; IEA:Compara.
 GO:0043560; F:insulin receptor substrate binding; ISS:UniProtKB.
 GO:0005520; F:insulin-like growth factor binding; ISS:UniProtKB.
 GO:0005010; F:insulin-like growth factor-activated receptor activity; ISS:UniProtKB.
 GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
 GO:0007409; P:axonogenesis; IEA:Compara.
 GO:0007420; P:brain development; IMP:MGI.
 GO:0030010; P:establishment of cell polarity; IEA:Compara.
 GO:0031017; P:exocrine pancreas development; IMP:MGI.
 GO:0006955; P:immune response; IEA:Compara.
 GO:0051389; P:inactivation of MAPKK activity; IEA:Compara.
 GO:0030238; P:male sex determination; IMP:MGI.
 GO:0030879; P:mammary gland development; IMP:MGI.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IMP:MGI.
 GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:Compara.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0032467; P:positive regulation of cytokinesis; IEA:Compara.
 GO:0045740; P:positive regulation of DNA replication; IEA:Compara.
 GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IMP:MGI.
 GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IEA:Compara.
 GO:0060740; P:prostate gland epithelium morphogenesis; IMP:MGI.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051262; P:protein tetramerization; ISS:UniProtKB.
 GO:0046328; P:regulation of JNK cascade; IEA:Compara.
 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.