Affinage

CD99

CD99 antigen · UniProt P14209

Length
185 aa
Mass
18.8 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD99 is a heavily O-glycosylated type I transmembrane glycoprotein that functions as a multifaceted regulator of cell adhesion, transendothelial migration, apoptosis, and differentiation across hematopoietic and mesenchymal lineages. In immune cells, CD99 engagement activates α4β1 integrin–dependent T cell adhesion, promotes leukocyte diapedesis through an endothelial ezrin–soluble adenylyl cyclase–PKA signaling axis that drives lateral border recycling compartment trafficking, and interacts heterophilically with neutrophil PILRs via O-glycosylated Thr-45/Thr-50 residues; its ectodomain is shed by meprin β followed by γ-secretase intramembrane cleavage (PMID:11069091, PMID:26101266, PMID:28223280, PMID:18234675, PMID:28003343). CD99 signals apoptosis in thymocytes and transformed T cells through covalent long/short isoform heterodimers localized in lipid rafts that activate sphingomyelinase, and in Ewing sarcoma the GDF6 prodomain binds CD99's ectodomain to recruit CSK to its cytoplasmic YQKKK motif, inhibiting Src and maintaining proliferation, while CD99 silencing derepresses MAPK/ERK signaling and triggers neural differentiation (PMID:12368226, PMID:33147457, PMID:20197622). Loss of CD99 expression—driven transcriptionally by EBV LMP-1 or post-transcriptionally by miR-30a-5p—generates Hodgkin/Reed-Sternberg cell features and deregulates Rac-Rho signaling, whereas in osteosarcoma CD99 suppresses migration by inactivating c-Src/ROCK2/ezrin and stabilizing N-cadherin/β-catenin at adherens junctions (PMID:10607715, PMID:22986530, PMID:9834235, PMID:23644663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 High

    Identification of CD99 as the molecular basis of T cell rosette formation established it as a transmembrane glycoprotein with a direct role in homotypic adhesion, answering the long-standing question of the MIC2 gene product's function.

    Evidence cDNA cloning plus mAb blocking of rosette formation in human T cells

    PMID:2479542

    Open questions at the time
    • Mechanism of homotypic adhesion (homophilic vs. heterophilic) not resolved
    • No signaling pathway identified downstream of engagement
  2. 1997 High

    The discovery that CD99 ligation induces caspase-dependent apoptosis of CD4+CD8+ thymocytes independent of Fas/CD95 revealed CD99 as a death-signaling receptor on immature T cells, reframing it from a pure adhesion molecule to a regulator of thymic selection.

    Evidence mAb ligation on thymocytes with caspase inhibitors and Fas pathway blockade

    PMID:9058785

    Open questions at the time
    • Proximal signaling intermediates between CD99 and caspase activation unknown
    • In vivo relevance in thymic selection not demonstrated
  3. 1998 High

    Two key advances defined CD99's roles beyond adhesion: it accelerates TCR/MHC transport to the surface of thymocytes (implicating it in positive selection), and its loss generates Hodgkin/Reed-Sternberg phenotype rescued by constitutively active Rac, placing CD99 upstream of Rac-Rho signaling.

    Evidence Confocal microscopy/subcellular fractionation for TCR transport; antisense knockdown with Rac rescue for H-RS phenotype

    PMID:9670951 PMID:9834235

    Open questions at the time
    • Direct physical link between CD99 and Rac-GTPase activation not shown
    • Mechanism of TCR/MHC vesicle mobilization undefined
  4. 2000 High

    Demonstrating that CD99 engagement activates α4β1 integrin–dependent arrest under shear stress on memory CD4+ T cells, and that EBV LMP-1 transcriptionally represses CD99, connected CD99 to physiological leukocyte trafficking and to Hodgkin lymphoma pathogenesis.

    Evidence Flow adhesion assay with integrin blocking; LMP-1 stable transfection with CD99 promoter-luciferase reporter

    PMID:10607715 PMID:11069091

    Open questions at the time
    • Signaling intermediates between CD99 and α4β1 activation not identified
    • LMP-1 cis-elements on CD99 promoter not mapped
  5. 2002 High

    The finding that apoptosis requires coexpression of both CD99 isoforms as covalent heterodimers in lipid rafts activating sphingomyelinase resolved how a single gene generates distinct adhesion versus death outcomes through isoform-specific oligomerization and membrane microdomain partitioning.

    Evidence Isoform reconstitution in CD99-deficient Jurkat cells, lipid raft fractionation, cholesterol depletion, sphingomyelin assay

    PMID:12368226

    Open questions at the time
    • Identity of the sphingomyelinase activated is unknown
    • Structural basis for covalent heterodimer formation undefined
  6. 2004 High

    Blocking experiments in vitro and in vivo showed that CD99 on both leukocytes and endothelium mediates homophilic interaction required for transendothelial migration, establishing CD99 as a gatekeeper of diapedesis distinct from PECAM-1.

    Evidence CHO transfection/aggregation, in vitro TEM assay, DTH model with anti-CD99 antibody in mice

    PMID:15280198

    Open questions at the time
    • Whether CD99 acts sequentially with or independently of PECAM-1 during TEM not fully resolved
    • Endothelial signaling downstream of homophilic engagement unknown at this point
  7. 2008 High

    Two studies in 2008 defined new molecular partnerships: CD99 associates with HLA class I via its transmembrane domain and p230/golgin-245 in the TGN to regulate MHC I surface transport, and CD99 serves as a sialylated O-glycoprotein ligand for PILRα/β with defined binding affinities and glycosylation-site specificity.

    Evidence Reciprocal co-IP and TGN fractionation for HLA/p230; SPR with site-directed mutagenesis for PILR binding

    PMID:18234675 PMID:18849489

    Open questions at the time
    • Functional consequence of PILR binding on neutrophil physiology not yet shown
    • Whether HLA I trafficking role applies beyond lymphocytes not tested
  8. 2010 High

    CD99 knockdown in Ewing sarcoma induced neural differentiation with increased ERK1/2 phosphorylation and reduced tumorigenicity, establishing CD99 as an oncogene-dependent differentiation brake acting through MAPK suppression in EWS.

    Evidence shRNA knockdown in EWS cells, xenograft model, neurite outgrowth, ERK1/2 phosphorylation assay

    PMID:20197622

    Open questions at the time
    • Mechanism by which CD99 suppresses ERK signaling not defined
    • Whether differentiation effect is cell-autonomous or microenvironment-dependent unclear
  9. 2013 High

    Three parallel studies expanded CD99's context-dependent signaling: in osteosarcoma it suppresses migration via c-Src/ROCK2/ezrin inactivation and N-cadherin stabilization; in glioma it promotes invasion via Rho activation; and in Ewing sarcoma miR-30a-5p post-transcriptionally silences CD99 downstream of EWS-FLI1 suppression.

    Evidence Forced expression in osteosarcoma with co-IP and actin analysis; overexpression/siRNA in glioma with Rac/Rho assays and orthotopic model; miR-30a-5p 3'UTR reporter assay in EWS

    PMID:22986530 PMID:23486730 PMID:23644663

    Open questions at the time
    • Opposing migratory effects in osteosarcoma vs. glioma/EWS not mechanistically reconciled
    • miR-30a-5p regulation of CD99 not validated in non-Ewing contexts
  10. 2015 High

    The identification of endothelial CD99's signaling complex—ezrin/sAC/PKA activating LBRC trafficking—provided the first complete signaling pathway explaining how CD99 homophilic engagement mechanistically drives leukocyte diapedesis.

    Evidence Co-IP of CD99-ezrin-sAC, pharmacologic and genetic inhibition of sAC/PKA, LBRC trafficking assay, in vivo peritonitis model

    PMID:26101266

    Open questions at the time
    • Whether the same sAC/PKA pathway operates in leukocyte CD99 signaling unknown
    • Structural basis for ezrin recruitment to CD99 cytoplasmic tail not resolved
  11. 2016 High

    Discovery that meprin β cleaves CD99's ectodomain at a conserved acidic motif followed by γ-secretase intramembrane proteolysis revealed a regulated proteolytic cascade that controls CD99 surface levels and promotes transendothelial migration.

    Evidence Biochemical shedding assay, MS cleavage site mapping, Mep1b−/− mice, γ-secretase inhibitor, TEM assay

    PMID:28003343

    Open questions at the time
    • Fate and function of the released intracellular domain after γ-secretase cleavage unknown
    • Physiological stimuli that activate meprin β–mediated CD99 shedding not identified
  12. 2017 High

    In vivo gene inactivation and intravital microscopy demonstrated that endothelial CD99 engages neutrophil PILRs heterophilically to support chemokine-induced arrest and diapedesis, unifying the earlier biophysical PILR-binding data with a physiological leukocyte trafficking function.

    Evidence CD99 KO mice, intravital video microscopy, co-precipitation and biotin-transfer assay, anti-PILR blocking

    PMID:28223280

    Open questions at the time
    • Relative contributions of homophilic CD99-CD99 vs. heterophilic CD99-PILR interactions during TEM not quantified
    • Whether PILR engagement triggers specific signaling in neutrophils unknown
  13. 2020 High

    Identification of the GDF6 prodomain as a CD99 extracellular ligand that recruits CSK to the intracellular YQKKK motif to inhibit Src answered how CD99 restrains growth arrest in Ewing sarcoma and provided the first defined receptor-ligand-effector signaling axis for CD99.

    Evidence Co-IP of GDF6 prodomain with CD99, domain mapping, CSK recruitment and Src activity assays, GDF6 silencing with p21 readout

    PMID:33147457

    Open questions at the time
    • Whether GDF6 prodomain-CD99 interaction occurs in non-Ewing tissues unknown
    • Crystal structure of CD99-GDF6 prodomain complex not available
    • Whether CSK recruitment to YQKKK motif is direct or scaffold-mediated not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of CD99 homo- and hetero-oligomerization, how opposing pro-migratory (EWS, glioma) versus anti-migratory (osteosarcoma) effects are contextually determined, and whether the meprin β–released intracellular domain has signaling activity.
  • No crystal or cryo-EM structure of CD99 extracellular domain
  • No unified model reconciling tissue-specific opposing migratory outcomes
  • Intracellular domain fragment function after γ-secretase cleavage uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 6 R-HSA-1500931 Cell-Cell communication 4 R-HSA-5357801 Programmed Cell Death 4
Partners
ADCY10CSKEZRGDF6ITGA4MEP1BPILRAPILRB
Complex memberships
CD99 long/short isoform heterodimerCD99-ezrin-sAC signaling complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD99 (E2/MIC2 gene product) is a 32 kDa transmembrane glycoprotein involved in spontaneous rosette formation (homotypic adhesion) of T cells with erythrocytes, establishing its role in T cell adhesion processes. cDNA cloning, mAb blocking of rosette formation, Northern blotting The EMBO journal High 2479542
1995 CD99 (E2) engagement by specific mAbs triggers homotypic aggregation exclusively of CD4+CD8+ double-positive thymocytes through a pathway dependent on temperature, energy, Mg2+, and intact cytoskeleton, likely mediated by an uncharacterized integrin. mAb crosslinking, cell aggregation assay, integrin blocking experiments, live cell imaging Journal of immunology High 7527813
1997 CD99 engagement mediates apoptosis of immature double-positive (CD4+CD8+) thymocytes through a caspase-dependent (CPP32/ICE-type protease) pathway involving early mitochondrial alterations and phosphatidylserine exposure, without DNA fragmentation, independent of the Fas/CD95 pathway. mAb-mediated ligation, morphologic analysis, phosphatidylserine exposure assay, caspase inhibitor studies, Fas pathway blockade Journal of immunology High 9058785
1998 CD99 engagement on immature thymocytes accelerates mobilization of TCR and MHC class I/II molecules from cytosolic compartments to the plasma membrane (particularly at cell-cell contact sites), without increasing RNA or protein synthesis, suggesting a role in positive selection. mAb ligation, flow cytometry, confocal microscopy, subcellular fractionation Journal of immunology High 9670951
1998 Downregulation of CD99 leads to generation of cells with Hodgkin's/Reed-Sternberg (H-RS) phenotype (multinuclearity, CD15 expression, decreased MHC class I and CD45RB, deregulated cytokine secretion), and forced CD99 expression or constitutively active Rac rescues this phenotype, placing CD99 upstream of a Rac-Rho signaling pathway. Antisense transfection, forced expression, constitutively active Rac expression, immunophenotyping Blood High 9834235
1999 CD99 crosslinking with anti-CD3 Ab markedly enhances T cell proliferation and induces tyrosine phosphorylation of an ~29 kDa protein, demonstrating that CD99 can deliver costimulatory signals via a specific signal transduction pathway in CD4+ peripheral T cells. mAb crosslinking, proliferation assay, tyrosine phosphorylation immunoblot, CD25/CD69/CD40L expression Cellular immunology Medium 10202109
2000 CD99 stimulation upregulates alpha4beta1 integrin-dependent T cell arrest on inflamed vascular endothelium under shear stress via the alpha4beta1-VCAM-1 pathway (not alphaLbeta2-ICAM-1), restricted to memory CD4+ T cells. Flow adhesion assay under shear stress, integrin blocking antibodies, T cell subset analysis European journal of immunology High 11069091
2000 EBV latent membrane protein 1 (LMP-1) downregulates CD99 expression at the transcriptional level by negatively regulating the CD99 promoter, contributing to H-RS cell generation in Hodgkin's disease. Stable transfection of LMP-1, CD99 promoter-luciferase reporter assay, Northern/Western blotting Blood High 10607715
2001 Engagement of specific CD99 epitopes rapidly induces caspase-independent programmed cell death in transformed T cells (but not normal peripheral T cells), distinct from Fas and TRAIL pathways and independent of CD3, CD4, CD45, and p56lck. mAb ligation, morphological analysis, phosphatidylserine exposure, propidium iodide uptake, pathway inhibition experiments Journal of immunology High 11290771
2002 The two CD99 isoforms (long form and short form) have distinct functional outcomes: the long form alone promotes CD99-induced cell adhesion, whereas coexpression of both isoforms is required to trigger T cell death. When coexpressed, the two proteins form covalent heterodimers located within glycosphingolipid rafts, and raft localization (cholesterol-dependent) is required for apoptosis induction, which involves sphingomyelin degradation. Isoform transfection in CD99-deficient Jurkat cells, lipid raft fractionation, cholesterol depletion, sphingomyelin assay, cell death assays FASEB journal High 12368226
2003 CD99 ligation via the YG32 epitope enhances Fas-mediated apoptosis in Jurkat T cells by inducing Fas oligomerization, in a caspase-8-dependent manner (blocked by z-IETD-fmk). Epitope-specific mAb ligation, Fas oligomerization assay, caspase inhibitor studies FEBS letters Medium 14623115
2004 Mouse CD99 mediates homophilic cell aggregation (divalent cation-dependent) when transfected into CHO cells; anti-CD99 antibodies block transendothelial migration (TEM) of lymphocytes in vitro independent of which cell type (T cell or endothelial) is pre-treated, and inhibit recruitment of T cells to inflamed skin in a DTH model in vivo. CHO transfection/aggregation assay, in vitro TEM assay, in vivo DTH model with antibody blockade Blood High 15280198
2006 CD99 knockdown in Ewing sarcoma cells reduces growth and migration; CD99 suppresses KCMF1 (potassium-channel modulatory factor 1) expression, and forced KCMF1 expression recapitulates reduced migration, identifying KCMF1 as a downstream mediator through which CD99 promotes cell migration in EWS. RNAi knockdown, rescue with ectopic KCMF1 expression, migration assays, gene expression analysis Oncogene High 16314831
2008 CD99 regulates HLA class I surface expression by physically associating with HLA class I molecules (via transmembrane domain) in the trans-Golgi network and binding p230/golgin-245 (a TGN trafficking protein); IFN-gamma-induced HLA class I upregulation requires CD99, and p230/golgin-245 overexpression downmodulates surface HLA class I. Co-immunoprecipitation, confocal microscopy, TGN fractionation, p230 overexpression, IFN-gamma stimulation Blood High 18849489
2008 CD99 is recognized as a sialylated O-glycoprotein ligand for paired Ig-like type 2 receptors (PILRs); PILRalpha binds CD99 with Kd ~2.2 µM and PILRbeta with ~85 µM affinity; both O-glycosylation sites (Thr-45 and Thr-50) act as independent PILRalpha binding sites, while PILRbeta specifically requires Thr-45; binding is enthalpically driven for PILRalpha. Surface plasmon resonance, site-directed mutagenesis, thermodynamic analysis The Journal of biological chemistry High 18234675
2010 CD99 knockdown in Ewing sarcoma cells reduces tumorigenicity and bone metastasis, induces neurite outgrowth and neural differentiation markers (beta-III tubulin), and increases ERK1/2 phosphorylation, placing CD99 as an inhibitor of neural differentiation acting through the MAPK pathway. shRNA knockdown, xenograft model, neurite outgrowth assay, ERK1/2 phosphorylation immunoblot, differentiation marker expression The Journal of clinical investigation High 20197622
2013 CD99 suppresses osteosarcoma cell migration by: forcing expression of CD99wt recruits N-cadherin and β-catenin to adherens junctions; inhibits ACTR2, ARPC1A, ROCK2, and ezrin expression; maintains c-Src in an inactive conformation, thereby inhibiting ROCK2 signaling and reducing ezrin at the cell membrane. Forced expression, migration assays, co-immunoprecipitation, immunoblotting, actin cytoskeleton analysis Oncogene High 23644663
2013 Overexpression of CD99 in glioma cells enhances migration and invasion; CD99 overexpression decreases Rac activity and increases Rho activity, promoting amoeboid cell morphology, independently of Akt, ERK, or JNK signaling. siRNA knockdown, overexpression, orthotopic mouse model, Rac/Rho activity assays, invasion assays Genes & cancer High 23486730
2013 miR-30a-5p binds the 3'UTR of CD99 and regulates its protein expression post-transcriptionally; EWS-FLI1 suppression decreases CD99 protein but not mRNA, mediated through miR-30a-5p induction; re-expression of miR-30a-5p in Ewing cells decreases proliferation and invasion. miRNA 3'UTR reporter assay, miRNA overexpression, protein/mRNA quantification, proliferation and invasion assays Oncogene High 22986530
2014 Anti-CD99 antibody (dAbd C7) triggers Ewing sarcoma cell death through Mdm2 degradation and p53 reactivation, with induction of p21, Bax, and mitochondrial depolarization; Mdm2 overexpression or p53 silencing reduces CD99-induced death, while nutlin-3 enhances it, requiring an aberrant (EWS-FLI1) genetic context. Anti-CD99 diabody treatment, Mdm2 overexpression, p53 siRNA, nutlin-3 treatment, in vivo xenograft Clinical cancer research High 25501132
2015 Endothelial CD99 signals during transendothelial migration (TEM) by forming a complex with the A-kinase anchoring protein ezrin and soluble adenylyl cyclase (sAC) via its lysine-rich juxtamembrane cytoplasmic tail; this activates PKA, which stimulates membrane trafficking from the lateral border recycling compartment (LBRC) to facilitate leukocyte passage; pharmacologic or genetic inhibition of sAC or PKA arrests neutrophils and monocytes partway through endothelial junctions in vitro and in vivo. Co-immunoprecipitation (CD99-ezrin-sAC complex), sAC pharmacologic inhibition, PKA inhibition, genetic knockdown, in vivo inflammation model, LBRC trafficking assay The Journal of experimental medicine High 26101266
2016 Ectodomain shedding of CD99 is mediated by the metalloprotease meprin β (with cleavage at an acidic region conserved across vertebrates, consistent with meprin β's preference for aspartate residues), followed by intramembrane proteolysis by γ-secretase; meprin β-induced CD99 shedding promotes transendothelial cell migration, and Mep1b-/- mice have significantly increased CD99 protein levels in lung. Biochemical shedding assay, mass spectrometry cleavage site identification, meprin β-/- mouse model, in vitro TEM assay, γ-secretase inhibitor FASEB journal High 28003343
2017 Endothelial CD99 (not leukocyte CD99) supports rapid chemokine-induced neutrophil arrest on venular endothelium and acts at the diapedesis step; endothelial CD99 binds heterophilically to paired immunoglobulin-like receptors (PILRs) on neutrophils, promoting shear-resistant attachment; this interaction was confirmed by co-precipitation and biotin-transfer assays. CD99 gene inactivation in mice, intravital video microscopy, co-precipitation, biotin-transfer assay, flow adhesion assay with anti-PILR antibodies Blood High 28223280
2018 Anti-CD99 monoclonal antibodies activate hyperstimulation of macropinocytosis in Ewing sarcoma cells leading to caspase-independent, non-apoptotic cell death resembling methuosis (cytoplasmic vacuole accumulation), requiring RAS-Rac1 downstream signaling; this effect is specific to tumor cells and active in xenografts without immune effectors or complement. Anti-CD99 mAb treatment, macropinocytosis assay, vacuole quantification, RAS-Rac1 pathway inhibition, xenograft model Journal of cell communication and signaling Medium 29305692
2018 Clofarabine directly binds the extracellular domain of CD99, inhibits CD99 dimerization and its interaction with downstream signaling components; a membrane-impermeable clofarabine analog retains cytotoxicity, indicating a CD99-surface mechanism independent of intracellular DNA metabolism. Small molecule library screen for CD99 binding, CD99 dimerization assay, membrane-impermeable analog, xenograft model Oncogene Medium 29382926
2019 CD99 long isoform transiently induces ERK and SRC phosphorylation followed by a dramatic decrease; it also induces reactive oxygen species, DNA damage, and apoptosis in AML cells, delaying disease progression in murine leukemia models. Isoform-specific transfection, ERK/SRC phosphorylation immunoblot, ROS assay, DNA damage assay, murine leukemia model Haematologica Medium 31371417
2019 Nrf2 transcriptionally activates CD99 expression (demonstrated by dual-luciferase reporter assay and ChIP), and this CD99 upregulation mediates Nrf2-induced cisplatin resistance in ovarian cancer cells; CD99 knockdown reverses Nrf2-driven resistance. Dual-luciferase reporter assay, ChIP, Nrf2 and CD99 knockdown/overexpression, CCK-8 viability assay Biochemical and biophysical research communications Medium 31472965
2020 The GDF6 prodomain (not the BMP domain) is a ligand for the CD99 extracellular domain; binding recruits CSK (C-terminal Src kinase) to the YQKKK motif in the CD99 intracellular domain, inhibiting Src activity and maintaining Ewing sarcoma cell proliferation; GDF6 silencing causes Src hyperactivation and p21-dependent growth arrest. Co-immunoprecipitation (GDF6 prodomain-CD99), domain mapping, CSK recruitment assay, Src activity assay, GDF6 silencing, p21 reporter Cell reports High 33147457
2011 CD99 upregulation in Hodgkin/Reed-Sternberg cells induces PRDM1/BLIMP1 expression by suppressing miR-9, which directly targets PRDM1; this CD99-miR-9-PRDM1 axis promotes terminal B-cell differentiation and reorganization of actin cytoskeleton in H/RS cells. CD99 overexpression, miR-9 inhibition, PRDM1 reporter, actin cytoskeleton staining, CD30/CD15/CD38/PAX5 expression analysis International journal of cancer Medium 22020966
2021 Mosaic loss of chromosome Y (LOY) in leukocytes reduces CD99 protein abundance on the cell surface (across all six leukocyte types studied), directly linking Y chromosome copy number to CD99 surface expression at the single-cell level. CITE-seq (simultaneous single-cell mRNA and protein quantification), comparison of LOY vs. non-LOY cells Scientific reports High 34312421

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex. The EMBO journal 204 12727875
2006 Toxoplasma MIC2 is a major determinant of invasion and virulence. PLoS pathogens 169 16933991
1990 Overexpression of the pseudoautosomal gene MIC2 in Ewing's sarcoma and peripheral primitive neuroectodermal tumor. Oncogene 166 1695726
2000 The Toxoplasma adhesive protein MIC2 is proteolytically processed at multiple sites by two parasite-derived proteases. The Journal of biological chemistry 155 10799515
1989 The E2 antigen, a 32 kd glycoprotein involved in T-cell adhesion processes, is the MIC2 gene product. The EMBO journal 153 2479542
1997 Molecular characterisation of an expressed sequence tag locus of Toxoplasma gondii encoding the micronemal protein MIC2. Molecular and biochemical parasitology 152 9084040
2010 CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. The Journal of clinical investigation 134 20197622
1997 Apoptosis of immature thymocytes mediated by E2/CD99. Journal of immunology (Baltimore, Md. : 1950) 124 9058785
1994 Ewing's sarcoma--routine diagnostic utilization of MIC2 analysis: a Pediatric Oncology Group/Children's Cancer Group Intergroup Study. Human pathology 122 8150461
2018 CD99 at the crossroads of physiology and pathology. Journal of cell communication and signaling 117 29305692
2004 Activation of natural killer cells and dendritic cells upon recognition of a novel CD99-like ligand by paired immunoglobulin-like type 2 receptor. The Journal of experimental medicine 114 14970179
1984 The cell surface antigen locus, MIC2X, escapes X-inactivation. American journal of human genetics 114 6540985
2004 Mouse CD99 participates in T-cell recruitment into inflamed skin. Blood 109 15280198
1994 Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood. Blood 108 7506950
2008 The Plasmodium TRAP/MIC2 family member, TRAP-Like Protein (TLP), is involved in tissue traversal by sporozoites. Cellular microbiology 94 18346224
1995 The E2 molecule (CD99) specifically triggers homotypic aggregation of CD4+ CD8+ thymocytes. Journal of immunology (Baltimore, Md. : 1950) 89 7527813
2015 Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. The Journal of experimental medicine 88 26101266
1999 Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements. Human pathology 88 10374776
1994 MIC2 analysis in pediatric lymphomas and leukemias. Human pathology 87 8163272
2014 The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma. Virchows Archiv : an international journal of pathology 84 25031013
2001 CD99 signals caspase-independent T cell death. Journal of immunology (Baltimore, Md. : 1950) 84 11290771
2000 Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. Human pathology 78 11014571
1994 Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp. Nature genetics 77 8054981
2018 CD99: A Cell Surface Protein with an Oncojanus Role in Tumors. Genes 72 29534016
2015 A Leukemia-Associated CD34/CD123/CD25/CD99+ Immunophenotype Identifies FLT3-Mutated Clones in Acute Myeloid Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 71 25957287
2013 MiR-30a-5p connects EWS-FLI1 and CD99, two major therapeutic targets in Ewing tumor. Oncogene 70 22986530
2002 C-terminal processing of the toxoplasma protein MIC2 is essential for invasion into host cells. The Journal of biological chemistry 69 12471033
1998 CD99, keratin, and vimentin staining of sex cord-stromal tumors, normal ovary, and testis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 65 9720506
2000 CD99 (E2) up-regulates alpha4beta1-dependent T cell adhesion to inflamed vascular endothelium under flow conditions. European journal of immunology 63 11069091
2002 CD99 isoforms expression dictates T cell functional outcomes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 62 12368226
2000 Viral latent membrane protein 1 (LMP-1)-induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype. Blood 61 10607715
2015 Immunohistochemical detection of STAT6, CD34, CD99 and BCL-2 for diagnosing solitary fibrous tumors/hemangiopericytomas. International journal of clinical and experimental pathology 59 26722515
2013 Poliovirus receptor (CD155) regulates a step in transendothelial migration between PECAM and CD99. The American journal of pathology 58 23333754
1998 Engagement of CD99 induces up-regulation of TCR and MHC class I and II molecules on the surface of human thymocytes. Journal of immunology (Baltimore, Md. : 1950) 57 9670951
2012 Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation. Shock (Augusta, Ga.) 51 22575993
2006 CD99 immunoreactivity in atypical fibroxanthoma and pleomorphic malignant fibrous histiocytoma: a useful diagnostic marker. Journal of cutaneous pathology 50 16972949
1998 Generation of cells with Hodgkin's and Reed-Sternberg phenotype through downregulation of CD99 (Mic2). Blood 50 9834235
1994 MIC2 analysis of small cell carcinoma. American journal of clinical pathology 50 7524308
2013 Neutrophil and monocyte recruitment by PECAM, CD99, and other molecules via the LBRC. Seminars in immunopathology 49 24337626
2003 The toxoplasma proteins MIC2 and M2AP form a hexameric complex necessary for intracellular survival. The Journal of biological chemistry 48 14670959
1999 A role for CD99 in T cell activation. Cellular immunology 48 10202109
1997 MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities. Human pathology 48 9343323
2021 CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity. Journal of hematology & oncology 46 34627328
2000 Immunoreactivity of MIC2 (CD99) in acute myelogenous leukemia and related diseases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 45 10786814
2014 CD99 triggering in Ewing sarcoma delivers a lethal signal through p53 pathway reactivation and cooperates with doxorubicin. Clinical cancer research : an official journal of the American Association for Cancer Research 44 25501132
2011 Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and CD99 are critical in lymphatic transmigration of human dendritic cells. The Journal of investigative dermatology 44 22189791
2006 Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells. Oncogene 44 16314831
2013 CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity. Oncogene 42 23644663
2008 Regulation of HLA class I surface expression requires CD99 and p230/golgin-245 interaction. Blood 42 18849489
2004 Multimerization of the Toxoplasma gondii MIC2 integrin-like A-domain is required for binding to heparin and human cells. Molecular and biochemical parasitology 42 15003840
1993 The genomic organisation of the human pseudoautosomal gene MIC2 and the detection of a related locus. Human molecular genetics 42 8504302
2007 The murine CD99-related molecule CD99-like 2 (CD99L2) is an adhesion molecule involved in the inflammatory response. Cell communication & adhesion 41 18163232
2012 Overexpression of CD99 Increases the Migration and Invasiveness of Human Malignant Glioma Cells. Genes & cancer 39 23486730
2005 In ovo administration of CpG oligodeoxynucleotides and the recombinant microneme protein MIC2 protects against Eimeria infections. Vaccine 39 15837209
2003 The CD99 signal enhances Fas-mediated apoptosis in the human leukemic cell line, Jurkat. FEBS letters 37 14623115
2000 CD99 immunoreactivity in gastrointestinal and pulmonary neuroendocrine tumours. Virchows Archiv : an international journal of pathology 37 11037347
2019 Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation. Cell death & disease 36 31209202
2008 Vaccination against CD99 inhibits atherogenesis in low-density lipoprotein receptor-deficient mice. Cardiovascular research 36 18250143
2021 Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99. Scientific reports 34 34312421
2002 Immunoreactivity of CD99 in stomach cancer. Journal of Korean medical science 34 12172043
1987 Recombination between the X and Y chromosomes: implications for the relationship between MIC2, XG and YG. Annals of human genetics 34 3502698
1999 High CD99 expression in memory T and B cells in reactive lymph nodes. Journal of Korean medical science 31 10642936
2023 EREG is the core onco-immunological biomarker of cuproptosis and mediates the cross-talk between VEGF and CD99 signaling in glioblastoma. Journal of translational medicine 30 36647156
2016 Cutting Edge: CD99 Is a Novel Therapeutic Target for Control of T Cell-Mediated Central Nervous System Autoimmune Disease. Journal of immunology (Baltimore, Md. : 1950) 30 26773145
2011 CD99 triggers upregulation of miR-9-modulated PRDM1/BLIMP1 in Hodgkin/Reed-Sternberg cells and induces redifferentiation. International journal of cancer 30 22020966
2008 Biophysical characterization of O-glycosylated CD99 recognition by paired Ig-like type 2 receptors. The Journal of biological chemistry 30 18234675
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