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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
    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
    Physical map
    FAM3B 21q22.3 family with sequence similarity 3, member B MX2 21q22.3 myxovirus (influenza virus) resistance 2 (mouse) MX1 21q22.3 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse) TMPRSS2 21q22.3 transmembrane protease, serine 2 C21orf129 21q22.3 chromosome 21 open reading frame 129 ANKRD3 21q22.3 ankyrin repeat domain 3 PRDM15 21q22.3 PR domain containing 15 LOC388827 21 similar to ZNF298 C21orf25 21q22.3 chromosome 21 open reading frame 25 LOC388828 21 similar to C21orf258 ZNF295 21q22.3 zinc finger protein 295 C21orf121 21 chromosome 21 open reading frame 121 C21orf128 21q22.3 chromosome 21 open reading frame 128 FLJ36335 21q22.3 hypothetical protein FLJ36335 ABCG1 21q22.3 ATP-binding cassette, sub-family G (WHITE), member 1 TFF3 21q22.3 trefoil factor 3 (intestinal) TFF2 21q22.3 trefoil factor 2 (spasmolytic protein 1) TFF1 21q22.3 trefoil factor 1 (breast cancer, estrogen-inducible sequence expressed in) TMPRSS3 21q22.3 transmembrane protease, serine 3 UBASH3A 21q22.3 ubiquitin associated and SH3 domain containing, A TSGA2 21q22.3 testes specific A2 homolog (mouse) SLC37A1 21q22.3 solute carrier family 37 (glycerol-3-phosphate transporter), member 1 PDE9A 21q22.3 phosphodiesterase 9A WDR4 21q22.3 WD repeat domain 4 NDUFV3 21q22.3 NADH dehydrogenase (ubiquinone) flavoprotein 3, 10kDa PKNOX1 21q22.3 PBX/knotted 1 homeobox 1 CBS 21q22.3 cystathionine-beta-synthase U2AF1 21q22.3 U2(RNU2) small nuclear RNA auxillary factor 1 MRPL51P2 21q22.3 U2(RNU2) small nuclear RNA auxillary factor 1 LOC388829 21 LOC388829 CRYAA 21q22.3 crystallin, alpha A SNF1LK 21q22.3 SNF1-like kinase C21orf125 21 chromosome 21 open reading frame 125 C21orf84 21q22.1 chromosome 21 open reading frame 84
    regionally located in the DFNB10 region, but not mutated
    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
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen     Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Connectivebone    Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • 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
    FAMILY TULA family
    CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    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
    a component
    small molecule
  • 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
    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
    Therapy target
  • Ubash3a/Ubash3b-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity