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Literature summary for 7.4.2.14 extracted from
- The peptide-loading complex - antigen translocation and MHC class I loading (2009), Biol. Chem., 390, 783-794 .
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| endoplasmic reticulum membrane | 10 transmembrane helices for TAP1 and predicted 9-10 TMs for TAP2, membrane topology of TAP, overview | Homo sapiens | 5789 | - |
| membrane | 10 transmembrane (TM) helices for TAP1 and predicted 9-10 TMs for TAP2, membrane topology of TAP, overview | Rattus norvegicus | 16020 | - |
| membrane | 10 transmembrane helices for TAP1 and predicted 9-10 TMs for TAP2, membrane topology of TAP, overview | Mus musculus | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mus musculus |  |
| Mg2+ | required | Homo sapiens | |
| Mg2+ | required | Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + antigen peptide[side 1] | Mus musculus | - |
ADP + phosphate + antigen peptide[side 2] | - |
? | |
| ATP + H2O + antigen peptide[side 1] | Homo sapiens | - |
ADP + phosphate + antigen peptide[side 2] | - |
? | |
| ATP + H2O + antigen peptide[side 1] | Rattus norvegicus | - |
ADP + phosphate + antigen peptide[side 2] | - |
? | |
| additional information | Mus musculus | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | ? | - |
- |
|
| additional information | Homo sapiens | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | ? | - |
- |
|
| additional information | Rattus norvegicus | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | ? | - |
- |
|
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q03518 AND Q03519 | TAP1 and TAP2 subunits | - |
| Mus musculus | P21958 AND P36371 | TAP1 and TAP2 subunits | - |
| Rattus norvegicus | P36370 AND P36372 | TAP1 and TAP2 subunits | - |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| ATP + H2O + antigen peptide[side 1] = ADP + phosphate + antigen peptide[side 2] | the hydrolysis cycle starts with ATP binding to monomeric NBDs, followed by dimerization and sequential hydrolysis of both ATP molecules. After ATP hydrolysis and phosphate release, the dimer disengages and ADP is replaced by new ATP, reaction mechanism, detailed overview | Mus musculus | |
| ATP + H2O + antigen peptide[side 1] = ADP + phosphate + antigen peptide[side 2] | the hydrolysis cycle starts with ATP binding to monomeric NBDs, followed by dimerization and sequential hydrolysis of both ATP molecules. After ATP hydrolysis and phosphate release, the dimer disengages and ADP is replaced by new ATP, reaction mechanism, detailed overview | Homo sapiens | |
| ATP + H2O + antigen peptide[side 1] = ADP + phosphate + antigen peptide[side 2] | the hydrolysis cycle starts with ATP binding to monomeric NBDs, followed by dimerization and sequential hydrolysis of both ATP molecules. After ATP hydrolysis and phosphate release, the dimer disengages and ADP is replaced by new ATP, reaction mechanism, detailed overview | Rattus norvegicus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + antigen peptide[side 1] | - |
Mus musculus | ADP + phosphate + antigen peptide[side 2] | - |
? | |
| ATP + H2O + antigen peptide[side 1] | - |
Homo sapiens | ADP + phosphate + antigen peptide[side 2] | - |
? | |
| ATP + H2O + antigen peptide[side 1] | - |
Rattus norvegicus | ADP + phosphate + antigen peptide[side 2] | - |
? | |
| additional information | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | Mus musculus | ? | - |
- |
|
| additional information | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | Homo sapiens | ? | - |
- |
|
| additional information | TAP transports proteasomal degradation products into the ER lumen for loading onto MHC class I molecules. Analysis of the translocation machinery is the peptide-binding event and its allosteric coupling with ATP hydrolysis, overview | Rattus norvegicus | ? | - |
- |
|
| additional information | importance of the three N-terminal and the last C-terminal residues in substrate recognition. The remaining residues do not significantly contribute to peptide binding, thus maximizing the pool of protein fragments presented on MHC I molecules | Homo sapiens | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ABC transporter TAP | - |
Mus musculus |
| ABC transporter TAP | - |
Homo sapiens |
| ABC transporter TAP | - |
Rattus norvegicus |
| ATP-binding cassette transporter TAP | - |
Mus musculus |
| ATP-binding cassette transporter TAP | - |
Homo sapiens |
| ATP-binding cassette transporter TAP | - |
Rattus norvegicus |
| peptide-loading complex | - |
Mus musculus |
| peptide-loading complex | - |
Homo sapiens |
| peptide-loading complex | - |
Rattus norvegicus |
| TAP | - |
Mus musculus |
| TAP | - |
Homo sapiens |
| TAP | - |
Rattus norvegicus |
| TAP1 | - |
Mus musculus |
| TAP1 | - |
Homo sapiens |
| TAP1 | - |
Rattus norvegicus |
| TAP2 | - |
Mus musculus |
| TAP2 | - |
Homo sapiens |
| TAP2 | - |
Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | TAP comprises two asymmetric ATPase sites | Mus musculus | |
| ATP | TAP comprises two asymmetric ATPase sites | Homo sapiens | |
| ATP | TAP comprises two asymmetric ATPase sites | Rattus norvegicus | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the enzyme belongs to the ABC transporters, which have a conserved architecture of two transmembrane domains (TMDs) and two cytosolic nucleotide-binding domains (NBD). These domains can be expressed individually or can be arranged on a single polypeptide chain. While the TMDs of ABC import and export systems show diversity in their structural organization, the NBDs are highly conserved. The species-dependent differences in substrate specificity correlate with the epitope repertoire presented by MHC class I molecules, reflecting a co-evolution of TAP, MHC, and the T-cell receptor | Mus musculus |
| evolution | the enzyme belongs to the ABC transporters, which have a conserved architecture of two transmembrane domains (TMDs) and two cytosolic nucleotide-binding domains (NBD). These domains can be expressed individually or can be arranged on a single polypeptide chain. While the TMDs of ABC import and export systems show diversity in their structural organization, the NBDs are highly conserved. The species-dependent differences in substrate specificity correlate with the epitope repertoire presented by MHC class I molecules, reflecting a co-evolution of TAP, MHC, and the T-cell receptor | Homo sapiens |
| evolution | the enzyme belongs to the ABC transporters, which have a conserved architecture of two transmembrane domains (TMDs) and two cytosolic nucleotide-binding domains (NBD). These domains can be expressed individually or can be arranged on a single polypeptide chain. While the TMDs of ABC import and export systems show diversity in their structural organization, the NBDs are highly conserved. The species-dependent differences in substrate specificity correlate with the epitope repertoire presented by MHC class I molecules, reflecting a co-evolution of TAP, MHC, and the T-cell receptor | Rattus norvegicus |
| metabolism | the enzyme complex is part of the antigen processing pathway via major histocompatibility complex I, MHC I, overview. Peptides, derived by proteasomal degradation are translocated by TAP into the ER lumen and afterwards loaded onto MHC class I molecules. The process is chaperoned by interaction of the peptide-loading complex (PLC). Assembly of high-affinity peptide-MHC complexes is catalyzed by the macromolecular peptide-loading complex (PLC), consisting of TAP1, TAP2, the chaperones tapasin (TSN), and calreticulin (CRT), the ER-resident disulfide isomerase ERp57, the MHC class I heavy chain and beta2-microglobulin | Mus musculus |
| metabolism | the enzyme complex is part of the antigen processing pathway via major histocompatibility complex I, MHC I, overview. Peptides, derived by proteasomal degradation are translocated by TAP into the ER lumen and afterwards loaded onto MHC class I molecules. The process is chaperoned by interaction of the peptide-loading complex (PLC). Assembly of high-affinity peptide-MHC complexes is catalyzed by the macromolecular peptide-loading complex (PLC), consisting of TAP1, TAP2, the chaperones tapasin (TSN), and calreticulin (CRT), the ER-resident disulfide isomerase ERp57, the MHC class I heavy chain and beta2-microglobulin | Homo sapiens |
| metabolism | the enzyme complex is part of the antigen processing pathway via major histocompatibility complex I, MHC I, overview. Peptides, derived by proteasomal degradation are translocated by TAP into the ER lumen and afterwards loaded onto MHC class I molecules. The process is chaperoned by interaction of the peptide-loading complex (PLC). Assembly of high-affinity peptide-MHC complexes is catalyzed by the macromolecular peptide-loading complex (PLC), consisting of TAP1, TAP2, the chaperones tapasin (TSN), and calreticulin (CRT), the ER-resident disulfide isomerase ERp57, the MHC class I heavy chain and beta2-microglobulin | Rattus norvegicus |
| additional information | monomeric as well as dimeric NBDs reveal an L-shaped molecule with two subdomains, a RecA-like domain (arm I) and an a-helical domain (arm II). The NBD harbors a P-loop Walker A motif, GXXGXGK(S/T)x, interacting with the alpha- and beta-phosphate of the bound ATP, a signature motif (C-Loop, LSGGQ), positioning the gamma-phosphate, and a conserved glutamate adjacent to the Walker B motif (PhiPhiPhiPhiD, with Phi being a hydrophobic residue), catalyzing the nucleophilic attack of the beta/gamma phosphoanhydride bond by a water molecule. In addition, the NBDs display a conserved histidine (H-loop, switch region) involved in ATP hydrolysis, a Q-Loop, which is suggested to sense the gamma-phosphate and to communicate with the TMDs, as well as the conserved D-Loop, displaying a contact-site within the NBD dimer interface. Walker A and Walker B as well as the H-loop and the Q-loop are arranged in arm I, while the signature motif is located in arm II. The ATP molecule is positioned by residues of the Walker A and Walker B motif and the C-loop of the opposite NBD. ATP binding results in a rigid body movement of arm I towards arm II, causing the largest conformational changes within the Q- and D-loop. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the endoplasmic reticulum (ER) lumen. Biogenesis of the heterodimer requires the assembly of preexisting TAP1 with newly synthesized TAP2. Three-dimensional modeling of the core TAP complex, overview | Homo sapiens |
| additional information | monomeric as well as dimeric NBDs reveal an L-shaped molecule with two subdomains, a RecA-like domain (arm I) and an a-helical domain (arm II). The NBD harbors a P-loop wWalker A motif, GXXGXGK(S/T)x, interacting with the alpha- and beta-phosphate of the bound ATP, a signature motif (C-Loop, LSGGQ), positioning the gamma-phosphate, and a conserved glutamate adjacent to the Walker B motif (PhiPhiPhiPhiD, with Phi being a hydrophobic residue), catalyzing the nucleophilic attack of the beta/gamma-phosphoanhydride bond by a water molecule. In addition, the NBDs display a conserved histidine (H-loop, switch region) involved in ATP hydrolysis, a Q-Loop, which is suggested to sense the gamma-phosphate and to communicate with the TMDs, as well as the conserved D-Loop, displaying a contact-site within the NBD dimer interface. Walker A and Walker B as well as the H-loop and the Q-loop are arranged in arm I, while the signature motif is located in arm II. The ATP molecule is positioned by residues of the Walker A and Walker B motif and the C-loop of the opposite NBD. ATP binding results in a rigid body movement of arm I towards arm II, causing the largest conformational changes within the Q- and D-loop. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the endoplasmic reticulum (ER) lumen. Biogenesis of the heterodimer requires the assembly of preexisting TAP1 with newly synthesized TAP2. Three-dimensional modeling of the core TAP complex, overview | Mus musculus |
| additional information | monomeric as well as dimeric NBDs reveal an L-shaped molecule with two subdomains, a RecA-like domain (arm I) and an alpha-helical domain (arm II). The NBD harbors a P-loop wWalker A motif, GXXGXGK(S/T)x, interacting with the alpha- and beta-phosphate of the bound ATP, a signature motif (C-Loop, LSGGQ), positioning the gamma-phosphate, and a conserved glutamate adjacent to the Walker B motif (PhiPhiPhiPhiD, with Phi being a hydrophobic residue), catalyzing the nucleophilic attack of the b/gphosphoanhydride bond by a water molecule. In addition, the NBDs display a conserved histidine (H-loop, switch region) involved in ATP hydrolysis, a Q-Loop, which is suggested to sense the gamma-phosphate and to communicate with the TMDs, as well as the conserved D-Loop, displaying a contact-site within the NBD dimer interface. Walker A and Walker B as well as the H-loop and the Q-loop are arranged in arm I, while the signature motif is located in arm II. The ATP molecule is positioned by residues of the Walker A and Walker B motif and the C-loop of the opposite NBD. ATP binding results in a rigid body movement of arm I towards arm II, causing the largest conformational changes within the Q- and D-loop. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the endoplasmic reticulum (ER) lumen. Biogenesis of the heterodimer requires the assembly of preexisting TAP1 with newly synthesized TAP2. Three-dimensional modeling of the core TAP complex, overview | Rattus norvegicus |
| physiological function | a large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex, and ABC transporter, ensures that only high-affinity peptides, which guarantee longterm stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. Mechanism of antigen translocation by the transporter associated with antigen processing and loading of MHC class I molecules in the ER, overview. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the ER lumen. The ATP-binding cassette (ABC) transporter TAP represents a key checkpoint within the antigen-processing pathway. Affinity, specificity, and diversity are optimally combined in one translocation machinery. Thus, human, mouse, and rat TAP have different substrate specificities | Homo sapiens |
| physiological function | a large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex, and ABC transporter, ensures that only high-affinity peptides, which guarantee longterm stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. Mechanism of antigen translocation by the transporter associated with antigen processing and loading of MHC class I molecules in the ER, overview. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the ER lumen. The ATP-binding cassette (ABC) transporter TAP represents a key checkpoint within the antigen-processing pathway. Affinity, specificity, and diversity are optimally combined in one translocation machinery. Thus, human, mouse, and rat TAP have different substrate specificities. A functional polymorphism has been identified for rodent TAPs only. The rat TAPu isoform, similar to mouse TAP, prefers hydrophobic residues at the C-terminus of the peptide, while the rat TAPa isoform, which is comparable to human TAP, accepts hydrophobic and basic residues at this position. Mouse TAPs display not only slight differences in the C-terminal but also in the N-terminal positions | Mus musculus |
| physiological function | a large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex, and ABC transporter, ensures that only high-affinity peptides, which guarantee longterm stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. Mechanism of antigen translocation by the transporter associated with antigen processing and loading of MHC class I molecules in the ER, overview. The TAP complex is composed of two half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3). Both subunits are essential and sufficient for ATP-dependent peptide translocation into the ER lumen. The ATP-binding cassette (ABC) transporter TAP represents a key checkpoint within the antigen-processing pathway. Affinity, specificity, and diversity are optimally combined in one translocation machinery. Thus, human, mouse, and rat TAP have different substrate specificities. A functional polymorphism has been identified for rodent TAPs only. The rat TAPu isoform, similar to mouse TAP, prefers hydrophobic residues at the C-terminus of the peptide, while the rat TAPa isoform, which is comparable to human TAP, accepts hydrophobic and basic residues at this position. Mouse TAPs display not only slight differences in the C-terminal but also in the N-terminal positions | Rattus norvegicus |
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