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The structure of HER2: domains and dimerization

HER2 contains extracellular, transmembrane, and intracellular domains. While the intracellular domain is responsible for phosphorylation and recruitment of proteins, the extracellular domain is where signal transduction is initiated through dimerization with other receptors.¹³ Preclinical research continues to uncover the individual roles of each sub-domain in receptor activation and signaling.

Select one to reveal more about HER2
1Sub-domain I
Extracellular sub-domain I and sub-domain III

Unlike other receptors in the HER family, sub-domain I on HER2 is constantly in contact with sub-domain III. Permanent interaction between these 2 sub-domains keeps the receptor in an open conformation, exposing sub-domain II, and ensuring the receptor is always ready to dimerize.³
2Sub-domain II
Extracellular sub-domain II

Sub-domain II is the dimerization domain. This domain enables HER2 to bind with other receptors in the HER family to initiate downstream signaling.³
3Sub-domain III
Extracellular sub-domain I and sub-domain III

Unlike other receptors in the HER family, sub-domain I on HER2 is constantly in contact with sub-domain III. Permanent interaction between these 2 sub-domains keeps the receptor in an open conformation, exposing sub-domain II, and ensuring the receptor is always ready to dimerize.³
4Sub-domain IV
Extracellular sub-domain IV

While the exact role of sub-domain IV in HER functioning is still unknown, it is believed to stabilize and lock the receptor in an open conformation. Other approaches to targeting HER2 bind to sub-domain IV to interfere with HER2 signaling, but sub-domain IV is not directly involved with dimerization. ¹³
5Transmembrane Domain
Transmembrane domain

The transmembrane domain of HER2 has been implicated in receptor activation control, but further research is required to understand its function in signaling initiation.¹³
6Intracellular Domain
Intracellular domain

The intracellular domain has a cytoplasmic linker, a tyrosine kinase component, and a tail that phosphorylates and recruits adapter proteins following dimerization.¹³ These adapter proteins can then initiate cell proliferation signaling, leading to cell growth, differentiation, and angiogenesis.¹²
Go back to all Domains

Related Resources for this page:

Dimerization Video

HER2+ Breast Cancer Slide Decks

New: HER2 Dimerization iTunes app

The structure of HER2: domains and dimerization

Extracellular sub-domain I and sub-domain III

Extracellular sub-domain II

Extracellular sub-domain I and sub-domain III

Extracellular sub-domain IV

Transmembrane domain

Intracellular domain