Affinage

SH3BP2

SH3 domain-binding protein 2 · UniProt P78314

Length
561 aa
Mass
62.2 kDa
Annotated
2026-04-28
50 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SH3BP2 is a multi-domain scaffold/adaptor protein that orchestrates signaling downstream of immune and cytokine receptors to control myeloid cell differentiation, osteoclast function, and inflammatory responses. It assembles signalosomes containing PLCγ1/2, SYK, and VAV2 to activate the PLCγ–calcineurin–NFATc1 transcriptional axis during RANKL- and TNF-α-induced osteoclastogenesis, and its activity is negatively regulated by PKC-dependent phosphorylation that recruits 14-3-3 proteins and by tankyrase-mediated ADP-ribosylation targeting it for proteasomal degradation (PMID:12501243, PMID:18440306, PMID:22153068). Gain-of-function missense mutations in exon 9 cause cherubism, an autosomal dominant disorder of excessive jaw bone resorption: these mutations disrupt tankyrase-dependent degradation, stabilize SH3BP2, and hyperactivate myeloid cells to produce elevated TNF-α and drive RANKL-independent osteoclastogenesis (PMID:11381256, PMID:17218256, PMID:32258251). Loss-of-function studies demonstrate that SH3BP2 is also required for normal osteoblast differentiation, dendritic cell development, and osteoclast resorptive activity via the SH3BP2–SYK axis, and it additionally functions at the neuromuscular junction where it promotes acetylcholine receptor clustering through phase-separation-mediated interactions with the dystrophin-glycoprotein complex (PMID:20117257, PMID:31613396, PMID:33920631).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Identifying SH3BP2 as the cherubism gene established that a signaling adaptor protein could drive a bone-resorptive disease, but left the molecular mechanism entirely open.

    Evidence Positional cloning and sequencing of multiple cherubism families identified seven exon 9 missense mutations

    PMID:11381256

    Open questions at the time
    • Whether mutations were gain-of-function or loss-of-function was unknown
    • No signaling pathway downstream of SH3BP2 had been defined
    • Affected cell type (osteoclast vs. osteoblast vs. other) was unresolved
  2. 2002 High

    Discovery that 14-3-3 proteins bind SH3BP2 in a PKC-phosphorylation-dependent manner and suppress NFAT/AP-1 activity revealed the first negative regulatory mechanism controlling SH3BP2 signaling output.

    Evidence Yeast two-hybrid, co-IP, in vitro PKC kinase assay, phospho-site mutagenesis, and NFAT luciferase reporter in lymphocytes

    PMID:12501243

    Open questions at the time
    • Relationship between 14-3-3 regulation and cherubism mutations was not tested
    • Whether the NFAT pathway was the effector in bone cells remained unclear
  3. 2006 Medium

    Demonstrating that cherubism mutations are gain-of-function alleles that hyperactivate NFAT transcription resolved the basic directionality of disease pathogenesis.

    Evidence NFAT luciferase reporter assays with multiple disease-associated SH3BP2 mutants vs. wild-type

    PMID:16786512

    Open questions at the time
    • Mechanism by which mutations increase NFAT activity was unknown
    • In vivo validation of gain-of-function was lacking
  4. 2007 High

    The P416R knock-in mouse model proved that gain-of-function SH3BP2 drives TNF-α-dependent systemic inflammation and bone loss through hyperactivated myeloid cells with increased ERK1/2 and SYK phosphorylation, establishing the myeloid-intrinsic origin of cherubism.

    Evidence Knock-in mouse, fetal liver transplantation, phospho-Western for ERK1/2 and SYK, osteoclast differentiation, TNF-α measurement

    PMID:17218256

    Open questions at the time
    • Direct biochemical mechanism linking mutation to SYK/ERK hyperactivation was not defined
    • Whether TNF-α was sufficient to drive osteoclastogenesis independently of RANKL was untested
  5. 2008 Medium

    Placing SH3BP2 upstream of PLCγ1/2 phosphorylation and calcineurin–NFATc1 nuclear translocation defined the core signaling cascade through which SH3BP2 promotes osteoclastogenesis.

    Evidence SH3BP2 overexpression in RAW264.7 cells with phospho-PLCγ1/2 Western blotting and NFATc1 nuclear translocation

    PMID:18440306

    Open questions at the time
    • Whether SH3BP2 directly binds PLCγ or acts through intermediaries was unknown
    • Loss-of-function validation was missing
  6. 2010 High

    Convergent studies established that SH3BP2 is required for normal osteoblast function and that cherubism mutations hyperactivate the PLCγ–NFAT axis more potently than wild-type, clarifying that disease involves both osteoclast hyperactivity and osteoblast impairment.

    Evidence Knock-in mouse bone spectroscopy, osteoblast cultures, and mutant vs. wild-type PLCγ phosphorylation/NFAT reporter assays in RAW264.7 cells

    PMID:20117257 PMID:20872577

    Open questions at the time
    • Molecular mechanism of SH3BP2 function in osteoblasts was uncharacterized
    • Whether osteoblast defect is cell-autonomous or secondary to inflammation was unclear
  7. 2011 High

    Discovery that tankyrase ADP-ribosylates SH3BP2 to target it for proteasomal degradation — and that cherubism mutations disrupt this interaction, stabilizing SH3BP2 protein — provided the biochemical explanation for the gain-of-function mechanism.

    Evidence Tankyrase–SH3BP2 interaction studies and degradation assays (described in Cell commentary citing Guettler et al. and Levaot et al.); complemented by SH3BP2 knockout and knockdown showing SH3BP2 is necessary for osteoclast differentiation and resorption

    PMID:21448930 PMID:22153068

    Open questions at the time
    • Structural basis of the tankyrase–SH3BP2 interaction at atomic resolution was not reported in this entry
    • Whether tankyrase inhibitors phenocopy cherubism in bone was untested at this point
  8. 2012 High

    Identification of PARP1 as a transcriptional regulator of SH3BP2 expression added a layer of transcriptional control, showing that PARP1 binds the SH3BP2 promoter and is required for its expression in bone marrow macrophages.

    Evidence Promoter deletion, EMSA, ChIP, Parp1 knockout mouse BMMs, luciferase reporter

    PMID:22820184

    Open questions at the time
    • Whether PARP1-dependent transcription is regulated during osteoclast differentiation was not addressed
    • Relationship between transcriptional and post-translational (tankyrase) regulation was unexplored
  9. 2014 High

    Demonstrating that SH3BP2 gain-of-function enables RANKL-independent, TNF-α-driven osteoclastogenesis through SYK–PLCγ2–NFATc1, and that SH3BP2 gain-of-function worsens inflammatory arthritis in a myeloid-specific manner, unified the TNF-α and RANKL signaling arms of SH3BP2 biology.

    Evidence Knock-in BMM assays with TNF-α, phospho-SYK/PLCγ2, NFATc1 translocation; collagen-induced arthritis model with micro-CT and cytokine profiling

    PMID:24916406 PMID:25144740

    Open questions at the time
    • Direct physical interaction between SH3BP2 and SYK in osteoclasts was not shown by reciprocal co-IP
    • Therapeutic potential of targeting SH3BP2 or SYK in arthritis was not tested
  10. 2018 High

    Extending SH3BP2 function beyond immune/bone cells, SH3BP2 silencing in GISTs downregulated KIT and PDGFRA via MITF, suppressing tumor growth, revealing SH3BP2 as a regulator of receptor tyrosine kinase expression in cancer.

    Evidence siRNA knockdown in GIST cell lines, Western blotting, xenograft model, MITF rescue experiment

    PMID:29885053

    Open questions at the time
    • Mechanism by which SH3BP2 regulates MITF expression or stability was not defined
    • Whether SH3BP2's adaptor function or a transcription-coupled mechanism is responsible was unclear
  11. 2019 High

    Conditional myeloid-specific SH3BP2 and SYK deletion established that the SH3BP2–SYK axis specifically controls osteoclast resorptive activity rather than osteoclast differentiation per se, while pharmacological tankyrase inhibition in vivo confirmed that SH3BP2 protein stabilization drives bone loss.

    Evidence LysM-Cre conditional knockout in periodontitis model, SYK inhibitor, micro-CT; tankyrase inhibitor treatment in mice with SH3BP2 protein measurement

    PMID:30813388 PMID:31613396

    Open questions at the time
    • How SH3BP2–SYK selectively controls resorption without affecting differentiation was mechanistically unexplained
    • Whether tankyrase inhibitor bone effects are entirely SH3BP2-dependent or involve other tankyrase substrates was not resolved
  12. 2021 Medium

    SH3BP2 loss-of-function ameliorated lupus in Fas-mutant mice by suppressing dendritic cell differentiation, expanding the known immune cell types regulated by SH3BP2 beyond macrophages and osteoclasts.

    Evidence Sh3bp2-/- × Fas lupus mouse, flow cytometry of dendritic cells, in vitro DC differentiation, renal histology

    PMID:33920631

    Open questions at the time
    • Signaling pathway by which SH3BP2 controls DC differentiation was not identified
    • Whether SH3BP2's role in DCs is cell-autonomous was not fully resolved
  13. 2024 Medium

    SH3BP2 was shown to form a PLCγ2–VAV2 signalosome in human podocytes driving glomerular disease, to regulate microglial JAK/STAT signaling in neuroinflammation, and to promote neuromuscular junction AChR clustering via phase separation with the dystrophin-glycoprotein complex, greatly expanding SH3BP2's functional repertoire beyond myeloid/bone biology.

    Evidence Co-IP of SH3BP2–PLCγ2–VAV2 in podocytes with KI mouse albuminuria phenotype; shSH3BP2 in SCI rats and BV2 microglia with phospho-JAK/STAT; muscle-specific conditional KO with NMJ imaging, phase separation assay, electrophysiology (preprint)

    PMID:38127456 PMID:39546158 PMID:bio_10.1101_2024.05.23.595491

    Open questions at the time
    • Podocyte signalosome composition beyond PLCγ2 and VAV2 is undefined
    • JAK/STAT pathway regulation by SH3BP2 lacks biochemical mechanism
    • Phase separation at the NMJ is from a preprint and awaits peer review

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SH3BP2 physically connects to SYK and PLCγ at the structural level, how cherubism mutations alter signalosome assembly beyond protein stabilization, and whether therapeutic targeting of the tankyrase–SH3BP2 axis can treat cherubism or inflammatory bone disease remain open questions.
  • No high-resolution structure of SH3BP2 in complex with SYK, PLCγ, or tankyrase has been reported
  • Whether SH3BP2 phase separation is a general mechanism across cell types is untested
  • Therapeutic validation of SH3BP2 pathway inhibition in cherubism patients is absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 3
Partners
MITFPLCG1PLCG2SYKTNKSVAV2YWHAB
Complex memberships
SH3BP2–PLCγ2–VAV2 signalosome

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Missense mutations in SH3BP2 (an SH3-binding adaptor protein with SH2, SH3-binding, and pleckstrin homology domains) cause cherubism, identifying SH3BP2 as the disease gene on chromosome 4p16.3 Direct DNA sequencing of affected families; identification of seven mutations in exon 9 Nature genetics High 11381256
2002 14-3-3 chaperone proteins physically interact with SH3BP2 in a phosphorylation-dependent manner; PKC-mediated phosphorylation of SH3BP2 at Ser225 and Ser277 is required for 14-3-3 binding, and this interaction negatively regulates SH3BP2-dependent NFAT/AP-1 transcriptional activity in lymphocytes Yeast two-hybrid, co-immunoprecipitation, alkaline phosphatase dephosphorylation, in vitro PKC kinase assay, deletion/point mutagenesis, NFAT luciferase reporter assay The Journal of biological chemistry High 12501243
2006 Cherubism-associated exon 9 missense mutations in SH3BP2 (R415Q, D419N, D420E, P418R) are gain-of-function mutations that increase NFAT transcriptional activity, indicating that cherubism results from gain-of-function SH3BP2 mutations acting through NFAT activation Transient transfection of mutant SH3BP2 constructs in cells with NFAT luciferase reporter assay Human mutation Medium 16786512
2007 SH3BP2 cherubism knock-in mice (P416R) exhibit TNF-α-dependent systemic inflammation and bone loss; mutant myeloid cells show increased ERK1/2 and SYK phosphorylation/activation upon M-CSF and RANKL stimulation, forming macrophages with elevated TNF-α and unusually large osteoclasts; the phenotype is lymphocyte-independent and transferable via fetal liver cells, establishing SH3BP2 as a gain-of-function regulator of myeloid cell responses Knock-in mouse model, bone marrow/fetal liver transplantation, phospho-Western blotting (ERK1/2, SYK), osteoclast differentiation assays, TNF-α measurement, M-CSF/RANKL stimulation experiments Cell High 17218256
2008 SH3BP2 overexpression in RAW 264.7 pre-osteoclast cells increases nuclear NFATc1 translocation, TRAP expression, and potentiates sRANKL-stimulated phosphorylation of PLCγ1 and PLCγ2, placing SH3BP2 upstream of PLCγ-calcineurin-NFATc1 in RANKL-induced osteoclastogenesis Overexpression of SH3BP2 in RAW264.7 cells, Western blotting for phospho-PLCγ1/2 and nuclear NFATc1, TRAP staining as osteoclast differentiation marker Biochemical and biophysical research communications Medium 18440306
2010 Mutant SH3BP2 (cherubism mutations) stimulates RANKL-induced PLCγ1/2 phosphorylation more potently than wild-type SH3BP2, resulting in greater NFAT activity and TRAP expression; gain-of-function mechanism operates through the PLCγ-calcineurin-NFAT axis Transfection of wild-type vs. mutant SH3BP2 in RAW264.7 cells, NFAT-luciferase reporter assay, phospho-PLCγ Western blotting, TRAP assay Journal of orthopaedic research Medium 20872577
2010 SH3BP2 is required for normal osteoblast differentiation and function; the P416R cherubism knock-in mutation reduces mature osteoblast numbers, decreases mineral content and crystallinity in bone, and impairs osteoblast-specific gene expression and mineralization in calvarial cultures Knock-in mouse model, FTIRI spectroscopy of bone, GFP-reporter transgenic cross for osteoblast counting, hematopoietic cell-depleted calvarial osteoblast cultures, gene expression analysis, co-culture osteoclastogenesis assay Bone High 20117257
2011 shRNA knockdown of SH3BP2 decreases PLCγ2 phosphorylation and NFATc1 expression, reduces osteoclast number, size, and TRAP staining, and dramatically blocks bone resorptive activity; Sh3bp2-/- BMMs form smaller osteoclasts with reduced TRAP staining, demonstrating SH3BP2 is necessary for osteoclast differentiation and function shRNA knockdown in RAW264.7 cells and BMMs, phospho-PLCγ2 Western blotting, NFATc1 expression analysis, TRAP staining, bone resorption pit assay, Sh3bp2-/- mouse BMM cultures Journal of orthopaedic research High 21448930
2011 Tankyrase (PARP5) interacts with SH3BP2 and marks it for degradation; cherubism mutations in SH3BP2 disrupt the tankyrase-SH3BP2 interaction, leading to SH3BP2 stabilization (gain-of-function) Referenced as described in Guettler et al. and Levaot et al. in the same Cell issue (commentary paper) Cell Medium 22153068
2012 PARP1 binds to a specific element (-44 to -21) in the SH3BP2 promoter and is required for SH3BP2 transcriptional expression; mutagenesis of the PARP1 binding site abolishes SH3BP2 promoter activity, and Parp1 knockout reduces SH3BP2 expression in BMMs Promoter deletion analysis, streptavidin-biotin DNA pulldown, EMSA, ChIP assay, Parp1 knockout mouse BMMs, luciferase reporter Biochemical and biophysical research communications High 22820184
2014 The P416R SH3BP2 cherubism mutation enables TNF-α-induced osteoclastogenesis independently of RANKL, through a mechanism involving SYK and PLCγ2 phosphorylation leading to increased NFATc1 nuclear translocation; SH3BP2 knockdown in RAW264.7 cells reduces TNF-α-induced osteoclastogenesis BMM differentiation assays from heterozygous knock-in mice with TNF-α, phospho-SYK/PLCγ2 Western blotting, NFATc1 nuclear translocation assay, calvarial TNF-α injection model, human TNF-α transgenic mouse model, shRNA knockdown Journal of bone and mineral research High 24916406
2014 SH3BP2 gain-of-function (P416R) augments inflammation and bone loss in collagen-induced arthritis through increased macrophage TNF-α production and enhanced RANKL-induced osteoclastogenesis with increased NFATc1 nuclear localization; lymphocyte responses are not significantly affected CIA model in Sh3bp2 KI/+ mice, histological joint analysis, micro-CT bone loss quantification, cytokine gene expression, BMM TNF-α production, NFATc1 immunostaining, lymph node proliferation assay, serum antibody measurement PloS one High 25144740
2019 Tankyrase (PARP5) catalyzes ADP-ribosylation of SH3BP2 targeting it for proteasomal degradation; pharmacological tankyrase inhibition in mice causes SH3BP2 accumulation leading to increased osteoclast formation and bone loss Tankyrase inhibitor treatment in mice, bone phenotype analysis, SH3BP2 protein level measurement (reviewed mechanistic pathway) Cells Medium 30813388
2019 SH3BP2-SYK signaling axis in osteoclasts controls alveolar bone resorption function (rather than osteoclast differentiation) in periodontitis; conditional knockout of SH3BP2 and SYK in myeloid cells (LysM-Cre) reduces alveolar bone loss without affecting inflammatory cytokine expression or osteoclast number Sh3bp2-/- mouse ligature-induced periodontitis model, micro-CT bone loss analysis, conditional myeloid-specific knockout (LysM-Cre), SYK inhibitor (GS-9973) treatment, in vitro mineral resorption assay Journal of bone and mineral research High 31613396
2019 SH3BP2 gain-of-function (P416R) mutation in a lupus-prone model increases TNF-α and cleaved caspase-3 in lymph nodes, reducing the B220+CD4-CD8- T cell population associated with lupus, suggesting SH3BP2 modulates lymphocyte apoptosis in autoimmune contexts Double-mutant mouse model (Sh3bp2 KI x B6.MRL-Fas), flow cytometry of lymphocyte subsets, caspase-3 immunostaining, survival and proteinuria monitoring Cells Medium 31052273
2020 SH3BP2 gain-of-function (homozygous P416R) drives RANKL-independent osteoclastogenesis in vivo; Sh3bp2 KI/KI Rankl-/- mice develop TRAP-positive, cathepsin K-positive multinucleated osteoclasts spontaneously, with elevated serum TNF-α suggesting TNF-α drives RANKL-independent osteoclast formation downstream of SH3BP2 Double-mutant mouse model (Sh3bp2 KI/KI × Rankl-/-), TRAP and cathepsin K staining, osteoclast marker gene expression in bone, serum TRAP5b and TNF-α measurement, micro-CT bone volume analysis Bone reports High 32258251
2021 SH3BP2 deficiency in a lupus-prone (Fas-mutant) model ameliorates lupus-like manifestations and suppresses dendritic cell differentiation in vitro and in vivo, without substantially affecting T cell or macrophage function, placing SH3BP2 as a regulator of dendritic cell development in autoimmunity SH3BP2-deficient lupus mouse model (Sh3bp2-/- x Fas mice), B cell-specific knockout, flow cytometry of lymphocyte/dendritic cell subsets, in vitro dendritic cell differentiation, serum anti-dsDNA antibody, renal histology International journal of molecular sciences Medium 33920631
2018 SH3BP2 regulates KIT and PDGFRA receptor expression in gastrointestinal stromal tumors (GISTs) through the microphthalmia-associated transcription factor (MITF); SH3BP2 silencing downregulates KIT, PDGFRA, and MITF, increases apoptosis, reduces cell migration, and suppresses tumor growth in vivo; reconstitution of both SH3BP2 and MITF restores cell viability siRNA silencing of SH3BP2 in GIST cell lines, Western blotting for KIT/PDGFRA/MITF, apoptosis assay, cell migration assay, xenograft tumor growth in vivo, MITF rescue experiment Molecular oncology High 29885053
2024 SH3BP2 forms a signalosome complex with PLCγ2 and VAV2 in human podocytes (demonstrated by co-immunoprecipitation), and this complex is upregulated in minimal change disease and focal segmental glomerulosclerosis; Sh3bp2 KI/KI transgenic mice develop albuminuria and foot process fusion, indicating SH3BP2 signalosome drives immune activation leading to glomerular barrier dysfunction Co-immunoprecipitation of SH3BP2 with PLCγ2 and VAV2 in human podocytes, transcriptomic analysis of human glomeruli (Nephrotic Syndrome Study Network), Sh3bp2 KI/KI transgenic mouse phenotyping (albuminuria, electron microscopy, histology) JCI insight Medium 38127456
2024 SH3BP2 silencing in a spinal cord injury model inhibits microglial activation and neuroinflammation by decreasing JAK and STAT phosphorylation, placing SH3BP2 upstream of the JAK/STAT signaling pathway in microglia Lentiviral shSH3BP2 injection in SCI rats, LPS-induced BV2 microglia model, phospho-JAK/STAT Western blotting, BBB scoring, immunofluorescence, KEGG pathway analysis Inflammation Medium 39546158
2024 SH3BP2 acts as a scaffold protein at the neuromuscular junction, exhibiting polyvalent interactions with the dystrophin-glycoprotein complex (DGC) and acetylcholine receptor (AChR) pentamers to promote AChR clustering through phase separation; muscle-specific SH3BP2 deletion impairs NMJ organization, synaptic transmission, and muscle strength Muscle-specific conditional knockout mouse, neuromuscular junction imaging, AChR clustering assay, phase separation assay, protein-protein interaction studies (DGC and AChR binding), electrophysiology of synaptic transmission, grip strength measurement bioRxivpreprint Medium bio_10.1101_2024.05.23.595491

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nature genetics 276 11381256
2007 Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell 149 17218256
2012 The role of SH3BP2 in the pathophysiology of cherubism. Orphanet journal of rare diseases 73 22640988
2014 SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 53 24916406
2002 The chaperone protein 14-3-3 interacts with 3BP2/SH3BP2 and regulates its adapter function. The Journal of biological chemistry 46 12501243
2003 Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. American journal of medical genetics. Part A 40 12900899
2003 A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 39 14577811
2006 Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation. Human mutation 35 16786512
1997 Identification and characterization of the human homologue of SH3BP2, an SH3 binding domain protein within a common region of deletion at 4p16.3 involved in bladder cancer. Genomics 34 9299232
2008 SH3BP2 is an activator of NFAT activity and osteoclastogenesis. Biochemical and biophysical research communications 30 18440306
2007 Mutations in SH3BP2, the cherubism gene, were not detected in central or peripheral giant cell tumours of the jaw. The British journal of oral & maxillofacial surgery 30 17544554
2019 Tankyrase (PARP5) Inhibition Induces Bone Loss through Accumulation of Its Substrate SH3BP2. Cells 29 30813388
2008 Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism. Oral diseases 29 19017279
2014 Etanercept administration to neonatal SH3BP2 knock-in cherubism mice prevents TNF-α-induced inflammation and bone loss. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 27 24978678
2006 A novel mutation in the SH3BP2 gene causes cherubism: case report. BMC medical genetics 26 17147794
2006 DNA analysis of the SH3BP2 gene in patients with aggressive central giant cell granuloma. The British journal of oral & maxillofacial surgery 22 16713042
2014 SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collagen-induced arthritis model. PloS one 21 25144740
2007 A novel mutation of the SH3BP2 gene in an aggressive case of cherubism. Oral oncology 17 17368082
2019 Alveolar Bone Protection by Targeting the SH3BP2-SYK Axis in Osteoclasts. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 31613396
2010 Pro416Arg cherubism mutation in Sh3bp2 knock-in mice affects osteoblasts and alters bone mineral and matrix properties. Bone 15 20117257
2007 SH3BP2 is rarely mutated in exon 9 in giant cell lesions outside cherubism. Clinical orthopaedics and related research 14 17545756
2019 Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Fas Mice. Cells 13 31052273
2010 Cherubism gene Sh3bp2 is important for optimal bone formation, osteoblast differentiation, and function. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 13 20691350
2018 Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth. Molecular oncology 12 29885053
2011 SH3BP2-encoding exons involved in cherubism are not associated with central giant cell granuloma. International journal of oral and maxillofacial surgery 11 21680150
2010 Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter - Case Report. Molecular syndromology 11 21045962
2021 SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus. International journal of molecular sciences 10 33920631
2008 Investigation of the SH3BP2 gene mutation in cherubism. Acta medica Okayama 10 18596838
2020 RANKL-independent osteoclastogenesis in the SH3BP2 cherubism mice. Bone reports 8 32258251
2010 SH3BP2 mutations potentiate osteoclastogenesis via PLCγ. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 8 20872577
2021 SH3BP2-related fibro-osseous disorders of the maxilla and mandible: A systematic review. International journal of oral and maxillofacial surgery 6 33941395
2012 A novel c.1255G>T (p.D419Y) mutation in SH3BP2 gene causes cherubism in a Turkish family. Oral surgery, oral medicine, oral pathology and oral radiology 6 23083484
2011 Tankyrase loses its grip on SH3BP2 in cherubism. Cell 6 22153068
2024 Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome. JCI insight 5 38127456
2022 SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors. Cancers 5 36551682
2021 Tlr2/4-Mediated Hyperinflammation Promotes Cherubism-Like Jawbone Expansion in Sh3bp2 (P416R) Knockin Mice. JBMR plus 5 35079675
2014 Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice. Bone 5 25445458
2012 Mutations of the SH3BP2 gene in 2 families of cherubism. Pediatric dentistry 5 22795151
2022 Overexpression of DEL-1 Downregulates SH3BP2 Expression and Inhibits Porphyromonas gingivalis-induced Gingival Inflammation In Vivo and In Vitro. Oral health & preventive dentistry 4 35481344
2014 A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature. Medicina oral, patologia oral y cirugia bucal 4 24608212
2013 Novel nucleotide mutation leading to a recurrent amino acid alteration in SH3BP2 in a patient with cherubism. Congenital anomalies 4 24712477
2012 Cloning and characterization of the human SH3BP2 promoter. Biochemical and biophysical research communications 3 22820184
2011 Decreased SH3BP2 inhibits osteoclast differentiation and function. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 3 21448930
2024 Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models. Inflammation 2 39546158
2006 [Mutation detection in SH3BP2 gene in a cherubism family]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 2 16836910
2024 Emerging Role of SH3BP2 as Regulator of Immune and Nonimmune Cells in Nephrotic Syndrome. Glomerular diseases 1 39991193
2008 SH3BP2 is a critical regulator of macrophage and osteoclast response to M-CSF and RANKL stimulation. HSS journal : the musculoskeletal journal of Hospital for Special Surgery 1 18953613
2026 Paeoniflorin Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by SYK/SH3BP2 Signaling Pathway. Research (Washington, D.C.) 0 41635508
2025 Comparative analysis of osteoclast function in symptomatic and asymptomatic individuals with cherubism-causing SH3BP2 mutation. JBMR plus 0 41019663
2009 [Gene mutation and expression of SH-3BP-2 in cherubism]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 0 19576004