Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene. [3] [4] [5]
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene. [3] [4] [5]
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. [6] The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. [3] TRIM22 is also a target gene of the tumor suppressor protein p53. [7]
TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore, TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase. [8]
The protein down-regulates transcription from the HIV-1 long terminal repeat promoter region, suggesting that function of this protein may be to mediate interferon's antiviral effects. [3] [4] Other proteins that function to restrict HIV replication include TRIM5alpha and APOBEC3G. [9]
It has been demonstrated that treatment of cells with interferon type I inhibits HIV replication and TRIM22 is strongly up-regulated by interferon treatment. Furthermore, HIV particle release from cells depleted of TRIM22 with RNA interference is enhanced. TRIM22 appears to prevent the movement of the HIV Gag protein to the plasma membrane and hence TRIM22 can block HIV replication in cell cultures by preventing the assembly of the virus. [10] [11]
Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.
Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specific early block to retrovirus infection.
Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids.
p21Cip1, also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2. p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans.
Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ISG15 gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response.
Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene.
Ubiquitin D is a protein that in humans is encoded by the UBD gene, also known as FAT10. UBD acts like ubiquitin, by covalently modifying proteins and tagging them for destruction in the proteasome.
Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the UBE2D2 gene.
Tripartite motif-containing protein 37 is an E3 ubiquitin ligase in humans that is encoded by the TRIM37 gene.
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.
Midline-2 is a protein that in humans is encoded by the MID2 gene.
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
E3 ubiquitin-protein ligase TRIM33, also known as (ectodermin homolog and tripartite motif-containing 33) is a protein encoded in the human by the gene TRIM33, a member of the tripartite motif family.
Tripartite motif-containing protein 3 is a protein that in humans is encoded by the TRIM3 gene.
Intrinsic immunity refers to a set of cellular-based anti-viral defense mechanisms, notably genetically encoded proteins which specifically target eukaryotic retroviruses. Unlike adaptive and innate immunity effectors, intrinsic immune proteins are usually expressed at a constant level, allowing a viral infection to be halted quickly. Intrinsic antiviral immunity refers to a form of innate immunity that directly restricts viral replication and assembly, thereby rendering a cell non-permissive to a specific class or species of viruses. Intrinsic immunity is conferred by restriction factors preexisting in certain cell types, although these factors can be further induced by virus infection. Intrinsic viral restriction factors recognize specific viral components, but unlike other pattern recognition receptors that inhibit viral infection indirectly by inducing interferons and other antiviral molecules, intrinsic antiviral factors block viral replication immediately and directly.
Probable E3 ubiquitin-protein ligase HERC5 is an enzyme that in humans is encoded by the HERC5 gene.
E3 ubiquitin-protein ligase RNF128 is an enzyme that in humans is encoded by the RNF128 gene.
Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.
Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. This enzyme localizes to the outer mitochondrial membrane, where it regulates mitochondrial morphology and apoptosis through multiple pathways, including the Akt, JNK, and NF-κB. Its proapoptotic function thus implicates it in cancer and Parkinson’s disease.