Disease relevance of SIGLEC12

• A retrospective analysis was performed on all aneurysms operated on by one of us (SLG) from July 1980 to October 1988 to determine the factors that govern outcome from the intraoperative rupture of aneurysms [1].

High impact information on SIGLEC12

• We conclude that SRK alone determines S haplotype specificity of the stigma, and that SLG acts to promote a full manifestation of the self-incompatibility response [2].
• The S-locus-specific glycoprotein of Brassica and the gene encoding it (the SLG gene) are thought to be involved in determining self-incompatibility phenotype in this genus [3].
• It has been shown that the Brassica genome contains multiple SLG-related sequences [3].
• Unlike SLG, the SLR1 genes isolated from different S-allele homozygotes are highly conserved, and this gene, which appears to be ubiquitous in crucifers, is expressed in self-compatible strains as well as self-incompatible strains [3].
• Two highly polymorphic S locus genes, SLG (S locus glycoprotein) and SRK (S receptor kinase), have been identified, both of which are expressed predominantly in the stigmatic papillar cell [4].

Biological context of SIGLEC12

• Upon tyrosine phosphorylation, S2V recruits both Src homology 2 (SH2) domain-containing protein-tyrosine phosphatases SHP-1 and SHP-2, two important inhibitory regulators of immunoreceptor signal transduction [5].
• The SLG gene is localized 32.9 kb downstream of Siglec-8 on chromosome 19q13 [6].
• (i) The striking sequence similarity observed in an inter-specific comparison (95.6% identity between SLG14 of B. oleracea and SLG25 of B. campestris in deduced amino acid sequence) suggests that SLG diversification predates speciation [7].
• SRK alleles derived from different S-locus genotypes are highly polymorphic and have apparently evolved in unison with genetically linked alleles of SLG [8].
• (iii) Comparison of the hypervariable regions of SLG alleles suggests that intragenic recombination, together with point mutations, has contributed to the generation of the high level of sequence variation in SLG alleles [7].

Anatomical context of SIGLEC12

• When expressed in COS-7 cells, S2V was able to mediate sialic acid-dependent binding to human red blood cells, suggesting that S2V may function through cell-cell interaction [5].
• Through RT-PCR we have examined the expression profile of both SLG splice variants in a panel of human tissues and have found that SLG-S is highly expressed in spleen, small intestine and adrenal gland, while SLG-L exhibits high levels of expression in spleen, small intestine, and bone marrow [6].

Associations of SIGLEC12 with chemical compounds

• A unique feature of S2V is the presence of two V-set Ig-like domains responsible for the binding to sialic acid, whereas all other known siglecs possess only one [5].
• The cDNA of S2V encodes a type 1 transmembrane protein with four extracellular immunoglobulin-like (Ig-like) domains and a cytoplasmic tail bearing a typical immunoreceptor tyrosine-based inhibitory motif (ITIM) and an ITIM-like motif [5].
• Sequence analyses revealed that these two proteins (i) differ only in that a proline residue near the N terminus is hydroxylated in SLR1-BP1 but not in SLR1-BP2, and (ii) are members of the class A pollen coat protein (PCP) family, which includes PCP-A1, an SLG (S locus glycoprotein)-binding protein isolated from Brassica oleracea [9].
• SLG encodes a secreted S locus glycoprotein whilst SRK encodes a putative S locus receptor kinase which consists of three domains: an extracellular domain sharing extensive sequence identity with SLG, transmembrane region, and a cytoplasmic domain exhibiting a serine/threonine protein kinase activity [10].
• DNA fragments of SLG alleles specifically amplified from eight S haplotypes by PCR with class I SLG-specific primers showed different profiles following polyacrylamide gel electrophoresis, after digestion with a restriction endonuclease [11].

Enzymatic interactions of SIGLEC12

• In vivo S2V was tyrosine-phosphorylated when co-expressed with exogenous c-Src kinase [5].

Other interactions of SIGLEC12

• Through the positional cloning approach we have identified and characterized a Siglec-like gene (SLG), a putative novel member of the Siglec-3-like subgroup of Siglecs [6].
• Identification and characterization of S2V, a novel putative siglec that contains two V set Ig-like domains and recruits protein-tyrosine phosphatases SHPs [5].

Analytical, diagnostic and therapeutic context of SIGLEC12

• We describe the molecular cloning and characterization of S2V, a novel sialic acid binding immunoglobulin-like lectin [5].
• Rye inbred lines segregating at the S-locus and homozygous at the Z-locus were investigated by PCR with primers derived from Brassica SLG-sequences [12].
• SLG showed 30-44-fold higher binding to H69 cells harvested from H69 xenografts than SL [13].
• Southern blot hybridization with the BcSLG2 DNA probe showed polymorphism in the SLG gene organization of the Chinese cabbage plants [14].
• Northern blot and Western blot analyses revealed that endogenous SLG and SRK were greatly reduced of the transcriptional and translational levels in the transformant [15].

References