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FLASH GENE
Symbol UBASH3A contributors: mct - updated : 10-07-2018
HGNC name ubiquitin associated and SH3 domain containing, A
HGNC id 12462
Location 21q22.3      Physical location : 43.824.018 - 43.867.772
Synonym name
  • gene similar to UBA containing SH3 domain
  • Cbl-interacting protein 4
  • T-cell ubiquitin ligand protein
  • Suppressor of TCR Signaling protein 2
  • Synonym symbol(s) STS-2, TULA, CLIP4, TULA-1
    DNA
    TYPE functioning gene
    STRUCTURE 43.82 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - TMPRSS3- UBASH3A - TSGA2 - qter
    regionally located in the DFNB10 region, but not mutated
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2492 74.1 661 - 2001 11281453
    14 - 2378 69.7 623 - 2001 11281453
    12 - 2225 - 526 - 2001 11281453
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Connectivebone    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal ubiquitin associated domain (UBA)
  • a central SH3 domain
  • a domain of homology to hypothetical proteins from C elegans and Drosophila (HCD)
  • a nuclear localization signal (NLS)
  • C-terminal domain has homology to the 2H-phosphatase family of enzymes , C-terminal histidine phosphatase domain capable of dephosphorylating phosphotyrosine-containing substrates
  • HOMOLOGY
    Homologene
    FAMILY TULA family
    CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • inhibits both clathrin-dependent and clathrin-independent endocytic pathways by functionally sequestering dynamin via the SH3 domain of UBASH3A binding proline-rich sequences in dynamin
  • facilitates T-cell apoptosis independent of either T-cell receptor/CD3-mediated signaling or caspase activity
  • implicated in the regulation of signaling mediated by protein tyrosine kinases (PTKs)
  • with UBASH3B, may exert opposite effects on PTK-mediated signaling
  • function as critical negative regulators of TCR signaling
  • instrumental in down-modulating proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination
  • its phosphatase activity is key for its ability to negatively regulate the signaling of membrane-bound receptors including TCR and the epidermal growth factor receptor (EGFR)
  • might function as an acid-dependent phosphatase
  • UBASH3A, UBASH3B function as critical negative regulators of TCR signaling
  • suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis
  • UBASH3A can be considered as a common genetic factor in autoimmune diseases
  • suppress T-cell-driven inflammatory responses
  • may involve in the pathogenesis of Systemic Lupus Erythematosus (SLE)
  • pivotal role of UBASH3A/UBASH3B in regulating hematopoietic stem and progenitor cell fitness
  • UBASH3A attenuates the NFKB1 signal transduction upon T-cell receptor (TCR) stimulation by specifically suppressing the activation of the IKB kinase complex
  • is a negative regulator of NFKB1 signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associated with CBL and ubiquitylated proteins and has been implicated in the regulation of signaling mediated by protein-tyrosine kinases
  • binds to the apoptosis-inducing protein AIFM1, previously shown to function as a key factor of caspase-independent apoptosis
  • bind to ABCE1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion
  • regulates the level of tyrosine phosphorylation on targets within T cells, among them the critical T cell tyrosine kinase ZAP70
  • interactions of UBASH3A with nondegradative polyubiquitin chains, NR2C2 and IKBKG, suggesting that UBASH3A regulates the NFKB1 signaling pathway by an ubiquitin-dependent mechanism
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to type 1 diabetes
    Variant & Polymorphism SNP
  • role for rs1893592 in T1D and its minor allele protects against T1D
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Ubash3a/Ubash3b-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity