SIGLEC9 Human
Description
Introduction to SIGLEC9 Human
SIGLEC9 (Sialic Acid-Binding Immunoglobulin-Type Lectin 9) is a transmembrane protein belonging to the CD33-related Siglec family, which plays critical roles in immune modulation. It is encoded by the SIGLEC9 gene located on chromosome 19q13.4 . Structurally, SIGLEC9 contains an N-terminal immunoglobulin (Ig)-like V-type domain responsible for sialic acid binding, two Ig-like C2-type domains, a transmembrane region, and a cytoplasmic tail with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) .
Expression Patterns
SIGLEC9 is expressed on neutrophils, monocytes, NK cells, B cells, and a subset of CD8+ T cells . Single-cell RNA sequencing reveals elevated SIGLEC9 expression in tumor-associated macrophages (TAMs) in cancers like glioblastoma and ovarian carcinoma .
Immune Regulation
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Inhibitory Signaling: ITIM motifs recruit SHP1/SHP2 phosphatases, dampening immune cell activation (e.g., mast cell degranulation, T-cell cytotoxicity) .
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Pathogen Interaction: Recognizes sialylated pathogens (e.g., Neisseria meningitidis), influencing immune evasion .
Role in Cancer
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Immunosuppression: High SIGLEC9 on TAMs correlates with reduced T-cell activity and poor prognosis in high-grade serous ovarian cancer (HGSC) and gliomas .
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Therapeutic Target: Blocking SIGLEC9 restores anti-tumor immunity in preclinical models .
Therapeutic Applications
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Antibody Blockade: Anti-SIGLEC9 monoclonal antibodies (e.g., 8A1E9) enhance NK cell cytotoxicity by 40–60% in vitro and reduce tumor volume by 70% in vivo .
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Combination Therapy: Co-blockade of SIGLEC9 and PD-1 synergistically improves T-cell responses in HGSC models .
Comparative Analysis with Related Siglecs
| Feature | SIGLEC9 | SIGLEC7 |
|---|---|---|
| Sequence Identity | ~80% with SIGLEC7 | – |
| Ligand Preference | α2,3- and α2,6-sialic acids | α2,8-sialic acids |
| Expression | Neutrophils, TAMs | NK cells, monocytes |
Evolutionary and Pathogenic Insights
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Rapid Evolution: SIGLEC9 shows species-specific adaptations, likely driven by host-pathogen interactions .
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Pathogen Exploitation: Certain pathogens mimic human sialic acids to engage SIGLEC9, suppressing immune clearance .
Future Directions
Product Specs
Belonging to the immunoglobulin superfamily, Sialic Acid Binding Ig Like Lectin 9 (SIGLEC9) is a member of the sialic acid-binding Ig-like lectin family. This family is primarily expressed on human blood leukocytes. SIGLEC9 is thought to function as an adhesion molecule and is found in the bone marrow, placenta, spleen, and fetal liver. Additionally, SIGLEC9 is a member of the recently identified CD33-related Siglec family, which consists of sialic acid-binding proteins.
Produced in Sf9 Insect cells, Recombinant Human SIGLEC9 is a single, glycosylated polypeptide chain. It encompasses 573 amino acids (18-348a.a.), has a molecular mass of 63.3 kDa, and appears as a band with a molecular size of approximately 70-100 kDa on SDS-PAGE. A 239 amino acid hIgG-His tag is added at the C-terminus of SIGLEC9, and the protein is purified using proprietary chromatographic techniques.
The SIGLEC9 protein solution is provided at a concentration of 0.5 mg/ml and contains Phosphate Buffered Saline (pH 7.4) and 10% glycerol.
The purity of the protein is greater than 95.0% as determined by SDS-PAGE analysis.
Sialic Acid Binding Ig Like Lectin 9, Protein FOAP-9, Siglec-9, CDw329, Sialic Acid Binding Ig-Like Lectin 9, Sialic Acid-Binding Ig-Like Lectin 9, CD329 Antigen, OBBP-LIKE, FOAP-9, CD329.
ADPQTSKLLT MQSSVTVQEG LCVHVPCSFS YPSHGWIYPG PVVHGYWFRE GANTDQDAPV ATNNPARAVW EETRDRFHLL GDPHTKNCTL SIRDARRSDA GRYFFRMEKG SIKWNYKHHR LSVNVTALTH RPNILIPGTL ESGCPQNLTC SVPWACEQGT PPMISWIGTS VSPLDPSTTR SSVLTLIPQP QDHGTSLTCQ VTFPGASVTT NKTVHLNVSY PPQNLTMTVF QGDGTVSTVL GNGSSLSLPE GQSLRLVCAV DAVDSNPPAR LSLSWRGLTL CPSQPSNPGV LELPWVHLRD AAEFTCRAQN PLGSQQVYLN VSLQSKATSG VTQGLEPKSC DKTHTCPPCP APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGKHHH HHH.
Product Science Overview
Sialic Acid Binding Ig Like Lectin 9 (Siglec-9) is a member of the sialic acid-binding immunoglobulin-like lectins (Siglecs) family. These are I-type (Ig-type) lectins belonging to the immunoglobulin superfamily. Siglec-9 is characterized by an N-terminal Ig-like V-type domain that mediates sialic acid binding, followed by varying numbers of Ig-like C2-type domains .
Siglec-9 is a glyco-immune negative checkpoint expressed on several immune cells, including myeloid cells, natural killer (NK) cells, and a subset of T cells . It exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance . This interaction facilitates tumor survival and growth by preventing recognition during immunosurveillance .
Siglec-9 is predominantly expressed on tumor-associated macrophages (TAMs). High levels of Siglec-9+ TAMs are associated with an immunosuppressive tumor microenvironment characterized by exhausted CD8+ T cells and increased immune checkpoint expression . Blockade of Siglec-9 has been shown to suppress the phosphorylation of the inhibitory phosphatase SHP-1, repolarize TAMs to an antitumorigenic phenotype, and retrieve the cytotoxic activity of CD8+ T cells .
Given its potent immunosuppressive properties, Siglec-9 is considered a promising target for cancer immunotherapy. The development of Siglec-9 blocking antibodies has shown potential in enhancing anti-tumor immunity by interfering with Siglec-9-mediated immunosuppression . In vitro and in vivo studies have demonstrated that these antibodies can augment anti-tumor immune activity and reduce tumor volume .
Recombinant human Siglec-9 is produced using recombinant DNA technology, which allows for the production of large quantities of the protein for research and therapeutic purposes. This recombinant form retains the functional properties of the native protein, making it a valuable tool for studying the role of Siglec-9 in immune regulation and its potential as a therapeutic target .
