CD34 antigen (IPR008083)
Short name: CD34
Overlapping homologous superfamilies
- CD34/Podocalyxin (IPR013836)
- CD34 antigen (IPR008083)
The CD34 group of monoclonal antibodies recognises CD34 (also termed CD34 antigen), a 105-120kDa cell surface glycoprotein, which is selectively expressed by human myeloid and lymphoid progenitor cells, including the haemopoietic stem cell. The protein is also expressed on vascular endothelial cells. Here, it is concentrated on the surface of the inter-digitating processes, suggesting a possible involvement in cell interactions or adhesion, by mediating the attachment of stem cells to the bone marrow extracellular matrix, or directly to stromal cells. The restricted pattern of expression of CD34 in haemopoiesis suggests that it may have a significant function in the earliest stages of blood cell differentiation in the bone marrow [PMID: 1694174, PMID: 1709048].
CD34 is a phosphoprotein shown to be activated by protein kinase C (PKC) in a developmental stage-specific manner. Analysis of the human CD34 sequence reveals that the protein appears to be a type I transmembrane (TM) molecule. The predicted internal portion of the protein appears to retain basic amino acid residues adjacent to Ser residues, presenting at least two potential target sites for PKC phosphorylation. In addition, there are two other consensus motifs that correspond to potential target sites for Ca+/calmodulin-dependent kinase and/or protease activated kinase I [PMID: 1694174].
The protein is not strongly similar to other known proteins, but some weak similarities do exist: e.g., to the S+T region (a region rich in potential O-linked carbohydrate attachment sites), the TM domain and cytoplasmic domain of cell surface proteins such as leukosialin, a major sialoglyco-protein of rat and human leukocytes; to the N-terminal glycosylated region of CD45 (the leukocyte common antigen); and to groups of interrelated proteins involved in cell adhesion or the regulation of complement.
A homologue of human CD34 is expressed in mouse. The amino acid sequences only diverge significantly at their N-termini, which are predicted to be highly glycosylated and whose functions are probably modulated by carbohydrate. The observed pattern of expression of the murine CD34 gene is consistent with that of the human antigen. That CD34 is also highly expressed outside haematopoiesis, by vascular endothelial cells and by fibroblasts in differentiated tissue, suggests a role common to a variety of cell types. Concentration of CD34 on the interdigitating membrane projections of adjacent capillary endothelial cells has strengthened the idea that it functions in the control of events leading to cell-cell or cell-matrix adhesion, which role could be modulated by variation in its levels of glycosylation. The conservation between the human and mouse cysteine-rich domain in the extracellular part of the protein, and the exceptionally high conservation of the cytoplasmic domain, imply that the protein is more than a carrier for either carbohydrate or negatively charged terminal sialic acid residues (a role postulated for leukosialin/sialophorin). The highly conserved domain may serve to provide an internal signal of external contact with a ligand.