Transporter Associated With Antigen Processing
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Transporter Associated With Antigen Processing
Transporter associated with antigen processing (TAP) protein complex belongs to the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules. The TAP structure is formed of two proteins: TAP-1 and TAP-2, which have one hydrophobic region and one ATP-binding region each. They assemble into a heterodimer, which results in a four-domain transporter. Function The TAP transporter is found in the ER lumen associated with the peptide-loading complex (PLC). This complex of β2 microglobulin, calreticulin, ERp57, TAP, tapasin, and MHC class I acts to keep hold of MHC molecules until they have been fully loaded with peptides. Peptide transport TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. Association with TAP is an ATP-independent event, ‘in a fast bimolecular association step, peptide binds to TAP, followed by a ...
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TAP1
Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the ''TAP1'' gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. See also * ATP-binding c ...
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TAP1
Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the ''TAP1'' gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. See also * ATP-binding c ...
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TAP2
TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2 (TAP1). The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, schizophrenia, and celiac disease. Alternative splicing of this gene produces two pro ...
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Protein Complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein complexes are a form of quaternary structure. Proteins in a protein complex are linked by non-covalent protein–protein interactions. These complexes are a cornerstone of many (if not most) biological processes. The cell is seen to be composed of modular supramolecular complexes, each of which performs an independent, discrete biological function. Through proximity, the speed and selectivity of binding interactions between enzymatic complex and substrates can be vastly improved, leading to higher cellular efficiency. Many of the techniques used to enter cells and isolate proteins are inherently disruptive to such large complexes, complicating the task of determining the components of a complex. Examples of protein complexes include th ...
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ATP-binding Cassette Transporter
The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum, phyla, from prokaryotes to humans. ABC transporters belong to translocases. ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated AAA proteins, AAA ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to provide the energy needed for the translocation of substrates across membranes, either for uptake or for export of the substrate. Most of the uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as RNA translation, translation of RNA and DNA repair. ABC transporters are considered to be an ABC su ...
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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 (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae (in the RER), and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa. The two types of ER share many of the same proteins and engage in certain common activities such as the synthesis of certain lipids and cholesterol. Different types of cells contain different ratios of the two types of ER depending on the activities of the cell. RER is found mainly toward the nucleus of cell and SER towards the cell membrane or plasma ...
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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 platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called ''cytosolic'' or ''endogenous pathway''. In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C. Function Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I:peptide complex is then inserted via endoplasmic reticulum into t ...
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Peptide Loading Complex
The peptide-loading complex (PLC) is a short-lived, multisubunit membrane protein complex that is located in the endoplasmic reticulum (ER). It orchestrates peptide translocation and selection by major histocompatibility complex class I (MHC-I) molecules. Stable peptide-MHC I complexes are released to the cell surface to promote T-cell response against malignant or infected cells. In turn, T-cells recognize the activated peptides, which could be immunogenic or non-immunogenic. Overview A PLC assembly consists of seven subunits, including the transporters associated with antigen processing (TAP1 and TAP2 – jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. TAP transports proteasomal degradation products from the cytosol into the lumen of the ER, where they are loaded onto MHC-I molecules. The peptide-MHC-I complexes then move via a secretory pathway to the cell surface, presenting their antigenic loa ...
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Beta-2 Microglobulin
β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by the ''B2M'' gene. Structure and function β2 microglobulin lies beside the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 (that is, further away from the cell) lies the α1 chain, which itself is next to the α2. β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 (5 genes in humans), MR1, the neonatal Fc receptor (FcRn), and Qa-1 (a form of alloantigen). Nevertheless, the β2 microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome. An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporte ...
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Calreticulin
Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 (ERp60) is a protein that in humans is encoded by the ''CALR'' gene. Calreticulin is a multifunctional soluble protein that binds Ca2+ ions (a second messenger in signal transduction), rendering it inactive. The Ca2+ is bound with low affinity, but high capacity, and can be released on a signal (see inositol trisphosphate). Calreticulin is located in storage compartments associated with the endoplasmic reticulum and is considered an ER resident protein. The term "Mobilferrin" is considered to be the same as calreticulin by some sources. Function Calreticulin binds to misfolded proteins and prevents them from being exported from the endoplasmic reticulum to the Golgi apparatus. A similar quality-control molecular chaperone, calnexin, performs the same service for soluble proteins as does calreticulin, however it is a membrane-bound protein. Bo ...
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Tapasin
TAP-associated glycoprotein, also known as tapasin or TAPBP, is a protein that in humans is encoded by the ''TAPBP'' gene. Function The ''TAPBP'' gene encodes a transmembrane glycoprotein that mediates interaction between newly assembled major histocompatibility complex ( MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction facilitates optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and tapasin may be bound to a single TAP molecule. Tapasin contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. In humans, the tapasin gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. Tapasin is a MHC class I antigen-processing molecule pr ...
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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 (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae (in the RER), and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa. The two types of ER share many of the same proteins and engage in certain common activities such as the synthesis of certain lipids and cholesterol. Different types of cells contain different ratios of the two types of ER depending on the activities of the cell. RER is found mainly toward the nucleus of cell and SER towards the cell membrane or plasma ...
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