功能Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV).
通路Protein modification; protein ubiquitination.
序列相似性Belongs to the TRIM/RBCC family. Contains 1 B box-type zinc finger. Contains 1 B30.2/SPRY domain. Contains 1 RING-type zinc finger.
结构域The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity (PubMed:22482711). The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs (PubMed:22482711). The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization (PubMed:22482711).
翻译后修饰Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus. Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation.
细胞定位Cytoplasm > P-body. Closely associates with proteasomal subunits in cytoplasmic bodies (By similarity). Colocalizes with SQSTM1 in cytoplasmic bodies.