Sialic acid-binding Ig-like lectin 12 explained

Sialic acid-binding Ig-like lectin 12, or Siglec-XII, is a protein that in humans, is encoded by the SIGLEC12 gene.^{[1] [2]}

Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs, ITIM and SLAM-like.

The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4.

Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene.^[3]

The Siglec-XII protein has been identified as a possible promoter of human carcinoma progression in research by Ajit Varki and Nissi Varki at the University of California San Diego School of Medicine.^[4] Approximately seventy percent of humans have a mutation that inactivates the protein, but those without the mutation may suffer an inordinate number of carcinomas when compared to other primates.^[5] The research is being conducted to determine whether inactivation of the gene might deter its promotional effect upon the progression of human carcinoma.

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Angata T, Varki NM, Varki A . A second uniquely human mutation affecting sialic acid biology . J. Biol. Chem. . 276 . 43 . 40282–7 . 2001 . 11546777 . 10.1074/jbc.M105926200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Clark HF, Gurney AL, Abaya E, etal . The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .

Notes and References

1. Foussias G, Taylor SM, Yousef GM, Tropak MB, Ordon MH, Diamandis EP . Cloning and molecular characterization of two splice variants of a new putative member of the Siglec-3-like subgroup of Siglecs . Biochem Biophys Res Commun . 284 . 4 . 887–99 . Jun 2001 . 11409877 . 10.1006/bbrc.2001.5052 .
2. Yu Z, Lai CM, Maoui M, Banville D, Shen SH . Identification and characterization of S2V, a novel putative siglec that contains two V set Ig-like domains and recruits protein-tyrosine phosphatases SHPs . J Biol Chem . 276 . 26 . 23816–24 . Jun 2001 . 11328818 . 10.1074/jbc.M102394200 . free .
3. Web site: Entrez Gene: SIGLEC12 sialic acid binding Ig-like lectin 12.
4. S.S. Siddiqui et al., Human-specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression, FASEB BioAdvances, 3:69–82, 2021
5. Jones, Asher, “Rogue” Protein Could Contribute to Humans’ High Cancer Rates, The Scientist, April 1, 2021