CASC3
Domain
The coiled coil domain may be involved in oligomerization.
Function
Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer.
Post-translational modifications
ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.
Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.
Sequence Similarities
Belongs to the CASC3 family.
Tissue Specificity
Widely expressed. Overexpressed in breast cancers and metastasis, as well as in gastric cancers.
Cellular localization
- Cytoplasm
- Cytoplasm
- Perinuclear region
- Nucleus
- Nucleus speckle
- Cytoplasm
- Stress granule
- Cytoplasm
- Cytoplasmic ribonucleoprotein granule
- Cell projection
- Dendrite
- Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner. Transported to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA (PubMed:15166247). In nuclear speckles, colocalizes with MAGOH. Under stress conditions, colocalizes with FMR1 and TIA1, but not MAGOH and RBM8A EJC core factors, in cytoplasmic stress granules (PubMed:17652158). In the dendrites of hippocampal neurons, localizes to dendritic ribonucleoprotein granules (By similarity).
Alternative names
MLN51, CASC3, Protein CASC3, Cancer susceptibility candidate gene 3 protein, Metastatic lymph node gene 51 protein, Protein barentsz, MLN 51, Btz