Sialic acid-binding Ig-like lectin 12, or Siglec-XII, is a protein that in humans, is encoded by the SIGLEC12gene.[3][4][5]
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.[5]
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.[6] 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.[7] The research is being conducted to determine whether inactivation of the gene might deter its promotional effect upon the progression of human carcinoma.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Foussias G, Taylor SM, Yousef GM, Tropak MB, Ordon MH, Diamandis EP (Jun 2001). "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. doi:10.1006/bbrc.2001.5052. PMID11409877.
^S.S. Siddiqui et al., Human-specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression, FASEB BioAdvances, 3:69–82, 2021
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
