Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester-containing proteins.
Cell surface antigen CD109 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein of approximately 170 kd found on a subset of hematopoietic stem and progenitor cells and on activated platelets and T cells. Although it has been suggested that T-cell CD109 may play a role in antibody-inducing T-helper function and it is known that platelet CD109 carries the Gov alloantigen system, the role of CD109 in hematopoietic cells remains largely unknown. As a first step toward elucidating the function of CD109, we have isolated and characterized a human CD109 cDNA from KG1a and endothelial cells. The isolated cDNA comprises a 4335 bp open-reading frame encoding a 1445 amino acid (aa) protein of approximately 162 kd that contains a 21 aa N-terminal leader peptide, 17 potential N-linked glycosylation sites, and a C-terminal GPI anchor cleavage-addition site. We report that CD109 is a novel member of the alpha 2 macroglobulin (alpha 2M)/C3, C4, C5 family of thioester-containing proteins, and we demonstrate that native CD109 does indeed contain an intact thioester. Analysis of the CD109 aa sequence suggests that CD109 is likely activated by proteolytic cleavage and thereby becomes capable of thioester-mediated covalent binding to adjacent molecules or cells. In addition, the predicted chemical reactivity of the activated CD109 thioester is complement-like rather than resembling that of alpha 2M proteins. Thus, not only is CD109 potentially capable of covalent binding to carbohydrate and protein targets, but the t(1/2) of its activated thioester is likely extremely short, indicating that CD109 action is highly restricted spatially to the site of its activation.
Lin
Martin
M
Department of Medical Biophysics, University of Toronto, ON, Canada.
Sutherland
D Robert
DR
Horsfall
Wendy
W
Totty
Nicholas
N
Yeo
Erik
E
Nayar
Rakash
R
Wu
Xiang-Fu
XF
Schuh
Andre C
AC
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003545:Cysteine; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D058851:GPI-Linked Proteins; D014644:Genetic Variation; D005973:Glutamine; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013440:Sulfides / Q000737:chemistry; D014407:Tumor Cells, Cultured; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C120523:CD109 protein, human; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D009363:Neoplasm Proteins; D013440:Sulfides; D000511:alpha-Macroglobulins; D005973:Glutamine; D003545:Cysteine