HGNC

HER1
Structure of the HER1 protein
Identifiers
Symbol	?
NCBI gene	1956
HGNC	3236
OMIM	131550
RefSeq	NM_005228
UniProt	P00533
Search for Structures Swiss-model Domains InterPro

HER1, also known as EGFR (Epidermal Growth Factor Receptor), is a transmembrane protein that is part of the ErbB family of receptors. It is a receptor tyrosine kinase that plays a crucial role in the regulation of cell growth, survival, proliferation, and differentiation. HER1 is encoded by the EGFR gene located on chromosome 7p11.2.

Structure

HER1 is composed of an extracellular ligand-binding domain, a single hydrophobic transmembrane domain, and an intracellular domain with tyrosine kinase activity. The extracellular domain is responsible for binding ligands such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α). Upon ligand binding, HER1 undergoes a conformational change that facilitates dimerization with other HER1 molecules or with other members of the ErbB family, such as HER2, HER3, and HER4.

Function

HER1 is involved in the activation of several downstream signaling pathways, including the Ras-Raf-MEK-ERK pathway, the PI3K-Akt pathway, and the JAK-STAT pathway. These pathways are critical for mediating cellular responses such as proliferation, differentiation, and survival. Dysregulation of HER1 signaling is implicated in the pathogenesis of various cancers, including non-small cell lung cancer, colorectal cancer, and glioblastoma.

Clinical Significance

Overexpression or mutation of HER1 is associated with poor prognosis in several types of cancer. Targeted therapies, such as tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib, and monoclonal antibodies like cetuximab, have been developed to inhibit HER1 signaling in cancer treatment. These therapies have shown efficacy in patients with specific mutations in the EGFR gene, particularly in non-small cell lung cancer.

Research and Development

Ongoing research is focused on understanding the mechanisms of resistance to HER1-targeted therapies and developing new strategies to overcome these challenges. Studies are also exploring the role of HER1 in other diseases and its potential as a biomarker for cancer diagnosis and prognosis.

Also see

• HER2
• HER3
• HER4
• Epidermal growth factor
• Receptor tyrosine kinase
• Cancer treatment