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FLASH GENE
Symbol SH3BP2 contributors: mct/npt - updated : 04-11-2015
HGNC name SH3-domain binding protein 2
HGNC id 10825
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrinepancreas    
Lymphoid/Immunespleen   highly
Nervousbrain    
 nerve   highly
Respiratorylung    
 respiratory tractlarynx   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly Homo sapiens
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte Homo sapiens
not specificmast cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal pleckstrin homology (PH) domain
  • a ten AA SH3 binding domain
  • three modular pepetide recognition domains
  • a proline-rich stretch that binds to Src homology (SH) 3 domain-containing proteins
  • a C terminal SH2 domain
  • HOMOLOGY
    interspecies homolog to murine Sh3bp2
    Homologene
    FAMILY
    CATEGORY adaptor , regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    text
  • cytoplasmic adaptor protein mainly expressed by hematopoietic cells
  • basic FUNCTION
  • involved in setting tresholds for the increased osteoclast and osteoblast activities essential for normal tooth eruption
  • participates in a phosphatidyl-inositol specific phospholipase C (PI-PLC), inositol phosphate-3 receptor (IP3R), and calcineurin dependent signaling cascade that activates calcineurin-induced nuclear translocation of NFATC1, leading to increased differentiation of TRAP-positive osteoclastic cells
  • regulates immune receptor-mediated signal transduction
  • role for the SH3BP2 adapter protein in osteoblast function and in coordinating bone homeostatic signals in both osteoclast and osteoblast lineages
  • is required for G protein-coupled receptor-mediated neutrophil functions
  • obligate requirement for SH3BP2 in G protein-coupled receptor-mediated neutrophil function
  • plays a role in osteoclastogenesis
  • is an important regulator of cytotoxic granule release in NK cells
  • by participating in FCER1A- mediated signal transduction SH3BP2 is an important regulator of human mast cells activation
  • playing an unexpected role in endocytic and cytoskeletal regulation through its interaction with SH3KBP1 and DBNL
  • SH3BP2 is a key regulator for TNF-induced osteoclastogenesis
  • cytoplasmic adaptor protein that acts as a positive regulator in mast cell FCER1A-dependent signaling
  • regulates human mast cells (huMCs) survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SH3 binding with ABL oncogene (negative regulation of ABL)
  • induces the protein complex with cellular signaling molecules through phosphorylation of Tyr(183) and SH2 domain leading to the activation of NFATC1 in B cells
  • PTPN6 inducibly interacts with the SH2 domain of SH3BP2 after the aggregation of FCER1A (directly interacts with Tyr(564) -phosphorylated form of PTPN6 and positively regulates the function of PTPN6 in FCER1A-mediated signaling in mast cells)
  • TNKS regulates SH3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts
  • endogenous SH3BP2 ubiquitylation is stimulated by TNKS2 and requires PARP activity
  • RNF146 is the functional E3-ligase controlling SH3BP2 protein levels
  • PARP1 can interact with a cis-DNA element in the SH3BP2 promoter/regulatory region and regulates the expression of SH3BP2
  • cell & other
    REGULATION
    Other PARP1 regulates expression of SH3BP2
    ASSOCIATED DISORDERS
    corresponding disease(s) CRBM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in bladder carcinoma
    constitutional     --over  
    was sufficient to induce osteoclast formation (even in the absence of RANKL) and elevated TNF secretion in macrophages, two critical features of the cherubism phenotype
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    therapeutic target in mast cell-mediated inflammatory diseases and deregulated KIT disorders
    osteoarticularbone 
    is a potential target for suppression of pathologic bone resorption
    ANIMAL & CELL MODELS
  • Sh3bp2-/- mice developed osteoporosis as a result of reduced bone formation despite the fact that bone resorption was impaired