IVNS1ABP
Domain
When the BTB domain is lacking, AHR signaling induction promoted by IVNS1ABP is massively increased; Thus, the BTB domain inhibits AHR signaling induced by IVNS1ABP (PubMed:16582008). Dimerization is necessary for proper splicing activity of IVNS1ABP and this is mediated by the BTB domain (PubMed:30538201). The BACK domain is necessary for proper viral M mRNA export (PubMed:30538201).
Function
Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (By similarity). Protects cells from cell death induced by actin destabilization (By similarity). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (PubMed:16582008). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (PubMed:25619834). Inhibits pre-mRNA splicing (in vitro) (PubMed:9696811). May play a role in mRNA nuclear export (PubMed:30538201).
(Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein (PubMed:23825951, PubMed:9696811). The BTB and Kelch domains are required for splicing activity (PubMed:30538201). Promotes export of viral M mRNA and RNP via its interaction with mRNA export factor ALYREF (PubMed:30538201).
Involvement in disease
Immunodeficiency 70
IMD70
A primary immunodeficiency clinically characterized by human papillomavirus-associated warts on the hands, feet and face, recurrent bacterial infections, and autoinflammatory features, such as colitis, celiac disease, and retinal vasculitis. Immunologic workup shows decreased CD4+ T cells, decreased CD19+ B cells, and hypogammaglobulinemia. IMD70 inheritance is autosomal dominant with incomplete penetrance.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the BTB-kelch protein family.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Nucleus
- Nucleoplasm
- Associated with actin filaments (By similarity). Localization related to speckle domains which correspond to interchromatin granules and are enriched in factors involved in pre-mRNA splicing (PubMed:9696811). Following influenza A virus infection, redistribution from speckles to a more diffuse distribution in the nucleoplasm (PubMed:9696811).
Alternative names
ARA3, FLARA3, KIAA0850, KLHL39, NS1, NS1BP, HSPC068, IVNS1ABP, Influenza virus NS1A-binding protein, NS1-BP, NS1-binding protein, Aryl hydrocarbon receptor-associated protein 3, Kelch-like protein 39