Affinage

CD248

Endosialin · UniProt Q9HCU0

Length
757 aa
Mass
80.9 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD248 (endosialin/TEM1) is a cell-surface glycoprotein of activated mesenchymal cells—tumor-associated fibroblasts, myofibroblasts, and a subset of pericytes—that acts as a stromal co-receptor and matrix-engagement scaffold driving proliferation, migration, and tissue remodeling (PMID:15862292, PMID:18187565). Its central mechanistic role is to potentiate platelet-derived growth factor receptor signaling: CD248 co-immunoprecipitates with PDGFRα, and its loss abrogates PDGF-BB-induced proliferation, ERK1/2 phosphorylation, c-Fos induction, migration, and collagen deposition across pericytes, hepatic stellate cells, fibroblasts, and osteoblasts (PMID:20484976, PMID:26078290, PMID:22674221, PMID:30986375). This PDGFR-dependent axis places CD248 at the center of capillary sprouting angiogenesis, wound healing, and fibrogenesis (PMID:30986375, PMID:25243742). CD248 engages the extracellular matrix and matrix-associated proteins directly, binding fibronectin and collagens I/IV to mediate adhesion and migration (PMID:17986615), the endothelial matrix protein MMRN2 through its C-type lectin domain (PMID:28671670), and Mac-2 BP/90K in a repulsive adhesion interaction (PMID:18490383). The conserved cytoplasmic domain is required for downstream effector functions including MMP-9 activation and HIF1α/VEGF expression, as cytoplasmic-domain-deleted mice show attenuated inflammatory arthritis and tumor growth (PMID:20722022, PMID:21549007). CD248 also derepresses Wnt/β-catenin signaling by sequestering the repressors IGFBP4 and LGALS3BP to upregulate angiogenic factors (PMID:35950912), and mediates cell-cell crosstalk with macrophages—binding galectin-3 to induce CCL17/CCL22-driven fibrosis (PMID:33033277) and promoting CXCL12-dependent M2 polarization in cancer-associated fibroblasts (PMID:35985448). Beyond its mesenchymal roles, CD248 on human naive CD8+ T cells paradoxically maintains quiescence by suppressing proliferation (PMID:21466550).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2005 Medium

    Establishing which cell type expresses endosialin resolved whether it marks tumor endothelium or stroma, redirecting the field toward a perivascular/fibroblast role.

    Evidence Monoclonal antibody characterization with immunofluorescence and flow cytometry localizing endosialin to tumor-associated fibroblasts and pericytes

    PMID:15862292

    Open questions at the time
    • Did not define a ligand or signaling function
    • Cellular identity assigned by antibody localization, not lineage tracing
  2. 2007 Medium

    Identifying fibronectin and collagens I/IV as direct ligands gave CD248 a concrete matrix-engagement function underlying adhesion and migration.

    Evidence Binding assays, cell adhesion and transwell migration assays with antibody blocking

    PMID:17986615

    Open questions at the time
    • Binding domain not mapped
    • Did not connect matrix binding to an intracellular signaling pathway
  3. 2008 Medium

    Loss-of-function and direct binding studies extended CD248's role to additional partners and functional outputs in stromal and vascular cells.

    Evidence siRNA knockdown of migration/proliferation in fibroblasts; co-IP and adhesion assays defining a repulsive Mac-2 BP/90K interaction; antibody-blocking of EPC and pericyte tube formation

    PMID:18187565 PMID:18490383 PMID:18723498 PMID:18761022

    Open questions at the time
    • Mechanism linking ligand binding to migration phenotype unresolved
    • Antibody-blocking EPC/pericyte assays were Low confidence and not mechanistically dissected
  4. 2010 High

    Genetic and knockdown studies established the PDGFR signaling axis and the requirement of the cytoplasmic domain, defining CD248 as a signaling co-receptor rather than a passive adhesion molecule.

    Evidence siRNA knockdown abolishing PDGF-BB-induced proliferation/ERK/c-Fos in pericytes; CD248 cytoplasmic-domain-deleted mice with reduced arthritis, impaired monocyte adhesion, and reduced HIF1α/VEGF/MMP-9; stromal KO impairing lymph node expansion

    PMID:20432232 PMID:20484976 PMID:20722022

    Open questions at the time
    • Cytoplasmic domain interactors mediating downstream signaling not identified
    • Direct physical PDGFR interaction not yet shown
  5. 2011 Medium

    In vivo tumor models and the discovery of a T-cell-specific quiescence role broadened CD248 function beyond stromal proliferation.

    Evidence CD248 cytoplasmic-domain-knockout tumor models with impaired fibroblast migration and MMP-9; CD248 cDNA transfection and knockdown in human naive CD8+ T cells altering proliferation

    PMID:21466550 PMID:21549007

    Open questions at the time
    • Mechanism of T-cell quiescence not defined
    • Why function is human-CD8-specific and not mouse unexplained
  6. 2012 Medium

    Knockout phenotypes in bone and thymus showed CD248 governs PDGFR-dependent mesenchymal function across diverse tissues.

    Evidence CD248-/- mice with increased bone mass and defective osteoblast PDGF signaling; CD248-/- mice with hypocellular thymus and impaired regeneration

    PMID:22674221 PMID:23650598

    Open questions at the time
    • Tissue-specific contribution of stromal vs other cell types not separated in bone
    • Molecular basis of thymic stromal requirement unresolved
  7. 2015 High

    Fibrosis and antibody-targeting models confirmed CD248 as a therapeutically tractable driver of PDGF-dependent fibrogenesis and pericyte maturation.

    Evidence CD248-/- mice protected from CCl4 liver fibrosis with PDGF-unresponsive hepatic stellate cells; MORAb-004 antibody internalization impairing pericyte maturation and tumor vessels in CD248 knock-in mice

    PMID:26078290 PMID:26327620

    Open questions at the time
    • Antibody mechanism of CD248 downregulation not fully defined
    • Pericyte vs fibroblast contribution to fibrosis not dissected
  8. 2017 High

    Domain-resolved binding to MMRN2 defined a C-type lectin-mediated interaction at the endothelial-pericyte interface, distinct from CLEC14A.

    Evidence Direct binding assays, C-type lectin domain mutagenesis abolishing MMRN2 binding, simultaneous binding with CLEC14A, and co-localization in human pancreatic cancer

    PMID:28671670

    Open questions at the time
    • Functional consequence of MMRN2 binding for signaling not established
    • Whether MMRN2 binding modulates PDGFR axis unknown
  9. 2019 High

    Reciprocal co-IP with PDGFRα and metabolic/regulatory studies cemented the receptor partnership and revealed transcriptional control and microenvironmental sensing roles.

    Evidence Co-IP of TEM1 with PDGFRα plus knockdown and KO wound-healing phenotypes; adipocyte-specific inducible KO improving metabolism and reducing hypoxia/fibrosis; Sp1/TLR/NF-κB and miR-125b-5p regulation of CD248 in colorectal cancer

    PMID:30986375 PMID:31221584 PMID:31746054

    Open questions at the time
    • Stoichiometry and structural basis of the PDGFRα interaction not resolved
    • How CD248 senses hypoxia mechanistically unclear
  10. 2022 High

    Wnt derepression and macrophage crosstalk mechanisms explained how CD248 amplifies angiogenesis and fibrosis through partner sequestration and paracrine chemokine induction.

    Evidence Co-IP of CD248 with IGFBP4/LGALS3BP and β-catenin reporter/rescue assays in KO lung cancer models; CD248-galectin-3 interaction inducing macrophage CCL17/CCL22; CAF CD248-CXCL12 axis driving M2 polarization via CXCR4

    PMID:33033277 PMID:35950912 PMID:35985448

    Open questions at the time
    • How a single surface protein coordinates PDGFR, Wnt, and chemokine outputs not integrated
    • Direct vs indirect nature of some interactions not all reciprocally validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and biochemical basis by which the cytoplasmic domain transduces signals from PDGFR and matrix engagement remains undefined.
  • No structure of CD248 or its cytoplasmic-domain interactome
  • Mechanism distinguishing co-receptor vs adhesion vs sequestration functions unresolved
  • Basis of cell-type-specific quiescence on CD8+ T cells unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098631 cell adhesion mediator activity 2 GO:0098772 molecular function regulator activity 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
FN1IGFBP4LGALS3LGALS3BPMMRN2PDGFRA

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CD248/endosialin binds extracellular matrix proteins fibronectin and collagen types I and IV as specific ligands; cells expressing CD248 show enhanced adhesion to fibronectin and enhanced migration through matrigel, both of which are blocked by a humanized anti-CD248 antibody. Binding assays, cell adhesion assays, transwell migration assay, antibody blocking Proceedings of the National Academy of Sciences of the United States of America Medium 17986615
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 established by monoclonal antibody characterization and cellular localization studies. Monoclonal antibody generation, immunofluorescence, flow cytometry, subcellular localization FEBS letters Medium 15862292
2010 CD248/endosialin mediates proliferation of primary human pericytes through PDGF receptor signaling: TEM-1 knockdown abrogates PDGF-BB-induced proliferation, ERK-1/2 phosphorylation, and c-Fos expression. siRNA knockdown, western blot (phospho-ERK), c-Fos expression assay, cell proliferation assay Cancer biology & therapy Medium 20484976
2015 CD248 deletion in hepatic stellate cells (HSCs) reduces susceptibility to liver fibrosis via PDGF signaling: CD248-/- HSCs do not proliferate in response to PDGF-BB, and c-fos expression is significantly reduced in CD248-/- HSCs after stimulation. CD248 knockout mouse model, CCl4-induced fibrosis, HSC isolation, PDGF-BB stimulation, c-fos expression assay Gut High 26078290
2010 CD248's cytoplasmic domain is required for inflammatory arthritis responses: CD248 cytoplasmic domain-deficient (CD248CyD/CyD) mice show reduced arthritis severity, with impaired TNFα-induced monocyte adhesion to fibroblasts and reduced HIF1α, PIGF, VEGF, and MMP-9 activity in response to TGF-β. Transgenic mice lacking the cytoplasmic domain (CD248CyD/CyD), CAIA model, ELISA, immunohistochemistry, in vitro fibroblast assays Arthritis and rheumatism High 20722022
2011 The cytoplasmic domain of CD248 facilitates tumor growth via fibroblast-mediated mechanisms: CD248CyD/CyD mice show reduced fibrosarcoma and lung carcinoma growth; CD248CyD/CyD fibroblasts have impaired PDGF-BB-induced migration, reduced MMP-9 activation, and increased expression of tumor suppressor factors (transgelin/SM22α, Hes, Hey1). CD248 cytoplasmic domain-knockout mouse tumor models, conditioned media experiments, fibroblast migration assay, RT-PCR, MMP activity assay BMC cancer Medium 21549007
2008 Endosialin (Tem1) is specifically expressed by tumor-associated myofibroblasts and mural cells (not endothelial cells); siRNA silencing of endosialin in fibroblasts strongly inhibits migration and proliferation. Expression profiling, immunostaining, siRNA knockdown, migration and proliferation assays The American journal of pathology Medium 18187565
2008 Endosialin (Tem1) binds Mac-2 BP/90K via a C-terminal fragment of Mac-2 BP/90K containing collagen and galectin-3 binding sites; this interaction is repulsive in loss-of-function adhesion experiments, with Mac-2 BP/90K-expressing tumor cells repelled from endosialin-expressing fibroblasts. Co-immunoprecipitation, biochemical binding assays, adhesion/loss-of-function experiments FASEB journal Medium 18490383
2017 CD248 directly binds to multimerin-2 (MMRN2) via its C-type lectin domain; the binding of CD248 to MMRN2 occurs on a region distinct from (non-competing with) the CLEC14A/CD93 binding region. Mutation within the C-type lectin domain long-loop region abolishes MMRN2 binding. CLEC14A and CD248 can simultaneously bind MMRN2 at the endothelial-pericyte interface in human pancreatic cancer. Direct binding assays, mutagenesis of C-type lectin domain, simultaneous binding assay, immunofluorescence in tumor tissue Oncogene High 28671670
2012 CD248 negatively regulates bone formation: CD248-/- mice have higher bone mass and superior mechanical properties. Primary osteoblasts from CD248-/- mice show increased mineralization in vitro and increased bone formation in vivo, associated with defective PDGF-BB/PDGFR signal transduction. CD248 knockout mouse, micro-CT, 3-point bending test, primary osteoblast culture, mineralization assay, calcein labeling (mineral apposition rate), PDGF-BB stimulation assay Arthritis and rheumatism High 22674221
2022 CD248 derepresses Wnt/β-catenin signaling in pericytes by interacting with Wnt pathway repressors IGFBP4 and LGALS3BP, leading to upregulation of angiogenic factors OPN and SERPINE1 and enhanced angiogenesis and lung tumor growth. Cd248 knockout mouse orthotopic lung cancer model, co-immunoprecipitation (CD248 with IGFBP4 and LGALS3BP), β-catenin reporter assays, OPN/SERPINE1 rescue experiments, β-catenin inhibitor treatment Cancer research High 35950912
2019 TEM1/CD248 interacts with PDGF receptor α (PDGFRα) by co-immunoprecipitation; TEM1 knockdown suppresses PDGF-BB-induced downstream signaling, migration, adhesion, and proliferation in fibroblasts, and TEM1-deleted mice show attenuated wound healing with reduced fibroblast activation and collagen deposition. Co-immunoprecipitation, shRNA knockdown, in vitro migration/adhesion/proliferation assays, in vivo wound healing model with TEM1-knockout mice, immunofluorescence The Journal of investigative dermatology High 30986375
2014 CD248 is required for PDGFR-β-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 in wild-type mice. CD248 knockout mouse, skeletal muscle functional overload and vasodilator angiogenesis models, imatinib treatment, gene expression assays PloS one Medium 25243742
2011 CD248 expressed on human naive CD8+ T cells (but not mouse CD8+ T cells) suppresses their proliferation: transfection of CD248-negative MOLT-4 cells with CD248 cDNA reduces proliferation, and knockdown of CD248 on naive CD8+ T cells increases proliferation, demonstrating a cell-type-specific quiescence-maintaining function. CD248 cDNA transfection, siRNA knockdown, flow cytometry, proliferation assay Immunology Medium 21466550
2020 CD248 on fibroblasts interacts specifically with galectin-3 on macrophages; this interaction induces CCL17 and CCL22 expression in macrophages, which activates collagen production in myofibroblasts, promoting tissue fibrosis. Cd248-/- mice show attenuated renal and peritoneal fibrosis with decreased macrophage-expressed CCL17/CCL22. Cd248 knockout mouse UUO/peritoneal fibrosis models, parabiosis with GFP reporter mice, CD248-galectin-3 interaction assay, macrophage chemokine expression (Ccl17, Ccl22) in isolated macrophages, galectin-3-deficient macrophages Scientific reports High 33033277
2019 Adipocyte-specific and inducible CD248 knockout in mice results in increased microvascular density and attenuated hypoxia, inflammation, and fibrosis in white adipose tissue, with improvements in insulin sensitivity and glucose tolerance, indicating CD248 acts as a microenvironmental sensor mediating adipose hypoxia response. Adipocyte-specific inducible Cd248 knockout mice (before and after diet-induced obesity), metabolic phenotyping, histology, omics analyses, gene knockdown in human adipocytes EBioMedicine Medium 31221584
2008 Anti-endosialin antibodies inhibit endothelial precursor cell (EPC) migration and tube formation in vitro, and inhibit circulating murine EPC in vivo, indicating a functional role for CD248/TEM1 in EPC-mediated tumor angiogenesis. Anti-endosialin antibody blocking, EPC migration assay, matrigel tube formation assay, flow cytometry, in vivo EPC inhibition assay Molecular cancer therapeutics Low 18723498
2008 Anti-endosialin antibodies prevent pericyte tube formation on matrigel and inhibit pericyte migration in culture, demonstrating a direct functional role for CD248 in pericyte behavior. Anti-endosialin antibody blocking, pericyte tube formation assay, migration assay Microvascular research Low 18761022
2015 CD248 targeting by antibody-mediated internalization (MORAb-004) reduces CD248 levels on pericyte surfaces, impairs pericyte maturation (reduced α-SMA expression, pericyte depolarization), and causes dysfunctional tumor microvessels, suppressing tumor growth and metastasis. Human CD248 knock-in mouse model, MORAb-004 antibody treatment, syngeneic tumor models, immunofluorescence, vessel morphology analysis Oncotarget Medium 26327620
2022 CD248 expressed on cancer-associated fibroblasts (CAFs) promotes CXCL12 secretion; CD248 knockdown on CAFs reduces CXCL12 secretion and M2 macrophage polarization/chemotaxis (blocked by CXCR4 antagonist), thereby impairing NSCLC progression. CAF isolation from NSCLC patients, CD248 siRNA knockdown, CXCL12 ELISA, macrophage co-culture polarization assay, CXCR4 blocking, in vitro and in vivo tumor progression assays Biochimica et biophysica acta. Molecular basis of disease Medium 35985448
2018 CD248 silencing in systemic sclerosis mesenchymal stem cells (SSc-MSCs) inhibits both TGF-β and PDGF-BB signaling pathways, blocking myofibroblast differentiation and proliferation, demonstrating that CD248 modulates both TGFβ and PDGF downstream signaling in stromal cells. CD248 siRNA silencing in SSc-MSCs, TGF-β and PDGF-BB stimulation, Western blotting, qRT-PCR, immunofluorescence Arthritis research & therapy Medium 30285896
2019 CD248 expression in colorectal cancer cells is transcriptionally regulated via Sp1 downstream of TLR2/6 and TLR5 activation through NF-κB; miR-125b-5p suppresses Sp1 and CD248 expression, and CD248 upregulation promotes drug resistance and epithelial-mesenchymal transition. TLR ligand stimulation, NF-κB inhibition, miR-125b-5p mimic transfection, Sp1/CD248 gene silencing, RT-PCR, drug resistance assays, invasion assays Molecular carcinogenesis Medium 31746054
2012 CD248 expression on thymic mesenchymal stromal cells is required for postnatal thymus development and regeneration following Salmonella infection: CD248-/- mice have a hypocellular thymus with loss of all thymocyte populations and impaired regeneration. CD248 knockout mouse model, thymus cellularity analysis, flow cytometry of thymocyte populations, Salmonella infection model FEBS open bio Medium 23650598
2010 CD248 expression on stromal cells is required for efficient lymph node expansion following immunization; in vitro, CD248 expression in stromal cells confers a pro-proliferative and pro-migratory phenotype. CD248 knockout mouse immunization model, LN cellularity analysis, in vitro CD248 transfection with proliferation/migration assays European journal of immunology Medium 20432232

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 631 10219244
1993 Crystal structure of Escherichia coli TEM1 beta-lactamase at 1.8 A resolution. Proteins 343 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 265 15292151
2015 Evolvability as a function of purifying selection in TEM-1 β-lactamase. Cell 214 25723163
2015 Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1. Molecular biology and evolution 187 26446903
2013 Capturing the mutational landscape of the beta-lactamase TEM-1. Proceedings of the National Academy of Sciences of the United States of America 181 23878237
1994 The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. Molecular and cellular biology 161 7935462
2001 The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis. Journal of cell science 152 11257003
2005 Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium. FEBS letters 146 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
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 122 20921316
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
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 97 26004540
2002 Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by Bub2 and Bfa1. The Journal of biological chemistry 94 12048186
2008 Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 88 18192970
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
1996 Systematic mutagenesis of the active site omega loop of TEM-1 beta-lactamase. Journal of bacteriology 86 8606154
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
2013 TEM-1 β-lactamase as a source of resistance to sulbactam in clinical strains of Acinetobacter baumannii. The Journal of antimicrobial chemotherapy 82 23838947
2006 Binding hot spots in the TEM1-BLIP interface in light of its modular architecture. Journal of molecular biology 78 17070843
2015 CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism. Gut 77 26078290
2008 Increased folding stability of TEM-1 beta-lactamase by in vitro selection. Journal of molecular biology 75 18706424
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 62 20722022
2019 CD248: A therapeutic target in cancer and fibrotic diseases. Oncotarget 56 30847027
2001 Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo. The Journal of biological chemistry 56 11489895
2009 Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchange by Tem1. The Journal of cell biology 55 19948498
1997 Cephalosporin substrate specificity determinants of TEM-1 beta-lactamase. The Journal of biological chemistry 54 9360991
2017 Enzyme Efficiency but Not Thermostability Drives Cefotaxime Resistance Evolution in TEM-1 β-Lactamase. Molecular biology and evolution 53 28087769
2012 CD248: reviewing its role in health and disease. Current drug targets 53 22206249
2011 Tem1 localization to the spindle pole bodies is essential for mitotic exit and impairs spindle checkpoint function. The Journal of cell biology 53 21321099
2022 CD248 Regulates Wnt Signaling in Pericytes to Promote Angiogenesis and Tumor Growth in Lung Cancer. Cancer research 52 35950912
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
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
1995 Investigation of the folding pathway of the TEM-1 beta-lactamase. Proteins 51 7567959
2008 Genetic and structural characterization of an L201P global suppressor substitution in TEM-1 beta-lactamase. Journal of molecular biology 50 18822298
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 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 49 35985448
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
1998 The role of residue 238 of TEM-1 beta-lactamase in the hydrolysis of extended-spectrum antibiotics. The Journal of biological chemistry 48 9756899
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
2008 Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248. Molecular cancer therapeutics 45 18723498
2015 Mistranslation drives the evolution of robustness in TEM-1 β-lactamase. Proceedings of the National Academy of Sciences of the United States of America 43 26392536
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
1991 Replacement of lysine 234 affects transition state stabilization in the active site of beta-lactamase TEM1. The Journal of biological chemistry 42 1910040
1996 The rate-limiting step in the folding of the cis-Pro167Thr mutant of TEM-1 beta-lactamase is the trans to cis isomerization of a non-proline peptide bond. Proteins 41 8727322
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
1995 Mechanisms of hyperproduction of TEM-1 beta-lactamase by clinical isolates of Escherichia coli. The Journal of antimicrobial chemotherapy 37 8821592
1997 Kinetic and thermodynamic consequences of the removal of the Cys-77-Cys-123 disulphide bond for the folding of TEM-1 beta-lactamase. The Biochemical journal 36 9020874
2018 Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase. Heredity 35 29967397
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
2000 Overexpression and biosynthetic deuterium enrichment of TEM-1 beta-lactamase for structural characterization by magnetic resonance methods. Protein expression and purification 35 10873536
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
2019 Pervasive Pairwise Intragenic Epistasis among Sequential Mutations in TEM-1 β-Lactamase. Journal of molecular biology 33 30922874
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 31 31034887
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
2020 Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis. Scientific reports 29 33033277
2011 Gene targeting and expression analysis of mouse Tem1/endosialin using a lacZ reporter. Gene expression patterns : GEP 29 21402174
1993 Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 beta-lactamase. Antimicrobial agents and chemotherapy 29 8285630
2020 CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes. BMC pulmonary medicine 28 31964365
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
1998 A collapsed intermediate with nonnative packing of hydrophobic residues in the folding of TEM-1 beta-lactamase. Biochemistry 27 9485321
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 26 38413223
2014 Inactivation of TEM-1 by avibactam (NXL-104): insights from quantum mechanics/molecular mechanics metadynamics simulations. Biochemistry 26 25050826
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
2014 Antibody-based tumor vascular theranostics targeting endosialin/TEM1 in a new mouse tumor vascular model. Cancer biology & therapy 23 24553243
2002 TEM-1 beta-lactamase as a scaffold for protein recognition and assay. Protein science : a publication of the Protein Society 23 12021449
1993 Site-directed mutagenesis of beta-lactamase TEM-1. Investigating the potential role of specific residues on the activity of Pseudomonas-specific enzymes. European journal of biochemistry 23 8223651
1987 Development of natural and synthetic DNA probes for OXA-2 and TEM-1 beta-lactamases. Antimicrobial agents and chemotherapy 23 3038006
2016 Low-stringency selection of TEM1 for BLIP shows interface plasticity and selection for faster binders. Proceedings of the National Academy of Sciences of the United States of America 22 27956635
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
2015 Coupling spindle position with mitotic exit in budding yeast: The multifaceted role of the small GTPase Tem1. Small GTPases 21 26507466
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

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