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Literature summary for 7.4.2.14 extracted from
- Tapasin - The keystone of the loading complex optimizing peptide binding by MHC class I molecules in the endoplasmic reticulum (2002), Mol. Immunol., 39, 217-233 .
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | construction and analysis of a Tpn-deficient cell line 220.B8, phenotype, overview. Because peptide depletion by lactacystin induces a time-dependent decay of preexisting surface Kb/Db molecules on Tpn-/- cells, it can be concluded that Tpn deficiency does not override the need of peptide ligands for ER exit and surface expression of class I | Homo sapiens |
| additional information | construction and analysis of mice harboring a disrupted tapasin (Tpn) gene, phenotype, overview. Tpn-/- mice demonstrate the importance of Tpn for the maturation of CD8+ T cells and their response to select class I-restricted antigens. Depending on the nature and the abundance of the antigen, antigen presentation can strongly be impaired in the absence of Tpn as a consequence of defective assembly of stable class I-peptide complexes and presumably also of the reduced TAP-mediated peptide transport | Mus musculus |
General Stability
| General Stability | Organism |
|---|---|
| stabilization of TAP by the transmembrane domain of tapasin (Tpn) | Mus musculus |
| stabilization of TAP by the transmembrane domain of tapasin (Tpn) | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| endoplasmic reticulum membrane | - |
Mus musculus | 5789 | - |
| endoplasmic reticulum membrane | - |
Homo sapiens | 5789 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mus musculus |  |
| Mg2+ | required | Homo sapiens | |
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] | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q03518 AND Q03519 | TAP1 and TAP2 subunits | - |
| Mus musculus | P21958 AND P36371 | subunits TAP1 and TAP2 | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| HeLa cell | - |
Homo sapiens | - |
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] | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| TAP | - |
Mus musculus |
| TAP | - |
Homo sapiens |
| TAP1 | - |
Mus musculus |
| TAP1 | - |
Homo sapiens |
| TAP2 | - |
Mus musculus |
| TAP2 | - |
Homo sapiens |
| transporter associated with antigen processing | - |
Mus musculus |
| transporter associated with antigen processing | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mus musculus | |
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | class I polymorphism influences the HC-Tpn-TAP interaction | Mus musculus |
| malfunction | class I polymorphism influences the HC-Tpn-TAP interaction | Homo sapiens |
| metabolism | molecular complexes of the endoplasmic reticlum (ER) involved in the maturation and peptide loading of class I molecules. After biosynthesis into the ER membrane class I HC assembles with Cnx. ERp57 may facilitate disulfide bond oxidation in early HC. HC releases Cnx and assembles with beta2m and chaperone calreticulin (Crt), and subsequently (or simultaneously) binds to TAP1/TAP2 heterodimers through the assistance of tapasin (Tpn). ERp57 recruited by Tpn may isomerize HC disulfide bonds in the loading complex. Mouse class I molecules can remain associated with Cnx throughout their stay in the ER. In the absence of TAP, HC/beta2m-Crt-Tpn-(ERp57) complexes can assemble, albeit less efficiently. Upon binding of a suitable peptide, the trimeric HC/beta2m/peptide complex is released from ER chaperones and migrates to the cell surface. Intermediate TAP-associated complexes contain Tpn, ERp57, and Cnx. Cnx is released from maturing human TAP complexes. Tpn-dependent/HC-independent association of beta2m and Crt with TAP has also been described, but the precursor relationship to the mature loading complex is not established. Tpn stabilizes steady-state levels of TAP1/TAP2 and, thereby, increases TAP-dependent peptide supply. In TAP-deficient cells, the assembly of HC/beta2m with Crt and Tpn and also the assembly of ERp57 with beta2m or Crt is less productive than in the presence of TAP. Roles of TAP-associated and TAP-independent loading complexes, overview | Mus musculus |
| metabolism | molecular complexes of the endoplasmic reticlum (ER) involved in the maturation and peptide loading of class I molecules. After biosynthesis into the ER membrane class I HC assembles with Cnx. ERp57 may facilitate disulfide bond oxidation in early HC. HC releases Cnx and assembles with beta2m and chaperone calreticulin (Crt), and subsequently (or simultaneously) binds to TAP1/TAP2 heterodimers through the assistance of tapasin (Tpn). ERp57 recruited by Tpn may isomerize HC disulfide bonds in the loading complex. Mouse class I molecules can remain associated with Cnx throughout their stay in the ER. In the absence of TAP, HC/beta2m-Crt-Tpn-(ERp57) complexes can assemble, albeit less efficiently. Upon binding of a suitable peptide, the trimeric HC/beta2m/peptide complex is released from ER chaperones and migrates to the cell surface. Intermediate TAP-associated complexes contain Tpn, ERp57, and Cnx. Cnx is released from maturing human TAP complexes. Tpn-dependent/HC-independent association of beta2m and Crt with TAP has also been described, but the precursor relationship to the mature loading complex is not established. Tpn stabilizes steady-state levels of TAP1/TAP2 and, thereby, increases TAP-dependent peptide supply. In TAP-deficient cells, the assembly of HC/beta2m with Crt and Tpn and also the assembly of ERp57 with beta2m or Crt is less productive than in the presence of TAP. Roles of TAP-associated and TAP-independent loading complexes, overview | Homo sapiens |
| additional information | stabilization of TAP by the transmembrane domain of tapasin (Tpn) | Mus musculus |
| additional information | stabilization of TAP by the transmembrane domain of tapasin (Tpn) | Homo sapiens |
| physiological function | MHC class I molecules are loaded with peptides that mostly originate from the degradation of cytosolic protein antigens and are translocated across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). The ER-resident molecule tapasin (Tpn) is uniquely dedicated to tether class I molecules jointly with the chaperone calreticulin (Crt) and the oxidoreductase ERp57 to TAP. The transient association of class I molecules with Tpn and TAP is critically important for the stabilization of class I molecules and the optimization of the peptide cargo presented to cytotoxic T cells. The different functions of molecular domains of Tpn and the highly coordinated formation of the TAP-associated peptide loading complex. In the presence of TAP, the assembly machinery appears to be skewed towards the TAP-associated complex. This is indicated by elegant pulse-chase experiments with HeLa cells, where no HC/beta2m-Crt complexes are detected outside of assemblages with Tpn-ERp57-TAP. TAP strongly supports the assembly of the other components of the peptide loading complex | Mus musculus |
| physiological function | MHC class I molecules are loaded with peptides that mostly originate from the degradation of cytosolic protein antigens and are translocated across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). The ER-resident molecule tapasin (Tpn) is uniquely dedicated to tether class I molecules jointly with the chaperone calreticulin (Crt) and the oxidoreductase ERp57 to TAP. The transient association of class I molecules with Tpn and TAP is critically important for the stabilization of class I molecules and the optimization of the peptide cargo presented to cytotoxic T cells. The different functions of molecular domains of Tpn and the highly coordinated formation of the TAP-associated peptide loading complex. In the presence of TAP, the assembly machinery appears to be skewed towards the TAP-associated complex. This is indicated by elegant pulse-chase experiments with HeLa cells, where no HC/beta2m-Crt complexes are detected outside of assemblages with Tpn-ERp57-TAP. TAP strongly supports the assembly of the other components of the peptide loading complex | Homo sapiens |
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