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FLASH GENE
Symbol RNF146 contributors: mct/npt - updated : 01-02-2014
HGNC name ring finger protein 146
HGNC id 21336
Location 6q22.33      Physical location : 127.588.019 - 127.609.502
Synonym name dactylidin
Synonym symbol(s) DKFZp434O1427, dJ351K20.1, RP3-351K20.1, 2610509H23Rik
DNA
TYPE functioning gene
STRUCTURE 21.88 kb     5 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 2670 - 358 - 2011 2179991
3 - 2103 - 359 - 2011 2179991
5 - 2650 - 358 - 2011 2179991
5 - 2670 - 358 - 2011 2179991
3 - 2433 - 359 - 2011 2179991
5 - 2519 - 358 - 2011 2179991
5 - 2400 - 358 - 2011 2179991
5 - 2432 - 358 - 2011 2179991
3 - 2163 - 359 - 2011 2179991
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
 thyroid   highly
Nervousbrain    
Reproductivefemale systemplacenta   
 female systemuteruscervix highly
 male systemtestis   
Visualeye    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal C3HC4 RING finger domain
  • a WWE domain, that recognizes poly(ADP-ribose) (PAR) by interacting with iso-ADP-ribose (iso-ADPR), the smallest internal PAR structural unit containing the characteristic ribose-ribose glycosidic bond formed during poly(ADP-ribosyl)ation
  • a PAR binding motif (PBM)
  • HOMOLOGY
    interspecies homolog to rattus LOC308051
    Homologene
    FAMILY
  • zinc finger family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location
    basic FUNCTION
  • likely functioning as a ubiquitin protein ligase
  • may function early in the progression of neurodegenerative diseases
  • promotes Wnt signalling by mediating tankyrase-dependent degradation of axin
  • RNF146-dependent protein degradation may emerge as a major mechanism by which tankyrase exerts its function
  • RING-type ubiquitin E3 ligase, and a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins
  • PAR-dependent ubiquitin E3 ligase, and its ligase activity requires PAR binding
  • PAR-dependent E3 ligase that regulates cell survival and DNA repair
  • is likely to regulate a variety of cellular processes where PARsylation plays a role
  • controls osteoclast activity by regulating SH3BP2 levels in an ADP-ribose-dependent manner
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • TNKS-RNF146-AMOT axis is an upstream pathway regulating YAP1
  • a component
  • ubiquitin ligase complex
  • RNF146, tankyrase, and Axin form a protein complex, and RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ion Zn2+
  • protein
  • directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins
  • BLZF1 and CASC3 are further substrates targeted by tankyrase and RNF146 for degradation
  • destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels
  • binds and ubiquitinates both PARsylated and PAR binding proteins via its PBM, marking these proteins for ubiquitin proteasomal degradation
  • is the functional E3-ligase controlling SH3BP2 protein levels
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in Alzheimer disease
    Susceptibility to breast cancer
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS