Affinage

CD248

Endosialin · UniProt Q9HCU0

Length
757 aa
Mass
80.9 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD248 (endosialin/TEM1) is a type I transmembrane C-type lectin-like glycoprotein expressed on fibroblasts, pericytes, and myofibroblasts that functions as an essential co-regulator of PDGF receptor signaling and extracellular matrix engagement, thereby controlling stromal cell proliferation, migration, and differentiation across diverse tissue contexts including tumor stroma, fibrosis, bone homeostasis, and wound healing (PMID:15862292, PMID:20484976, PMID:22674221, PMID:30986375). CD248 physically associates with PDGFRα and is required for PDGF-BB–induced ERK1/2 phosphorylation, c-Fos expression, and downstream proliferative responses in pericytes, hepatic stellate cells, and fibroblasts, while its C-type lectin domain directly binds extracellular matrix ligands (fibronectin, collagens I/IV) and multimerin-2 at the endothelial–pericyte interface (PMID:17986615, PMID:28671670, PMID:26078290). The cytoplasmic domain transduces signals that regulate HIF-1α, VEGF, MMP-9 activity, and Wnt/β-catenin pathway activation—the latter through sequestration of the Wnt repressors IGFBP4 and LGALS3BP—collectively supporting angiogenesis, tumor growth, and organ fibrosis (PMID:20722022, PMID:21549007, PMID:35950912). CD248 on fibroblasts also engages galectin-3 on macrophages to induce CCL17 and promote a profibrotic macrophage–myofibroblast feedback loop, and on cancer-associated fibroblasts it drives CXCL12 secretion that polarizes macrophages toward an M2 phenotype (PMID:33033277, PMID:35985448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 High

    Resolving the cellular identity of CD248-expressing cells in tumors established that endosialin marks fibroblasts and pericytes rather than endothelial cells, redefining the stromal context for all subsequent functional studies.

    Evidence Monoclonal antibody characterization and immunohistochemistry on tumor sections

    PMID:15862292

    Open questions at the time
    • No signaling function or binding partner identified at this stage
    • Expression in non-tumor tissues not systematically profiled
  2. 2007 High

    Identification of fibronectin and collagens I/IV as direct ECM ligands for CD248, and demonstration that this binding promotes cell adhesion and migration, established CD248 as a functional adhesion/migration receptor on stromal cells.

    Evidence Pulldown/binding assays, cell adhesion assays, Matrigel migration with anti-CD248 antibody blocking

    PMID:17986615

    Open questions at the time
    • ECM-binding domain not mapped
    • Signaling events downstream of ECM engagement not defined
  3. 2008 High

    siRNA knockdown demonstrating that CD248 is required for fibroblast proliferation and migration, together with identification of Mac-2 BP/90K as a binding partner, broadened the receptor's functional repertoire beyond ECM adhesion to include cell-cell interactions and proliferative signaling.

    Evidence siRNA knockdown proliferation/migration assays; biochemical binding analysis and co-IP for Mac-2 BP/90K interaction

    PMID:18187565 PMID:18490383

    Open questions at the time
    • Signaling pathway downstream of Mac-2 BP/90K engagement unknown
    • Relationship between ECM binding and proliferative roles unclear
  4. 2010 High

    Mechanistic dissection showed CD248 is required for PDGF-BB–induced ERK1/2 phosphorylation and c-Fos expression in pericytes, while cytoplasmic domain deletion in mice revealed that this domain controls HIF-1α, VEGF, MMP-9, and monocyte adhesion in inflammatory arthritis, establishing CD248 as a signaling co-receptor upstream of PDGFR.

    Evidence siRNA knockdown with phospho-ERK/c-Fos Western blots; CD248-KO and cytoplasmic domain-deleted transgenic mice in collagen antibody–induced arthritis with ELISA and fibroblast stimulation

    PMID:20484976 PMID:20722022

    Open questions at the time
    • Direct physical interaction with PDGFRs not yet demonstrated
    • How the cytoplasmic domain couples to HIF-1α and MMP-9 transcription not defined
  5. 2011 High

    Cytoplasmic domain deletion reduced tumor growth in vivo and derepressed tumor suppressors (transgelin/SM22α, Hes, Hey1) in fibroblasts, while CD248 expression on naive CD8+ T cells maintained quiescence, revealing functions beyond stromal cells.

    Evidence Transgenic mouse tumor models with conditioned media and gene expression analysis; flow cytometry with gain/loss-of-function in human T cells

    PMID:21466550 PMID:21549007

    Open questions at the time
    • Mechanism of tumor suppressor derepression upon cytoplasmic domain loss unknown
    • T cell quiescence role not replicated in mouse and species difference unexplained
  6. 2012 High

    CD248 knockout increased bone mass and osteoblast mineralization due to defective PDGF signal transduction, extending the PDGFR co-receptor function to bone homeostasis.

    Evidence CD248-KO mice with micro-CT, three-point bending, in vitro mineralization, and PDGF-BB stimulation

    PMID:22674221

    Open questions at the time
    • Whether CD248 interacts with PDGFRα or PDGFRβ in osteoblasts not determined
    • Structural basis of PDGFR co-receptor function unknown
  7. 2015 High

    CD248 loss protected against liver and renal fibrosis—hepatic stellate cells and pericytes showed impaired PDGF-BB proliferation and migration, and anti-CD248 antibody internalization disrupted pericyte maturation and tumor vasculature—consolidating CD248 as a master regulator of PDGF-dependent fibrotic and angiogenic remodeling.

    Evidence CD248-KO mice in CCl4 liver fibrosis and UUO renal fibrosis models; anti-CD248 antibody treatment in human CD248 knock-in syngeneic tumor models

    PMID:25243742 PMID:26078290 PMID:26327620 PMID:26633297

    Open questions at the time
    • How CD248 modulates PDGFR signaling without altering receptor expression remains mechanistically undefined
    • Whether CD248 affects PDGFR internalization or clustering not tested
  8. 2017 High

    Mapping the MMRN2-binding site to the C-type lectin domain of CD248 via mutagenesis, and showing simultaneous CLEC14A/CD248 engagement of MMRN2, defined a molecular bridge at the endothelial–pericyte interface.

    Evidence Direct binding assays with C-type lectin domain mutants; co-localization in human pancreatic cancer sections

    PMID:28671670

    Open questions at the time
    • Functional consequence of MMRN2 binding for angiogenesis not shown in loss-of-function models
    • Crystal structure of CD248 C-type lectin domain not available
  9. 2019 High

    Co-immunoprecipitation demonstrated physical association of CD248 with PDGFRα, and KO mouse wound healing showed CD248 is required for fibroblast activation and collagen deposition, confirming CD248 as a direct PDGFR-associated co-receptor.

    Evidence Co-IP and subcellular co-localization; TEM1-KO mouse wound healing model with shRNA validation in vitro

    PMID:30986375

    Open questions at the time
    • Whether CD248 also physically interacts with PDGFRβ via co-IP not shown
    • Stoichiometry and domain requirements for the CD248–PDGFRα complex unknown
  10. 2019 High

    Adipocyte-specific CD248 knockout revealed a role as a microenvironmental hypoxia sensor in adipose tissue, improving insulin sensitivity and reducing fibrosis, extending CD248 function to metabolic regulation.

    Evidence Conditional adipocyte-specific CD248-KO mice on high-fat diet with metabolic phenotyping and omics analysis

    PMID:31221584

    Open questions at the time
    • Molecular mechanism of hypoxia sensing by CD248 not defined
    • Relationship to HIF-1α regulation in adipocytes not directly tested
  11. 2020 High

    Identification of galectin-3 on macrophages as a CD248 binding partner driving a CCL17-dependent macrophage–myofibroblast profibrotic loop established a direct intercellular signaling mechanism for CD248 in organ fibrosis.

    Evidence CD248-KO and galectin-3-KO mice, parabiosis with GFP reporter, co-interaction studies in renal and peritoneal fibrosis

    PMID:33033277

    Open questions at the time
    • Whether the CD248–galectin-3 interaction uses the C-type lectin domain not mapped
    • Downstream signaling in macrophages leading to CCL17 induction not characterized
  12. 2022 High

    CD248 was shown to derepress Wnt/β-catenin signaling by sequestering IGFBP4 and LGALS3BP, and separately to drive CXCL12 secretion from cancer-associated fibroblasts to polarize macrophages toward M2, revealing two new effector mechanisms in the tumor microenvironment.

    Evidence Co-IP of CD248 with IGFBP4 and LGALS3BP, β-catenin inhibitor rescue, KO orthotopic lung cancer models; CD248 siRNA in patient-derived CAFs with CXCL12 ELISA and macrophage polarization assays

    PMID:35950912 PMID:35985448

    Open questions at the time
    • Whether Wnt derepression and CXCL12 secretion are linked or independent pathways not resolved
    • Structural basis for IGFBP4/LGALS3BP sequestration unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for CD248's co-receptor function with PDGFRs, the identity of the intracellular adaptors coupling the cytoplasmic domain to HIF-1α/MMP-9/Wnt pathways, and whether CD248's multiple extracellular ligand interactions are coordinated or context-specific remain unresolved.
  • No crystal or cryo-EM structure of CD248 or its complexes
  • Cytoplasmic domain interactome not defined by unbiased proteomics
  • Relative contributions of ECM binding vs. PDGFR co-receptor function to each disease phenotype not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
FN1IGFBP4LGALS3LGALS3BPMMRN2PDGFRA

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Endosialin (TEM1/CD248) is a cell surface glycoprotein predominantly expressed by fibroblasts and a subset of pericytes associated with tumor vessels, not by tumor endothelium, as demonstrated by monoclonal antibody characterization and cell localization studies. Monoclonal antibody characterization, immunohistochemistry, cell fractionation/surface expression analysis FEBS letters High 15862292
2007 CD248/endosialin directly binds fibronectin and collagen types I and IV as extracellular matrix ligands, and cells expressing CD248 exhibit enhanced adhesion to fibronectin and enhanced migration through Matrigel; these effects are blocked by a humanized anti-CD248 antibody. Binding assays (pulldown/co-precipitation), cell adhesion assays, Matrigel migration assay, antibody blocking Proceedings of the National Academy of Sciences of the United States of America High 17986615
2008 Endosialin (Tem1) is expressed by tumor-associated myofibroblasts and mural cells (not endothelial cells); siRNA knockdown of endosialin in fibroblasts strongly inhibited migration and proliferation. Extensive expression profiling, siRNA knockdown, migration and proliferation assays The American journal of pathology High 18187565
2008 Tumor stroma marker endosialin (Tem1) binds specifically to Mac-2 BP/90K via a C-terminal fragment of Mac-2 BP/90K that contains binding sites for galectin-3 and collagens; this interaction results in a repulsive outcome when Mac-2 BP/90K-expressing tumor cells contact endosialin-expressing fibroblasts. Biochemical binding analysis, Co-IP, loss-of-function adhesion experiments FASEB journal Medium 18490383
2008 Anti-endosialin antibodies inhibit pericyte tube formation in culture and pericyte migration, demonstrating a functional role for CD248 in pericyte behavior during angiogenesis. Antibody blocking, in vitro tube formation assay, migration assay Microvascular research Medium 18761022
2010 CD248 mediates proliferation of primary human pericytes through a PDGF receptor signaling pathway: TEM-1 knockdown impairs PDGF-BB-induced proliferation, ERK-1/2 phosphorylation, and c-Fos expression. siRNA knockdown, Western blotting for phospho-ERK and c-Fos, proliferation assays with PDGF-BB stimulation Cancer biology & therapy High 20484976
2010 The cytoplasmic domain of CD248 is required for its role in arthritis: CD248-deficient or cytoplasmic domain-deleted mice show reduced synovial hyperplasia, reduced leukocyte accumulation, and impaired TNF-α-induced monocyte adhesion to fibroblasts; cytoplasmic domain-deleted fibroblasts show reduced HIF-1α, placental growth factor, VEGF expression, and MMP-9 activity in response to TGF-β. Transgenic mouse models (CD248-KO and cytoplasmic domain deletion), collagen antibody-induced arthritis, ELISA, immunohistochemistry, in vitro fibroblast assays Arthritis and rheumatism High 20722022
2011 The cytoplasmic domain of CD248 is required for tumor growth support: CD248 cytoplasmic domain-deleted mice show significantly reduced fibrosarcoma and Lewis lung carcinoma growth; CD248-CyD fibroblasts produce conditioned media less effective at supporting tumor cell survival, show reduced MMP-9 activity, impaired PDGF-BB-induced migration, and express higher levels of tumor suppressor factors (transgelin/SM22α, Hes, Hey1). Transgenic mouse tumor models, conditioned media assay, MMP-9 activity, migration assay, gene expression analysis BMC cancer High 21549007
2011 CD248 is expressed on naive CD8+ human (but not mouse) T cells and maintains them in a quiescent state: transfection of CD248 into CD248-negative T cells reduces proliferation, while CD248 knockdown on naive CD8+ T cells increases proliferation. Flow cytometry, cDNA transfection, siRNA knockdown, proliferation assays Immunology Medium 21466550
2012 Genetic deletion of CD248 results in higher bone mass and increased osteoblast-mediated bone formation; CD248-knockout osteoblasts show increased mineralization in vitro and do not proliferate in response to PDGF-BB, attributable to a defect in PDGF signal transduction. CD248-KO mouse model, micro-CT, 3-point bending, in vitro mineralization, PDGF-BB stimulation assays Arthritis and rheumatism High 22674221
2015 CD248 deletion reduces susceptibility to liver fibrosis via impaired PDGF signaling: CD248-/- hepatic stellate cells (HSCs) fail to proliferate in response to PDGF-BB, with significantly reduced c-Fos expression, while PDGFR-α and PDGFR-β expression levels are unchanged. CD248-/- mouse model, CCl4-induced fibrosis, isolated primary HSC proliferation assays, PDGF-BB stimulation, c-Fos gene expression Gut High 26078290
2014 CD248 is required specifically for PDGFRβ-dependent capillary sprouting but not splitting angiogenesis in skeletal muscle; CD248-/- mice have a specific defect in capillary sprouting that can be mimicked by blocking PDGFRβ signaling with Imatinib. CD248-/- mouse model, mechanical angiogenesis induction models (shear stress vs. functional overload), Imatinib treatment, gene expression analysis PloS one High 25243742
2017 CD248 (endosialin) directly binds multimerin-2 (MMRN2) via its C-type lectin domain, with binding dependent on a long-loop region and abrogated by mutations within the domain; the binding site on MMRN2 is distinct from (non-competing with) the sites bound by CLEC14A and CD93, and CLEC14A and CD248 can simultaneously bind MMRN2 at the endothelial-pericyte interface. Direct binding assays, mutagenesis of C-type lectin domain, co-localization in human pancreatic cancer sections Oncogene High 28671670
2019 TEM1/CD248 physically associates with PDGF receptor α (co-localization in subcellular organelles and co-immunoprecipitation), and TEM1 knockdown impairs PDGF-BB-induced downstream signaling as well as migration, adhesion, and proliferation of fibroblasts; wound healing is retarded in TEM1-deleted mice with attenuated fibroblast activation and collagen deposition. Co-immunoprecipitation, subcellular co-localization, shRNA knockdown, migration/adhesion/proliferation assays, TEM1-knockout mouse wound healing model The Journal of investigative dermatology High 30986375
2019 CD248 acts as a microenvironmental sensor mediating part of the adipose tissue response to hypoxia; adipocyte-specific CD248 knockout increases microvascular density and attenuates hypoxia, inflammation, and fibrosis, leading to improved insulin sensitivity and glucose tolerance. Adipocyte-specific and inducible CD248 knockout mice, diet-induced obesity model, omics analysis, in vitro gene knockdown in human adipocytes EBioMedicine High 31221584
2022 CD248 derepresses Wnt/β-catenin signaling in pericytes by interacting with Wnt pathway repressors IGFBP4 and LGALS3BP (galectin-3BP/SERPINE1), leading to upregulation of OPN and SERPINE1, enhanced angiogenesis, and lung cancer growth. CD248-knockout mouse orthotopic lung cancer models, co-immunoprecipitation of CD248 with IGFBP4 and LGALS3BP, Wnt/β-catenin pathway analysis, β-catenin inhibitor treatment, recombinant factor rescue experiments Cancer research High 35950912
2022 CD248 expression on cancer-associated fibroblasts (CAFs) promotes CXCL12 secretion, which mediates M2 macrophage polarization and NSCLC progression; CD248 knockdown in CAFs reduces CXCL12 secretion, and CXCR4 blockade reduces M2 macrophage chemotaxis. CD248 siRNA knockdown in primary patient-derived CAFs, CXCL12 ELISA, macrophage polarization assays, CXCR4 blocking, in vivo tumor models Biochimica et biophysica acta. Molecular basis of disease Medium 35985448
2020 CD248 on fibroblast/myofibroblasts interacts specifically with galectin-3 on macrophages; this interaction induces CCL17 expression in macrophages, which then activates collagen production in myofibroblasts; Cd248 knockout reduces macrophage infiltration and attenuates renal and peritoneal fibrosis. Cd248-/- mouse models, parabiosis with GFP reporter mice, galectin-3-deficient macrophage experiments, co-interaction studies, in vivo DNA vaccination Scientific reports High 33033277
2015 CD248 deletion protects against renal fibrosis and microvascular rarefaction following unilateral ureteral obstruction; CD248-/- pericytes show less migration and differentiation toward myofibroblast phenotype, and CD248-/- fibroblasts proliferate less and deposit less collagen in vitro. UUO mouse model, CD248-/- genetic deletion, pericyte migration assay, collagen deposition assay Nephron Medium 26633297
2015 Targeting endosialin/CD248 via antibody-mediated internalization (MORAb-004) reduces CD248 levels on pericyte surfaces, impairs pericyte maturation (reduced α-SMA expression, pericyte depolarization), results in dysfunctional tumor microvessels, and suppresses tumor growth and metastasis. Human CD248 knock-in mouse syngeneic tumor models, anti-CD248 antibody treatment, immunofluorescent staining for vessel markers, α-SMA Oncotarget Medium 26327620
2019 In TLR2/6- and TLR5-modified chemoresistant colon cancer cells, TLR activation reduces miR-125b-5p levels, leading to Sp1-mediated CD248 upregulation via NF-κB; elevated CD248 promotes invasiveness and drug resistance, which are reversed by miR-125b-5p mimic transfection or CD248 gene silencing. TLR2/6 and TLR5 ligand stimulation, miR-125b-5p mimic transfection, Sp1 and CD248 siRNA knockdown, invasion and drug resistance assays Molecular carcinogenesis Medium 31746054
2018 CD248 silencing in systemic sclerosis mesenchymal stem cells inhibits both TGF-β-induced myofibroblast differentiation and PDGF-BB-induced proliferation, demonstrating CD248 is required upstream of both TGF-β and PDGF-BB signaling pathways in fibrotic perivascular stromal cells. siRNA knockdown of CD248 in SSc-MSCs, TGF-β and PDGF-BB stimulation, Western blot for α-SMA and Ki-67 Arthritis research & therapy Medium 30285896

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 630 10219244
1993 Crystal structure of Escherichia coli TEM1 beta-lactamase at 1.8 A resolution. Proteins 341 8356032
2004 Identification of the secretion and translocation domain of the enteropathogenic and enterohemorrhagic Escherichia coli effector Cif, using TEM-1 beta-lactamase as a new fluorescence-based reporter. Journal of bacteriology 264 15292151
2015 Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1. Molecular biology and evolution 185 26446903
1994 The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. Molecular and cellular biology 160 7935462
2001 The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis. Journal of cell science 152 11257003
1999 The effect of high-frequency random mutagenesis on in vitro protein evolution: a study on TEM-1 beta-lactamase. Journal of molecular biology 152 9878443
2005 Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium. FEBS letters 145 15862292
2008 Endosialin (Tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. The American journal of pathology 136 18187565
2001 Order of function of the budding-yeast mitotic exit-network proteins Tem1, Cdc15, Mob1, Dbf2, and Cdc5. Current biology : CB 133 11378390
2006 Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumors. Proceedings of the National Academy of Sciences of the United States of America 130 16492758
2007 Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration. Proceedings of the National Academy of Sciences of the United States of America 122 17986615
2010 Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrobial agents and chemotherapy 121 20921316
1994 Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors. Antimicrobial agents and chemotherapy 113 8067742
2000 Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,). Biochemistry 107 10820001
2001 A secondary drug resistance mutation of TEM-1 beta-lactamase that suppresses misfolding and aggregation. Proceedings of the National Academy of Sciences of the United States of America 105 11114163
1996 The catalytic mechanism of beta-lactamases: NMR titration of an active-site lysine residue of the TEM-1 enzyme. Proceedings of the National Academy of Sciences of the United States of America 97 8700829
2015 Negative Epistasis and Evolvability in TEM-1 β-Lactamase--The Thin Line between an Enzyme's Conformational Freedom and Disorder. Journal of molecular biology 96 26004540
2002 Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by Bub2 and Bfa1. The Journal of biological chemistry 93 12048186
1997 A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate. Antimicrobial agents and chemotherapy 88 9174192
2009 Plasmid pKpQIL encoding KPC-3 and TEM-1 confers carbapenem resistance in an extremely drug-resistant epidemic Klebsiella pneumoniae strain. The Journal of antimicrobial chemotherapy 85 19939824
1995 TEM1 beta-lactamase structure solved by molecular replacement and refined structure of the S235A mutant. Acta crystallographica. Section D, Biological crystallography 85 15299797
2008 Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization. Microvascular research 83 18761022
2001 Crystal structure and kinetic analysis of beta-lactamase inhibitor protein-II in complex with TEM-1 beta-lactamase. Nature structural biology 78 11573088
2006 Binding hot spots in the TEM1-BLIP interface in light of its modular architecture. Journal of molecular biology 77 17070843
2015 CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism. Gut 76 26078290
2010 Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling. Cancer biology & therapy 74 20484976
2017 Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface. Oncogene 68 28671670
1992 Beta-lactamase TEM1 of E. coli. Crystal structure determination at 2.5 A resolution. FEBS letters 66 1544485
2005 Structure of the wild-type TEM-1 beta-lactamase at 1.55 A and the mutant enzyme Ser70Ala at 2.1 A suggest the mode of noncovalent catalysis for the mutant enzyme. Acta crystallographica. Section D, Biological crystallography 63 16041072
2010 CD248 and its cytoplasmic domain: a therapeutic target for arthritis. Arthritis and rheumatism 61 20722022
2019 CD248: A therapeutic target in cancer and fibrotic diseases. Oncotarget 56 30847027
2009 Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchange by Tem1. The Journal of cell biology 55 19948498
2006 Backbone dynamics of TEM-1 determined by NMR: evidence for a highly ordered protein. Biochemistry 55 16981701
2012 CD248: reviewing its role in health and disease. Current drug targets 53 22206249
2017 Enzyme Efficiency but Not Thermostability Drives Cefotaxime Resistance Evolution in TEM-1 β-Lactamase. Molecular biology and evolution 52 28087769
2011 Tem1 localization to the spindle pole bodies is essential for mitotic exit and impairs spindle checkpoint function. The Journal of cell biology 52 21321099
2011 CD248 facilitates tumor growth via its cytoplasmic domain. BMC cancer 52 21549007
2001 A novel functional domain of Cdc15 kinase is required for its interaction with Tem1 GTPase in Saccharomyces cerevisiae. Genetics 52 11290702
2015 A triple mutant in the Ω-loop of TEM-1 β-lactamase changes the substrate profile via a large conformational change and an altered general base for catalysis. The Journal of biological chemistry 51 25713062
2011 Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit. Genes & development 51 21937712
2008 Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis-related protein Mac-2 BP/90K. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 51 18490383
2004 Site-saturation mutagenesis of Tyr-105 reveals its importance in substrate stabilization and discrimination in TEM-1 beta-lactamase. The Journal of biological chemistry 51 15326193
1998 Selection and characterization of beta-lactam-beta-lactamase inactivator-resistant mutants following PCR mutagenesis of the TEM-1 beta-lactamase gene. Antimicrobial agents and chemotherapy 51 9660980
1995 Investigation of the folding pathway of the TEM-1 beta-lactamase. Proteins 51 7567959
2003 Determinants of binding affinity and specificity for the interaction of TEM-1 and SME-1 beta-lactamase with beta-lactamase inhibitory protein. The Journal of biological chemistry 50 12933802
2022 CD248 Regulates Wnt Signaling in Pericytes to Promote Angiogenesis and Tumor Growth in Lung Cancer. Cancer research 49 35950912
1995 Electrostatic analysis of TEM1 beta-lactamase: effect of substrate binding, steep potential gradients and consequences of site-directed mutations. Structure (London, England : 1993) 49 8590021
2022 CXCL12 derived from CD248-expressing cancer-associated fibroblasts mediates M2-polarized macrophages to promote nonsmall cell lung cancer progression. Biochimica et biophysica acta. Molecular basis of disease 47 35985448
2007 CD248/Endosialin is dynamically expressed on a subset of stromal cells during lymphoid tissue development, splenic remodeling and repair. FEBS letters 46 17628549
2002 Noncovalent interaction energies in covalent complexes: TEM-1 beta-lactamase and beta-lactams. Proteins 46 11870868
2011 CD248+ stromal cells are associated with progressive chronic kidney disease. Kidney international 45 21490589
2010 Rapid isolation of high-affinity human antibodies against the tumor vascular marker Endosialin/TEM1, using a paired yeast-display/secretory scFv library platform. Journal of immunological methods 45 20837020
1991 Site-directed mutagenesis on TEM-1 beta-lactamase: role of Glu166 in catalysis and substrate binding. Protein engineering 45 1798703
2008 Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248. Molecular cancer therapeutics 44 18723498
2002 Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 43 11959999
1999 X-ray structure of the Asn276Asp variant of the Escherichia coli TEM-1 beta-lactamase: direct observation of electrostatic modulation in resistance to inactivation by clavulanic acid. Biochemistry 43 10423234
1991 Replacement of lysine 234 affects transition state stabilization in the active site of beta-lactamase TEM1. The Journal of biological chemistry 42 1910040
2021 TEM1 combinatorially binds to FLOWERING LOCUS T and recruits a Polycomb factor to repress the floral transition in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 41 34446554
2011 Fluorogenic cephalosporin substrates for β-lactamase TEM-1. Analytical biochemistry 41 21867672
2012 The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice. Arthritis and rheumatism 40 22674221
2009 Characterization of TEM1/endosialin in human and murine brain tumors. BMC cancer 40 19948061
2001 Outer membrane protein change combined with co-existing TEM-1 and SHV-1 beta-lactamases lead to false identification of ESBL-producing Klebsiella pneumoniae. The Journal of antimicrobial chemotherapy 40 11389107
2017 Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 39 28464475
2014 A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis. PloS one 35 25243742
2011 False extended-spectrum {beta}-lactamase phenotype in clinical isolates of Escherichia coli associated with increased expression of OXA-1 or TEM-1 penicillinases and loss of porins. The Journal of antimicrobial chemotherapy 35 21742679
2010 The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion. European journal of immunology 35 20432232
1994 Reversal of clavulanate resistance conferred by a Ser-244 mutant of TEM-1 beta-lactamase as a result of a second mutation (Arg to Ser at position 164) that enhances activity against ceftazidime. Antimicrobial agents and chemotherapy 35 8067751
2019 Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation. EBioMedicine 34 31221584
2018 Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: a new potential target for antifibrotic therapy. Arthritis research & therapy 34 30285896
2011 The stromal cell antigen CD248 (endosialin) is expressed on naive CD8+ human T cells and regulates proliferation. Immunology 34 21466550
2015 Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature. Oncotarget 33 26327620
2016 Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis. BMC pulmonary medicine 32 27080864
2005 Isolation and characterization of a scFv antibody specific for tumor endothelial marker 1 (TEM1), a new reagent for targeted tumor therapy. Cancer letters 32 15953677
2019 Fitness Effects of Single Amino Acid Insertions and Deletions in TEM-1 β-Lactamase. Journal of molecular biology 30 31034887
2010 TEM-1 backbone dynamics-insights from combined molecular dynamics and nuclear magnetic resonance. Biophysical journal 30 20159160
1992 Effects of CO2 and pH on inhibition of TEM-1 and other beta-lactamases by penicillanic acid sulfones. Antimicrobial agents and chemotherapy 30 1329633
2011 Gene targeting and expression analysis of mouse Tem1/endosialin using a lacZ reporter. Gene expression patterns : GEP 29 21402174
2020 CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes. BMC pulmonary medicine 28 31964365
2020 Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis. Scientific reports 28 33033277
2019 Modified TLR-mediated downregulation of miR-125b-5p enhances CD248 (endosialin)-induced metastasis and drug resistance in colorectal cancer cells. Molecular carcinogenesis 28 31746054
2015 Genetic Deletion of the Stromal Cell Marker CD248 (Endosialin) Protects against the Development of Renal Fibrosis. Nephron 28 26633297
2019 Tumor Endothelial Marker 1 (TEM1/Endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors. The Journal of investigative dermatology 27 30986375
2014 Development of 124I immuno-PET targeting tumor vascular TEM1/endosialin. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 27 24525208
2014 Inactivation of TEM-1 by avibactam (NXL-104): insights from quantum mechanics/molecular mechanics metadynamics simulations. Biochemistry 26 25050826
2024 Targeting the activated microenvironment with endosialin (CD248)-directed CAR-T cells ablates perivascular cells to impair tumor growth and metastasis. Journal for immunotherapy of cancer 24 38413223
2015 Asymmetry of the budding yeast Tem1 GTPase at spindle poles is required for spindle positioning but not for mitotic exit. PLoS genetics 24 25658911
2010 Emergence of CTX-M-3, TEM-1 and a new plasmid-mediated MOX-4 AmpC in a multiresistant Aeromonas caviae isolate from a patient with pneumonia. Journal of medical microbiology 24 20339022
2014 Antibody-based tumor vascular theranostics targeting endosialin/TEM1 in a new mouse tumor vascular model. Cancer biology & therapy 23 24553243
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2015 Contribution of PBP3 Substitutions and TEM-1, TEM-15, and ROB-1 Beta-Lactamases to Cefotaxime Resistance in Haemophilus influenzae and Haemophilus parainfluenzae. Microbial drug resistance (Larchmont, N.Y.) 22 26683319
2014 Increased expression of P2RY2, CD248 and EphB1 in gastric cancers from Chilean patients. Asian Pacific journal of cancer prevention : APJCP 22 24716914
2012 CD248 expression on mesenchymal stromal cells is required for post-natal and infection-dependent thymus remodelling and regeneration. FEBS open bio 21 23650598
2008 Structural insight into the kinetics and DeltaCp of interactions between TEM-1 beta-lactamase and beta-lactamase inhibitory protein (BLIP). The Journal of biological chemistry 21 18840610
1987 Oligonucleotide probes for the detection of TEM-1 and TEM-2 beta-lactamase genes and their transposons. Canadian journal of microbiology 21 3032386
2015 Coupling spindle position with mitotic exit in budding yeast: The multifaceted role of the small GTPase Tem1. Small GTPases 20 26507466
1994 Effect of threonine-to-methionine substitution at position 265 on structure and function of TEM-1 beta-lactamase. Antimicrobial agents and chemotherapy 20 7840555
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