EMR1

EMR1 Full Name

EGF-like module containing, mucin-like, hormone receptor-like sequence 1

EMR1 Introduction

EMR1, now officially named ADGRE1 (adhesion G protein-coupled receptor E1), encodes an unusual member of the adhesion G protein-coupled receptor family that is best known as a defining marker of mature macrophages. The protein was originally identified as the human ortholog of the molecule recognized by the F4/80 antibody, a monoclonal antibody that has been used for decades to identify mouse macrophages, and in humans EMR1 is likewise expressed on the surface of mature tissue macrophages. Adhesion GPCRs are distinguished by very large extracellular regions that are thought to mediate cell-cell and cell-matrix interactions; EMR1's extracellular domain contains multiple epidermal growth factor-like modules followed by a mucin-like stalk, from which the receptor's descriptive name is derived. These EGF-like domains, several of which are calcium-binding, are believed to engage ligands on neighboring cells or in the extracellular matrix, while the seven-transmembrane region couples to intracellular signaling pathways. Because EMR1 expression is restricted to the macrophage lineage in most tissues, it has been exploited both as a research tool for macrophage identification and as a potential target for therapies aimed at modulating macrophage function in inflammatory diseases and cancer. Understanding how EMR1 regulates macrophage adhesion and signaling may reveal new ways to control the many diseases in which macrophages play a central role.

Figure 1. EMR1 gene (adgre1) and f4/80 protein.

Adhesion GPCR Architecture and Extracellular Module Organization
EMR1 is a type I transmembrane protein whose structure combines a very large extracellular region with a seven-transmembrane domain characteristic of G protein-coupled receptors.
The extracellular region begins with a series of EGF-like modules, several of which contain calcium-binding consensus sequences that stabilize their structure and enable ligand recognition.
Following the EGF repeats is a mucin-like, heavily glycosylated stalk that extends the ligand-binding domains away from the cell surface and may itself participate in adhesive interactions.
The seven-transmembrane domain is followed by intracellular loops and a C-terminal tail that couple the receptor to heterotrimeric G proteins and to downstream signaling cascades.
The EMR1 gene is located on human chromosome 19 within a cluster of related adhesion GPCR genes, and its transcript undergoes alternative splicing that generates receptor isoforms differing in their extracellular domains.
ADGRE1 is a member of the EGF-TM7 family of adhesion GPCRs, whose name reflects the combination of EGF-like modules with a transmembrane (7TM) region.
Like other adhesion GPCRs, EMR1 may be subject to autoproteolytic cleavage at a GPCR proteolysis site, which influences the conformation and signaling of the receptor.

Macrophage Marker, Immune Function, and Therapeutic Applications
EMR1 is expressed at high levels on mature macrophages in most tissues, where it serves as the standard marker for identifying these cells by flow cytometry, immunohistochemistry, and cell sorting.
In the mouse, the F4/80 antigen recognized by the classical macrophage antibody is the orthologous protein, and the F4/80 antibody remains one of the most widely used reagents in immunology.
The expression of EMR1 increases as monocytes mature into macrophages, making it a useful indicator of macrophage differentiation and of the presence of tissue-resident macrophage populations.
Although the precise ligands and signaling outputs of EMR1 are still being characterized, its adhesion-GPCR architecture suggests roles in macrophage adhesion, migration, and interactions with the tissue microenvironment.
Because macrophages contribute to inflammatory diseases, fibrosis, and tumor progression, EMR1 has been investigated as a target for delivering therapies selectively to macrophages and for depleting or reprogramming pathogenic macrophage populations.
Antibodies against EMR1 and related adhesion GPCRs are being explored in preclinical models of cancer and inflammation, with the goal of exploiting the restricted expression of the receptor to achieve cell-type-specific effects.

Alternate Names for EMR1

EMR1; EGF-like module containing, mucin-like, hormone receptor-like sequence 1; Ly71; F4/80; Gpf480; TM7LN3; DD7A5-7; EGF-TM7; EGF-like module-containing mucin-like hormone receptor-like 1; EMR1 hormone receptor; lymphocyte antigen 71; EGF-like module receptor 1; cell surface glycoprotein F4/80;