HLA-DPA1 encodes the alpha chain of the HLA-DP class II major histocompatibility molecule. It is a single-pass type I membrane glycoprotein whose N-terminal alpha-1 domain forms one half of the peptide-binding groove and whose C1-set immunoglobulin-like alpha-2 domain supports it; the chain is obligately heterodimeric with an HLA-DPB1 beta chain, and the two together create the cleft that binds peptides of roughly 10-30 residues. Newly made alpha and beta chains pair in the endoplasmic reticulum, where three heterodimers assemble onto a trimer of the invariant chain CD74 that occupies the groove and routes the complex through the Golgi and trans-Golgi network into the endocytic system. In the late endosomal/lysosomal MHC class II compartment CD74 is trimmed by cathepsins to the CLIP fragment, HLA-DM catalyses its release, and antigenic peptides generated from endocytosed or autophagy-delivered proteins are loaded into the groove. The peptide-loaded molecule is then delivered to the plasma membrane, where it displays its cargo to CD4 T cells, so that HLA-DP contributes to CD4 T-cell selection, activation and the ensuing helper responses. Expression is restricted largely to professional antigen-presenting cells and some epithelia and is driven by the CIITA/X-box promoter machinery, which makes the gene strongly interferon-gamma-inducible. The DP alpha chain is modestly polymorphic compared with the beta chain; crystallography of the DPA1*01:03/DPB1*02:01 molecule (HLA-DP2) shows alpha-chain residues shaping the peptide pockets and stabilising the cleft, and HLA-DP alleles are associated with chronic beryllium disease, hard metal lung disease and several autoimmune and infectious-disease susceptibilities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2130393 | KEEP AS NON CORE | Summary: Reactome TAS placing the MHC class II:invariant chain (CD74) complex in the Golgi membrane as it moves from the ER through the Golgi stack to the trans-Golgi network. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2213243 | KEEP AS NON CORE | Summary: Reactome TAS placing the MHC class II:invariant chain (CD74) complex in the Golgi membrane as it moves from the ER through the Golgi stack to the trans-Golgi network. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also |
| GO:0002503 peptide antigen assembly with MHC class II protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA on the class II PAINT node for the loading of an antigenic peptide into the class II binding groove. Reason: This is the process the DP alpha chain is a direct participant in rather than merely a requirement for: the term is defined as "The binding of a peptide to the antigen binding groove of an MHC class II protein complex", and the DP2 crystal structure shows that the groove is built jointly by the alpha-1 and beta-1 domains, with alpha-chain residues (alphaAla11 shaping the p6 pocket floor, alphaArg76 forming the cleft-stabilising salt bridge) determining its shape. The IBD node placement is sound: peptide loading is the ancestral, defining activity of the whole class II alpha/beta family and there is no evidence of divergence or loss in the DP isotype, which has been shown crystallographically to bind self-peptide in exactly this manner. Supporting Evidence: PMID:20356827 The Ξ±1 and Ξ²1 domains of DP2 form the peptide-binding groove, and the peptide takes an extended polyproline-like helical course through the groove. PMID:20356827 its depth is due to the amino acids Ξ±Ala11 and Ξ²Gly11, whose small side chains open up the bottom of the pocket PMID:20356827 forming a conserved salt bridge across to Ξ±Arg76 that is important in the formation of the antigen-binding cleft PMID:20356827 we crystallized DP2 ( DPA1*0103 , DPB1*0201 ) with a bound self-peptide derived from the HLA-DR Ξ±-chain (pDRA) file:human/HLA-DPA1/HLA-DPA1-uniprot.txt binding cleft accommodates peptides of 10-30 residues. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding IPI recording a high-throughput AP-MS association between HLA-DPA1 and SREBF2 (UniProtKB:Q12772) in the BioPlex ORFEOME interactome survey. Reason: Per repository curation policy generic protein binding is uninformative and is removed rather than retained: it conveys no molecular function for the DP alpha chain. Removal does not assert that the reported interaction is false - UniProt records the same HLA-DPA1/SREBF2 pair with three experiments - but no mechanism, directionality or biological consequence has been reported for it, and SREBF2 is a sterol-regulated ER/nuclear transcription factor with no described role in class II assembly, trafficking or peptide loading. There is therefore no evidence-backed informative molecular function to MODIFY to; inventing one from a high-throughput co-purification alone would be unsupported. The informative molecular functions of this chain are already captured by the GO:0042605 peptide antigen binding rows and by part_of GO:0042613. Supporting Evidence: PMID:28514442 we have established a robust AP-MS pipeline capable of targeting up to 500 human open reading frames (ORFβs) per month file:human/HLA-DPA1/HLA-DPA1-uniprot.txt P20036; Q12772: SREBF2; NbExp=3; IntAct=EBI-2802853, EBI-465059; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding IPI recording the same HLA-DPA1/SREBF2 (UniProtKB:Q12772) association in the BioPlex 3.0 dual-cell-line interactome, from immunoprecipitations in HCT116 and HEK293T cells. Reason: Per repository curation policy generic protein binding is uninformative and is removed rather than retained: it conveys no molecular function for the DP alpha chain. Removal does not assert that the reported interaction is false - UniProt records the same HLA-DPA1/SREBF2 pair with three experiments - but no mechanism, directionality or biological consequence has been reported for it, and SREBF2 is a sterol-regulated ER/nuclear transcription factor with no described role in class II assembly, trafficking or peptide loading. There is therefore no evidence-backed informative molecular function to MODIFY to; inventing one from a high-throughput co-purification alone would be unsupported. The informative molecular functions of this chain are already captured by the GO:0042605 peptide antigen binding rows and by part_of GO:0042613. Supporting Evidence: PMID:33961781 immunoprecipitations in HCT116 cells. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt P20036; Q12772: SREBF2; NbExp=3; IntAct=EBI-2802853, EBI-465059; |
| GO:0005515 protein binding | IPI PMID:34819669 A multi-scale map of cell structure fusing protein images an... | REMOVE | Summary: Generic protein binding IPI recording the same HLA-DPA1/SREBF2 (UniProtKB:Q12772) association, here propagated through the MuSIC map that fuses Human Protein Atlas immunofluorescence with BioPlex affinity purifications. Reason: Per repository curation policy generic protein binding is uninformative and is removed rather than retained: it conveys no molecular function for the DP alpha chain. Removal does not assert that the reported interaction is false - UniProt records the same HLA-DPA1/SREBF2 pair with three experiments - but no mechanism, directionality or biological consequence has been reported for it, and SREBF2 is a sterol-regulated ER/nuclear transcription factor with no described role in class II assembly, trafficking or peptide loading. There is therefore no evidence-backed informative molecular function to MODIFY to; inventing one from a high-throughput co-purification alone would be unsupported. The informative molecular functions of this chain are already captured by the GO:0042605 peptide antigen binding rows and by part_of GO:0042613. Supporting Evidence: PMID:34819669 affinity purifications in BioPlex5 to create a file:human/HLA-DPA1/HLA-DPA1-uniprot.txt P20036; Q12772: SREBF2; NbExp=3; IntAct=EBI-2802853, EBI-465059; |
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in) placing the class II molecule in the lysosomal membrane, the MIIC compartment where CD74/CLIP is degraded and antigenic peptide is loaded. Reason: This is where the DP molecule does its peptide-loading work, so is_active_in is the right relation and the compartment is a core location rather than a transit stop. The node placement is well grounded: lysosomal/MIIC residence is a conserved property of the class II family, with mouse H2-Aa/H2-Ab1 and the human DR, DM and DO chains among the descendant evidences, and the DP isotype follows the same CD74-dependent endosomal route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from the UniProt subcellular location keyword SL-0157 (lysosome membrane). Reason: The automatic SubCell-to-GO mapping reproduces a curated UniProt location statement for this protein, and it agrees with the independent IBA and Reactome rows for the same compartment. The lysosome/MIIC membrane is where class II peptide loading occurs, so the term is both correct and at the right granularity. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2130336 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2130349 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2130504 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213235 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213236 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213244 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213246 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213248 | ACCEPT | Summary: Reactome TAS rows placing the class II:CD74 complex in the lysosomal membrane for the steps of sequential invariant-chain proteolysis (lip22, lip10, CLIP), CLIP release and antigenic peptide loading. Reason: These TAS rows describe the DP molecule in the compartment where it is actually functional: CD74 is trimmed to CLIP, HLA-DM catalyses CLIP release, and antigenic peptide is loaded into the alpha-1/beta-1 groove. Unlike the biosynthetic transit compartments this is a core location, and it is independently supported by the IBA and the curated UniProt location. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from the UniProt subcellular location keyword SL-0097 (endoplasmic reticulum membrane), where the newly synthesised alpha chain pairs with a DP beta chain and three heterodimers assemble onto a CD74 trimer. Reason: The localisation is correct and curated in UniProt, and the ER is where alpha/beta pairing and heterononamer assembly occur. It is kept as non-core because the chain has no peptide-presenting activity here - the groove is occupied by CD74 rather than by antigen - so the ER is a biogenesis compartment rather than a site of function. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from the UniProt subcellular location keyword SL-0132 (Golgi apparatus), covering passage of the class II:CD74 complex through the Golgi. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from the UniProt subcellular location keyword SL-0039 (cell membrane) for this single-pass type I membrane protein. Reason: The plasma membrane is the site where the peptide-loaded DP molecule performs its function, displaying antigen to CD4 T cells, so this is a core location. It is independently confirmed by conformation-dependent anti-DP antibody staining of transfected fibroblasts and by DP alpha-chain-specific antibody staining of cell surfaces. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | NAS PMID:2461352 Epitope recognition by a DP alpha chain-specific monoclonal ... | ACCEPT | Summary: NAS row from the DP11.1 antibody study, which detects the DP alpha chain on the surface of intact cells typed as DPw2/DPw3/DPw4. Reason: Although the evidence code is NAS, the cited paper is itself a cell-surface staining study of the DP alpha chain, so the claim is directly in line with its content, and the location agrees with the curated UniProt record and with independent anti-DP surface staining in the DP2 structural paper. Plasma membrane is the functional location for antigen display. Supporting Evidence: PMID:2461352 The HLA-DP alpha chain-specific monoclonal antibody DP11.1 binds only to the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1031716 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202165 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202168 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202174 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202216 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202233 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202245 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202248 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202291 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202307 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202344 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130500 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130640 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130725 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2213248 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389758 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8852200 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855381 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8856157 | ACCEPT | Summary: Reactome TAS rows placing class II at the plasma membrane, both for the delivery/display steps of the class II pathway (insertion of the class II:CD74 complex, transport of antigen-loaded class II to the surface, LAG3 binding) and as the antigen-presenting-cell ligand in the TCR-signalling reactions. Reason: The plasma membrane is the location where the loaded DP molecule functions, and that is exactly what these Reactome reactions model, whether the reaction is written from the APC side (surface delivery, LAG3 engagement) or from the T-cell side (the class II ligand engaging the TCR while downstream ITAM/LCK/ZAP-70 events are phosphorylated). Many of these rows are redundant with one another, but each records a correct localisation. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0006955 immune response | IEA GO_REF:0000002 | MODIFY | Summary: IEA from the InterPro class II alpha-chain signatures (IPR001003, IPR014745) to the broad term immune response. Reason: The InterPro signatures correctly identify the protein as a class II alpha chain, so a role in immunity is certain, but immune response sits near the top of the process branch and says nothing a class II annotation should say. The specific process this chain executes - display of exogenously derived peptide on class II to CD4 T cells - is established by the DP2 structure and presentation experiments and is already annotated by IBA and IMP, so the generic parent is replaced by that child, consistently with the NAS row for the same term. Proposed replacements: antigen processing and presentation of exogenous peptide antigen via MHC class II Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Belongs to the MHC class II family. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. |
| GO:0006955 immune response | NAS PMID:2461352 Epitope recognition by a DP alpha chain-specific monoclonal ... | MODIFY | Summary: NAS row asserting a role in the immune response, traced to the DP11.1 antibody epitope study. Reason: The role in immunity is real but immune response is far too general to be informative for a class II alpha chain, and the specific process the protein executes - display of exogenously derived peptide on class II to CD4 T cells - is established directly by the DP2 structure and presentation experiments. Replacing the uninformative parent with GO:0019886 states what the protein actually does; note that the cited antibody paper on its own establishes only surface expression of the DP alpha chain, which is why the supporting evidence for the replacement is drawn from the structural/functional work and the curated UniProt function statement. Proposed replacements: antigen processing and presentation of exogenous peptide antigen via MHC class II Supporting Evidence: PMID:2461352 epitope is influenced by the associations between the DP alpha chain and its file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts |
| GO:0009986 cell surface | IMP PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | ACCEPT | Summary: IMP row for cell-surface localisation from the DP2 study, in which DP alpha-expressing fibroblasts transfected with wild-type or mutant DP beta chains were shown by conformation-dependent anti-DP antibody staining to display assembled DP2 at the surface. Reason: Surface display of the assembled DP alpha/beta molecule is directly demonstrated with the conformation-dependent mAb B7.21 in cells whose alpha chain is DPA1*01:03, and it is corroborated by DP alpha-chain-specific antibody staining of intact cells in the earlier DP11.1 study and by the curated UniProt cell-membrane location. The cell surface is where the molecule functions. Supporting Evidence: PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 PMID:20356827 Transfection into mouse DAP.3 L cells expressing DPA1*0103 was performed using Lipofectamine 2000 PMID:2461352 The HLA-DP alpha chain-specific monoclonal antibody DP11.1 binds only to the |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from the UniProt subcellular location keyword SL-0100 (endosome membrane). Reason: The endosomal membrane is part of the MIIC peptide-loading compartment continuum where class II molecules acquire antigenic peptide, so this is a functional rather than merely transitional location; the mapping reproduces a curated UniProt statement and agrees with the late endosome membrane IBA. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endosome membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-2130731 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 heterononamer in the membrane of COPII vesicles budding from the ER and fusing with the Golgi. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-2213243 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 heterononamer in the membrane of COPII vesicles budding from the ER and fusing with the Golgi. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: IEA from the InterPro class II alpha-chain signatures to the root-level component term membrane. Reason: The claim is true - the chain is a single-pass type I membrane protein - but membrane is the top of the component branch and conveys nothing that the specific rows do not already say. The curated locations where this protein resides and functions are the plasma membrane (antigen display) and the lysosomal/MIIC membrane (peptide loading), both of which are independently supported, so the generic term should be replaced by those. Proposed replacements: plasma membrane lysosomal membrane Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Cell membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Lysosome membrane; Single-pass type I membrane protein. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Belongs to the MHC class II family. |
| GO:0019882 antigen processing and presentation | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from the InterPro class II alpha-chain signatures to the parent process antigen processing and presentation. Reason: The InterPro signatures correctly identify the protein as a class II alpha chain, and antigen processing and presentation is the process family it belongs to. Unlike the root-level membrane mapping, this term is genuinely informative about what the gene does, even though the IBA and IMP rows supply the more specific GO:0019886 child; an electronic annotation that is broader than the experimental ones is acceptable where, as here, the broader term is unambiguously true. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Belongs to the MHC class II family. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II | IBA GO_REF:0000033 | ACCEPT | Summary: IBA on the class II PAINT node for presentation of exogenously derived peptide via class II, with human HLA-DPA1 itself (UniProtKB:P20036) among the descendant evidences. Reason: This is the defining process of the gene product and the IBD node placement is as secure as such a judgement gets: the descendant evidences span the mouse H2-A/H2-E chains and the human DR, DQ and DP chains, so the function is ancestral to the whole class II family and inherited by DP. HLA-DPA1 appearing in its own WITH/FROM list is expected and correct - it reflects the gene's own experimental annotation being one of the descendant evidences the curator used - and the IBA adds the further claim that the function is inherited rather than DP-specific. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts |
| GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II | IMP PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | ACCEPT | Summary: IMP row from the DP2 study: DP alpha-chain-expressing fibroblasts carrying wild-type DP beta presented beryllium to a patient-derived CD4 T-cell line, while acidic-pocket mutants of the beta chain abolished presentation without affecting assembly or superantigen presentation. Reason: The DP2 molecule assayed here is DPA1*01:03/DPB1*02:01, so the presenting entity whose function was measured includes this alpha chain, which supplies half of the groove that holds the self-peptide seen in the crystal structure. The mutational series targets the beta chain, but the readout is the presenting activity of the assembled alpha/beta molecule, and the curator who made this IMP had the full text. The chain is a direct participant in the process, not merely required for it: it builds part of the peptide-binding cleft that is displayed to the T cell. Supporting Evidence: PMID:20356827 Transfection into mouse DAP.3 L cells expressing DPA1*0103 was performed using Lipofectamine 2000 PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts PMID:20356827 all four of the mutant DP2 molecules were unable to present Be to the T-cell line PMID:20356827 The Ξ±1 and Ξ²1 domains of DP2 form the peptide-binding groove, and the peptide takes an extended polyproline-like helical course through the groove. |
| GO:0023026 MHC class II protein complex binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA on the class II PAINT node for binding to a class II protein complex, seeded from the HLA-DM and HLA-DO chains (P28067/P28068 = DMA/DMB, P06340/P13765 = DOA/DOB). Reason: The term means binding to a class II complex as a ligand. That is precisely what the donor genes on this node do: DM and DO act in trans on the alpha-beta-CLIP complex to catalyse or modulate CLIP release. The DP alpha chain is instead a constituent of the class II complex, so applying the term to it inverts the relationship in the same way GO:0032395 does, and the correct statements for this chain are part_of GO:0042613 and the GO:0042605 peptide antigen binding rows, all of which it already carries. It is marked as over-annotated rather than removed because the node placement is a defensible family-level call - the PANTHER node mixes class II subunits with class II binders - and the DP alpha chain does contact other class II molecules within the CD74 heterononamer, so the claim is not flatly false, merely uninformative and misdirected for this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000460629 Β· MHC class II-related ancestral node SOURCE WEAK OR INFERRED Node spans both class II constituent subunits and trans-acting class II binders, so a binder-specific term propagates to constituents. UniProtKB:P28067 Β· HLA-DMA SUPPORTS SOURCE BUT NOT TARGET HLA-DM acts in trans on the alpha-beta-CLIP complex, so it genuinely binds class II; DP alpha is a constituent instead. UniProtKB:P28068 Β· HLA-DMB SUPPORTS SOURCE BUT NOT TARGET Same DM catalytic role as DMA; the term fits the donor but inverts the relationship for DP alpha. UniProtKB:P06340 Β· HLA-DOA SUPPORTS SOURCE BUT NOT TARGET HLA-DO modulates DM activity on class II complexes in trans, again a binder rather than a constituent. UniProtKB:P13765 Β· HLA-DOB SUPPORTS SOURCE BUT NOT TARGET Same DO role as DOA. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also PMID:20356827 we crystallized DP2 ( DPA1*0103 , DPB1*0201 ) with a bound self-peptide derived from the HLA-DR Ξ±-chain (pDRA) |
| GO:0030658 transport vesicle membrane | TAS Reactome:R-HSA-2130378 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in transport vesicle membranes during TGN-to-plasma-membrane and TGN-to-lysosome delivery. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass |
| GO:0030658 transport vesicle membrane | TAS Reactome:R-HSA-2130500 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in transport vesicle membranes during TGN-to-plasma-membrane and TGN-to-lysosome delivery. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-2130486 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in endocytic vesicle membranes after internalisation from the plasma membrane and during trafficking of the heterononamer in the endocytic pathway. Reason: The route is correct - surface-delivered class II:CD74 is internalised and carried into the endosomal system - and these rows describe real steps of the pathway. They are kept as non-core because the chain acquires antigenic peptide further along, in the late endosomal/lysosomal MIIC that is already annotated with the stronger IBA rows, so the carrier vesicle is a transport intermediate rather than a site of function. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endosome membrane; Single-pass type I membrane |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-2213235 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in endocytic vesicle membranes after internalisation from the plasma membrane and during trafficking of the heterononamer in the endocytic pathway. Reason: The route is correct - surface-delivered class II:CD74 is internalised and carried into the endosomal system - and these rows describe real steps of the pathway. They are kept as non-core because the chain acquires antigenic peptide further along, in the late endosomal/lysosomal MIIC that is already annotated with the stronger IBA rows, so the carrier vesicle is a transport intermediate rather than a site of function. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endosome membrane; Single-pass type I membrane |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-2130486 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in clathrin-coated endocytic vesicle membranes during CD74-driven internalisation from the plasma membrane and subsequent uncoating. Reason: Internalisation of the class II:CD74 complex in clathrin-coated vesicles is driven by CD74's cytoplasmic sorting motifs rather than by anything the DP alpha chain does, and the coated vesicle is a short-lived transport intermediate. The localisation is correct for the complex but is not a site at which this chain functions. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-2130725 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in clathrin-coated endocytic vesicle membranes during CD74-driven internalisation from the plasma membrane and subsequent uncoating. Reason: Internalisation of the class II:CD74 complex in clathrin-coated vesicles is driven by CD74's cytoplasmic sorting motifs rather than by anything the DP alpha chain does, and the coated vesicle is a short-lived transport intermediate. The localisation is correct for the complex but is not a site at which this chain functions. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also |
| GO:0031902 late endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in) placing the class II molecule in the late endosome membrane, the MIIC compartment where CLIP is exchanged for antigenic peptide. Reason: The late endosome/MIIC is the compartment in which the DP molecule is catalytically engaged - CD74 is trimmed, HLA-DM releases CLIP, and antigenic peptide binds the alpha-1/beta-1 groove - so is_active_in is the appropriate relation. The node placement is consistent with experimental localisation of the human DR and DM/DO chains and with the curated UniProt endosome-membrane location for DP alpha itself. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endosome membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt degradation by various proteases; leaving a small fragment file:human/HLA-DPA1/HLA-DPA1-uniprot.txt presentation pathway is usually referred to as exogenous. |
| GO:0032395 MHC class II receptor activity | NAS PMID:2461352 Epitope recognition by a DP alpha chain-specific monoclonal ... | REMOVE | Summary: NAS row asserting MHC class II receptor activity for the DP alpha chain, traced to the DP11.1 antibody epitope paper. Reason: The term is explicitly scoped by GO to the opposite side of this interaction: its comment reads "Note that this term is intended for annotation of gene products that act as receptors for MHC class II protein complexes, not for components of the MHC class II protein complexes themselves" (verified in OLS). HLA-DPA1 is a constituent subunit of a class II complex, not a receptor for one - that role belongs to CD4 and LAG3 - so the annotation inverts the relationship. The cited NAS reference is a monoclonal-antibody epitope-mapping study that makes no receptor-activity claim at all; it supports only surface expression and alpha/beta pairing. The correct molecular function statements for this chain, GO:0042605 peptide antigen binding and part_of GO:0042613, are already present. Supporting Evidence: PMID:2461352 epitope is influenced by the associations between the DP alpha chain and its file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2130378 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2130393 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2130619 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2130641 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2213236 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-8951498 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II:CD74 complex in the trans-Golgi network membrane during AP-1/clathrin coat assembly and sorting towards the lysosome or the plasma membrane. Reason: The assembled class II alpha/beta heterodimer does traverse this compartment on its way from the ER to the peptide-loading compartment and the cell surface, so the localisation claim is correct and the Reactome reaction it is drawn from is a real step in the class II pathway. It is kept as non-core because the DP alpha chain executes no function here: peptide loading happens in the late endosomal/lysosomal MIIC and presentation at the plasma membrane, and this is a transit stop en route. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Golgi apparatus, trans-Golgi network membrane; Single-pass file:human/HLA-DPA1/HLA-DPA1-uniprot.txt The MHC class II complex transits through a number of file:human/HLA-DPA1/HLA-DPA1-uniprot.txt intracellular compartments in the endocytic pathway until it reaches |
| GO:0032729 positive regulation of type II interferon production | IMP PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | KEEP AS NON CORE | Summary: IMP row based on the DP2 study, where beryllium presented by DP2-expressing fibroblasts drove IFN-gamma production by a patient-derived CD4 T-cell line (16% responding versus 0.2% unpulsed), an effect abolished by acidic-pocket mutations. Reason: The experiment is sound and the DP molecule is genuinely upstream of the response, so the row is retained. It is non-core because the IFN-gamma is produced by the responding T cell, not by the antigen-presenting cell: the DP alpha chain's own activity is peptide display, and cytokine induction is a downstream consequence in a second cell. Treating it as a core function would conflate the presenting molecule with the responding cell's effector programme. Supporting Evidence: PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts PMID:20356827 all four of the mutant DP2 molecules were unable to present Be to the T-cell line file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. |
| GO:0042102 positive regulation of T cell proliferation | IMP PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | KEEP AS NON CORE | Summary: IMP row from the same DP2 study, where beryllium-induced proliferation of the DP2-restricted CD4 T-cell line required an intact DP2 acidic pocket. Reason: Correct as an indirect, downstream effect of antigen display: the proliferating cell is the responding CD4 T cell, and the DP molecule contributes by presenting the ligand that triggers it. Retained as non-core for the same reason as the IFN-gamma row - the proliferation programme is executed in another cell, not by this gene product. Supporting Evidence: PMID:20356827 Similar findings were seen when Be-induced proliferation was used as a measure of T-cell response PMID:20356827 all four of the mutant DP2 molecules were unable to present Be to the T-cell line PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts |
| GO:0042605 peptide antigen binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA on the class II PAINT node for peptide antigen binding, with human HLA-DPA1 (UniProtKB:P20036) among the descendant evidences. Reason: Peptide binding by the alpha-1/beta-1 groove is the ancestral molecular function of the class II family, and the GO term carries the explicit comment that it "can be used to describe the binding of a peptide to an MHC molecule" (verified in OLS). The IBD node is supported by experimental data in mouse H2-A chains and human DR as well as by DP alpha's own crystallographic evidence, so the target is squarely inside the clade that inherited the function. Supporting Evidence: PMID:20356827 The Ξ±1 and Ξ²1 domains of DP2 form the peptide-binding groove, and the peptide takes an extended polyproline-like helical course through the groove. PMID:20356827 its depth is due to the amino acids Ξ±Ala11 and Ξ²Gly11, whose small side chains open up the bottom of the pocket file:human/HLA-DPA1/HLA-DPA1-uniprot.txt binding cleft accommodates peptides of 10-30 residues. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the |
| GO:0042605 peptide antigen binding | IDA PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | ACCEPT | Summary: IDA row from the DP2 crystal structure, which resolves a self-peptide derived from the HLA-DR alpha chain bound in the groove formed by the DP alpha-1 and DP beta-1 domains. Reason: This is direct structural demonstration of the activity for this very gene product: the crystallised molecule is DPA1*01:03/DPB1*02:01 with pDRA occupying the cleft, and alpha-chain residues are shown to define the pockets that read out peptide side chains (alphaAla11 opening the bottom of the p6 pocket; alphaArg76 forming the conserved cleft-stabilising salt bridge). This is the core molecular function of the protein. Supporting Evidence: PMID:20356827 we crystallized DP2 ( DPA1*0103 , DPB1*0201 ) with a bound self-peptide derived from the HLA-DR Ξ±-chain (pDRA) PMID:20356827 The Ξ±1 and Ξ²1 domains of DP2 form the peptide-binding groove, and the peptide takes an extended polyproline-like helical course through the groove. PMID:20356827 its depth is due to the amino acids Ξ±Ala11 and Ξ²Gly11, whose small side chains open up the bottom of the pocket PMID:20356827 forming a conserved salt bridge across to Ξ±Arg76 that is important in the formation of the antigen-binding cleft |
| GO:0042613 MHC class II protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (part_of) on the class II PAINT node for membership of the MHC class II protein complex, with HLA-DPA1 itself among the descendant evidences. Reason: Complex membership is the structural fact underpinning everything else this gene does; the complex is defined as an alpha plus a beta chain with or without bound antigen, and the DP alpha chain is the alpha constituent. The node placement is unambiguous for the class II alpha/beta family and HLA-DPA1 appearing in its own WITH/FROM reflects its own IDA evidence contributing to the IBD, which is expected rather than circular. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as PMID:20356827 we crystallized DP2 ( DPA1*0103 , DPB1*0201 ) with a bound self-peptide derived from the HLA-DR Ξ±-chain (pDRA) file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Belongs to the MHC class II family. |
| GO:0042613 MHC class II protein complex | IDA PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | ACCEPT | Summary: IDA (part_of) from the DP2 crystal structure and the accompanying surface-staining experiments, which show the DP alpha chain assembled with a DP beta chain into a peptide-bearing class II heterodimer. Reason: The structure of DPA1*01:03/DPB1*02:01 with a bound self-peptide is direct evidence of membership in the class II complex, and conformation-dependent anti-DP antibody staining confirms the assembled heterodimer reaches the cell surface. Independently, the DP11.1 study shows that the DP alpha chain's surface epitope depends on which polymorphic beta chain it pairs with, i.e. obligate heterodimerisation. Supporting Evidence: PMID:20356827 we crystallized DP2 ( DPA1*0103 , DPB1*0201 ) with a bound self-peptide derived from the HLA-DR Ξ±-chain (pDRA) PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 PMID:2461352 epitope is influenced by the associations between the DP alpha chain and its file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0042613 MHC class II protein complex | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from the InterPro class II alpha-chain signatures (IPR001003 MHC_II_a_N, IPR014745 MHC_II_a/b_N) to membership of the MHC class II protein complex. Reason: The signatures that fire on this protein are the class II alpha N-terminal domain families, so the inference that the protein is a class II complex constituent is exactly what the domain content implies, and it agrees with the IDA and IBA rows for the same term. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Belongs to the MHC class II family. file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0050778 positive regulation of immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA on a broad node for positive regulation of the immune response, seeded from class II chains together with CD74 (MGI:88127) and B2M (P61769). Reason: The direction of effect is right - class II-restricted presentation activates CD4 T-cell responses - but the term is a high-level regulatory grouping that says much less than the GO:0019886 and GO:0050870 rows the gene already carries, and the donor set mixes class II chains with accessory molecules from both class I and class II pathways. Retained as a true but non-core statement rather than removed, since the node placement itself is not in doubt. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts |
| GO:0050870 positive regulation of T cell activation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA on the class II PAINT node for positive regulation of T cell activation, with HLA-DPA1 among the descendant evidences. Reason: Activating CD4 T cells by displaying peptide to them is the purpose of the molecule, and the gene product does part of the work rather than merely being required for the outcome: the groove it half-builds, with its bound peptide, is the ligand the TCR reads. The node placement is supported by experimental data across mouse and human class II chains. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Binds peptides derived from antigens that access the file:human/HLA-DPA1/HLA-DPA1-uniprot.txt the cell surface for recognition by the CD4 T-cells. PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts PMID:20356827 Similar findings were seen when Be-induced proliferation was used as a measure of T-cell response |
| GO:0050870 positive regulation of T cell activation | IMP PMID:20356827 Crystal structure of HLA-DP2 and implications for chronic be... | ACCEPT | Summary: IMP row from the DP2 study: DP2-expressing fibroblasts pulsed with beryllium activated a DP2-restricted CD4 T-cell line (IFN-gamma production and proliferation), and acidic-pocket mutants that still assembled and still presented superantigen failed to do so. Reason: The assayed presenting molecule is the DPA1*01:03-containing DP2 heterodimer, and the mutant controls show the effect depends on an intact antigen-binding surface rather than on expression level, so the activation of the T cell is attributable to the presenting molecule's ligand-display activity. The curator had the full text; the specificity controls make this a strong row. Supporting Evidence: PMID:20356827 16% of the T cells responded with production of IFN-Ξ³ versus only 0.2% when using unpulsed fibroblasts PMID:20356827 Similar findings were seen when Be-induced proliferation was used as a measure of T-cell response PMID:20356827 all four of the mutant DP2 molecules were unable to present Be to the T-cell line PMID:20356827 Fibroblasts transfected with each of the mutant DP2 molecules expressed DP2 equally well on the cell surface, as detected by staining with a conformation-dependent anti-DP mAb, B7.21 |
| GO:0071346 cellular response to type II interferon | IDA PMID:8568247 A zinc finger protein that represses transcription of the hu... | KEEP AS NON CORE | Summary: IDA row traced to the XBR study, which showed that the DPA promoter is induced by IFN-gamma in HeLa cells and that this induction is repressed by overexpression of the X2-box-binding zinc finger protein XBR. Reason: The underlying observation is sound and the gene is a canonical IFN-gamma-inducible class II gene, so the row is retained. It is non-core because what the paper demonstrates is transcriptional induction of the DPA gene - the protein is the output of the interferon response, not a transducer of it - and the regulatory machinery that executes the response is CIITA and the X-box factors, not the DP alpha chain. The chain's own activities are peptide binding and antigen display. Supporting Evidence: PMID:8568247 reporter gene activity driven from the DPA promoter in HeLa cells treated with PMID:8568247 The proximal promoters of all MHC class II genes contain a sequence element, the |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-2130478 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II ectodomains on the lumenal side of the ER membrane during alpha/beta heterodimer formation, heterononamer assembly with CD74, calnexin release and COPII budding. Reason: The topology is right - the alpha-1/alpha-2 ectodomain of this single-pass type I membrane protein faces the ER lumen, which is where alpha/beta pairing and CD74 assembly occur under calnexin supervision. Kept as non-core for the same reason as the other biosynthetic rows: assembly is biogenesis, and the groove is occupied by CD74 rather than antigen at this stage, so the chain is not yet functioning as a peptide-display molecule. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-2130731 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II ectodomains on the lumenal side of the ER membrane during alpha/beta heterodimer formation, heterononamer assembly with CD74, calnexin release and COPII budding. Reason: The topology is right - the alpha-1/alpha-2 ectodomain of this single-pass type I membrane protein faces the ER lumen, which is where alpha/beta pairing and CD74 assembly occur under calnexin supervision. Kept as non-core for the same reason as the other biosynthetic rows: assembly is biogenesis, and the groove is occupied by CD74 rather than antigen at this stage, so the chain is not yet functioning as a peptide-display molecule. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-2213239 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II ectodomains on the lumenal side of the ER membrane during alpha/beta heterodimer formation, heterononamer assembly with CD74, calnexin release and COPII budding. Reason: The topology is right - the alpha-1/alpha-2 ectodomain of this single-pass type I membrane protein faces the ER lumen, which is where alpha/beta pairing and CD74 assembly occur under calnexin supervision. Kept as non-core for the same reason as the other biosynthetic rows: assembly is biogenesis, and the groove is occupied by CD74 rather than antigen at this stage, so the chain is not yet functioning as a peptide-display molecule. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-2213241 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II ectodomains on the lumenal side of the ER membrane during alpha/beta heterodimer formation, heterononamer assembly with CD74, calnexin release and COPII budding. Reason: The topology is right - the alpha-1/alpha-2 ectodomain of this single-pass type I membrane protein faces the ER lumen, which is where alpha/beta pairing and CD74 assembly occur under calnexin supervision. Kept as non-core for the same reason as the other biosynthetic rows: assembly is biogenesis, and the groove is occupied by CD74 rather than antigen at this stage, so the chain is not yet functioning as a peptide-display molecule. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
| GO:0098553 lumenal side of endoplasmic reticulum membrane | TAS Reactome:R-HSA-8951500 | KEEP AS NON CORE | Summary: Reactome TAS rows placing the class II ectodomains on the lumenal side of the ER membrane during alpha/beta heterodimer formation, heterononamer assembly with CD74, calnexin release and COPII budding. Reason: The topology is right - the alpha-1/alpha-2 ectodomain of this single-pass type I membrane protein faces the ER lumen, which is where alpha/beta pairing and CD74 assembly occur under calnexin supervision. Kept as non-core for the same reason as the other biosynthetic rows: assembly is biogenesis, and the groove is occupied by CD74 rather than antigen at this stage, so the chain is not yet functioning as a peptide-display molecule. Supporting Evidence: file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Endoplasmic reticulum membrane; Single-pass type I membrane file:human/HLA-DPA1/HLA-DPA1-uniprot.txt 3 MHC class II molecules bind to a CD74 homotrimer (also file:human/HLA-DPA1/HLA-DPA1-uniprot.txt Heterodimer of an alpha and a beta subunit; also referred as |
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Download this section (compressed HTML)Q: Does the HLA-DP alpha chain contribute measurably to the T-cell receptor interface? The one published DP/TCR co-complex reports a tilted footprint made "at the expense of the DP2 alpha chain helix", which is the opposite of the usual class II geometry and leaves it unclear whether a GO:0042608 T cell receptor binding annotation (which HLA-DRA and HLA-DRB1 both carry by IDA) is appropriate for DP alpha chains in general or is excluded by an isotype-specific geometry.
Suggested experts: Clayton GM, Kappler JW, Dai S
Q: How much of HLA-DP peptide-repertoire specificity is set by the modestly polymorphic alpha chain rather than by DPB1? The DP2 structure shows alpha-chain residues forming part of the p6 pocket floor, yet DP disease associations are nearly always reported in terms of beta-chain positions, and DPA1-DPB1 haplotype linkage makes the contributions hard to separate epidemiologically.
Suggested experts: Dai S, Fontenot AP
Q: Is the reported HLA-DPA1/SREBF2 association biologically meaningful, or an artefact of overexpressing a membrane protein in AP-MS? It is the only interaction UniProt records for P20036, it recurs across BioPlex datasets, and no mechanism has been proposed; resolving it would determine whether any informative molecular function should replace the removed generic protein binding rows.
Suggested experts: Huttlin EL, Harper JW
Q: Should the HLA-DP alpha chain carry an annotation for its role as a ligand of the activating NK-cell receptor NKp44? NKp44 binds a subset of assembled HLA-DP molecules directly (PMID:31358998), and the DPA1*02:01~DPB1*01:01 haplotype drives NKp44+ NK-cell degranulation against cholangiocyte organoids (PMID:37788895), which would make HLA-DP a class II ligand for an innate receptor in addition to its CD4 T-cell role. Both the binding and the genetics are resolved at the level of the DPA1-DPB1 pair rather than the alpha chain alone, so no annotation was proposed here.
Suggested experts: Altfeld M, Carrington M, Niehrs A
Q: Does the HLA-DP-specific use of the class I processing route change which process terms apply to the DP alpha chain? DP molecules whose beta chain carries Gly84 do not present CLIP and constitutively display proteasome-generated, TAP-transported endogenous peptides (PMID:28489076), so for those allotypes GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II may understate the repertoire. The decisive residue is in DPB1, and the existing rows were left unchanged.
Suggested experts: Hirano N
Q: Does the DPA1 allele itself select which endogenous antigens are presented? Holding DPB1*05:01 constant, an EBNA1 epitope was naturally processed and presented by DPA1*02:02 but not DPA1*01:03 (PMID:38412034), which is the most direct evidence that the modestly polymorphic alpha chain sets part of the DP peptide repertoire.
Suggested experts: Chen L
Q: Should GO provide a way to state that a class II constituent subunit contacts the other class II molecules within the CD74 heterononamer, distinct from GO:0023026 MHC class II protein complex binding, which is meant for trans-acting binders such as HLA-DM and HLA-DO? At present the same term is applied to both roles through a shared PANTHER node.
Experiment: Solve or compare additional DP/peptide/TCR co-complexes with TCRs selected against conventional peptide antigens rather than against a metal-modified surface, and quantify per-chain buried surface area and atom-to-atom contacts against matched DR and DQ co-complexes. Complement with surface plasmon resonance on DP molecules carrying alanine substitutions along the alpha-1 helix (alpha55-alpha76) to test whether alpha-chain contacts contribute measurably to TCR affinity.
Hypothesis: The HLA-DP alpha chain makes a smaller contribution to the TCR interface than the alpha chains of other class II isotypes, because of the widened groove and tilted TCR docking seen in DP2.
Type: X-ray crystallography and surface plasmon resonance
Experiment: Express matched sets of DP heterodimers in which the DPB1 allele is held constant while DPA1*01:03, *02:01 and *03:01 are varied, immunopurify the molecules from the same cell background, and compare eluted peptide repertoires by immunopeptidomics, scoring motif changes at the p1, p4, p6 and p9 anchor positions. The prediction is a measurable shift at p6, whose pocket floor includes alphaAla11.
Hypothesis: Polymorphic positions in the DPA1 alpha-1 domain alter the bound peptide repertoire independently of the paired DPB1 allele.
Type: Immunopeptidomics (LC-MS/MS of eluted peptides)
Experiment: Test the pair at endogenous levels in a class II-positive cell type (primary monocyte-derived dendritic cells or a B-lymphoblastoid line) by reciprocal endogenous immunoprecipitation followed by immunoblot, and by proximity labelling (BioID or APEX2) from a knock-in tagged HLA-DPA1 allele. Score whether SREBF2 is recovered above the control-bait background, and whether SREBF2 knockdown changes DP surface level, CLIP occupancy or presentation of a model antigen.
Hypothesis: The HLA-DPA1/SREBF2 co-purification does not reflect an interaction that occurs at endogenous expression levels in antigen-presenting cells.
Type: Endogenous co-immunoprecipitation and proximity labelling
Experiment: In a DPA1-knockout antigen-presenting line reconstituted with wild-type DPA1 or with groove-face alpha-chain point mutants (e.g. alphaAla11 substitutions that fill the p6 pocket floor, or alphaArg76 substitutions that break the conserved salt bridge), measure surface DP level with a conformation-dependent antibody, CLIP occupancy, and presentation of a defined DP-restricted peptide to a reporter T-cell line. Mutants that assemble and reach the surface normally but fail to present would separate the chain's structural role from its direct contribution to peptide binding.
Hypothesis: The DP alpha chain is required for, and does part of the work of, peptide loading rather than only enabling beta-chain expression.
Type: CRISPR knockout and structure-guided mutant reconstitution with T-cell reporter assay
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