Molecular cloning and analysis of SSc5D, a new member of the scavenger receptor cysteine-rich superfamily
Gonçalves CM, Castro MA, Henriques T, Oliveira MI, Pinheiro HC, Oliveira C, Sreenu VB, Evans EJ, Davis SJ, Moreira A, Carmo AM. (2009), Mol Immunol. 46, 2585-96
Glycoproteins of the scavenger receptor cysteine-rich (SRCR) superfamily contain one or more protein modules homologous to the membrane-distal domain of macrophage scavenger receptor I. These domains can be found in the extracellular regions of membrane proteins and in secreted glycoproteins, from the most primitive species to vertebrates. A systematic, bioinformatics-based search for putative human proteins related to the forty-seven known human group B SRCR domains identified a new family member that we have called Soluble Scavenger with 5 Domains (SSc5D). SSc5D is a new soluble protein whose expression is restricted to monocytes/macrophages and T-lymphocytes, and is particularly enriched in the placenta. The gene encoding SSc5D spans 30kb of genomic DNA, and contains fourteen exons producing a 4.8kb-long mRNA. The mature polypeptide is predicted to consist of 1573 amino acids comprising, towards the N-terminus, five very similar SRCR domains that are highly conserved among non-marsupial mammals, and a large (>250nm), very heavily glycosylated, mucin-like sequence towards the C-terminus. Each of the SRCR domains is encoded by a single exon, and contains eight cysteine residues, as observed for all other group B SRCR domains. A shorter isoform encoded by a weakly expressed, alternatively spliced transcript, which lacks the mucin-like C-terminal region, was also identified. It seems likely that SSc5D has a role at the interface between adaptive and innate immunity, or in placental function.
Key figure: Model of SSc5D—comparison with all known class B SRCR molecules
SRCR domains (shown as grey trapezoid/heart shaped) are tentatively drawn to scale, according to the X-ray data described for the SRCR domain of Mac-2 binding protein, and of the third SRCR domain of CD5 (Hohenester et al., 1999 and Rodamilans et al., 2007). The representation of CUB (diamond shaped) and Zona Pellucida (oval) domains of DMBT1 and the relative position of their N- and C-termini are based on the data described for the CUB domains of two spermadhesins and of the C1s (Romero et al., 1997 and Gregory et al., 2003), and the Zona Pellucida domain of ZP3 (Monné et al., 2008). Unstructured amino acid sequences are drawn as having a degree of extension of ∼2.5 Å per residue (Shogren et al., 1989 and Merry et al., 2003). O- and N-linked glycans are represented as short lines and lines/circles respectively, also roughly to scale.