Igf1r
entrez
16001
canonical
uniprot
Q60751
canonical
ensembl
ENSMUSG00000005533
resolver
ensp
ENSMUSP00000005671
resolver
ensp
ENSMUSP00000239642
resolver
ensp
ENSMUSP00000239644
resolver
enst
ENSMUST00000005671
resolver
genesymbol
Igf1r
resolver
uniprot
E9QNX9
resolver
uniprot
O70438
resolver
uniprot
Q3U1L4
resolver
uniprot
Q62123
resolver
uniprot_entry
E9QNX9_MOUSE
resolver
uniprot_entry
IGF1R_MOUSE
resolver
uniprot_entry
Q3U1L4_MOUSE
resolver
uniprot_sec
O70438
resolver
uniprot_sec
Q62123
resolver
activity_regulation
ACTIVITY REGULATION: Activated by autophosphorylation at Tyr-1163, Tyr-1167 and Tyr-1168 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 (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MKSGSGGGSPTSLWGLVFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGFLHILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTIDWSLILDAVSNNYIVGNKPPKECGDLCPGTLEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSVCGKRACTENNECCHPECLGSCHTPDDNTTCVACRHYYYKGVCVPACPPGTYRFEGWRCVDRDFCANIPNAESSDSDGFVIHDDECMQECPSGFIRNSTQSMYCIPCEGPCPKVCGDEEKKTKTIDSVTSAQMLQGCTILKGNLLINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSFYVLDNQNLQQLWDWNHRNLTVRSGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTRNNGERASCESDVLRFTSTTTWKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDGQDACGSNSWNMVDVDLPPNKEGEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSEILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPTLPNGNLSYYIVRWQRQPQDGYLYRHNYCSKDKIPIRKYADGTIDVEEVTENPKTEVCGGDKGPCCACPKTEAEKQAEKEEAEYRKVFENFLHNSIFVPRPERRRRDVMQVANTTMSSRSRNTTVADTYNITDPEEFETEYPFFESRVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTWEPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGNYTARIQATSLSGNGSWTDPVFFYVPAKTTYENFMHLIIALPVAILLIVGGLVIMLYVFHRKRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMNRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEVEQNNLVLIPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTHSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIIGSIKDEMEPSFQEVSFYYSEENKPPEPEELEMELEMEPENMESVPLDPSASSASLPLPERHSGHKAENGPGPGVLVLRASFDERQPYAHMNGGRANERALPLPQSSTC
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 (By similarity). When present in a hybrid receptor with INSR, binds IGF1 (By similarity). {ECO:0000250}.
uniprot
proteins
mass_dalton
155788
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on tyrosine residues in response to ligand binding (By similarity). Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (By similarity). Autophosphorylation occurs in a sequential manner; Tyr-1167 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1163 and Tyr-1168 (By similarity). While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1163, Tyr-1167 and Tyr-1168) have to be phosphorylated for optimal activity (By similarity). Can be autophosphorylated at additional tyrosine residues (in vitro) (By similarity). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines (By similarity). May also be phosphorylated at Tyr-1163 and Tyr-1168 by mTORC2 (By similarity). Phosphorylation of Tyr-981 is required for IRS1- and SHC1-binding (By similarity). Phosphorylation of Ser-1280 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1284 (PubMed:22685298). Dephosphorylated by PTPN1 (By similarity). {ECO:0000250|UniProtKB:P08069, ECO:0000269|PubMed:22685298}.; PTM: Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation (By similarity). {ECO:0000250}.; PTM: Sumoylated with SUMO1. {ECO:0000250}.; 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 (By similarity). {ECO:0000250}.
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
11884589
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
19656770
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22685298
uniprot
proteins
pubmed
2482828
uniprot
proteins
pubmed
26692333
uniprot
proteins
pubmed
8234298
uniprot
proteins
pubmed
8402901
uniprot
proteins
sequence_length
1373
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
uniprot
proteins
transmembrane_region
TRANSMEM 937..960; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins