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FLASH GENE
Symbol TRIM21 contributors: mct - updated : 11-07-2018
HGNC name tripartite motif-containing 21
HGNC id 11312
Location 11p15.4      Physical location : 4.406.126 - 4.414.926
Synonym name
  • Sicca syndrome antigen A
  • tripartite motif protein TRIM21
  • Sjogren syndrome antigen A1 (52kDa, ribonucleoprotein autoantigen SS-A/Ro)
  • RING finger protein 81
  • Synonym symbol(s) LA-SS-B, Ro-SSA, Ro52, SSA1, RNF81
    EC.number 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 8.00 kb     7 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 1946 54.2 475 - 1995 7561701
    SSA1 Valpha
    - splicing 5200 45 411 - Chan,Wang
    skipping exons
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselcapillary   
    Lymphoid/Immunelymph node   highly
    Nervousbrain    
    Skeletonaxial    
    Visualeyelens   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoietic   highly Homo sapiens
    Connectivebonesubchondral highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythrocyte
    Blood/Hematopoieticleukocyte
    Cardiovascularendothelial cell
    Respiratoryalveolar macrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a RING zinc finger domain
  • two B boxes, that occupies an E2 binding site on the catalytic RING domain by mimicking E2-E3 interactions, inhibiting TRIM21 ubiquitination and preventing immune activation, and B-Box is a critical regulator of RING E3 ligase activity
  • a leucine zipper coiled coil domain RBCC (the so called tripartite motif TRIM), coiled-coil is necessary for the cytoplasmic localization
  • a SPRY domain
  • a C-terminal B30-2, RFP-like domain, and PRYSPRY domain that commonly determines function by acting as a targeting module
  • conjugated RiboP
    HOMOLOGY
    Homologene
    FAMILY
  • B box family
  • RBCC/TRIM family
  • C-IV TRIM family
  • CATEGORY transcription factor , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus,nucleoplasm
    text
  • predominantly cytoplasmic, but may relocate to the surface of cells during apoptosis
  • localize to distinct structures called cytoplasmic bodies, unidentified structures that are transported along the microtubule network and function as an E3 ubiquitin ligase
  • basic FUNCTION
  • RING-dependent E3 ligase involved in ubiquitination
  • may be playing a role in brain vascular involvement in autoimmune diseases
  • mediate innate immunity and other critical cellular functions
  • E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1
  • has both cytoplasmic and nuclear substrates, and mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus
  • essential to sustain IFN regulatory factor 3 activation during antiviral response
  • plays a previously unrecognized role in the negative regulation of NF-kappaB-dependent proinflammatory cytokine responses (
  • major autoantigen in diseases including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome
  • highly conserved mammalian Fc receptor that is structurally and mechanistically distinct from previously identified Fc receptors
  • TRIM21-mediated monoubiquitination plays a critical role in the downregulation of active IKK beta through autophagy
  • rapidly recruits to incoming antibody-bound virus and targets it to the proteasome via its E3 ubiquitin ligase activity
  • utilizes both IgM and IgG, and is capable of operating alongside both innate immunity during the early stages of infection and adaptive immunity to provide long-term protection
  • can impart ubiquitin modification onto its cellular targets
  • FADD and TRIM21 together negatively regulate the late IFN-alpha pathway in response to viral infection
  • FADD and TRIM21 constitute a negative feedback loop of the late interferon pathway during viral infection
  • negative regulator of pathways that affect several cytokines
  • is recruited to antibody-bound virus and targets the complex to the proteasome for degradation
  • TRIM21 targets virions for destruction in the proteasome,
  • TRIM21 is an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA (PMIS: 23222971)
  • well-controlled expression of the E3 ligase TRIM21 is important for regulation of immune responses
  • is a cytosolic antibody receptor that neutralizes antibody-coated viruses that penetrate the cell and simultaneously activates innate immunity
  • is a novel regulator of PAWR in colon and pancreatic cancer cells
  • is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease
  • TRIM21 influences atherosclerosis via regulation of Th17 responses
  • is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • minor component of the RoSSA ribonucleoprotein complex
  • INTERACTION
    DNA binding
    RNA
    small molecule other,
  • IgG molecules
  • interaction between FADD and TRIM21 enhances TRIM21 ubiquitin ligase activity, and together they cooperatively repress IFNA activation in Sendai virus-infected cells
  • TRIM21 is an interacting partner of IFI35 and NMI
  • protein
  • significantly induced and interacts with IRF3 upon RNA virus infection
  • interaction between FADD and TRIM21 enhances TRIM21 ubiquitin ligase activity
  • VCP, an enzyme with segregase and unfoldase activity, is a key player in TRIM21-mediated virus neutralization
  • TRIM21 is a DDX41-interacting protein
  • IRF5 is degraded following TLR7 activation and TRIM21 is involved in this process
  • TRIM21 appears to be a critical regulator of the functions of the NMI-IFI35 complex
  • MEFV and TRIM21 directly bind their respective cargo and recruit autophagic machinery to execute degradation, and TRIM21 targets IRF3
  • TRIM21 is a novel interacting partner of PAWR, and interact with PAWR endogenously and through its PRY-SPRY domain
  • TRIM21 is likely involved in nuclear SALL4 degradation
  • TRIM21 degrades both SALL1 and SALL4
  • cell & other
    REGULATION
    induced by IFN-gamma and LPS
    Other TRIM21 signalling is constitutively repressed by its B-Box domain and activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in systemic lupus erythematosus and Sjögren syndrome
    constitutional     --over  
    involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren's syndrome and SLE (lupus), and may contribute to the autoantigenic load and induction of autoimmune B and T cell responses in rheumatic patients
    constitutional     --over  
    in SLE peripheral blood mononuclear cell (PBMC) as compared to healthy controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS