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This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
INSR (Insulin Receptor) is a Protein Coding gene. Diseases associated with INSR include Donohue Syndrome and Pineal Hyperplasia, Insulin-Resistant Diabetes Mellitus, And Somatic Abnormalities. Among its related pathways are PI3K/AKT activation and Selenium Micronutrient Network. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is IGF1R.
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:0001540 | amyloid-beta binding | IPI | 19406747 |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IMP,IDA | 7537849 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA | 21873635 |
GO:0005009 | insulin-activated receptor activity | IDA | 6849137 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005635 | colocalizes_with nuclear envelope | IDA | 19406747 |
GO:0005886 | plasma membrane | IC,TAS | -- |
GO:0005887 | integral component of plasma membrane | IDA | 9092559 |
GO:0005899 | insulin receptor complex | IBA,IMP | 15069075 |
GO:0005901 | caveola | IDA,IEA | 15182363 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
|
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 | Regulation of lipid metabolism Insulin signaling-generic cascades |
.01
|
|
4 | PI3K/AKT activation |
.89
|
|
5 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000187 | activation of MAPK activity | IMP | 17001305 |
GO:0001934 | positive regulation of protein phosphorylation | IDA | 7556070 |
GO:0003007 | heart morphogenesis | IMP | 7693131 |
GO:0005975 | carbohydrate metabolic process | IEA | -- |
GO:0006355 | regulation of transcription, DNA-templated | IMP | 12881524 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Insulin Aspart | Approved | Pharma | Target, agonist | 522 | ||
Insulin Detemir | Approved | Pharma | Target, agonist | 219 | ||
Insulin glargine | Approved | Pharma | Target, agonist | 605 | ||
Insulin glulisine | Approved | Pharma | Target, agonist | 110 | ||
Cyclophosphamide | Approved, Investigational | Pharma | Nitrogen mustard alkylating agent and prodrug. | 3484 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor | 58-64-0 |
|
||
GSK 1838705 |
|
1116235-97-2 |
|
|
||
Insulin (human) recombinant |
|
11061-68-0 |
|
|
||
Picropodophyllotoxin |
|
477-47-4 |
|
|
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 |
---|---|---|
BMS-536924 | IR/IGF-1R inhibitor | 468740-43-4 |
BMS-754807 | IGF-1R/InsR inhibitor,potent and selective | 1001350-96-4 |
Demethylasterriquinone B1 | 78860-34-1 | |
GSK1838705A | IGF-IR/IR/ALK inhibitor, ATP-competitive | 1116235-97-2 |
GSK1904529A | Selective IGF-1R/IR inhibitor | 1089283-49-7 |
HNGF6A | 1093111-54-6 | |
Linsitinib | IGF1R/IR inhibitor,potent and novel | 867160-71-2 |
ExUns: | 1a | · | 1b | · | 1c | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16 | ^ | 17 | ^ | 18 | ^ | 19 | ^ | 20 | ^ | 21 | ^ | 22 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP3: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | INSR 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | IR-A 33 |
|
OneToOne | |
INSR 32 |
|
||||
dog (Canis familiaris) |
Mammalia | INSR 33 32 |
|
OneToOne | |
mouse (Mus musculus) |
Mammalia | Insr 17 33 32 |
|
||
rat (Rattus norvegicus) |
Mammalia | Insr 32 |
|
||
oppossum (Monodelphis domestica) |
Mammalia | INSR 33 |
|
OneToOne | |
platypus (Ornithorhynchus anatinus) |
Mammalia | INSR 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | CTK-1 33 |
|
OneToOne | |
INSR 32 |
|
||||
tropical clawed frog (Silurana tropicalis) |
Amphibia | LOC100492718 32 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | LOC398006 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | insra 33 32 |
|
OneToMany | |
insrb 33 |
|
OneToMany | |||
rainbow trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.8035 32 |
|
||
fruit fly (Drosophila melanogaster) |
Insecta | InR 34 |
|
|
|
CG3837 33 34 |
|
OneToMany | |||
CG10702 34 |
|
|
|||
worm (Caenorhabditis elegans) |
Secernentea | W02A2.4 34 |
|
|
|
K09B11.5 34 |
|
|
|||
T21G5.1 34 |
|
|
|||
Y69E1A.3 34 |
|
|
|||
T25B9.5 34 |
|
|
|||
daf-2 33 |
|
OneToMany | |||
sea squirt (Ciona savignyi) |
Ascidiacea | -- 33 |
|
OneToMany |
SNP ID | Clin | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs10413914 | likely-benign, Insulin-resistant diabetes mellitus AND acanthosis nigricans, Leprechaunism syndrome, Pineal hyperplasia AND diabetes mellitus syndrome | 7,112,454(-) | G/A | 3_prime_UTR_variant | |
rs10415841 | benign, Insulin-resistant diabetes mellitus AND acanthosis nigricans, Pineal hyperplasia AND diabetes mellitus syndrome, Leprechaunism syndrome | 7,112,262(-) | A/G | 3_prime_UTR_variant, downstream_transcript_variant, genic_downstream_transcript_variant | |
rs10416396 | benign, Leprechaunism syndrome, Insulin-resistant diabetes mellitus AND acanthosis nigricans, Pineal hyperplasia AND diabetes mellitus syndrome | 7,112,838(-) | C/G | 3_prime_UTR_variant | |
rs1051651 | benign, Insulin-resistant diabetes mellitus AND acanthosis nigricans, Leprechaunism syndrome, Pineal hyperplasia AND diabetes mellitus syndrome | 7,116,272(-) | G/C | 3_prime_UTR_variant | |
rs1051690 | benign, Leprechaunism syndrome, Insulin-resistant diabetes mellitus AND acanthosis nigricans, Pineal hyperplasia AND diabetes mellitus syndrome | 7,116,952(-) | T/C | 3_prime_UTR_variant |