Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as ARTS-1, 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 ARTS-1 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...

.

ARTS1 is also known as:

• ER aminopeptidase 1 (ERAP1)
• ER aminopeptidase associated with antigen processing (ERAAP)
• Adipocyte-derived leucine aminopeptidase (ALAP)
• Puromycin-insensitive leucine aminopeptidase (PILS-AP)

Endoplasmic reticulum aminopeptidase 1 is active in the endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

, which is involved in protein processing and transport. This protein is an aminopeptidase

Aminopeptidase

Aminopeptidase is a zinc-dependent enzyme produced and secreted by glands of the small intestine. It helps the enzymatic digestion of proteins. Additional digestive enzymes produced by these glands include dipeptidases, maltase, sucrase, lactase, and enterokinase.Aminopeptidases catalyze the...

, which is an enzyme that cleaves other proteins into smaller fragments called peptides.

ERAP1 has two major functions in the immune system:

• First, ERAP1 cleaves several proteins called cytokine
  Cytokine
  Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
  
   receptors on the surface of cells. Cleaving these receptors reduces their ability to transmit chemical signals into the cell, which affects the process of inflammation
  Inflammation
  Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
  
  .

• Second, ERAP1 cleaves many types of proteins into small peptides that can be recognized by the immune system. These peptides are exported to the cell surface, where they attach to major histocompatibility complex
  Major histocompatibility complex
  Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
  
   (MHC) class I proteins. MHC class I proteins display the peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.

Function

ARTS-1 is a member of the M1 family of zinc metallopeptidase

Metalloproteinase

Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...

s which acts as a aminopeptidase

Aminopeptidase

Aminopeptidase is a zinc-dependent enzyme produced and secreted by glands of the small intestine. It helps the enzymatic digestion of proteins. Additional digestive enzymes produced by these glands include dipeptidases, maltase, sucrase, lactase, and enterokinase.Aminopeptidases catalyze the...

 that degrades oligopeptides by cleavage starting at the amino terminus. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

.

ARTS-1 is a transmembrane protein that is localized to the endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

. It has been implicated in the following functions:

• Shedding of various cytokine receptor
  Cytokine receptor
  Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
  
  s and decoy receptors
• Trimming of antigenic peptides before binding to MHC class I
  MHC class I
  MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...
  
  , affecting antigen presentation to cytotoxic T lymphocyte
  Cytotoxic T cell
  A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
  
  s

Clinical significance

Aminopeptidases play a role in the metabolism of several peptides that may be involved in blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 and the pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

 of essential hypertension. Mutations in the ARTS-1 have been linked to an increased risk of ankylosing spondylitis

Ankylosing spondylitis

Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

.

The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer

Monomer

A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

 or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin

Angiotensin

Angiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...

 II. Three transcript variants encoding two different isoforms have been found for this gene.

Further reading