Tripartite motif-containing 22, also known as TRIM22, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

which in humans is encoded by the ''TRIM22''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a

RING Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...

, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

and its expression is induced by interferon. TRIM22 is also a target gene of the

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

protein

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

. TRIM22 possesses

E3 ubiquitin ligase A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquiti ...

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.

Clinical significance

The protein down-regulates transcription from the

HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...

long terminal repeat A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or ...

promoter region, suggesting that function of this protein may be to mediate interferon's antiviral effects. Other proteins that function to restrict HIV replication include

TRIM5alpha 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-specif ...

and

APOBEC3G APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic subunit 3G) is a human enzyme encoded by the ''APOBEC3G'' gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in ...

. It has been demonstrated that treatment of cells with

interferon type I The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyt ...

inhibits

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

replication and TRIM22 is strongly up-regulated by interferon treatment. Furthermore, HIV particle release from cells depleted of TRIM22 with

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

is enhanced. TRIM22 appears to prevent the movement of the HIV

Gag A gag is usually an item or device designed to prevent speech, often as a restraint device to stop the subject from calling for help and keep its wearer silent. This is usually done by blocking the mouth, partially or completely, or attemptin ...

protein to the plasma membrane and hence TRIM22 can block HIV replication in cell cultures by preventing the assembly of the virus.

References

External links

* * {{Transcription coregulators