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Symbol TSC22D3 contributors: mct/npt/pgu - updated : 17-01-2014
HGNC name TSC22 domain family, member 3
HGNC id 3051
Location Xq22.3      Physical location : 106.956.459 - 107.019.017
Synonym name
  • transforming growth factor (TGF)-beta-stimulated clone 22 domain 3
  • delta sleep inducing peptide, immunoreactor
  • glucocorticoid-induced leucine zipper protein
  • Synonym symbol(s) DIP, GILZ, DSIPI, TSC-22R, DKFZp313A1123, GILZ1, L-GILZ
    TYPE functioning gene
    STRUCTURE 64.11 kb     2 Exon(s)
    regulatory sequence Promoter
    text structure FOXO3 (Forkhead box class O3) binding to the Forkhead responsive elements identified in the promoter is necessary for induction of TSC22D3 expression upon IL-2 withdrawal.
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2228 29.2 270 . in skeletal muscle tissue and in myoblasts, highly expressed in spermatogonia and primary spermatocytes 2010 20124407
  • Long GILZ
  • characterized by a non-AUG translational start codon
  • only isoform expressed in testis, and controls spermatogenesis
  • 3 - 2312 22.2 200 - 2010 20124407
    2 splicing 1986 14 134 - 2010 20124407
  • having a different 5' end exon compared to transcript variant 1
  • 3 splicing 1781 - 77 - 2010 20124407
  • differing in the 5' UTR and the 5' coding region compared to variant 1
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   moderately
     thymus   predominantly
    Reproductivemale systemtestis  moderately Homo sapiens
    Visualeye   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Muscularstriatumskeletal highly
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    Reproductivespermatocyte Homo sapiens
    Reproductivespermatogonia Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    Text expressed during myoblast differentiation, at a time when myotube formation became evident
  • a leucine-zipper involved in homodimerization
  • a C-terminal proline-rich and acidic region
  • an N-glycosylation site
  • several sites for threonine and serine phosphorylation
  • mono polymer homomer , monomer , dimer
    interspecies ortholog to rattus Dsipi
    ortholog to murine Tsc22d3
  • TSC-22/Dip/Bun family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes
  • basic FUNCTION
  • being a candidate for a mediator of glucocorticoid-induced immunosuppression
  • can inhibit a variety of activation-induced events
  • protecting T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3 transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11
  • in macrophages, playing a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10
  • in T-cells, inhibiting anti-CD3-induced NFKB1 nuclear translocation
  • inhibits peroxisome proliferator-activated receptor gamma-2 (PPARG2) expression and blocks adipocyte differentiation
  • functioning as a modulator of mesenchymal stem cells and overexpression of TSC22D3 shifts the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells toward the osteogenic pathway
  • with L-GILZ behave as modulators of myogenic differentiation, being able to inhibit myogenesis and to dampen the expression of differentiation markers such as MYHC and myogenin
  • involved in the regulation of myogenesis and mediate glucocorticoids-induced anti-myogenic activity
  • general inhibitor of FOXO factors acting through an original mechanism by preventing them from reaching target genes within the nucleus
  • aldosterone-induced chaperone, inhibiting SGK1 ubiquitinylation and subsequent proteasome-mediated degradation, thereby prolonging its half-life and increasing its steady-state expression
  • key role in controlling SGK1 protein stability and availability in specific subcellular compartments, thus selectively enhancing its regulation of a particular end point, in this case, Na+ transport
  • is a novel important factor for undifferentiated spermatogonia function and spermatogenesis
  • acts as an inhibitor of undifferentiated spermatogonia proliferation
  • its overexpression antagonized the inhibitory effects of TNF on mesenchymal stem cell osteogenic differentiation and the mRNA and protein expression of SP7 and RUNX2, two pivotal osteogenic regulators
  • essential role in mediating spermatogonial survival and spermatogenesis
  • role in maintenance of the male germline and spermatogenesis
  • anti-inflammatory protein first identified in T lymphocytes
  • its overexpression inhibits endothelial cell adhesive function through regulation of NFKB and MAPK activity
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription, regulation
    a component
    small molecule
  • AP1
  • NFKB1
  • interacting with ANXA1 (TSC22D3 is a previously unrecognized mechanism of the anti-inflammatory effects of ANXA1)
  • bind and regulate MYOD1/HDAC1 transcriptional activity, thus mediating the anti-myogenic effect of glucocorticoids
  • binds RAS and inhibits RAS-dependent cell proliferation
  • interacting with SGK1 (TSC22D3 and SGK1 synergize to markedly stimulate SCNN1A surface expression, by antagonizing the effects of the inhibitory components)
  • is a GC effecter and mediates GC anti-inflammatory activity
  • can suppress FOXO1 nuclear translocation, promotes Spermatogonia stem cell (SSC) differentiation over self-renewal, and favours germ cell survival through inhibition of BIM-dependent pro-apoptotic signals
  • FKBP5 acts as an important regulator of glucocorticoid receptor (GR) activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while TSC22D3 mediates glucocorticoid anti-inflammatory effects
  • cell & other
    induced by glucocorticoids in lymphoid cells and monocyte/macrophage cells
    IL4 treatment in monocyte/macrophage cells
    IL10 treatment in monocyte/macrophage cells
    IL13 treatment in monocyte/macrophage cells
    IL2 deprivation in T-cells
    upon IL-2 withdrawal that protects T cells from the onset of apoptosis
    by estrogen which is important for bone homeostasis, and by sonic hedgehog (SHH) a morphogen that plays a critical role in embryogenesis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in synovial endothelial cells in rheumatoid arthritis
    Variant & Polymorphism
    Candidate gene
    Therapy target
    absence of TSC22D3/L-GILZ in skeletal muscle tissue enhances muscle regeneration and glucocorticoids might be more effective in the symptomatic treatment of dystrophy
    Induction of GILZ expression in endothelial cells may represent a novel therapeutic modality with the potential to inhibit inflammatory leukocyte recruitment
    possible target for novel therapies to intervene in male sterility
  • Tsc22d3-2-deficient mice demonstrated a previously uncharacterized function of glucocorticoid-induced leucine zipper protein in testis development