Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), 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, respo ...

which in humans is encoded by the ''ARTS-1''

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 ba ...

. Endoplasmic reticulum amino peptidase 1 is active in the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

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

aminopeptidase Aminopeptidases are enzymes that catalyze the cleavage of amino acids from the amino terminus (N-terminus) of proteins or peptides (exopeptidases). They are widely distributed throughout the animal and plant kingdoms and are found in many subcell ...

, which is an enzyme that cleaves peptides at the N-terminal into smaller fragments called amino acids.

Nomenclature

ARTS1 is also known as: * ER aminopeptidase 1 (ERAP1) the name accepted by the Hugo Gene Nomenclature Committee * ER aminopeptidase associated with antigen processing (ERAAP) in mice * Adipocyte-derived leucine aminopeptidase (ALAP) * Puromycin-insensitive leucine aminopeptidase (PILS-AP)

Function

ERAP1 has two major functions in the immune system: *First, ERAP1 cleaves several proteins called

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

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 (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

. *Second, ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

(MHC) class I. These peptides are attached to MHC class I in the endoplasmic reticulum and exported to the cell surface, where they are displayed 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. ARTS-1 is a member of the M1 family of zinc

metallopeptidase A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogen ...

s which acts as an

that degrades oligopeptides by cleavage starting at the

amino terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

. ARTS-1 is a transmembrane protein that is localized to the

. It has been implicated in the following functions: * Shedding of various

cytokine receptor Cytokine receptors are receptors that bind to 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 bec ...

s and decoy receptors * Trimming of antigenic peptides before binding to

MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on plat ...

, affecting antigen presentation to

cytotoxic T lymphocyte A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T cell, T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracel ...

s *Stimulation of phagocytosis upon release by macrophages

Clinical significance

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

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

and the

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

essential hypertension Essential hypertension (also called primary hypertension, or idiopathic hypertension) is the form of hypertension that by definition has no identifiable secondary cause. It is the most common type affecting 85% of those with high blood pressure. T ...

. Mutations in the ARTS-1 have been linked to an increased risk of

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...

but only in

HLA-B27 Human leukocyte antigen (HLA) B27 (subtypes B*2701-2759) is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents antigenic peptides (derived from self and non-self antigens) to ...

positive patients. 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 In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

or as a

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of

angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrena ...

II. Three transcript variants encoding two different

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

have been found for this gene.

Nomenclature

Function

Clinical significance

References

External links

Further reading