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- Table of Contents
Facts about Sialic acid-binding Ig-like lectin 5.
The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. .
Human | |
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Gene Name: | SIGLEC5 |
Uniprot: | O15389 |
Entrez: | 8778 |
Belongs to: |
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immunoglobulin superfamily |
Siglec-5/Siglec-14
Mass (kDA):
60.715 kDA
Human | |
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Location: | 19q13.41 |
Sequence: | 19; NC_000019.10 (51610967..51630474, complement) |
Expressed by monocytic/myeloid lineage cells. Found at high levels in peripheral blood leukocytes, spleen, bone marrow and at lower levels in lymph node, lung, appendix, placenta, pancreas and thymus. Expressed by monocytes and neutrophils but absent from leukemic cell lines representing early stages of myelomonocytic differentiation.
Membrane; Single-pass type I membrane protein.
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The CD33 family of Siglecs proteins is a group of proteins that mature innate immune systems cells express. It also regulates cellular proliferation/differentiation. This family of proteins also contains several other proteins, including CD33 which may be expressed during later stages in haemopoiesis. Additionally, signaling properties may be affected if the ITIM contains a sequence motif.
Siglec protein may be a therapeutic target. It has been shown to deliver antigen-specific drugs to cancer cells and induce tolerance in antigen-specific T cells. There are still many questions about the therapeutic value of this drug. In preclinical studies, it may be necessary to use different high-affinity ligands. However, mice that express human Siglec are also available, although their expression level is lower in mice.
There were many strategies used to develop a Siglec anti-body. Novel substituents at C-9 of sialic acid were identified. The TCC–neu5Ac compound was tested for selectivity, and its affinity. Its high affinity compound was also selective to several Siglecs. High affinity glycan-ligands have the potential to affect signaling and decide a cell's fate.
In addition to its immunological function, Siglecs are also known to regulate cell-cell interactions and signalling functions. The problem is to identify biologically relevant ligands. A variety of experimental methods are needed to identify biologically relevant molecules, including genetically modified mice and biochemical analyses. Additionally, it is possible to uncover the complex factors involved by dissecting signalling channels.
The SIGLEC5 marker, which has been recently identified in a variety of cancer cells, is an important target for drug discovery. The marker is widely regarded as a targeting mechanism. However, its activities are also regulated by several parameters, including the presence of cis and trans interactors, density of ligands, and rate of internalization and recycling. Siglec activity can be a hurdle to drug development.
Its role as a biomarker in cancer research and inflammatory diseases has been recognized. Inflammatory phenotypes are correlated with the levels of siglecs, which regulate the production of cytokines, which help the body fight off pathogens. The siglec activity of immune cells is also correlated with many diseases and inflammatory phenotypes. However, very few therapies are currently geared toward Siglec glycobiology.
Siglecs are a group of receptors that have ITIM domains expressed in their cytoplasmic tailed. Siglec-8, a Siglec-5 and Siglec-8 for humans and mice are closely related. However, they diverged in evolutionary time. They are a type if immunoglobulins and have a V-set domain at the amino-terminal, as well immunoglobulin-like domains in the carboxy-terminus. The SIGLEC5- and SIGLEC8 homologues are also included in the family.
The sSIGLEC5 biomarker may be used as an exitus predictor in the context of CRC. Pre-operative sSIGLEC5 levels might be a good indicator of CRC progress, as sSIGLEC5 is closely related with IC candidates. However, further experiments are necessary to establish the origin of sSIGLEC5, as well as its mechanism of action in CRC.
The gene SIGLEC5 is expressed in high levels on neutrophils. This protein is likely to play a role in the cellular interaction between neutrophils during acute allergic responses. This protein is high in concentrations on neutrophils. These are the main cells that are involved during inflammatory responses. Its use is restricted because it isn't accessible to Siglec-5 in these processes.
Studies of the soluble SIGLEC5 marker among colorectal cancer patients have shown that it can be used to predict survival. The soluble SIGLEC5 levels were significantly higher in colorectal cancer patients than in healthy subjects. This preliminary study does not prove that this marker can be used to predict outcomes. This gene could be a target for treatment, although more research is needed.
The siglec-5 gene can be expressed on B lymphocytes as well as monocytes. In mice, however, it is very restricted in myelomonocytic cell lines. However, it is possible that the siglec-5 gene plays a unique function. It could be present on neutrophils, but absent on leukemic cell. It could also be found within the blood of mice, in addition to these two uses.
Arthritis can be linked to the SIGLEC-5 genetic marker. This genetic marker increases the risk of developing osteoarthritis in people who have it. Interestingly, this gene also plays a role in autoimmune diseases. It is found in other primates and is deleted in humans. This gene recruits DAP protein, which can increase the risk of arthritis. Although SIGLEC5's genetic code is rare, it is found in approximately 13% of patients with osteoarthritis.
Reactive arthritis is a type of autoimmune disease that develops because of an infection in a different part of the body. Reactive joint disease can be caused by a bacterial problem or a minor infection. It is difficult to diagnose reactive arthritis because symptoms are often absent or infrequent. The most common cause of reactive arthritis is chlamydia, which is acquired through sexual intercourse. Other causes include Shigella, Yersinia and Campylobacter.
Reactive arthritis is defined by vague symptoms. The symptoms may not manifest until weeks or even months after the onset. Reactive arthritis can also be associated with gastrointestinal infection, fever, and unintended weight loss. Reactive arthritis symptoms can also be caused by a virus, bacteria, or viral infection. Rare cases of the disease may not be detected because there are no specific diagnostic criteria.
SIGLEC5's protein family includes many members. Each member has a specific function in the immune system. The SiaSiglec/Siglec system regulates the balance of self and not-self recognition, by altering cell adhesion/signaling. Siglecs regulate immune responses and are essential for tumor immunity. Siglec is highly expressed in tumors.
The Siglec proteins are able to recognize many sialic acid structure in mammalian cells. They also have distinct specificity profiles. For example, Siglec-7 and Siglec-11 prefer the Neu5Ac(a2-8) structure, while CD33 and OBBP2 bind leptin weakly. For these reasons, siglec proteins are important in leukemia research.
The Siglec-5 gene is most commonly expressed on neutrophils. Siglec-5 gene expression strongly associates with hematopoietic cells, which means that Siglec-5 proteins are expressed in these cells. It is absent from neutrophils, which is why it is important in leukemia. This protein could therefore be an indicator of the early stages in myelomonocytic development.
A new study was conducted to determine if preoperative levels soluble SIGLEC5 could predict survival in colorectal carcinoma patients. The results showed that sSIGLEC5 levels before surgery were predictive for survival. The study also showed that SIGLEC5 may be an IC candidate in CRC. This protein has strong similarities to many IC-candidates and has been described as a patent IC potential in sepsis. To evade immune surveillance, hypersialylation found on cancer cells may be recruiting the sSIGLEC5. Nonetheless, further experiments are needed to determine the origin of the protein and the mechanism of action.
PMID: 9731071 by Cornish A.L., et al. Characterization of siglec-5, a novel glycoprotein expressed on myeloid cells related to CD33.
PMID: 10428856 by Patel N., et al. OB-BP1/Siglec-6. A leptin- and sialic acid-binding protein of the immunoglobulin superfamily.