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This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
IGF1R (Insulin Like Growth Factor 1 Receptor) is a Protein Coding gene. Diseases associated with IGF1R include Insulin-Like Growth Factor I and Ring Chromosome 15. Among its related pathways are Apoptosis Modulation and Signaling and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is INSR.
Insulin receptors (IRs) and insulin-like growth factor receptors (IGFRs) are formed from two subunits, each of which is comprised of an extracellular alpha-subunit and a transmembrane beta-subunit with intracellular tyrosine kinase activity. IR homodimers are activated by insulin.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA,TAS | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IEA,IBA | 21873635 |
GO:0005009 | insulin-activated receptor activity | IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005886 | plasma membrane | ISS,TAS | -- |
GO:0005887 | integral component of plasma membrane | IBA,IC | 7679099 |
GO:0005899 | insulin receptor complex | IBA | 21873635 |
GO:0016020 | membrane | IEA,IDA | 8452530 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
2 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
3 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
4 | Glioma |
.49
.46
|
|
5 | Nanog in Mammalian ESC Pluripotency |
GSK3 Signaling
.62
Nanog in Mammalian ESC Pluripotency
.62
|
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0006955 | immune response | IMP | 16886151 |
GO:0007165 | signal transduction | TAS | 3003744 |
GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | IEA,IBA | 21873635 |
GO:0007275 | multicellular organism development | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Mecasermin | Approved, Investigational | Pharma | Target, agonist, inhibitor | 36 | ||
Paclitaxel | Approved, Vet_approved | Pharma | Tubulin and Bcl2 inhibitor, Taxanes | 3701 | ||
brigatinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
Insulin aspart | Approved | Pharma | Target | 544 | ||
Insulin degludec | Approved | Pharma | Target | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
IGF1 |
|
|
|
|||
IGF2 |
|
|
|
|||
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
GSK 1838705 |
|
1116235-97-2 |
|
|
||
Insulin (human) recombinant |
|
11061-68-0 |
|
|
Compound | Action | Cas Number |
---|---|---|
Demethylasterriquinone B1 | Selective insulin RTK activator | 78860-34-1 |
GSK 1838705 | Potent IR and IGF1R inhibitor; also inhibits anaplastic lymphoma kinase (ALK) | 1116235-97-2 |
Insulin (human) recombinant | Endogenous peptide agonist | 11061-68-0 |
Picropodophyllotoxin | Selective IGF1R inhibitor | 477-47-4 |
PQ 401 | IGF1R inhibitor | 196868-63-0 |
Compound | Action | Cas Number |
---|---|---|
AG-1024 | Selective IGF-1R inhibitor | 65678-07-1 |
AXL1717 | IGF-1R inhibitor,orally active | 477-47-4 |
AZD-3463 | ALK/IGF1R inhibitor | 1356962-20-3 |
BMS-536924 | IR/IGF-1R inhibitor | 468740-43-4 |
BMS-754807 | IGF-1R/InsR inhibitor,potent and selective | 1001350-96-4 |
GSK1838705A | IGF-IR/IR/ALK inhibitor, ATP-competitive | 1116235-97-2 |
GSK1904529A | Selective IGF-1R/IR inhibitor | 1089283-49-7 |
Linsitinib | IGF1R/IR inhibitor,potent and novel | 867160-71-2 |
MK 0893 | Glucagon receptor/IGF-1R antagonist | 870823-12-4 |
NVP-ADW742 | Selective IGF-1R inhibitor | 475488-23-4 |
NVP-AEW541 | IGF-IR inhibitor, novel, potent and selective | 475489-16-8 |
PQ 401 | IGF1R inhibitor,potent and cell-permeable | 196868-63-0 |
TAE226 (NVP-TAE226) | FAK inhibitor,potent and ATP-competitive | 761437-28-9 |
XL228 | IGF1R/AURORA /FGFR1-3/ABL/SRC family kinases inhibitor | 898280-07-4 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | · | 10c | · | 10d | ^ | 11a | · | 11b | · | 11c | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15a | · | 15b | ^ | 16 | ^ | 17a | · | 17b | ^ | 18 | ^ | 19a | · |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||
SP2: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP12: |
ExUns: | 19b | ^ | 20 | ^ | 21 | ^ | 22 | ^ | 23 | ^ | 24 | ^ | 25 | ^ | 26a | · | 26b | ^ | 27 | ^ | 28 | ^ | 29 | ^ | 30a | · | 30b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||
SP2: | |||||||||||||||||||||||||||
SP3: | |||||||||||||||||||||||||||
SP4: | |||||||||||||||||||||||||||
SP5: | |||||||||||||||||||||||||||
SP6: | |||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||
SP8: | |||||||||||||||||||||||||||
SP9: | |||||||||||||||||||||||||||
SP10: | |||||||||||||||||||||||||||
SP11: | |||||||||||||||||||||||||||
SP12: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | IGF1R 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | IGFR1 31 |
|
OneToOne | |
IGF1R 30 |
|
||||
Dog (Canis familiaris) |
Mammalia | IGF1R 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Igf1r 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Igf1r 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | IGF1R 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | IGF1R 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | IGF1R 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | IGF1R 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | igf1r 30 |
|
||
Str.14302 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | LOC398022 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | igf1ra 30 31 |
|
OneToMany | |
igf1rb 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | InR 30 32 |
|
||
sev 32 |
|
|
|||
hop 32 |
|
|
|||
CG3837 31 32 |
|
OneToMany | |||
CG10702 32 |
|
|
|||
African malaria mosquito (Anopheles gambiae) |
Insecta | INR 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | daf-2 30 31 32 |
|
OneToMany | |
R151.4 32 |
|
|
|||
K09B11.5 32 |
|
|
|||
W02A2.4 32 |
|
|
|||
C24G6.2a 32 |
|
|
|||
C24G6.2b 32 |
|
|
|||
T25B9.5 32 |
|
|
|||
Y69E1A.3 32 |
|
|
|||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.344 30 |
|
SNP ID | Clinical significance and condition | Chr 15 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
635840 | Likely Pathogenic: Growth delay due to insulin-like growth factor I resistance | 98,707,585(+) | C/T | MISSENSE_VARIANT | |
635841 | Pathogenic: Growth delay due to insulin-like growth factor I resistance | 98,707,851(+) | T/C | SYNONYMOUS_VARIANT | |
635842 | Pathogenic: Growth delay due to insulin-like growth factor I resistance | 98,891,588(+) | G/T | NONSENSE | |
635843 | Likely Pathogenic: Growth delay due to insulin-like growth factor I resistance | 98,896,798(+) | G/A | MISSENSE_VARIANT | |
635844 | Pathogenic: Growth delay due to insulin-like growth factor I resistance | 98,899,619(+) | A/AG | SPLICE_DONOR_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv466e214 | CNV | gain | 21293372 |
dgv4763n54 | CNV | gain | 21841781 |
dgv4764n54 | CNV | gain+loss | 21841781 |
dgv4765n54 | CNV | loss | 21841781 |
dgv4766n54 | CNV | loss | 21841781 |
esv27037 | CNV | loss | 19812545 |
esv2750108 | CNV | deletion | 23290073 |
esv2750109 | CNV | deletion |