IGF1R
entrez
3480
canonical
uniprot
P08069
canonical
ensembl
ENSG00000140443
resolver
ensp
ENSP00000496919
resolver
ensp
ENSP00000497069
resolver
enst
ENST00000649865
resolver
enst
ENST00000650285
resolver
genesymbol
IGF1R
resolver
hgnc
HGNC:5465
resolver
uniprot
B1B5Y2
resolver
uniprot
C9J5X1
resolver
uniprot
Q14CV2
resolver
uniprot
Q9UCC0
resolver
uniprot_entry
C9J5X1_HUMAN
resolver
uniprot_entry
IGF1R_HUMAN
resolver
uniprot_sec
B1B5Y2
resolver
uniprot_sec
Q14CV2
resolver
uniprot_sec
Q9UCC0
resolver
activity_regulation
ACTIVITY REGULATION: Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop. {ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:14729630, ECO:0000269|PubMed:17317169, ECO:0000269|PubMed:18566589, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20545947, ECO:0000269|PubMed:20675137, ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, ECO:0000269|Ref.55}.
uniprot
proteins
amino_acid_sequence
MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLHILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGDLCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCSAPDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHDGECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNLLINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSFYVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTRNNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDGQDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSEILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRHNYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRKVFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFESRVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTWEPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGNYTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHRKRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRHSGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC
uniprot
proteins
disease_involvement
DISEASE: Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450]: A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels. {ECO:0000269|PubMed:14657428, ECO:0000269|PubMed:15928254, ECO:0000269|PubMed:25040157}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: 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.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
uniprot
proteins
mass_dalton
154793
uniprot
proteins
mutagenesis
MUTAGEN 980; /note="Y->F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10."; /evidence="ECO:0000269|PubMed:10454568, ECO:0000269|PubMed:7541045"; MUTAGEN 1033; /note="K->A: Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1."; /evidence="ECO:0000269|PubMed:7541045"; MUTAGEN 1280; /note="Y->F: No effect on GRB10-binding."; /evidence="ECO:0000269|PubMed:10454568"; MUTAGEN 1281; /note="Y->F: No effect on GRB10-binding."; /evidence="ECO:0000269|PubMed:10454568"; MUTAGEN 1346; /note="Y->F: Loss of GRB10-binding."; /evidence="ECO:0000269|PubMed:10454568
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on tyrosine residues in response to ligand binding (PubMed:11694888, PubMed:18501599, PubMed:19041240). Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (PubMed:11694888, PubMed:18501599, PubMed:19041240). Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166 (PubMed:11694888, PubMed:18501599, PubMed:19041240). While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity (PubMed:11694888, PubMed:18501599, PubMed:19041240). Can be autophosphorylated at additional tyrosine residues (in vitro) (PubMed:11694888, PubMed:18501599, PubMed:19041240). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines (PubMed:11694888, PubMed:18501599, PubMed:19041240). May also be phosphorylated at Tyr-1161 and Tyr-1166 by mTORC2 (PubMed:26584640). Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding (PubMed:7541045). Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282 (By similarity). Dephosphorylated by PTPN1. {ECO:0000250|UniProtKB:Q60751, ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:7541045}.; PTM: Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation. {ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:21994939, ECO:0000269|PubMed:7541045}.; PTM: Sumoylated with SUMO1. {ECO:0000269|PubMed:20596523}.; PTM: Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment. {ECO:0000269|PubMed:17524361}.
uniprot
proteins
protein_family
Insulin receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10454568
uniprot
proteins
pubmed
10579905
uniprot
proteins
pubmed
10747872
uniprot
proteins
pubmed
11071852
uniprot
proteins
pubmed
11162456
uniprot
proteins
pubmed
11591350
uniprot
proteins
pubmed
11694888
uniprot
proteins
pubmed
11884618
uniprot
proteins
pubmed
12019176
uniprot
proteins
pubmed
12138094
uniprot
proteins
pubmed
12138114
uniprot
proteins
pubmed
12556535
uniprot
proteins
pubmed
12821780
uniprot
proteins
pubmed
1316909
uniprot
proteins
pubmed
14501110
uniprot
proteins
pubmed
14657428
uniprot
proteins
pubmed
14729630
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15878855
uniprot
proteins
pubmed
15928254
uniprot
proteins
pubmed
15998644
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
16831875
uniprot
proteins
pubmed
1711844
uniprot
proteins
pubmed
17317169
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17524361
uniprot
proteins
pubmed
17624760
uniprot
proteins
pubmed
1846292
uniprot
proteins
pubmed
18501599
uniprot
proteins
pubmed
18566589
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19041240
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19578119
uniprot
proteins
pubmed
19778024
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20545947
uniprot
proteins
pubmed
20596523
uniprot
proteins
pubmed
20675137
uniprot
proteins
pubmed
21414779
uniprot
proteins
pubmed
21441024
uniprot
proteins
pubmed
21994939
uniprot
proteins
pubmed
22351760
uniprot
proteins
pubmed
25040157
uniprot
proteins
pubmed
26584640
uniprot
proteins
pubmed
26692333
uniprot
proteins
pubmed
2877871
uniprot
proteins
pubmed
32494007
uniprot
proteins
pubmed
7541045
uniprot
proteins
pubmed
7679099
uniprot
proteins
pubmed
8247543
uniprot
proteins
pubmed
8257688
uniprot
proteins
pubmed
8452530
uniprot
proteins
pubmed
9202395
uniprot
proteins
pubmed
9355755
uniprot
proteins
pubmed
9581554
uniprot
proteins
pubmed
9690478
uniprot
proteins
pubmed
9727029
uniprot
proteins
pubmed
9822622
uniprot
proteins
sequence_length
1367
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17524361}; Single-pass type I membrane protein {ECO:0000269|PubMed:17524361}.
uniprot
proteins
transmembrane_region
TRANSMEM 936..959; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins