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Gene Review

CD99  -  CD99 molecule

Homo sapiens

Synonyms: 12E7, CD99 antigen, E2 antigen, HBA71, MIC2, ...
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Disease relevance of CD99


Psychiatry related information on CD99

  • Lower cotransfer of the more distant X-linked gene, MIC-2, was statistically significant in this kindred, but not in other patients with familial Alzheimer's disease [6].
  • We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and MIC2 within the pseudoautosomal region in 85 families with two or more siblings suffering from schizophrenia or schizoaffective disorder [7].

High impact information on CD99

  • Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp [8].
  • The predicted amino acid sequence of the 540 bp coding region is 48% homologous to 12E7, the product of MIC2 [8].
  • Previously we have shown that the pseudoautosomal gene MIC2 only rarely recombines between the sex chromosomes and, based on the elevated recombination rates in the pseudoautosomal region, we predicted that this gene would lie close to the Y-specific region [9].
  • The X-located homologue, MIC2X, escapes X-inactivation and the equivalent Y-located locus, MIC2Y, was one of the first genes shown to reside on a mammalian Y chromosome [10].
  • By using a bacterial expression system we have previously cloned a complementary DNA sequence corresponding to a MIC2 gene and have used this probe to show that the MIC2X and MIC2Y loci are closely related, if not identical [10].

Chemical compound and disease context of CD99

  • ER and AR were never expressed by SFT or by chronic pleuritis, whereas PR were demonstrated in 2/16 "large" (>8 cm) and in 6/16 "small" (< or =8 cm) pleural SFT (all expressing CD34, bcl-2 and CD99) [11].
  • The monoclonal antibody 013, which detects the cell surface glycoprotein p30/32mic2 (CD99) is a characteristic, if nonspecific, marker for peripheral neuroepithelioma and Ewing's sarcoma [12].
  • Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma [13].
  • Sixty recent Streptococcus pneumoniae isolates with different susceptibilities to ciprofloxacin (14 with MIC 0.5 mg/L, 10 with MIC 1 mg/L, eight with MIC 2 mg/L, 11 with MIC 4 mg/L and 17 with MIC > or =8 mg/L) were tested against five new quinolones using Todd-Hewitt broth with and without 80% serum [14].
  • One hybridoma produced an IgM antibody (12E7) which recognized the capsular polysaccharide in ELISA and specifically labelled all tested Hib strains in immune fluorescent microscopy [15].

Biological context of CD99

  • Human CD99 (MIC2) is a 32 kDa cell surface protein and its encoding gene is localized to the pseudoautosomal regions of both Xp and Yp chromosomes [16].
  • On the basis of these findings, we suggest that CD99 belongs to the ancient PAR genes, and that the rapid interspecies divergence of its present sequence and map position is due to a high recombination frequency and the occurrence of chromosomal translocation, supporting the addition-attrition hypothesis for PAR evolution [17].
  • Amino acid sequence alignment revealed five putative functional regions highly conserved between CD99L2 and CD99, indicating a close relationship between the two genes [16].
  • Quantitative differences were confirmed by Western blot analysis of red cell membrane preparations from individuals of different Xga and CD99 phenotypes and by Northern blot analysis showing that the reticulocytes from CD99-L individuals expressed a reduced level of MIC2 transcripts compared to CD99-H donors [18].
  • These results demonstrate that CD99 signal transduction can deliver effective costimulatory signals to T cells [19].

Anatomical context of CD99

  • No evidence of association or complex formation between XG and CD99 proteins could be proven, either on transfected RAG cells or on human erythrocytes [20].
  • A role for CD99 in T cell activation [19].
  • Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells [2].
  • In addition, in our experience, CD99 should be routinely evaluated on bone marrow clots, owing to decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution-decalcified specimens [4].
  • CD99 is a cell surface molecule involved in the aggregation of lymphocytes and apoptosis of immature cortical thymocytes [21].

Associations of CD99 with chemical compounds


Regulatory relationships of CD99


Other interactions of CD99

  • Unlike the rapidly evolved CD99 gene, these CD99L2 genes were highly conserved among those species [16].
  • These findings suggest that the phenotypic relationship between XG and CD99 is mostly regulated at the transcriptional level, but they do not formally exclude some posttranscriptional effect [20].
  • These findings further support the hypothesis of a single genetic control of CD99 and Xga expression by the XGR locus [18].
  • These results show that CD99 has a costimulatory function for T cells and acts by a mechanism distinct from CD28 [28].
  • Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1 [17].

Analytical, diagnostic and therapeutic context of CD99


  1. BCL-1 (PRAD-1/cyclin D-1) overexpression distinguishes the blastoid variant of mantle cell lymphoma from B-lineage lymphoblastic lymphoma. Soslow, R.A., Zukerberg, L.R., Harris, N.L., Warnke, R.A. Mod. Pathol. (1997) [Pubmed]
  2. Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells. Lee, H.J., Kim, E., Jee, B., Hahn, J.H., Han, K., Jung, K.C., Park, S.H., Lee, H. Exp. Mol. Med. (2002) [Pubmed]
  3. Solitary sclerotic fibroma of skin: a possible link with pleomorphic fibroma with immunophenotypic expression for O13 (CD99) and CD34. Mahmood, M.N., Salama, M.E., Chaffins, M., Ormsby, A.H., Ma, C.K., Linden, M.D., Lee, M.W. J. Cutan. Pathol. (2003) [Pubmed]
  4. Immunoreactivity of MIC2 (CD99) and terminal deoxynucleotidyl transferase in bone marrow clot and core specimens of acute myeloid leukemias and myelodysplastic syndromes. Kang, L.C., Dunphy, C.H. Arch. Pathol. Lab. Med. (2006) [Pubmed]
  5. CD99 isoforms dictate opposite functions in tumour malignancy and metastases by activating or repressing c-Src kinase activity. Scotlandi, K., Zuntini, M., Manara, M.C., Sciandra, M., Rocchi, A., Benini, S., Nicoletti, G., Bernard, G., Nanni, P., Lollini, P.L., Bernard, A., Picci, P. Oncogene (2007) [Pubmed]
  6. Chromosomal fragility associated with familial Alzheimer's disease. Ettinger, S., Weksler, M.E., Zhou, X., Blass, J., Szabo, P. Ann. Neurol. (1994) [Pubmed]
  7. An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3). Crow, T.J., Delisi, L.E., Lofthouse, R., Poulter, M., Lehner, T., Bass, N., Shah, T., Walsh, C., Boccio-Smith, A., Shields, G. The British journal of psychiatry : the journal of mental science. (1994) [Pubmed]
  8. Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp. Ellis, N.A., Ye, T.Z., Patton, S., German, J., Goodfellow, P.N., Weller, P. Nat. Genet. (1994) [Pubmed]
  9. Mapping the limits of the human pseudoautosomal region and a candidate sequence for the male-determining gene. Pritchard, C.A., Goodfellow, P.J., Goodfellow, P.N. Nature (1987) [Pubmed]
  10. Homologous expressed genes in the human sex chromosome pairing region. Buckle, V., Mondello, C., Darling, S., Craig, I.W., Goodfellow, P.N. Nature (1985) [Pubmed]
  11. Steroid hormone receptor in pleural solitary fibrous tumours and CD34+ progenitor stromal cells. Bongiovanni, M., Viberti, L., Pecchioni, C., Papotti, M., Thonhofer, R., Hans Popper, H., Sapino, A. J. Pathol. (2002) [Pubmed]
  12. 013 (CD99) positivity in hematologic proliferations correlates with TdT positivity. Robertson, P.B., Neiman, R.S., Worapongpaiboon, S., John, K., Orazi, A. Mod. Pathol. (1997) [Pubmed]
  13. Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma. Scotlandi, K., Perdichizzi, S., Bernard, G., Nicoletti, G., Nanni, P., Lollini, P.L., Curti, A., Manara, M.C., Benini, S., Bernard, A., Picci, P. Eur. J. Cancer (2006) [Pubmed]
  14. Influence of the decrease in ciprofloxacin susceptibility and the presence of human serum on the in vitro susceptibility of Streptococcus pneumoniae to five new quinolones. Balcabao, I.P., Alou, L., Aguilar, L., Gomez-Lus, M.L., Giménez, M.J., Prieto, J. J. Antimicrob. Chemother. (2001) [Pubmed]
  15. Characterization of a monoclonal antibody to the capsule of Haemophilus influenzae type b, generated by in vitro immunization. Bunse, R., Heinz, H.P. J. Immunol. Methods (1994) [Pubmed]
  16. Cloning, genomic organization, alternative transcripts and expression analysis of CD99L2, a novel paralog of human CD99, and identification of evolutionary conserved motifs. Suh, Y.H., Shin, Y.K., Kook, M.C., Oh, K.I., Park, W.S., Kim, S.H., Lee, I.S., Park, H.J., Huh, T.L., Park, S.H. Gene (2003) [Pubmed]
  17. Rapid divergency of rodent CD99 orthologs: implications for the evolution of the pseudoautosomal region. Park, S.H., Shin, Y.K., Suh, Y.H., Park, W.S., Ban, Y.L., Choi, H.S., Park, H.J., Jung, K.C. Gene (2005) [Pubmed]
  18. Quantitative analysis of XG blood group and CD99 antigens on human red cells. Fouchet, C., Gane, P., Cartron, J.P., Lopez, C. Immunogenetics (2000) [Pubmed]
  19. A role for CD99 in T cell activation. Wingett, D., Forcier, K., Nielson, C.P. Cell. Immunol. (1999) [Pubmed]
  20. A study of the coregulation and tissue specificity of XG and MIC2 gene expression in eukaryotic cells. Fouchet, C., Gane, P., Huet, M., Fellous, M., Rouger, P., Banting, G., Cartron, J.P., Lopez, C. Blood (2000) [Pubmed]
  21. Engagement of CD99 induces up-regulation of TCR and MHC class I and II molecules on the surface of human thymocytes. Choi, E.Y., Park, W.S., Jung, K.C., Kim, S.H., Kim, Y.Y., Lee, W.J., Park, S.H. J. Immunol. (1998) [Pubmed]
  22. CD99 signals caspase-independent T cell death. Pettersen, R.D., Bernard, G., Olafsen, M.K., Pourtein, M., Lie, S.O. J. Immunol. (2001) [Pubmed]
  23. Engagement of CD99 triggers the exocytic transport of ganglioside GM1 and the reorganization of actin cytoskeleton. Yoon, S.S., Jung, K.I., Choi, Y.L., Choi, E.Y., Lee, I.S., Park, S.H., Kim, T.J. FEBS Lett. (2003) [Pubmed]
  24. Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature. Dargent, J.L., de Saint Aubain, N., Galdón, M.G., Valaeys, V., Cornut, P., Noël, J.C. J. Cutan. Pathol. (2003) [Pubmed]
  25. Molecular mechanisms of CD99-induced caspase-independent cell death and cell-cell adhesion in Ewing's sarcoma cells: actin and zyxin as key intracellular mediators. Cerisano, V., Aalto, Y., Perdichizzi, S., Bernard, G., Manara, M.C., Benini, S., Cenacchi, G., Preda, P., Lattanzi, G., Nagy, B., Knuutila, S., Colombo, M.P., Bernard, A., Picci, P., Scotlandi, K. Oncogene (2004) [Pubmed]
  26. Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma. Sung, C.O., Ko, Y.H., Park, S., Kim, K., Kim, W. J. Korean Med. Sci. (2005) [Pubmed]
  27. Gingipains of Porphyromonas gingivalis modulate leukocyte adhesion molecule expression induced in human endothelial cells by ligation of CD99. Yun, P.L., Decarlo, A.A., Hunter, N. Infect. Immun. (2006) [Pubmed]
  28. CD99 costimulation up-regulates T cell receptor-mediated activation of JNK and AP-1. Yoon, S.S., Kim, H.J., Chung, D.H., Kim, T.J. Mol. Cells (2004) [Pubmed]
  29. Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. Kommoss, F., Oliva, E., Bittinger, F., Kirkpatrick, C.J., Amin, M.B., Bhan, A.K., Young, R.H., Scully, R.E. Hum. Pathol. (2000) [Pubmed]
  30. Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs). Goto, A., Niki, T., Terado, Y., Fukushima, J., Fukayama, M. Histopathology (2004) [Pubmed]
  31. Identification of cyclophilin A as a CD99-binding protein by yeast two-hybrid screening. Kim, H.J., Chong, K.H., Kang, S.W., Lee, J.R., Kim, J.Y., Hahn, M.J., Kim, T.J. Immunol. Lett. (2004) [Pubmed]
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