CD177

What is CD177 protein?

CD177 gene (CD177 molecule) is a protein coding gene which situated on the long arm of chromosome 19 at locus 19q13. This gene encodes a glycosyl-phosphatidylinositol (GPI)-linked cell surface glycoprotein that plays a role in neutrophil activation. The protein can bind platelet endothelial cell adhesion molecule-1 and function in neutrophil transmigration. Mutations in this gene are associated with myeloproliferative diseases. Autoantibodies against the protein may result in pulmonary transfusion reactions, and it may be involved in Wegener's granulomatosis. The CD177 protein is consisted of 437 amino acids and CD177 molecular weight is approximately 46.4 kDa.

What is the function of CD177 protein?

The CD177 protein is a glycosylphosphatidylinositol (GPI) -anchored cell surface protein that plays a role in a variety of biological processes. In neutrophils, CD177 is associated with a variety of functions, including regulation of cell migration, recognition of platelet endothelial cell adhesion molecule -1 (PECAM-1), and interaction with β2 integrins that influence cell activation status and migration capacity. In the field of oncology, the expression level of CD177 is increased in some cancers, which is associated with the proliferation, invasion and prognosis of tumor cells. In addition, CD177 is also expressed in regulatory T cells (TREGs), which can regulate the function and homeostasis of Treg cells and affect immunosuppressive activity in the tumor microenvironment. These findings suggest that CD177 not only has an important role in hematology and immunology, but is also a potential therapeutic target in tumor immunotherapy.

CD177 related signaling pathway

The CD177-related signaling pathway is associated with neutrophil activation and immune response regulation. CD177, also known as NB1 glycoprotein, is primarily expressed on the surface of neutrophils and functions in the mobilization of these cells to sites of infection or inflammation. It facilitates the release of granules containing inflammatory mediators and antimicrobial peptides. The CD177 signaling pathway involves the interaction of CD177 with platelet activating factor (PAF) and other ligands, leading to downstream signaling events that enhance neutrophil adhesion, migration, degranulation, and production of reactive oxygen species. This pathway is important for effective immunity against bacterial and fungal infections but can also contribute to inflammatory and autoimmune disorders when dysregulated.

CD177 related diseases

The CD177 protein plays a role in a variety of diseases, especially in oncology and autoimmune diseases. In the tumor microenvironment, the expression of CD177 is closely related to the proliferation, invasion and prognosis of tumor cells, and its high expression is associated with poor prognosis of many cancers, such as breast cancer, gastric cancer and colorectal cancer. CD177 is specifically expressed on regulatory T cells (TREGs) and may be involved in the regulation of immunosuppressive activities in the tumor microenvironment, affecting tumor growth and the effect of immunotherapy. In addition, CD177 also plays a role in neutrophil-mediated inflammatory responses and is associated with the pathogenesis of diseases such as inflammatory bowel disease (IBD) and acute pancreatitis. In IBD, CD177+ neutrophils play a protective role by increasing bactericidal activity and IL-22 production, while in acute pancreatitis, CD177 may play a role by inhibiting the formation of neutrophils extracellular traps (NETs).

Fig1. Mechanisms of CD177-regulated NETs in acute pancreatitis (AP) and AP-associated ALI. (Junxian Zhang, 2023)

Bioapplications of CD177

The bioapplications of rhCD177 focus on its potential role in modulating immune responses and inflammatory conditions. rhCD177 could be utilized as a therapeutic target in autoimmune diseases where excessive neutrophil activation occurs, such as in vasculitis or rheumatoid arthritis. It might also be applied in the development of diagnostic tools for identifying and monitoring inflammatory disorders involving neutrophils. Furthermore, rhCD177 could aid in researching pathogen-host interactions and neutrophil function by serving as a tool for in vitro studies. Its potential as a component in vaccine development against bacterial infections is also being explored.

Case Study 1: Jillian L Astarita, 2021

Podoplanin (PDPN), a marker for cancer-associated fibroblasts (CAFs), is linked to poor cancer patient outcomes, making it a potential therapeutic target. However, its cellular functions and binding partners are not well understood, hindering drug development. Using a high-throughput approach, we identified CD177 as a new PDPN interactor and found that PDPN plays a role in cell signaling, growth, and actomyosin contractility. Cellular assays showed that CD177 acts as a functional antagonist, mimicking the effects seen in PDPN-deficient CAFs.

Fig1. PDPN screens identify CD177 as a specific, high-scoring hit.

Fig2. Volcano plots depicting significant changes in CD177- (circle) and CLEC-2- (triangle) treated CAFs.

Case Study 2: Claudia Eulenberg-Gustavus, 2017

CD177, a neutrophil antigen presenter in autoimmune diseases, varies in expression among individuals. This study found that only CD177-positive neutrophils express the protein and mRNA, and this expression follows a unique monoallelic pattern inherited from one parent. Epigenetic factors, such as DNA methylation, and transcription factors like c-Jun and c-Fos regulate CD177 expression. This discovery explains the existence of two distinct neutrophil subsets defined by CD177 expression.

Fig3. Acquired neutrophil surface markers CD11b and CD18, together with a bimodal CD177 phenotype.

Fig4. ChIP analysis for c-Jun, c-Fos, and c-Ets-1 binding was performed in CD177 neutrophils.

CD177 has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CD177 itself. We selected most functions CD177 had, and list some proteins which have the same functions with CD177. You can find most of the proteins on our site.

CD177 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CD177 here. Most of them are supplied by our site. Hope this information will be useful for your research of CD177.

KCNIP3;EWSR1