CD164 is a mucin-like receptor, or sialomucin, with specificity inreceptor/ligand interactions that depends on the structural characteristics of themucin-like receptor. Its functions include mediating, or regulating,haematopoietic progenitor cell adhesion and the negative regulation of theirgrowth and/or-differentiation. It exists in the native state as adisulphide-linked homodimer of two 80-85kDa subunits. It is usually expressed by CD34+and CD341o/- haematopoietic stem cells and associated microenvironmentalcells. It contains, in its extracellular region, two mucin domains (I andII)linked by a non-mucin domain, which has been predicted to contain intra-disulphide bridges. This receptor may play a key role in haematopoiesisby facilitating the adhesion of human CD34+ cells to bone marrow stroma andby negatively regulating CD34+ CD341o/- haematopoietic progenitor cellproliferation. These effects involve the CD164 class I and/or II epitopesrecognised by the monoclonal antibodies (mAbs) 105A5 and 103B2/9E10. Theseepitopes are carbohydrate-dependent and are located on the N-terminalmucin domain I [, ].It has been found that murine MGC-24v and rat endolyn share significantsequence similarities with human CD164. However, CD164 lacks the consensusglycosaminoglycan (GAG)-attachment site found in MGC-24; it is possiblethat GAG-association is responsible for the high molecular weight of theepithelial-derived MGC-24 glycoprotein [].Genomic structure studies have placed CD164 within the mucin-subgroupthatcomprises multiple exons, and demonstrate the diverse chromosomaldistribution of this family of molecules. Molecules with such multipleexons may have sophisticated regulatory mechanisms that involve not onlypost-translational modifications of the oligosaccharide side chains, butalso differential exon usage. Although differences in the intron and exonsizes are seen between the mouse and human genes, the predicted proteinsare similar in size and structure, maintaining functionally importantmotifs that regulate cell proliferation or subcellular distribution [].CD164 is a gene whose expression depends on differential usage of poly-adenylation sites within the 3'-UTR. The conserved distribution of the3.2- and 1.2-kb CD164 transcripts between mouse and human suggests that(i) a mechanism may exist to regulate tissue-specific polyadenylation, and(ii) differences in polyadenylation are important for the expression andfunction of CD164 in different tissues. Two other aspects of the structureof CD164 are of particular interest. First, it shares one of severalconserved features of a cytokine-binding pocket - in this respect, it isnotable that evidence exists for a class of cell-surface sialomucinmodulators that directly interact with growth factor receptors to regulatetheir response to physiological ligands. Second, its cytoplasmic tailcontains a C-terminal YHTL motif found in many endocytic membrane proteinsor receptors. These Tyr-based motifs bind to adaptor proteins, which mediatethe sorting of membrane proteins into transport vesicles from the plasmamembrane to the endosomes, and between intracellular compartments.
