Alternative titles; symbolsLEUKOSIALIN; LSNLEUKOCYTE LARGE SIALOGLYCOPROTEINCD43GPL115HGNC Approved Gene Symbol: SPNCytogenetic location: 16p11.2 Genomic coo...
Alternative titles; symbols
HGNC Approved Gene Symbol: SPN
Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38): 16:29,662,962-29,670,875 (from NCBI)
Sialophorin (leukosialin) is a major sialoglycoprotein on the surface of human T lymphocytes, monocytes, granulocytes, and some B lymphocytes, which appears to be important for immune function and may be part of a physiologic ligand-receptor complex involved in T-cell activation.
▼ Cloning and Expression
Pallant et al. (1989) stated that sialophorin had been identified by the L10 monoclonal antibody. Pallant et al. (1989) isolated a cDNA clone encoding leukosialin from a library constructed from human peripheral blood cells. Southern blot analysis suggested that the gene is present in single copy.
Shelley et al. (1988, 1989) isolated and sequenced cDNA clones for sialophorin. The longest sequenced clone was 1.7 kb and encoded 5 of 7 isolated tryptic peptides. Northern blot analysis indicated that the sialophorin transcript is 2.5 kb long. The nucleotide sequence of the 1.7-kb clone showed that the sialophorin transcript has a 3-prime-noncoding region of 587 nucleotides, is polyadenylated, and has the AATAAA polyadenylation signal. The derived sequence of 341 amino acids showed that the sialophorin protein has 3 domains: an extracellular domain of 195 amino acids, a hydrophobic transmembrane domain of 23 amino acids, and a C-terminal intracellular domain of 123 amino acids which contains a number of sites that might be phosphorylated by protein kinase C.
▼ Gene Function
By introducing a cDNA encoding the human CD43 protein into an antigen-responsive murine T-cell hybridoma, Park et al. (1991) found that the antigen-specific activation of T cells was enhanced. The intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, was required for this function.
Rosenstein et al. (1991) noted that CD43 is defective in lymphocytes of patients with Wiskott-Aldrich syndrome (see 301000) and that specific interaction of CD43 with a ligand on the surface of T cells appears to contribute to T-cell activation. Rosenstein et al. (1991) presented evidence that intercellular adhesion molecule-1 (ICAM1; 147840) is a ligand for CD43. The authors suggested that the defect in T-cell function in Wiskott-Aldrich syndrome may result from defective CD43/ICAM1 interaction. Many patients with HIV infection have circulating anti-CD43 antibodies; these autoantibodies may contribute to the severe immunodeficiency found in AIDS patients.
Schmid et al. (1992) presented evidence that the galactoglycoprotein of plasma represents the extracellular portion of CD43 derived by proteolytic cleavage from the transmembrane portion. Bazil and Strominger (1993) showed that CD43 is proteolytically cleaved from the surface of stimulated lymphocytes and granulocytes. They suggested that induced enzymatic cleavage of leukocyte receptors may represent a general mechanism regulating surface expression of these molecules.
Using immunoprecipitation and cell-binding analyses, van den Berg et al. (2001) showed that both the 240-kD SELPLG (600738) and the 130-kD CD43 proteins bind to macrophage-restricted SIGLEC1 (SN; 600751) in solution. However, only T cell-bound CD43, and not SELPLG, in either the branched or unbranched glycoform binds when expressed on the cell surface. Thus, CD43 is the T-cell counterreceptor for SN.
The immunologic synapse is the T cell-APC (antigen-presenting cell) contact site where T-cell receptors (TCRs), coreceptors, signaling molecules, and adhesion receptors polarize upon antigen recognition. The formation of the immunologic synapse is thought to be important for receptor signal transduction and full T-lymphocyte activation. CD43 is a large sialoprotein diffusely expressed in unactivated T cells. Using antigen-activated T cells and confocal microscopy, Delon et al. (2001) demonstrated that moesin (309845) is excluded from the region of T cell-APC contact and colocalizes with CD43. Western blot and immunocytochemical analyses showed that moesin is rapidly dephosphorylated upon antigen recognition and then rephosphorylated on threonine residues. Only phosphorylated moesin was able to bind CD43. Delon et al. (2001) concluded that T-cell activation requires the removal of CD43 from the immunologic synapse to allow efficient engagement of the TCR with molecules on the APC.
Using mouse helper T cell lines and confocal microscopy, Allenspach et al. (2001) determined that the cytoplasmic tail of CD43 is necessary and sufficient for CD43 removal from the immunologic synapse. In at least some cells, CD43 is located at the distal pole of the T cell together with ezrin (123900) and moesin. No differences in the behavior of ezrin and moesin were noted throughout the study. Using cells from Cd43 -/- mice, Allenspach et al. (2001) observed that ezrin-radixin (179410)-moesin (ERM) family proteins move independently of the large CD43 mucin. Overexpression of a dominant-negative ERM mutant containing the N-terminal 320 amino acids of ezrin inhibited the activation-induced movement of CD43 without affecting conjugate formation. The dominant-negative mutant reduced cytokine production but not the expression of T-cell activation markers.
▼ Gene Structure
Shelley et al. (1990) reported that the CD43 gene has a single intron of 378 bp that interrupts the sequence specifying the 5-prime untranslated region of the mRNA. The gene is, therefore, unusual in that the discrete extracellular, transmembrane, and intracellular regions of the protein, including repeat sequences in the extracellular region, are not encoded by separate exons.
Shelley et al. (1989) determined that the human sialophorin gene appears to be unique within the haploid genome, and they assigned it to chromosome 16 by Southern blot analysis of DNA from rodent-human cell hybrids. By study of somatic cell hybrids, Pallant et al. (1989) demonstrated that the leukosialin gene is not X-linked; by in situ hybridization, they mapped the gene to 16p11.2. Baecher et al. (1990) demonstrated that the mouse leukosialin gene, designated Ly48, is encoded by chromosome 7.