| Literature References | 1. FACKLERT, M.J., CIVINS, C.I., SUTHERLAND, D.R., BAKER, M.A. AND MAY, W.S.
Activated protein kinase C directly phosphorylates the CD34 antigen on
hemopoietic cells.
J.BIOL.CHEM. 265 11056-11061 (1990).
2. BROWN, J., G REAVES, M.F. AND MOLGAARD, H.V.
The gene encoding the stem cell antigen CD34 is conserved in mouse and
expressed in haemopoietic progenitor cell lines, brain and embryonic
fibroblasts.
INT.IMMUNOL. 3 175-184 (1991).
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| Documentation | 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 [1,2].
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 [1].
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 [1].
CD34ANTIGEN is an 8-element fingerprint that provides a signature for the
CD34 haematopoietic stem cell antigens. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning the C-terminal portion of the alignment - motifs 4 and 5
span the N- and C-terminal regions of the predicted TM domain; and motifs 7
and 8 contain putative N-glycosylation sites. A single iteration on
SPTR39_17f was required to reach convergence, no further sequences being
identified beyond the starting set.
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