CD3 epsilon is a single-pass membrane subunit of the T-cell antigen-receptor complex. Its extracellular and transmembrane contacts assemble CD3 gamma-epsilon and delta-epsilon heterodimers with the clonotypic receptor, while its cytoplasmic basic region, proline-rich sequence and ITAM recruit signaling proteins including LCK, NCK, ZAP70 and SYK. CD3 epsilon coordinates these interactions without intrinsic kinase activity. Ligand recognition by the clonotypic chains is thereby coupled to T-cell signaling; CD3 epsilon also receives an inhibitory input from ITPRIPL1 and participates in LAG3-associated regulation of the receptor. CD3E disruption causes immunodeficiency 18, a T-B+NK+ severe combined immunodeficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001772 immunological synapse | IEA GO_REF:0000107 | ACCEPT | Summary: CD3 epsilon participates in the immunological synapse. Reason: The exact mouse orthology source remains intact. Synaptic localization is consistent with its membrane TCR-complex role and human NCK-recruitment evidence; this does not relabel the original transfer as a direct human localization experiment. Supporting Evidence: |
| GO:0001954 positive regulation of cell-matrix adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-derived cell-matrix adhesion response. Reason: The original mouse-CD3-epsilon transfer is retained. In the author reproduction of PMID:12652296 (https://doi.org/10.1038/ni913), anti-mouse-CD3 stimulation increases binding to fibronectin, with BSA-coated and unstimulated controls; human SKAP55 is the transfected adaptor in mouse T8.1 cells, not a human CD3E construct. This supports receptor-dependent positive regulation in the donor context, not intrinsic integrin binding or a human-specific assay. The 2025 correction replaces a Vector image and states that results and conclusions are unaffected. Supporting Evidence: |
| GO:0001954 positive regulation of cell-matrix adhesion | ISS PMID:12652296 SKAP-55 regulates integrin adhesion and formation of T cell-... | KEEP AS NON CORE | Summary: Retain the mouse-derived cell-matrix adhesion response. Reason: The original mouse-CD3-epsilon transfer is retained. In the author reproduction of PMID:12652296 (https://doi.org/10.1038/ni913), anti-mouse-CD3 stimulation increases binding to fibronectin, with BSA-coated and unstimulated controls; human SKAP55 is the transfected adaptor in mouse T8.1 cells, not a human CD3E construct. This supports receptor-dependent positive regulation in the donor context, not intrinsic integrin binding or a human-specific assay. The 2025 correction replaces a Vector image and states that results and conclusions are unaffected. Supporting Evidence: |
| GO:0002250 adaptive immune response | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | KEEP AS NON CORE | Summary: CD3 epsilon supports adaptive immune responses through antigen-receptor signaling. Reason: This broad NAS process is consistent with the signaling and assembly role summarized in PMID:29789755. It is retained as broader biological context; the core uses the more specific T-cell receptor signaling process. The cited synthesis is not presented as a new target perturbation experiment. Supporting Evidence: |
| GO:0002250 adaptive immune response | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | KEEP AS NON CORE | Summary: CD3 epsilon supports adaptive immune responses through antigen-receptor signaling. Reason: This broad NAS process is consistent with the signaling and assembly role summarized in PMID:30976362. It is retained as broader biological context; the core uses the more specific T-cell receptor signaling process. The cited synthesis is not presented as a new target perturbation experiment. Supporting Evidence: |
| GO:0004888 transmembrane signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the curated inherited transmembrane receptor function. Reason: The PAINT assertion describes a conserved receptor-complex subunit function. Human assembly and signaling evidence supports this placement; the family tree/MSA and IBD node were not independently reconstructed. Inclusion of the target among descendant evidence is valid, not circular. |
| GO:0004888 transmembrane signaling receptor activity | IC PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: CD3 epsilon contributes to signaling by the assembled TCR. Reason: The IC derives from alpha-beta TCR complex membership. CD3 epsilon provides physical assembly and cytoplasmic signaling interfaces, while the clonotypic chains recognize peptide-MHC. Retain the source assertion without assigning intrinsic kinase activity or peptide-MHC specificity to epsilon. |
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: CD3 epsilon is a receptor for the inhibitory ligand ITPRIPL1. Reason: The original primary abstract reports binding of ITPRIPL1 to CD3 epsilon and inhibition of TCR responses. This is target-specific receptor evidence, distinct from its complex-level peptide-MHC contribution. The canonical source is abstract-only; detailed human, mouse and canine assay contexts must not be conflated. Supporting Evidence: PMID:38614099 an inhibitory ligand of CD3Ξ΅ |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: The domain-based receptor annotation agrees with target biology. Reason: The InterPro source is retained. Independent human TCR assembly and ITPRIPL1 receptor evidence supports the general transmembrane signaling role; the annotation does not imply that CD3 epsilon supplies catalytic chemistry. |
| GO:0005515 protein binding | IPI PMID:11855827 Phosphorylation of the N-terminal and C-terminal CD3-epsilon... | MODIFY | Summary: Specify binding to the tyrosine kinase ZAP70. Reason: The annotated partner is ZAP70. The original CD8/CD3-epsilon tail chimera and ITAM tyrosine mutants support phosphorylation-dependent ZAP70 association; that construct context is retained. Direct phospho-ITAM/SH2 measurements independently corroborate this interface. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:11855827 phenylalanine substitution at the N-terminal tyrosine residue of the CD3-epsilon-ITAM abolished signal transduction functions of this ITAM, including phosphorylation at the C-terminal ITAM tyrosine, and its association with ZAP-70 PMID:7761456 The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. |
| GO:0005515 protein binding | IPI PMID:17617578 Reciprocal regulation of SH3 and SH2 domain binding via tyro... | MODIFY | Summary: Specify CD3-epsilon binding to the SH3 domain of NCK2. Reason: The primary phage-library and recombinant-domain study identifies NCK2 among SH3 proteins recognizing the CD3-epsilon PxxDY region. The target supplies the proline-rich binding sequence; the SH3 domain belongs to the partner. The original partner accession is preserved. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0005515 protein binding | IPI PMID:17617578 Reciprocal regulation of SH3 and SH2 domain binding via tyro... | MODIFY | Summary: Specify CD3-epsilon binding to the SH3 domain of NCK1. Reason: The primary phage-library and recombinant-domain study identifies NCK1 among SH3 proteins recognizing the CD3-epsilon PxxDY region. The target supplies the proline-rich binding sequence; the SH3 domain belongs to the partner. The original partner accession is preserved. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0005515 protein binding | IPI PMID:17617578 Reciprocal regulation of SH3 and SH2 domain binding via tyro... | MODIFY | Summary: Specify CD3-epsilon binding to the SH3 domain of EPS8L1. Reason: The primary phage-library and recombinant-domain study identifies EPS8L1 among SH3 proteins recognizing the CD3-epsilon PxxDY region. The target supplies the proline-rich binding sequence; the SH3 domain belongs to the partner. The original partner accession is preserved. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0005515 protein binding | IPI PMID:18424730 Carcinoembryonic antigen-related cell adhesion molecule 1 in... | KEEP AS NON CORE | Summary: Retain the CEACAM1-associated TCR/CD3 interaction. Reason: The primary abstract explicitly reports CEACAM1 association with the TCR/CD3 complex and recruitment of SHP1 in activated human T-cell contexts. This supports the curated qualitative association; it does not demonstrate a purified binary CD3-epsilon/CEACAM1 interface or make epsilon a phosphatase. The exact epsilon-specific original co-IP panel was not independently recovered. Supporting Evidence: PMID:18424730 CEACAM1 associates with and recruits SHP-1 to the TCR/CD3 complex |
| GO:0005515 protein binding | IPI PMID:18644376 Structural basis of PxxDY motif recognition in SH3 binding. | MODIFY | Summary: Specify EPS8L1 SH3-domain recognition. Reason: The original NMR study examines the EPS8L1 SH3 domain with a CD3-epsilon peptide and defines the extended binding interface. This is binding by the epsilon peptide to a partner SH3 domain, not an SH3 domain on epsilon. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:18644376 The CD3epsilon peptide binds Eps8L1 SH3 in a class II orientation, but neither adopts a polyproline II helical conformation nor engages the first proline-binding pocket of the SH3 ligand binding interface. |
| GO:0005515 protein binding | IPI PMID:18955169 Interaction between the N-terminal SH3 domain of Nck-alpha a... | MODIFY | Summary: Specify the NCK1 SH3.1 interaction. Reason: The original NMR complex uses the NCK1 SH3.1 domain and the CD3-epsilon peptide. It directly supports a domain-specific refinement with the annotated NCK1 partner retained. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:18955169 The first SH3 domain (SH3.1) of Nckalpha specifically recognizes the proline-rich region of CD3varepsilon, a subunit of the T cell receptor complex. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the independently corroborated NCK2 interaction to SH3-domain binding. Reason: The original HuRI source remains an interaction-screen citation whose exact target table was not re-read. The same human NCK2-CD3E edge is present in reviewed UniProt, and independent PMID:17617578 establishes NCK2 SH3 recognition of the CD3-epsilon motif. This refinement uses that separate target/partner evidence, not an inferred screen interface. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the curated ZFPL1 interaction. Reason: The exact O95159 partner is also recorded in the IntAct-derived UniProt interaction block. The GOA and UniProt records surface the same underlying interaction evidence; they are not independent experimental replications. The original HuRI pair-level table and construct were not inspected. Under the standing binding policy, this curated same-source record supports retention; partner identity alone does not establish a signaling mechanism, interface or a more specific activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the curated ADAM33 interaction. Reason: The exact Q08AM2 partner is also recorded in the IntAct-derived UniProt interaction block. The GOA and UniProt records surface the same underlying interaction evidence; they are not independent experimental replications. The original HuRI pair-level table and construct were not inspected. Under the standing binding policy, this curated same-source record supports retention; partner identity alone does not establish a signaling mechanism, interface or a more specific activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the curated BNIP3 interaction. Reason: The exact Q12983 partner is also recorded in the IntAct-derived UniProt interaction block. The GOA and UniProt records surface the same underlying interaction evidence; they are not independent experimental replications. The original HuRI pair-level table and construct were not inspected. Under the standing binding policy, this curated same-source record supports retention; partner identity alone does not establish a signaling mechanism, interface or a more specific activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the curated MUC15 interaction. Reason: The exact Q8N387 partner is also recorded in the IntAct-derived UniProt interaction block. The GOA and UniProt records surface the same underlying interaction evidence; they are not independent experimental replications. The original HuRI pair-level table and construct were not inspected. Under the standing binding policy, this curated same-source record supports retention; partner identity alone does not establish a signaling mechanism, interface or a more specific activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the curated PKMYT1 isoform 2 interaction. Reason: The exact Q99640-2 partner is also recorded in the IntAct-derived UniProt interaction block. The GOA and UniProt records surface the same underlying interaction evidence; they are not independent experimental replications. The original HuRI pair-level table and construct were not inspected. Under the standing binding policy, this curated same-source record supports retention; partner identity alone does not establish a signaling mechanism, interface or a more specific activity. |
| GO:0005515 protein binding | IPI PMID:7761456 Analysis of the interaction of ZAP-70 and syk protein-tyrosi... | MODIFY | Summary: Specify binding of the CD3-epsilon ITAM to ZAP70. Reason: The primary surface-plasmon-resonance study directly measures binding of the tandem SH2 domains of ZAP70 to the CD3-epsilon phospho-ITAM. This supports protein tyrosine kinase binding without assigning kinase catalysis to CD3E. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:7761456 The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. |
| GO:0005515 protein binding | IPI PMID:7761456 Analysis of the interaction of ZAP-70 and syk protein-tyrosi... | MODIFY | Summary: Specify binding of the CD3-epsilon ITAM to SYK. Reason: The primary surface-plasmon-resonance study directly measures binding of the tandem SH2 domains of SYK to the CD3-epsilon phospho-ITAM. This supports protein tyrosine kinase binding without assigning kinase catalysis to CD3E. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:7761456 The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. |
| GO:0005515 protein binding | IPI PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | MODIFY | Summary: Specify heterodimer formation with CD3 delta. Reason: The original biochemical study identifies epsilon dimers with CD3 delta; the human 2019 structure independently resolves the corresponding assembly interface. Retaining heterodimerization does not endorse the older paperβs proposed two-TCR-alpha-beta stoichiometry. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:9485181 dimers of CD3 epsilon with either CD3 gamma or CD3 delta |
| GO:0005515 protein binding | IPI PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | MODIFY | Summary: Specify heterodimer formation with CD3 gamma. Reason: The original biochemical study identifies epsilon dimers with CD3 gamma; the human 2019 structure independently resolves the corresponding assembly interface. Retaining heterodimerization does not endorse the older paperβs proposed two-TCR-alpha-beta stoichiometry. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:9485181 dimers of CD3 epsilon with either CD3 gamma or CD3 delta |
| GO:0005515 protein binding | IPI PMID:9698567 Structural basis for Syk tyrosine kinase ubiquity in signal ... | MODIFY | Summary: Specify SYK binding with the original structural source retained. Reason: The source reports a SYK tandem-SH2/phospho-ITAM complex; its abstract does not identify every peptide construct. The original curated partner is independently corroborated by the direct CD3-epsilon binding measurements in PMID:7761456 and reviewed UniProt. The broader tyrosine-kinase-binding refinement is supported without inventing the original crystal peptide sequence. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:7761456 The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. |
| GO:0005886 plasma membrane | EXP PMID:10384095 The CD3 epsilon subunit of the TCR contains endocytosis sign... | ACCEPT | Summary: Retain plasma-membrane localization. Reason: The primary abstract explicitly studies cell-surface CD3-epsilon endocytosis determinants. Trafficking of the subunit is compatible with its established surface-receptor role; no isolated endosomal core is inferred. Supporting Evidence: PMID:10384095 expressed on the cell surface independently of other TCR-CD3 subunits |
| GO:0005886 plasma membrane | EXP PMID:15294938 Relevance of CD6-mediated interactions in T cell activation ... | ACCEPT | Summary: Retain plasma-membrane CD3-epsilon. Reason: The complete PMID:15294938 abstract reports CD6 association with TCR/CD3 by coimmunoprecipitation, cocapping and FRET, and localization of the complexes at T-cell/APC synapses. It is not a CD3 structural paper. Retain the curated plasma-membrane assertion with independent human CD3-epsilon surface labeling in PMID:11390434; the original CD6 study's exact epsilon-specific reagent and full Methods were not inspected. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the curated immunofluorescence localization. Reason: This method-coded direct annotation agrees with independent human surface labeling and receptor assembly. The individual GO_REF:0000052 imaging record was not inspected; method provenance is not substituted for a biological quote. |
| GO:0005886 plasma membrane | IDA PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell rece... | ACCEPT | Summary: Human Jurkat assays directly place CD3-epsilon at the cell surface. Reason: The inspected original Methods use CD3-epsilon antibodies, external biotinylation and immunoprecipitation; Results measure surface epsilon and its internalization. TRIM manipulation changes receptor abundance, not the identity of the epsilon localization. Supporting Evidence: PMID:11390434 CD3Ξ΅ expression on the cell surface |
| GO:0005886 plasma membrane | IDA PMID:31461748 Structural basis of assembly of the human T cell receptor-CD... | ACCEPT | Summary: The human TCR structure contains membrane-spanning CD3-epsilon. Reason: The primary structure resolves extracellular and transmembrane regions of the assembled human complex. The canonical cache is abstract-only; an external author reproduction and the official correction identify construct-information additions, not an alternate localization. Supporting Evidence: PMID:31461748 two transmembrane helices of CD3΢΢ with those of CD3γΡ and CD3δΡ |
| GO:0005886 plasma membrane | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: The inhibitory-ligand study supports membrane CD3-epsilon activity. Reason: Preserve the source qualifier is_active_in. The receptor-ligand abstract and independent human surface assays support the plasma membrane as a site of function. Mouse and canine tumor outcomes do not by themselves establish the human molecular interface. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined-method plasma-membrane annotation. Reason: This electronic assertion combines subcellular-location and orthology inputs. Independent human surface measurements establish the localization, without claiming to have inspected each automated mapping step. Supporting Evidence: |
| GO:0005886 plasma membrane | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: Retain plasma membrane as the established receptor location. Reason: This NAS reference is a review of CD3 signaling. The location is independently supported by primary human cell-surface labeling and the assembled human receptor structure. |
| GO:0005886 plasma membrane | NAS PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: Retain membrane localization of the human assembly intermediates and receptor. Reason: The original biochemical work examines the human TCR/CD3 complex. Its epsilon heterodimers and surface-complex observations support localization without endorsing the historical receptor stoichiometric model. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-198955 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places TCR binding to peptide-MHC I in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202165 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places LCK-mediated ITAM phosphorylation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202168 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places ZAP70 phosphorylation by LCK in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202174 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places ZAP70 activation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places CD45-dependent LCK dephosphorylation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202216 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places SLP76 phosphorylation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202233 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places CSK-dependent LCK inactivation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202245 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places LAT phosphorylation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202248 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places PLC-gamma1 phosphorylation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202291 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places LCK activation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202307 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places PKC-theta conformational activation in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202344 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places ZAP70 recruitment to ITAMs in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389758 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places PD1-associated phosphatase action in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850326 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places TCR recognition of self-lipid/CD1 in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850356 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places TCR recognition of microbial lipid/CD1 in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8852200 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places PTPN22 action on LCK in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855381 | ACCEPT | Summary: Retain the plasma-membrane receptor context. Reason: The complete cached Reactome summary places PTPN22 action on ZAP70 in a membrane receptor-signaling context. CD3E is retained as a TCR-complex component localized to the plasma membrane; this location row does not assign the catalytic or ligand-recognition step to epsilon. Human primary surface evidence independently supports the compartment. |
| GO:0005911 cell-cell junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain broad cell-cell-junction localization. Reason: The mouse-derived electronic location is compatible with recruitment of the TCR complex to lymphocyte contact interfaces. It is a broader contextual location than the immunological synapse, not evidence that CD3E is an epithelial junction scaffold. The exact donor imaging record was not re-read. Supporting Evidence: |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the broad receptor-signaling process. Reason: The curated PAINT placement is retained; its ancestral node and alignment were not independently reconstructed. CD3E itself assembles and recruits signaling proteins; the core uses the more specific T-cell receptor signaling pathway. |
| GO:0007166 cell surface receptor signaling pathway | IC PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | KEEP AS NON CORE | Summary: Retain the broad receptor-signaling process. Reason: The IC follows membership in the alpha-beta TCR complex. CD3E itself assembles and recruits signaling proteins; the core uses the more specific T-cell receptor signaling pathway. |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain the broad receptor-signaling process. Reason: The InterPro-derived inference agrees with the established signaling subunit role. CD3E itself assembles and recruits signaling proteins; the core uses the more specific T-cell receptor signaling pathway. |
| GO:0007166 cell surface receptor signaling pathway | NAS PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | KEEP AS NON CORE | Summary: Retain the broad receptor-signaling process. Reason: The original NCK-recruitment study explicitly couples TCR engagement to the CD3-epsilon signaling interface. CD3E itself assembles and recruits signaling proteins; the core uses the more specific T-cell receptor signaling pathway. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | TAS PMID:8530500 Interaction between G proteins and tyrosine kinases upon T c... | MARK AS OVER ANNOTATED | Summary: The source supports TCR-associated kinase signaling rather than the specified receptor-kinase pathway. Reason: GO:0007169 requires a cell-surface receptor that possesses tyrosine kinase activity. The cited report describes anti-CD3-triggered signaling, G-alpha-q/11 nucleotide exchange and regulation involving associated protein tyrosine kinases; these are not receptor-intrinsic kinase chemistry. CD3 epsilon recruits kinases within a nonenzymatic receptor complex. This source-specific term mismatch supports overannotation, not a claim that CD3E could never influence another receptor pathway. The original full Methods remain inaccessible. |
| GO:0007172 signal complex assembly | TAS PMID:8490660 Independent mutations of the human CD3-epsilon gene resultin... | ACCEPT | Summary: CD3 epsilon contributes directly to assembly of a signaling receptor complex. Reason: The current GO definition describes aggregation, arrangement and bonding of components to form a complex capable of relaying a signal within a cell, and GO:0007172 sits under both protein-containing complex assembly and regulation of signal transduction. CD3 epsilon directly contributes extracellular and transmembrane interfaces that assemble the TCR-CD3 signaling complex, so the term fits the physical receptor assembly step. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:8530500 Interaction between G proteins and tyrosine kinases upon T c... | UNDECIDED | Summary: The reported G-protein coupling merits source-specific uncertainty. Reason: The original abstract reports G-alpha-q/11 nucleotide exchange, CD3-epsilon association and G-alpha11-dependent PLC-beta signaling after anti-CD3 stimulation. GO:0007186 defines receptor-promoted GDP/GTP exchange on an associated heterotrimeric G protein and does not explicitly impose a seven-transmembrane topology. Thus the term cannot be rejected solely from CD3E architecture. The complete original coupling controls and construct context remain inaccessible; retain uncertainty about this particular assignment rather than declaring the observation impossible or unreplicated. Supporting Evidence: |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the extracellular side of the plasma membrane. Reason: The inherited localization agrees with the extracellular CD3-epsilon domain of the human receptor. A single-pass subunit also has a cytoplasmic tail, so this assertion does not place the entire molecule outside the cell. The PAINT tree and node were not independently reconstructed. |
| GO:0009897 external side of plasma membrane | IDA PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell rece... | ACCEPT | Summary: External labeling directly supports the extracellular membrane face. Reason: The inspected human Jurkat Methods label external proteins and capture CD3-epsilon; surface antibody recognition and immunofluorescence support the external-facing domain. This is not a claim that the cytoplasmic ITAM is extracellular. Supporting Evidence: PMID:11390434 For biotinylation of cell surface molecules, Jurkat T cells were washed twice with ice cold PBS, adjusted to 10 Γ 106 cells/ml, and labeled with 100 ΞΌl biotin (10 mg/ml in PBS; Pierce Chemical Co.) for 20 min at 4Β°C. |
| GO:0009897 external side of plasma membrane | IDA PMID:17213291 FcRL6, a new ITIM-bearing receptor on cytolytic cells, is br... | ACCEPT | Summary: Retain external-facing CD3-epsilon localization. Reason: The complete PMID:17213291 abstract concerns FcRL6 expression and signaling in cytolytic lymphocytes, including samples from HIV-infected individuals; it does not expose the exact CD3-epsilon surface-localization assay. Retention defers to the curated location with independent human extracellular antibody labeling and surface-biotinylation evidence from PMID:11390434 and the extracellular domain in the human TCR-CD3 structure. No wrong-gene attribution or reconstruction of the original FcRL6 study's CD3E reagent is asserted. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the electronic external-membrane-side assignment. Reason: The combined rule and mouse inputs match the established type-I membrane topology. Independent human structure and surface labeling support the biological conclusion; the exact ARBA rule logic was not inspected. |
| GO:0009966 regulation of signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CD3 epsilon regulates receptor signaling through recruitment interfaces. Reason: Direct LCK recruitment and its effect on phosphorylation, together with state-dependent partner recognition, support a regulatory role as well as signal transmission. The broad ARBA process is retained without claiming inspection of its internal rule or a separate core beyond TCR signaling. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: The ARBA gene-expression output is an indirect downstream consequence of TCR signaling. Reason: Receptor-triggered reporter and expression readouts place CD3 epsilon upstream of transcriptional responses, but do not show that it directly regulates gene expression or occupies promoters. The broad ARBA inference projects a pathway output onto the receptor subunit and overstates CD3E's participation. |
| GO:0010628 positive regulation of gene expression | IMP PMID:23817958 Proinflammatory stimuli induce galectin-9 in human mesenchym... | UNDECIDED | Summary: The source-specific positive gene-expression assay is unresolved. Reason: The complete abstract describes human mesenchymal-stromal-cell galectin-9 regulation and effects on stimulated lymphocytes. It does not expose the exact CD3E perturbation or expression endpoint supporting this IMP. Original full Methods/Results were not recovered; neither wrong-gene misattribution nor an antibody-only artifact is asserted. The original Wiley full-text endpoint failed, and the author institutional repository at https://iris.unimore.it/handle/11380/972112 exposes the abstract but restricts the deposited PDF; these access attempts did not resolve the target assay. Supporting Evidence: |
| GO:0010629 negative regulation of gene expression | IMP PMID:23817958 Proinflammatory stimuli induce galectin-9 in human mesenchym... | UNDECIDED | Summary: The source-specific negative gene-expression assay is unresolved. Reason: The complete abstract describes human mesenchymal-stromal-cell galectin-9 regulation and effects on stimulated lymphocytes. It does not expose the exact CD3E perturbation or expression endpoint supporting this IMP. Original full Methods/Results were not recovered; neither wrong-gene misattribution nor an antibody-only artifact is asserted. The original Wiley full-text endpoint failed, and the author institutional repository at https://iris.unimore.it/handle/11380/972112 exposes the abstract but restricts the deposited PDF; these access attempts did not resolve the target assay. Supporting Evidence: |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain the broad membrane parent. Reason: CD3 epsilon is a single-pass membrane receptor subunit. The broad domain-derived compartment is correct but less informative than the experimentally established plasma membrane core. Supporting Evidence: |
| GO:0016358 dendrite development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-derived dendrite development contribution with its knockout limits. Reason: The official dated MGI donor graph links this transfer to PMID:17502348. Selected original mouse Methods and Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC1951947/) show altered Purkinje dendritic development and cerebellar phenotypes in Cd3e-deficient mice. The line also lacks detectable Cd3d and has reduced Cd3g, so the perturbation does not isolate an epsilon-only mechanism; no neuron-specific rescue or direct human neural assay was established. Retain the curated orthology assertion as non-core with that complex-level and species boundary. Supporting Evidence: |
| GO:0017124 SH3 domain binding | IPI PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | ACCEPT | Summary: Retain NCK2 SH3-domain binding. Reason: The NCK recruitment study and independent recombinant-domain mapping support CD3-epsilon recognition by NCK SH3.1. Epsilon supplies the proline-rich binding sequence, whereas the partner carries the SH3 domain. Binding is included mechanistically in the receptor-adaptor core. Supporting Evidence: PMID:12110186 ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3 epsilon and results in recruitment of the adaptor protein Nck PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0017124 SH3 domain binding | IPI PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | ACCEPT | Summary: Retain NCK1 SH3-domain binding. Reason: The NCK recruitment study and independent recombinant-domain mapping support CD3-epsilon recognition by NCK SH3.1. Epsilon supplies the proline-rich binding sequence, whereas the partner carries the SH3 domain. Binding is included mechanistically in the receptor-adaptor core. Supporting Evidence: PMID:12110186 ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3 epsilon and results in recruitment of the adaptor protein Nck PMID:17617578 binding of Nck and Eps8L1 SH3 domains was mapped to a PxxDY motif that shared its tyrosine residue (Y166) with the ITAM of CD3epsilon |
| GO:0019901 protein kinase binding | NAS PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | MODIFY | Summary: Refine the broad kinase-binding claim to tyrosine kinase binding. Reason: The original NAS describes the TCR signaling machinery. Independent CD3-epsilon phospho-ITAM/ZAP70-SYK binding and direct LCK recruitment establish the narrower kinase class. This does not claim that the NCK paper alone assayed every kinase interaction. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:7761456 The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. PMID:28659468 CD3Ξ΅ is the only CD3 chain that can efficiently interact with Lck, mainly through the ionic interactions between CD3Ξ΅ basic residue-rich sequence (BRS) and acidic residues in the Unique domain of Lck. |
| GO:0021549 cerebellum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-derived cerebellum development contribution with its knockout limits. Reason: The official dated MGI donor graph links this transfer to PMID:17502348. Selected original mouse Methods and Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC1951947/) show altered Purkinje dendritic development and cerebellar phenotypes in Cd3e-deficient mice. The line also lacks detectable Cd3d and has reduced Cd3g, so the perturbation does not isolate an epsilon-only mechanism; no neuron-specific rescue or direct human neural assay was established. Retain the curated orthology assertion as non-core with that complex-level and species boundary. Supporting Evidence: |
| GO:0030159 signaling receptor complex adaptor activity | NAS PMID:9886373 T lymphocyte development in the absence of CD3 epsilon or CD... | ACCEPT | Summary: CD3 epsilon organizes the receptor signaling complex. Reason: The mouse reconstitution study supports epsilon-dependent pre-TCR assembly, with neighboring CD3D/CD3G suppression explicitly controlled by reconstitution. Human structural and biochemical recruitment evidence independently supports its receptor-adaptor function. It is not a kinase. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:40592325 Proximity between LAG-3 and the T cell receptor guides suppr... | ACCEPT | Summary: Retain direct protein-macromolecule adaptor activity. Reason: The primary LAG3 paper reports association/condensation involving the LAG3 FSAL motif and CD3 epsilon that interferes with LCK recruitment. This supports organization of interacting signaling proteins. The available original abstract and selected publisher text do not justify relabeling all construct/species contexts as human, nor infer intrinsic catalysis. Supporting Evidence: PMID:40592325 LAG-3 forms condensate with TCR signaling component CD3Ξ΅ |
| GO:0030674 protein-macromolecule adaptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the broad adaptor inference. Reason: The combined electronic source agrees with independent human receptor assembly and LCK/NCK recruitment evidence. The core uses the more specific receptor-complex adaptor activity; the individual automated rule was not reconstructed. |
| GO:0032395 MHC class II receptor activity | IDA PMID:1323144 Activation-induced ubiquitination of the T cell antigen rece... | ACCEPT | Summary: Retain the contributes_to qualifier for complex-level MHC-II receptor activity. Reason: The machine qualifier is contributes_to, not a claim that isolated CD3E binds peptide-MHC II. Cached GO-CAM 685de18700002961 assigns this activity to an alpha-beta TCR protein complex containing CD3E, with PMID:1323144 activity evidence and PMID:31461748 subunit evidence. Epsilon supplies assembly and signaling interfaces while clonotypic chains determine specificity; the historical rejection ignored that complex role. |
| GO:0033634 positive regulation of cell-cell adhesion mediated by integrin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-derived integrin-dependent cell-contact response. Reason: Selected original Methods and Results from the author reproduction (https://doi.org/10.1038/ni913) show anti-mouse-CD3-dependent ICAM1 adhesion and T-cell/APC conjugation, with anti-LFA1 blockade, vector and stimulus controls. Human SKAP55 was introduced into mouse T8.1 cells, and primary mouse T-cell experiments were also reported; this is not direct human CD3E perturbation. Retain the qualified orthology transfer without assigning an integrin-binding molecular function to CD3E. The actual 2025 correction is an image replacement, not a retraction of these conclusions. Supporting Evidence: |
| GO:0033634 positive regulation of cell-cell adhesion mediated by integrin | ISS PMID:12652296 SKAP-55 regulates integrin adhesion and formation of T cell-... | KEEP AS NON CORE | Summary: Retain the mouse-derived integrin-dependent cell-contact response. Reason: Selected original Methods and Results from the author reproduction (https://doi.org/10.1038/ni913) show anti-mouse-CD3-dependent ICAM1 adhesion and T-cell/APC conjugation, with anti-LFA1 blockade, vector and stimulus controls. Human SKAP55 was introduced into mouse T8.1 cells, and primary mouse T-cell experiments were also reported; this is not direct human CD3E perturbation. Retain the qualified orthology transfer without assigning an integrin-binding molecular function to CD3E. The actual 2025 correction is an image replacement, not a retraction of these conclusions. Supporting Evidence: |
| GO:0042101 T cell receptor complex | IDA PMID:8176201 Differential expression of ZAP-70 and Syk protein tyrosine k... | ACCEPT | Summary: Retain membership in the TCR complex. Reason: The PMID:8176201 abstract describes human/mouse ZAP70 and SYK expression and their association with the stimulated TCR, with a heterologous Src-dependent zeta-chain interaction assay. It does not expose the exact epsilon-specific membership control. Retain curated CD3-epsilon membership using the independent human TCR-CD3 structure in PMID:31461748, without transferring kinase chemistry or zeta construct details to epsilon. |
| GO:0042102 positive regulation of T cell proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain proliferation as a receptor-mediated outcome. Reason: The broad electronic process is consistent with CD3-epsilon-dependent signaling and target-specific NCK perturbation evidence. Proliferation is a downstream cellular outcome rather than a separate catalytic or structural core; exact rule logic was not inspected. Supporting Evidence: |
| GO:0042102 positive regulation of T cell proliferation | IMP PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | KEEP AS NON CORE | Summary: Retain the experimentally supported proliferative outcome. Reason: The original NCK-recruitment study links the epsilon proline-rich region to T-cell activation and proliferation. The curated IMP is retained with original experimental provenance; this does not make epsilon a cell-cycle enzyme. Supporting Evidence: |
| GO:0042105 alpha-beta T cell receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain alpha-beta TCR complex membership. Reason: The curated inherited complex membership is retained without reinterpreting the IBD from donor count. The stoichiometry and membrane/extracellular contacts are independently supported by PMID:31461748. Supporting Evidence: |
| GO:0042105 alpha-beta T cell receptor complex | IDA PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: Retain alpha-beta TCR complex membership. Reason: The original biochemical epsilon-delta/gamma assembly evidence supports membership; its historical two-TCR model is not adopted. The stoichiometry and membrane/extracellular contacts are independently supported by PMID:31461748. |
| GO:0042105 alpha-beta T cell receptor complex | IEA GO_REF:0000120 | ACCEPT | Summary: Retain alpha-beta TCR complex membership. Reason: The combined electronic/orthology assignment agrees with the resolved human assembly. The stoichiometry and membrane/extracellular contacts are independently supported by PMID:31461748. Supporting Evidence: |
| GO:0042105 alpha-beta T cell receptor complex | IPI PMID:31461748 Structural basis of assembly of the human T cell receptor-CD... | ACCEPT | Summary: Retain alpha-beta TCR complex membership. Reason: The human cryo-EM structure directly resolves CD3 epsilon within the assembled alpha-beta receptor. The stoichiometry and membrane/extracellular contacts are independently supported by PMID:31461748. Supporting Evidence: |
| GO:0042106 gamma-delta T cell receptor complex | NAS PMID:16418397 Stoichiometry of the murine gammadelta T cell receptor. | ACCEPT | Summary: Retain gamma-delta TCR complex membership with species limits. Reason: The source directly measures murine gamma-delta receptors and discusses distinct human assembly observations. Both contexts include epsilon; its membership is retained without transferring the mouse gamma-versus-delta chain stoichiometry to human receptors. Selected Results and Discussion explicitly identify that species boundary. Supporting Evidence: PMID:16418397 two CD3Ξ³Ι dimers |
| GO:0042110 T cell activation | NAS PMID:12110186 Recruitment of Nck by CD3 epsilon reveals a ligand-induced c... | KEEP AS NON CORE | Summary: Retain T-cell activation as the broader receptor outcome. Reason: The original CD3-epsilon/NCK mechanism supports T-cell activation. The core states the specific TCR signaling process, avoiding a second outcome-only core. Supporting Evidence: |
| GO:0042608 T cell receptor binding | NAS PMID:11186279 Fourteen years' follow-up of an autoimmune patient lacking t... | KEEP AS NON CORE | Summary: Retain TCR binding as an assembly-associated interaction. Reason: The current binding definition does not exclude a receptor-associated subunit. Independent human assembly interfaces establish CD3E association with TCR chains. The original PMID:11186279 cache contains bibliography but no scientific abstract, so its particular NAS statement is not reconstructed; retention rests on the independently supported interaction, without inventing an external ligand role. |
| GO:0042802 identical protein binding | IDA PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell ... | KEEP AS NON CORE | Summary: Retain the in-vitro CD3-epsilon self-association observation. Reason: The primary abstract reports self-association of isolated cytoplasmic domains, including epsilon. This is not proof of an epsilon-epsilon dimer in the native membrane receptor. Quantitative dissociation constants stated specifically for zeta must not be transferred to epsilon. Supporting Evidence: |
| GO:0042981 regulation of apoptotic process | NAS PMID:12567487 [Overexpression of Bcl-2 inhibited T lymphocyte apoptosis me... | KEEP AS NON CORE | Summary: Retain context-dependent regulation of apoptosis. Reason: The original study uses cross-linked CD8/CD3-epsilon cytoplasmic-tail chimeras and BCL2-sensitive apoptosis in T-cell lines. That is an upstream regulatory activity in a defined construct context; the GO process does not require epsilon to execute caspase chemistry or join an apoptosome. Do not generalize the chimera result to every native TCR stimulation condition. Supporting Evidence: PMID:12567487 CD8 epsilon chimera molecule |
| GO:0043197 dendritic spine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred neuronal dendritic spine localization. Reason: The official MGI donor record maps the mouse IDA evidence to PMID:17502348. Selected primary Methods and Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC1951947/) describe CD3-epsilon immunostaining of Purkinje somata and dendritic shafts/spines, alongside Bergmann-glial expression. Preserve the electronic mouse-to-human transfer; the actual observed localization is mouse and cell-context dependent, not an independently demonstrated human-neuron compartment. The immune receptor core does not exclude these locations. Supporting Evidence: |
| GO:0044297 cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred neuronal cell body localization. Reason: The official MGI donor record maps the mouse IDA evidence to PMID:17502348. Selected primary Methods and Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC1951947/) describe CD3-epsilon immunostaining of Purkinje somata and dendritic shafts/spines, alongside Bergmann-glial expression. Preserve the electronic mouse-to-human transfer; the actual observed localization is mouse and cell-context dependent, not an independently demonstrated human-neuron compartment. The immune receptor core does not exclude these locations. Supporting Evidence: |
| GO:0045059 positive thymic T cell selection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited participation in positive T-cell selection. Reason: The PAINT assertion is consistent with the receptor-assembly and signaling role in thymocytes. Its node placement and alignment were not independently reconstructed; the single displayed mouse source is not evidence of weak inference. Selection is a developmental outcome of the core receptor mechanism. Supporting Evidence: |
| GO:0046629 gamma-delta T cell activation | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | KEEP AS NON CORE | Summary: Retain gamma-delta T-cell activation as receptor context. Reason: The NAS synthesis supports CD3-epsilon in gamma-delta TCR signaling. The core states the receptor-signaling mechanism rather than adding redundant activation-outcome cores; review-level support is distinguished from a direct assay. Supporting Evidence: |
| GO:0046631 alpha-beta T cell activation | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | KEEP AS NON CORE | Summary: Retain alpha-beta T-cell activation as receptor context. Reason: The NAS synthesis supports CD3-epsilon in alpha-beta TCR signaling. The core states the receptor-signaling mechanism rather than adding redundant activation-outcome cores; review-level support is distinguished from a direct assay. Supporting Evidence: |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:11368773 Mapping the Zap-70 phosphorylation sites on LAT (linker for ... | ACCEPT | Summary: Retain direct participation in TCR signaling. Reason: The PMID:11368773 abstract concerns ZAP70-dependent LAT phosphorylation, LAT mutants and downstream signaling-protein recruitment. It is not the original CD3-epsilon conformational-change paper. Retain the curated TCR-signaling assertion because direct CD3-epsilon participation is independently established by the human recruitment/reconstitution work in PMID:28659468; the original LAT study's exact CD3E-specific assay remains uninspected. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:1323144 Activation-induced ubiquitination of the T cell antigen rece... | ACCEPT | Summary: Retain the signaling contribution within the TCR complex. Reason: The original antigen-receptor source and cached GO-CAM complex activity support epsilon as a signaling component. The annotation does not imply that epsilon is the isolated peptide-MHC recognition site. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: The inhibitory-ligand experiments support modulation of TCR signaling. Reason: ITPRIPL1 binding to CD3 epsilon alters calcium/ZAP70-associated receptor responses in the primary report. A signaling-pathway annotation includes this inhibitory receptor input and does not require a uniformly activating effect. Supporting Evidence: |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:40592325 Proximity between LAG-3 and the T cell receptor guides suppr... | ACCEPT | Summary: LAG3 regulation acts through the CD3-epsilon signaling interface. Reason: The primary report places CD3 epsilon in a LAG3-associated inhibitory assembly that disrupts LCK recruitment. Retain target participation while separating this organization from LCK catalysis and from the paperβs mouse therapeutic outcomes. Supporting Evidence: |
| GO:0050852 T cell receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the electronic TCR signaling assignment. Reason: The exact ARBA source is retained; independent human structure, recruitment and reconstitution studies support the process. The internal rule was not inspected and is not used to invent a more specific branch. |
| GO:0050852 T cell receptor signaling pathway | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | ACCEPT | Summary: Retain the central TCR signaling process. Reason: The NAS reference PMID:29789755 synthesizes the established role. Independent target primary work supports CD3-epsilon recruitment and signaling, without assigning the associated kinase reactions to epsilon. |
| GO:0050852 T cell receptor signaling pathway | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: Retain the central TCR signaling process. Reason: The NAS reference PMID:30976362 synthesizes the established role. Independent target primary work supports CD3-epsilon recruitment and signaling, without assigning the associated kinase reactions to epsilon. |
| GO:0065003 protein-containing complex assembly | NAS PMID:9886373 T lymphocyte development in the absence of CD3 epsilon or CD... | KEEP AS NON CORE | Summary: Retain broad protein-complex assembly as a parent process. Reason: The original mouse reconstitution evidence supports epsilon-dependent assembly with neighboring-gene effects controlled. Human structure corroborates an own physical assembly role. The more informative signal-complex-assembly process is used in the core instead of this redundant ancestor. |
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Download this section (compressed HTML)Q: Which human neural cell contexts preserve the mouse CD3-epsilon localization and developmental roles, and can an epsilon-specific rescue separate them from loss of other CD3 subunits?
Q: What exact CD3E perturbation and expression endpoints underlie the two IMP mappings to PMID:23817958, whose accessible abstract does not expose those assays?
Q: How do native human CD3-epsilon phosphorylation states control competition among LCK, NCK, ZAP70 and CSK at physiological receptor occupancy, separately from phosphomimetic mutants and CAR constructs?
Q: Which ITPRIPL1 concentrations and cellular presentation states engage native human CD3 epsilon, and how does this inhibitory input interact with LAG3-associated regulation?
Experiment: Use expression-matched human CD3E knock-in mutants with surface-receptor controls, timed phosphoproteomics and partner-specific binding measurements to separate assembly effects from recruitment and signaling effects.
Hypothesis: Distinct CD3-epsilon recruitment interfaces coordinate receptor assembly and signal strength without intrinsic kinase chemistry.
Type: genetic and biochemical
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