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FLASH GENE
Symbol RNF128 contributors: mct - updated : 20-03-2012
HGNC name ring finger protein 128
HGNC id 21153
Location Xq22.3      Physical location : 105.937.067 - 106.040.244
Synonym name
  • gene related to anergy in lymphocytes
  • Synonym symbol(s) FLJ23516, GRAIL
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 103.18 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 2851 46 428 - 2003 12705856
    7 splicing 2688 - 402 - 2003 12705856
    an alternative 5'exon, an isoform with a distinct and shorter N-terminus
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver   highly Homo sapiens
    Lymphoid/Immunethymus    
    Nervousbrain    
    Reproductivefemale systemovary   
     male systemtestis   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    cell lineage anergic CD4+ T cells
    cell lines retrovirally transduced T cell hybridoma
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a cytosolic RING finger
  • an equally large luminal region consisting primarily of an uncharacterized protease-associated (PA) domain
  • unique single transmembrane protein with a split-function motif
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Rnf128
    homolog to rattus LOC315911
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    text
  • type 1 transmembrane E3 ligase
  • basic FUNCTION
  • an E3 ubiquitin ligase activity
  • inhibits activation-induced IL2 and IL4 cytokines production
  • a biochemical pathway composed of RNF128 and/or RNF128-interacting proteins is important in the development of the CD4 T cell anergic phenotype
  • differentially expressed in naturally occurring and peripherally induced CD25(+) T regulatory cells and its expression is linked to their functional regulatory activity
  • may have a role in the induction of anergic phenotype
  • plays an important role in maintaining remission in patients with ulcerative colitis
  • induces T cell anergy through the ubiquitination activity of its cytosolic RING finger
  • E3 ubiquitin ligase that regulates energy in T-lymphocytes
  • transmembrane RING finger ubiquitin E3 ligase, initially described as induced during the induction of CD4 T cell anergy, is also expressed in resting CD4 T cells
  • its expression during hematopoiesis results in dysregulated differentiation
  • role in primary T cell activation, survival, and differentiation, and indispensable role in T cell anergy and oral tolerance-a promising, antigen-specific strategy to treat autoimmune diseases.
  • E3 ubiquitin ligase associated with T cell tolerance
  • by mediating TCR-CD3 degradation, regulates naive T cell tolerance induction and Treg cell function
  • important gatekeeper of T-cell unresponsiveness, characterized as a negative regulator of T-cell receptor responsiveness and cytokine production
  • impaired lamellipodium formation and reduced the accumulation of F-actin at the immunological synapse
  • regulates proteins involved in the actin cytoskeletal organization, thereby maintaining the unresponsive state of anergic T cells
  • regulates cytoskeletal reorganization to keep cells unresponsive to further antigen stimulation through the ubiquitination and down-regulation of the ARPC5 complex and coronin 1A
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    ion Zn2+
    protein
  • bound to the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 using its PA domain, which promoted ubiquitination of cytosolic lysine residues
  • can down-modulate the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells
  • ARPC5 and CORO1A interact with RNF128
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    target to treat autoimmune diseases
    ANIMAL & CELL MODELS
  • blood glucose levels of the mice with hepatic Rnf128 deficiency did not differ from those of control animals in the fasted or fed states, but manifested glucose intolerance in association with a normal increase in plasma insulin levels during glucose challenge, and an increase in the serum concentration of free fatty acids