CD33-related SIGLECs

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Sialic acid binding Ig like lectins (SIGLECS)
CD33-related SIGLECs

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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CD33-related SIGLECs (3, 5, 6, 7, 8, 9, 10, 11, 12, 14, and 16) are more broadly expressed in myeloid and lymphoid tissues and cells than the conserved SIGLECs. The structurally and functionally related SIGLECs 7 and 9 from this subfamily [13] have been implicated in myeloid cell-mediated modulation in cancer [1-2,5,8,10-11], making these proteins novel therapeutic targets to enhance antitumour immunity (cancer immunotherapy).

Targets

3301

SIGLEC3 (CD33) C Show summary »« Hide summary More detailed page go icon to follow link

sialic acid binding Ig like lectin 6 Show summary »« Hide summary

Target Id	3301
Nomenclature	sialic acid binding Ig like lectin 6
Previous and unofficial names	CD327 \| CD33L \| OB-BP1 \| SIGLEC-6
Genes	SIGLEC6 (Hs)
Ensembl ID	ENSG00000105492 (Hs), ENSMUSG00000004609 (Mm), ENSRNOG00000021474 (Rn)
UniProtKB AC	O43699 (Hs), A2RT59 (Mm)
Comment	SIGLEC6 binds sialyl-TN glycans and leptin. It was considered as a therapeutic target for the treatment of eosinophil- and mast cell-mediated inflammation [6-7,9]. However, development of the anti-SIGLEC6 monoclonal antibody AK006 was discontinued at phase 1 due to lack of efficacy in patients with moderate-to-severe chronic spontaneous urticaria.

SIGLEC8 (sialic acid binding Ig like lectin 8) Show summary »« Hide summary More detailed page go icon to follow link

SIGLEC10 (sialic acid binding Ig like lectin 10) Show summary »« Hide summary More detailed page go icon to follow link

References

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1. Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ et al.. (2019) CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature, 572 (7769): 392-396. [PMID:31367043]

2. Beatson R, Tajadura-Ortega V, Achkova D, Picco G, Tsourouktsoglou TD, Klausing S, Hillier M, Maher J, Noll T, Crocker PR et al.. (2016) The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. Nat Immunol, 17 (11): 1273-1281. [PMID:27595232]

3. Bernstein ID. (2000) Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia, 14 (3): 474-5. [PMID:10720144]

4. Caron PC, Co MS, Bull MK, Avdalovic NM, Queen C, Scheinberg DA. (1992) Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res, 52 (24): 6761-7. [PMID:1458463]

5. Ibarlucea-Benitez I, Weitzenfeld P, Smith P, Ravetch JV. (2021) Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity. Proc Natl Acad Sci U S A, 118 (26). [PMID:34155121]

6. Korver W, Benet Z, Wong A, Negri GL, Chang K, Sanchez R, Leung J, De Freitas N, Luu T, Schanin J et al.. (2024) Regulation of mast cells by overlapping but distinct protein interactions of Siglec-6 and Siglec-8. Allergy, 79 (3): 629-642. [PMID:38186079]

7. O'Sullivan JA, Youngblood BA, Schleimer RP, Bochner BS. (2023) Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases. Semin Immunol, 69: 101799. [PMID:37413923]

8. Rodriguez E, Boelaars K, Brown K, Eveline Li RJ, Kruijssen L, Bruijns SCM, van Ee T, Schetters STT, Crommentuijn MHW, van der Horst JC et al.. (2021) Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9. Nat Commun, 12 (1): 1270. [PMID:33627655]

9. Schanin J, Korver W, Brock EC, Leung J, Benet Z, Luu T, Chang K, Xu A, De Freitas N, Luehrsen K et al.. (2022) Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells. Commun Biol, 5 (1): 1226. [PMID:36369358]

10. Theruvath J, Menard M, Smith BAH, Linde MH, Coles GL, Dalton GN, Wu W, Kiru L, Delaidelli A, Sotillo E et al.. (2022) Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat Med, 28 (2): 333-344. [PMID:35027753]

11. Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X et al.. (2019) Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med, 25 (4): 656-666. [PMID:30833750]

12. Zheng X, Wu W, Liu Y, Zheng P. (2013) Methods of use of soluble cd24 for therapy of rheumatoid arthritis. Patent number: US20130231464A1. Assignee: Oncolmmune, Inc.. Priority date: 28/04/2010. Publication date: 05/09/2013.

13. Zheng Y, Ma X, Su D, Zhang Y, Yu L, Jiang F, Zhou X, Feng Y, Ma F. (2020) The Roles of Siglec7 and Siglec9 on Natural Killer Cells in Virus Infection and Tumour Progression. J Immunol Res, 2020: 6243819. [PMID:32322597]

How to cite this family page

Database page citation:

CD33-related SIGLECs. Accessed on 08/05/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1000.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.