CD164-related protein (CD164_MGC24)
Type: Family

CD164 is a mucin-like receptor, or sialomucin, with specificity in receptor/ ligand interactions that depends on the structural characteristics of the mucin-like receptor. Its functions include mediating, or regulating, haematopoietic progenitor cell adhesion and the negative regulation of their growth and/or-differentiation. It exists in the native state as a disulphide-linked homodimer of two 80-85kDa subunits. It is usually expressed by CD34+ and CD341o/-haematopoietic stem cells and associated microenvironmental cells. It contains, in its extracellular region, two mucin domains (I and II) linked by a non-mucin domain, which has been predicted to contain intra-disulphide bridges. This receptor may play a key role in haematopoiesis by facilitating the adhesion of human CD34+ cells to bone marrow stroma and by negatively regulating CD34+ CD341o/-haematopoietic progenitor cell proliferation. These effects involve the CD164 class I and/or II epitopes recognised by the monoclonal antibodies (mAbs) 105A5 and 103B2/9E10. These epitopes are carbohydrate-dependent and are located on the N-terminal mucin domain I .

It has been found that murine MGC-24v and rat endolyn share significant sequence similarities with human CD164. However, CD164 lacks the consensus glycosaminoglycan (GAG)-attachment site found in MGC-24; it is possible that GAG-association is responsible for the high molecular weight of the epithelial-derived MGC-24 glycoprotein .

Genomic structure studies have placed CD164 within the mucin-subgroup that comprises multiple exons, and demonstrate the diverse chromosomal distribution of this family of molecules. Molecules with such multiple exons may have sophisticated regulatory mechanisms that involve not only post-translational modifications of the oligosaccharide side chains, but also differential exon usage. Although differences in the intron and exon sizes are seen between the mouse and human genes, the predicted proteins are similar in size and structure, maintaining functionally important motifs 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 the 3.2-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 and function of CD164 in different tissues. Two other aspects of the structure of CD164 are of particular interest. First, it shares one of several conserved features of a cytokine-binding pocket -in this respect, it is notable that evidence exists for a class of cell-surface sialomucin modulators that directly interact with growth factor receptors to regulate their response to physiological ligands. Second, its cytoplasmic tail contains a C-terminal YHTL motif found in many endocytic membrane proteins or receptors. These Tyr-based motifs bind to adaptor proteins, which mediate the sorting of membrane proteins into transport vesicles from the plasma membrane to the endosomes, and between intracellular compartments.