Recombinant Human IGSF4A/SynCAM1 Protein, CF

IGSF4A is a 75 kDa immunoglobulin superfamily protein that mediates calcium-independent adhesive interactions, either homophilic or heterophilic with CRTAM (class I-restricted T cell-associated molecule), Necl-1 (SynCAM3) or Nectin-3 (1, 4, 5). Alternate names for IGSF4A reflect its activities. As TSLC-1 (tumor suppressor in lung cancer-1), it is downregulated in non-small cell lung cancer (2). This may allow evasion of antitumor responses, since TSLC-1 interaction with CRTAM on activated NK and CD8⁺ T cells stimulates cytotoxicity and upregulates IFN-gamma production (3, 4). As Necl-2 (nectin-like 2), it is expressed on T zone-restricted BDCA3⁺ dendritic cells, again interacting with CRTAM (4). As SynCAM-1 (synaptic cell adhesion molecule-1) it binds homotypically across synaptic clefts and, like neuroligin/neurexin adhesion pairs, promotes formation of neural cell synapses (6, 7). Expression on mast cells allows attachment to neurites and fibroblasts (8, 9). As SgIGSF (spermatogenic IgSF), expression on developing sperm allows adhesion to an unknown partner on Sertoli cells that is critical for normal development (10, 11). Human IGSF4A cDNA encodes 442 amino acids including a signal peptide, three Ig-like domains (a V-type, a divergent C1-type and an I-type), a transmembrane domain and a cytoplasmic domain with protein 4.1 and PDZ domain binding sites. These sites allow connections to adaptor molecules and are critical in synaptogenesis (6, 7). The outer Ig-like domain is most likely to mediate adhesion, with altered affinity in splice variants with shorter spacing of this domain from the plasma membrane or varied glycosylation (1, 3). The five reported splice variants include a prominently expressed soluble form of about 45 kDa that inhibits adhesion (12). Human IGSF4A ECD shares 99%, 91%, 89% and 97% amino acid identity with mouse, bovine, rat and canine IGSF4A, respectively.