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

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the TRIM22 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Function

The protein encoded by this gene is a member of the tripartite motif

Tripartite motif family

-Function:Many TRIM proteins are induced by interferons, which are important component of resistance to pathogens and several TRIM proteins are known to be required for the restriction of infection by lentiviruses...

 (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING

RING finger domain

In molecular biology, a RING finger domain is a protein structural domain of zinc finger type which contains a Cys3HisCys4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids...

, a B-box type 1 and a B-box type 2, and a coiled-coil region

Coiled coil

A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...

. This protein localizes to the cytoplasm

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

 and its expression is induced by interferon

Interferon

Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

. TRIM22 is also a target gene of the tumor suppressor

Tumor suppressor gene

A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

 protein p53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

.

TRIM22 possesses E3 ubiquitin ligase

Ubiquitin ligase

A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...

 activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B

UBE2D2

Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the UBE2D2 gene.-Interactions:UBE2D2 has been shown to interact with PJA1, Baculoviral IAP repeat-containing protein 3, PJA2, UBE3A and NEDD4.-Further reading:...

. 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

Subtypes of HIV

One of the obstacles to treatment of the human immunodeficiency virus is its high genetic variability. HIV can be divided into two major types, HIV type 1 and HIV type 2 . HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to...

 long terminal repeat

Long terminal repeat

Long terminal repeats are sequences of DNA that repeat hundreds or thousands of times. They are found in retroviral DNA and in retrotransposons, flanking functional genes...

 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 and APOBEC3G

APOBEC3G

APOBEC3G 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 innate anti-viral immunity...

.

It has been demonstrated that treatment of cells with interferon type I

Interferon type I

Human type I interferons comprise a vast and growing group of IFN proteins.All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor that consists of IFNAR1 and IFNAR2 chains....

 inhibits HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

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

RNA interference

RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...

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

Group-specific antigen

Group-specific antigen is the genetic material that codes for the core structural proteins of a retrovirus.It comprises part of the gag-onc fusion protein.-Gag in HIV:...

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