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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Insulin receptor

A receptor tyrosine kinase: insulin switches it on and it phosphorylates the proteins that move GLUT4 to the membrane and store glucose.

Updated 2026-11-01

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## Key facts

- An α₂β₂ heterotetramer held by disulfide bridges; it is made from a single precursor chain cut in the Golgi apparatus.
- Insulin binds the (outer) α subunits; the (transmembrane) β subunits carry the kinase domain.
- Autophosphorylation of three activation-loop tyrosines (1158, 1162, 1163) switches the kinase on, and it phosphorylates IRS-1 and IRS-2.
- Structure 1IR3 is the phosphorylated human kinase with an ATP analogue (ANP), Mg²⁺ and a substrate peptide: it shows the active site at work.

**Also called**
INSR

**EC number**
[2.7.10.1](https://www.enzyme-database.org/query.php?ec=2.7.10.1)

**Genes**
INSR

**Structure (PDB)**
[1IR3](https://www.rcsb.org/structure/1IR3)

## Regulation

- Activation: insulin binding (and, with lower affinity, IGF-1 and IGF-2).
- Switched off by tyrosine phosphatases (PTP1B) and receptor endocytosis.
- Serine phosphorylation of IRS-1 (JNK, IKKβ, PKC, S6K1) weakens the signal in insulin resistance.

## Inhibitors and toxins

- PTP1B (endogenous phosphatase that dephosphorylates the receptor)
- Antibodies against the receptor (type B insulin resistance)

## Clinical notes

- Severe INSR mutations: Donohue syndrome (leprechaunism) and Rabson–Mendenhall syndrome, with very high insulin and growth problems.
- Type A insulin resistance (milder mutations) shows up in young women with acanthosis nigricans and hyperandrogenism.
- High insulin stimulates ovarian insulin and IGF-1 receptors and raises androgens, as in polycystic ovary syndrome.

## Drugs that act here

- [Isophane (NPH) insulin](https://durgical.com/en/pharmacology/isophane-insulin/)
- [Insulin glargine](https://durgical.com/en/pharmacology/insulin-glargine/)
- [Insulin lispro](https://durgical.com/en/pharmacology/insulin-lispro/)
- [Insulin aspart](https://durgical.com/en/pharmacology/insulin-aspart/)
- [Insulin degludec](https://durgical.com/en/pharmacology/insulin-degludec/)
- [Insulin detemir](https://durgical.com/en/pharmacology/insulin-detemir/)
- [Insulin glulisine](https://durgical.com/en/pharmacology/insulin-glulisine/)

## Related conditions

- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)
- [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/)

## Related

- [Insulin signalling](https://durgical.com/en/biochemistry/topics/insulin-signalling/)
- [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/)
- [mTOR (mechanistic target of rapamycin)](https://durgical.com/en/biochemistry/enzymes/mtor/)
- [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/)

## Test yourself

Think of the answer, then tap the question to see it.

## What is the structure of the insulin receptor?

An α₂β₂ heterotetramer held by disulfide bridges; the β subunits carry the tyrosine kinase domain.

## What happens right after insulin binds the receptor?

The β subunits phosphorylate each other on activation-loop tyrosines and the kinase phosphorylates IRS-1 and IRS-2.

## Which phosphatase switches the insulin receptor off?

PTP1B, which dephosphorylates its tyrosines.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/biochemistry/enzymes/insulin-receptor/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [INSR: Insulin receptor (human)](https://www.uniprot.org/uniprotkb/P06213/entry) (UniProt, 2026); [INSR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/insr/) (MedlinePlus, US National Library of Medicine, 2026); [1IR3: PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG](https://www.rcsb.org/structure/1IR3) (RCSB Protein Data Bank, 2026); [Donohue syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/donohue-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/insulin-receptor/