The Scavenger Receptor Cysteine-Rich (SRCR) Domain: An Ancient and Highly Conserved Protein Module of the Innate Immune System

Abstract

The Scavenger Receptor Cysteine-Rich (SRCR) domain is an ancient and highly conserved protein module of ~100-110 amino acids, which defines a superfamily (SRCR-SF) of either soluble or membrane-bound receptors expressed by hematopoietic and nonhematopoietic cells, at either embryonic or adult stages. The existence of two types of SRCR domains allows the division of the SRCR-SF into two groups. Members of group A contain SRCR domains with 6 cysteine residues and are encoded by two exons, whereas those of group B usually contain 8 cysteines and are encoded by a single exon. Group A members usually present as multidomain mosaic proteins containing single SRCR domains associated to other functional domains, such as enzymatic (protease) domains or collagenous regions. On the contrary, group B members generally present as proteins exclusively composed of tandem repeats of SRCR domains, with or without the presence of CUB and ZP domains thought to be involved in oligomerization but never associated to protease domains. Representatives of either group are found in different animal species, from low invertebrates (sponges) to high vertebrates (mammals). Although no unifying function has been defined for SRCR-SF members, accumulated data, together with the high degree of structural and phylogenetic conservation of SRCR domains indicates that they might subserve basic homeostatic functions, including innate immune defense.

Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

“…Based on the profiles of their gene expression, WC1 1 gd T cells of cattle represent the inflammatory population, whereas WC1 À gd T cells are regulatory cells [2,3]. WC1, a member of the scavenger receptor cysteine-rich (SRCR) superfamily, is categorized into group B along with CD5, CD6, and CD163, based on the organization of cysteine residues in its extracellular SRCR domains [4]. Like the SRCR family member SpSRCR, which is expressed in the immune cells of the purple sea urchin [5], WC1 molecules are products of a large gene family, and thus have the potential to increase the diversity of immune responses independently of the adaptive immune response receptor, i.e.…”

Phylogenomic Approach to the Evolutionary Dynamics of Gene Duplication in Birds

“…For example, most of the expansions in gene families within chicken are associated with the immune system and host defense against parasites (Ota and Nei, 1994;Nei et al, 1997). The chicken genome project found an expansion of the scavenger receptor cysteine-rich (SRCR) domain (Hillier et al, 2004), a highly conserved protein module involved in the innate immune system (Sarrias et al, 2004). Linked with the major histocompatibility complex (MHC) class I gene cluster in humans are certain olfactory receptors which also underwent a lineage-specific expansion within the chicken.…”

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

“…CD6 belongs to the scavenger receptor cysteinerich (SRCR) 3 superfamily of protein receptors based on the presence in its extracellular region of three 100-to 110-aa-long cysteine-rich domains characteristic of that family (3,4). The most membrane-proximal SRCR domain of CD6 is directly involved in the interaction with the CD6 ligand, CD166/activated leukocyte cell adhesion molecule (ALCAM) (5).…”