Other entities represented in this entry:
HGNC Approved Gene Symbol: CD109
Cytogenetic location: 6q13 Genomic coordinates (GRCh38): 6:73,679,192-73,828,313 (from NCBI)
CD109 is a GPI-linked cell surface antigen expressed by CD34+ acute myeloid leukemia cell lines, T-cell lines, activated T lymphoblasts, endothelial cells, and activated platelets (Lin et al., 2002). In addition, the platelet-specific Gov antigen system, implicated in refractoriness to platelet transfusion, neonatal alloimmune thrombocytopenia, and posttransfusion purpura, is carried by CD109 (Kelton et al., 1990; Lin et al., 2002).
Lin et al. (2002) isolated and characterized human CD109 from the acute myeloid leukemia cell line KG1a and from a human umbilical vein endothelial cell (HUVEC) library. CD109 encodes a deduced 1,445-amino acid protein with a predicted molecular mass of approximately 162 kD. The protein contains a cleavable 21 residue N-terminal sequence, 17 potential N-linked glycosylation sites, a GPI anchor site, and a thioester motif characteristic of the alpha-2-macroglobulin (A2M; 103950)/complement (AMCOM) family. Northern blot analysis detected 11.4-, 7.4-, and 5.5-kb CD109 transcripts in KG1a cells, with the 2 smaller transcripts resulting from an alternative 3-prime UTR. CD109 expression was widespread, with highest levels in adult uterus, aorta, heart, lung, trachea, and placenta, and in fetal heart, kidney, liver, spleen, and lung.
Solomon et al. (2004) identified CD109 orthologs several species, including mouse. Sequence comparisons revealed a conserved motif of 4 positively charged residues, a known cleavage site for furin (136950)-like enzymes. Phylogenetic analysis suggested that CD109 represents a novel branch of the AMCOM family, showing early divergence from other family members including A2M, C3 (120700), C4 (120810), and C5 (120900).
Using peptide sequencing, Giesert et al. (2003) determined that the cell surface antigen recognized by the monoclonal antibody W7C5, expressed on fetal liver CD34+ cells and on CD34+ and CD34- bone marrow stem cells, is CD109. The authors also showed recognition of CD109 by the W7C5 antibody on CHO cells transiently transfected with CD109.
Lin et al. (2002) showed that CD109 contains an intact thioester that undergoes autolytic cleavage under denaturing conditions.
Solomon et al. (2004) determined that the CD109 gene contains 33 exons and spans approximately 128 kb. Two CD109 isoforms, 150 kD and 180 kD, contain the same 5-prime exon encoding a 12-amino acid N-terminal sequence, but have divergent downstream sequence resulting from alternative downstream exons.
By sequence analysis, Solomon et al. (2004) mapped the CD109 gene to chromosome 6q.
By RT-PCR analysis on 6 phenotypically homozygous Gov(aa) and Gov(bb) individuals, Schuh et al. (2002) determined that the Gov(b) allele differs from the Gov(a) allele by an A-to-C transition at nucleotide 2108 of the CD109 gene, resulting in a tyr703-to-ser substitution. Analysis of 99 additional individuals by RT-PCR, RFLP, or real-time PCR confirmed correlation of the CD109 polymorphism with Gov phenotypes.
Giesert, C., Marxer, A., Sutherland, D. R., Schuh, A. C., Kanz, L., Buhring, H.-J. Antibody W7C5 defines a CD109 epitope expressed on CD34+ and CD34- hematopoietic and mesenchymal stem cell subsets. Ann. New York Acad. Sci. 996: 227-230, 2003. [PubMed: 12799300] [Full Text: https://doi.org/10.1111/j.1749-6632.2003.tb03250.x]
Kelton, J. G., Smith, J. W., Horsewood, P., Humbert, J. R., Hayward, C. P. M., Warkentin, T. E. Gov(a/b) alloantigen system on human platelets. Blood 75: 2172-2176, 1990. [PubMed: 2346781]
Lin, M., Sutherland, D. R., Horsfall, W., Totty, N., Yeo, E., Nayar, R., Wu, X.-F., Schuh, A. C. Cell surface antigen CD109 is a novel member of the alpha-2 macroglobulin/C3, C4, C5 family of thioester-containing proteins. Blood 99: 1683-1691, 2002. [PubMed: 11861284] [Full Text: https://doi.org/10.1182/blood.v99.5.1683]
Schuh, A. C., Watkins, N. A., Nguyen, Q., Harmer, N. J., Lin, M., Prosper, J. Y. A., Campbell, K., Sutherland, D. R., Metcalfe, P., Horsfall, W., Ouwehand, W. H. A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens. Blood 99: 1692-1698, 2002. [PubMed: 11861285] [Full Text: https://doi.org/10.1182/blood.v99.5.1692]
Solomon, K. R., Sharma, P., Chan, M., Morrison, P. T., Finberg, R. W. CD109 represents a novel branch of the alpha-2-macroglobulin/complement gene family. Gene 327: 171-183, 2004. [PubMed: 14980714] [Full Text: https://doi.org/10.1016/j.gene.2003.11.025]