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FLASH GENE
Symbol TRIM33 contributors: mct/npt/pgu - updated : 17-05-2019
HGNC name tripartite motif-containing 33
HGNC id 16290
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an N-terminal RING zinc finger domain
  • two zinc binding B-box (one type 1 and one type 2) domains
  • an alpha-helical coiled-coil domain (RBCC) so called tripartite motif (TRIM)
  • a PHD (plant homeodomain) motif, involved in ability to ubiquitinate its substrate SMAD4
  • a C-terminal bromodomain
    • conjugated PhosphoP
    mono polymer homomer , heteromer , trimer , oligo
    HOMOLOGY
    interspecies ortholog to rattus Trim33 (97.1pc)
    ortholog to murine Trim33 (96.3pc)
    intraspecies paralog to TIF1
    paralog to TRIM28
    Homologene
    FAMILY
  • B-box family
  • transcriptional coregulator-encoding genes family
  • C-VI TRIM family
    • CATEGORY enzyme , regulatory , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • possible involvement of Tif1gamma in the control of embryonic development and spermatogenesis
  • acting as a transcriptional repressor (inhibiting the transcriptional response to TGF-beta/BMP signaling cascade)
  • acting as an E3 ubiquitin-protein ligase
  • potentially critical for tumor suppression in the pancreas
  • playing a role in the control of cell proliferation
  • stimulating erythroid differentiation of hematopoietic stem/progenitor, by association with SMAD2 and SMAD3
  • nuclear factor having a prominent role as SMAD4 monoubiquitin ligase
  • acts on the TGFB pathway either as a monoubiquitin ligase for SMAD4 and/or as a cofactor for phosphorylated SMAD2/3
  • TRIM33-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing
  • direct role in TGFB-dependent gene expression
  • TRIM33 is essential for the terminal differentiation of mammary alveolar epithelial cells and for lactation through SMAD4 inhibition
  • contributes to the repression of TGFB1 activity during late pregnancy and prevents lactation by inhibiting SMAD4
  • requires sumoylation to exert its repressive activity on TGFB1 signaling
  • TRIM33 plays a role in PARP-dependent DNA damage response and regulates CHD1L activity by promoting its timely removal from sites of DNA damage
  • is a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear CTNNB1
  • switches off IFNB1 gene transcription during the late phase of macrophage activation
  • is an important transcriptional actor of monocyte/macrophage mediated inflammation
  • essential for the navigation of macrophages and neutrophils towards developmental or inflammatory cues within vertebrate tissues
  • TRIM33 is required for appropriate differentiation of precardiogenic mesoderm during late gastrulation
    • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text transcriptional corepressor
    PATHWAY
    metabolism
    signaling
    a component
  • heterooligomer with TRIM24 and TRIM28 family members
  • found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta
  • TRIM24 exists in a major complex with TRIM33 and a lesser abundant complex with TRIM33 and TRIM28
    • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • interacting with SMAD4 in unstimulated cells
  • interacting with SMAD2 and SMAD3
  • inhibiting SMAD4 responses and binds phospho-SMAD2
  • with USPX act as antagonistic SMAD4 regulator during embryonic development
  • acting as SMAD4 monoubiquitin ligase
  • regulation of adult hematopoiesis through TRIM33-mediated transcriptional repression of TAL1 and SPI1 target genes
  • cooperative action of TRIM24 and TRIM33 in tumor suppression
  • molecular relationship between TRIM33 and SMAD4 in TGFB signalling and epithelial-to-mesenchymal transition
  • contributes to the repression of TGFB1 activity during late pregnancy and prevents lactation by inhibiting SMAD4
  • controls TGFBR1 turnover and promotes physiological aging of hematopoietic stem cells
  • ubiquitination of DHX33 by TRIM33 is lysine 63 specific and is required for the formation of the DHX33-NLRP3 inflammasome complex
  • TRIM33 inhibited TGFB1-induced EMT through competing with SMAD4 in in non-small-cell lung cancer (NSCLC) cells
  • macrophage-specific regulation of IFNB1 transcription whereby TRIM33 is critical for IFNB1 gene transcription shutdown
  • TRIM33 can be a positive target of osteoblast proliferation and differentiation through BMP pathway
  • modulator of TGFB1 signaling that associates with SMAD2, and regulates the proinflammatory function of Th17 cell
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    chimeric protein 5' - RET - TRIM33 - 3' in thyroid nodules
    tumoral       loss of function
    leads to the expansion of a subset of myeloid cells characterizing the myelodysplastic/myeloproliferative neoplasm
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in the mouse embryos a low level of ubiquitous expression at midgestation, and higher expression levels within the brain and spinal cord epithelium at later developmental stages
  • Trim33-deficient mouse bone marrow-derived macrophages display a strongly reduced three-dimensional amoeboid mobility in fibrous collagen gels