|CD34||gp105-120, My10, Mucosialin|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
Hematopoietic Progenitor Cell
|40 / 40|
|CD34 is expressed on hematopoietic stem and progenitor cells, bone marrow stromal cells, small-vessel endothelial cells, embryonic fibroblasts, and some cells in fetal and adult nervous tissue. Also, CD34 is expressed on hematopoietic progenitors derived from fetal yolk sac, embryonic liver, and extra-hepatic embryonic tissue including aorta-associated hematopoietic progenitors in the 5 week human embryo. Fibroblast-like dendritic cells express CD34. Besides the embryonic fibroblasts, in adult dermis, areolar tissue, fat, and somatic and visceral collagenous connective tissue, there is an almost ubiquitous network of interstitial and adventitial fibroblast-like dendritic cells that express CD34.|
|MOLECULAR FAMILY NAME: Belongs to the mucin family.|
CD34 is a single-pass type-1 glycoprotein. It contains a 258 aa extracellular domain which contains a cysteine-rich Ig-like domain and is highly N- and O-glycosylated, an transmembrane domain and a 73 aa cytoplasmic domain. The complete extracellular region is present in both isoforms of CD34. The full-length form of CD34 molecule has an intracellular cytoplasmic domain, which contains consensus sites for protein kinase C (PKC) phosphorylation, serine and threonine phosphorylation by other kinases, and tyrosine phosphorylation. To date, only serine phosphorylation has been actually demonstrated. The short isoform of CD34 lacks most of the intracellular cytoplasmic domain, including many of the potential phosphorylation sites. The 1st 130 aa are predicted to be heavily O-glycosylated and have a mucin-like structure. This is followed by a sequence of about 100 aa that can be expected to have a globular structure, based on the presence of 6 Cys residues.
Alternative splicing yields 2 different isoforms. One species contains exons 1 through 8 and forms the full length form of CD34. An alternative splice isoform results in the insertion of an additional exon, exon X, 194bp, between exon 7 and 8. This introduces a translational stop codon, which results in the truncated form of CD34 with a shorter cytoplasmic domain (only 16 aa). This shorter isoform lacks most of the cytoplasmic region including the phosphorylation sites. The transmembrane and extracellular regions of both isoforms of CD34 are identical.
Beginning at the NH2 terminus, the extracellular domain is heavily N- and O-sialoglycosylated. Only serine phosphorylation of the intracellular domain has been demonstrated, but there are potential sites for serine, threonine, and tyrosine phosphorylation.
|CD62L (L-selectin) and CD62E (E-selectin) binds to sialoglycoconjugates present on a subpopulation of CD34 glycoforms. This binding requires sulfation and probably fucosylation of CD34. CD62E (E-selectin) can also bind CD34.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD34
|CD34 functions in cell-cell adhesion and in the inhibition of hematopoietic differentiation. The ability of CD34 to bind the selectins CD62L and CD62E and its expression on the endothelium suggests a role in leukocyte-endothelial interactions. In support of this, CD34 interacts with CD62E and is the major CD62L ligand in tonsillar high-endothelial venules and can mediate attachment and rolling of leukocytes in vitro. Curiously, CD34-deficient mice exhibit no detectable abnormality in neutrophil or lymphocyte trafficking but show decreased eosinophil accumulation in the lung following inhalation of allergen. Only minor hematopoietic defects have been reported in CD34-deficient mice. There is speculation on factor XIIIa signaling via CD34 to dendritic fibroblasts. In many myxoid, fibrovascular, and fibrohistiocytic mesenchymal tumors, CD34+ fibroblasts are often associated with numerous dendritic histiocytes that express the coagulation factor XIIIa. FXIIIa is a pleiotropic fibroblast mitogen that also catalyzes crosslinking of matrix proteins and modulates cytoskeletal organization, adhesion, and spreading of cultured fibroblasts. There is a proposed role of CD34 as a signaling molecule. CD34 reactivity disappears in vivo as primitive fibroblast-like dendritic cells in many tumors and healing wounds attain a more differentiated actin positive myofibroblastic or collagenous synthetic phenotype. This is similar to CD34 downregulation in differentiating hematopoietic progenitor cells. In vitro, cultured CD34+ dendritic cells and umbilical vein endothelium both lose CD34 reactivity after a few passages and this has hampered study of the biology of CD34. In certain murine fibroblast lines, increased CD34 expression correlates with lack of contact inhibition. Observations suggest that CD34 is involved in the maintenance of a phenotypically plastic state in undifferentiated cells. Engagement of determinants on CD34 is also involved in controlling these cells cytoskeletal organization and thus their adhesion and migration. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD34 IN INTACT ANIMAL
No abnormality in leukocyte trafficking was detected in the CD34 knockout mice. In 1 of 2 reports of CD34 knockout mice, a decrease in hematopoietic progenitors was found in the knockout mice. The utilization of CD34 mAb was used to quantitate and purify lymphohematopoietic stem/progenitor cells for research and for clinical bone marrow transplantation. A study of mast stem cell adhesion in CD34-deficient mice found increased mast cell aggregation and an inability to repopulate with mast cells and hematopoietic precursors in the absence of CD34 suggesting a role for CD34 as a negative receptor of cell adhesion.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD34
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD34: No information.
Database accession numbers
Revised June 25, 2008