CD247 encodes the zeta chain (CD3ΞΆ) of the T cell receptor complex, a 164-amino acid type I transmembrane protein that serves as the principal signaling component of the TCR-CD3 complex. CD3ΞΆ forms disulfide-linked homodimers and contains three immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic domain - more than any other TCR component. Upon TCR engagement with peptide-MHC, Lck phosphorylates the six ITAM tyrosines, creating docking sites for ZAP-70 kinase tandem SH2 domains. Activated ZAP-70 then phosphorylates LAT adaptor, initiating downstream Ras-ERK, PLCΞ³1-calcium, PKC-NF-ΞΊB, and NFAT pathways. The cytoplasmic tail contains a basic-rich stretch (BRS) that binds membrane phosphoinositides, sequestering ITAMs until ligand-induced conformational change releases them for phosphorylation. CD3ΞΆ also participates in Fc-gamma receptor III (CD16) signaling in NK cells. Mutations cause severe combined immunodeficiency; downregulation in tumor-infiltrating lymphocytes contributes to cancer immune evasion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0050852 T cell receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: T cell receptor signaling pathway - core function of CD3ΞΆ as ITAM-containing signaling adaptor. Reason: Core biological process. CD3ΞΆ ITAMs are phosphorylated by Lck to recruit ZAP-70, initiating TCR signaling cascades. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md Upon T cell receptor engagement by peptide-major histocompatibility complex (pMHC) molecules, CD247 undergoes phosphorylation-dependent activation that recruits the protein tyrosine kinase ZAP-70 |
| GO:0042105 alpha-beta T cell receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-beta TCR complex - CD3΢ is integral component of TCR complex. Reason: Core cellular component. CD3΢΢ homodimer associates with TCRαβ and CD3γΡ, CD3δΡ to form complete signaling complex. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The complex consists of one T cell receptor α/β heterodimer (in the majority of T cells expressing this receptor type) noncovalently associated with CD3γΡ, CD3δΡ, and CD3΢΢ homodimers |
| GO:0002250 adaptive immune response | IEA GO_REF:0000043 | ACCEPT | Summary: Adaptive immune response - CD3ΞΆ essential for T cell-mediated adaptive immunity. Reason: Core biological process. T cell receptor signaling through CD3ΞΆ ITAMs is essential for adaptive immune responses. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md activating downstream signaling cascades that drive T cell proliferation, cytokine production, and effector functions |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: Immune system process - general parent term. Reason: Correct general term. More specific child terms are also annotated. |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Transmembrane signaling receptor activity - CD3ΞΆ is part of TCR signaling complex. Reason: Correct. CD3ΞΆ is a transmembrane protein that transduces signals as part of TCR complex. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md encodes a 164-amino acid transmembrane protein that serves as an essential signaling component of the T cell antigen receptor-CD3 (TCR-CD3) complex |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane localization - CD3ΞΆ is integral membrane protein. Reason: Core localization. CD3ΞΆ is a type I transmembrane protein in the plasma membrane. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md CD247, as a component of the integral TCR-CD3 membrane complex, exhibits subcellular localization exclusively at the plasma membrane |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Cell surface receptor signaling - general term for TCR signaling. Reason: Correct general term. CD3ΞΆ functions in TCR signaling at cell surface. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane - general parent term for plasma membrane. Reason: Correct but very general. More specific term (plasma membrane) is preferred. |
| GO:0098797 plasma membrane protein complex | IEA GO_REF:0000117 | ACCEPT | Summary: Plasma membrane protein complex - TCR-CD3 is membrane protein complex. Reason: Correct. CD3ΞΆ is part of TCR-CD3 multisubunit plasma membrane complex. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The TCR-CD3 complex represents one of the most intricate membrane receptor structures known, comprising six distinct polypeptide chains |
| GO:0005515 protein binding | IPI PMID:10704231 Activation of Zap-70 tyrosine kinase due to a structural rea... | REMOVE | Summary: Protein binding from ZAP-70 activation study. Reason: Generic "protein binding" is uninformative. The specific ZAP-70 interaction is better captured by protein tyrosine kinase binding (GO:1990782). Supporting Evidence: PMID:10704231 Activation of Zap-70 tyrosine kinase due to a structural rearrangement induced by tyrosine phosphorylation and/or ITAM binding. |
| GO:0005515 protein binding | IPI PMID:10752619 Alternative modes of binding of proteins with tandem SH2 dom... | REMOVE | Summary: Protein binding from SH2 domain binding study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:10752619 Alternative modes of binding of proteins with tandem SH2 domains. |
| GO:0005515 protein binding | IPI PMID:15832366 Peptide microarrays for the detection of molecular interacti... | REMOVE | Summary: Protein binding from peptide microarray study. Reason: Generic "protein binding" from high-throughput study is uninformative. Supporting Evidence: PMID:15832366 Peptide microarrays for the detection of molecular interactions in cellular signal transduction. |
| GO:0005515 protein binding | IPI PMID:16461343 Identification of substrates of human protein-tyrosine phosp... | REMOVE | Summary: Protein binding from PTPN22 substrate study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:16461343 2006 Feb 6. Identification of substrates of human protein-tyrosine phosphatase PTPN22. |
| GO:0005515 protein binding | IPI PMID:18320063 T cell receptor engagement triggers its CD3epsilon and CD3ze... | REMOVE | Summary: Protein binding from TCR conformational study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:18320063 T cell receptor engagement triggers its CD3epsilon and CD3zeta subunits to adopt a compact, locked conformation. |
| GO:0005515 protein binding | IPI PMID:21957439 The transmembrane adaptor protein SIT inhibits TCR-mediated ... | REMOVE | Summary: Protein binding from SIT adaptor study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:21957439 The transmembrane adaptor protein SIT inhibits TCR-mediated signaling. |
| GO:0005515 protein binding | IPI PMID:22912825 The adaptor protein SAP directly associates with CD3ΞΆ chain ... | REMOVE | Summary: Protein binding from SAP adaptor study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:22912825 The adaptor protein SAP directly associates with CD3ΞΆ chain and regulates T cell receptor signaling. |
| GO:0005515 protein binding | IPI PMID:22922463 End-binding protein 1 controls signal propagation from the T... | REMOVE | Summary: Protein binding from EB1 study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:22922463 End-binding protein 1 controls signal propagation from the T cell receptor. |
| GO:0005515 protein binding | IPI PMID:24502978 Ξ²-Arrestin-1 mediates the TCR-triggered re-routing of distal... | REMOVE | Summary: Protein binding from beta-arrestin study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:24502978 Ξ²-Arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding from high-throughput interactome study. Reason: Generic "protein binding" from high-throughput study is uninformative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:7509083 Sequential interactions of the TCR with two distinct cytopla... | REMOVE | Summary: Protein binding from Lck/ZAP-70 kinase study. Reason: Generic "protein binding" is uninformative. Specific kinase binding captured by GO:1990782. Supporting Evidence: PMID:7509083 Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:7528772 ZAP-70 binding specificity to T cell receptor tyrosine-based... | REMOVE | Summary: Protein binding from ZAP-70 SH2 domain study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:7528772 ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. |
| GO:0005515 protein binding | IPI PMID:8626561 Association between mitogen-activated protein kinase and the... | REMOVE | Summary: Protein binding from Lck SH2/SH3 domain study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:8626561 Association between mitogen-activated protein kinase and the zeta chain of the T cell receptor (TcR) with the SH2,3 domain of p56lck. |
| GO:0005515 protein binding | IPI PMID:8648092 Human and mouse killer-cell inhibitory receptors recruit PTP... | REMOVE | Summary: Protein binding from phosphatase recruitment study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:8648092 Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. |
| GO:0005515 protein binding | IPI PMID:8901551 Mechanism of activation for Zap-70 catalytic activity. | REMOVE | Summary: Protein binding from ZAP-70 activation study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:8901551 Mechanism of activation for Zap-70 catalytic activity. |
| GO:0005515 protein binding | IPI PMID:9185620 Interaction between the SH2 domains of ZAP-70 and the tyrosi... | REMOVE | Summary: Protein binding from ZAP-70 ITAM binding study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:9185620 Interaction between the SH2 domains of ZAP-70 and the tyrosine-based activation motif 1 sequence of the zeta subunit of the T-cell receptor. |
| GO:0042802 identical protein binding | IPI PMID:17055436 The structure of the zetazeta transmembrane dimer reveals fe... | ACCEPT | Summary: Identical protein binding - CD3ΞΆ forms disulfide-linked homodimers. Reason: Correct. CD3ΞΆ forms homodimers through transmembrane domain interactions stabilized by interchain disulfide bond. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The CD247 protein exists as a disulfide-linked homodimer PMID:17055436 The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor. |
| GO:0042802 identical protein binding | IPI PMID:24502978 Ξ²-Arrestin-1 mediates the TCR-triggered re-routing of distal... | ACCEPT | Summary: Identical protein binding - duplicate annotation. Reason: Correct. Same function as above with different evidence. Supporting Evidence: PMID:24502978 Ξ²-Arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Golgi apparatus localization - likely transient during biosynthesis. Reason: CD3ΞΆ transits through Golgi during biosynthesis and assembly, but primary functional location is plasma membrane. |
| GO:0042105 alpha-beta T cell receptor complex | IEA GO_REF:0000107 | ACCEPT | Summary: Alpha-beta TCR complex - duplicate with IBA annotation. Reason: Core component with different evidence code. |
| GO:0050852 T cell receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: TCR signaling - duplicate with IBA annotation. Reason: Core function with different evidence code. |
| GO:2000010 positive regulation of protein localization to cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of protein localization to cell surface. Reason: CD3ΞΆ is required for stable TCR surface expression, but this is secondary to its signaling function. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md In CD247-deficient mice, all other TCR-CD3 components can assemble, but their cell surface expression is profoundly reduced |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:7509083 Sequential interactions of the TCR with two distinct cytopla... | ACCEPT | Summary: Protein-macromolecule adaptor activity - CD3ΞΆ ITAMs recruit ZAP-70 kinase. Reason: Core molecular function. Phosphorylated CD3ΞΆ ITAMs serve as docking sites for ZAP-70 tandem SH2 domains. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The phosphorylated tyrosine residues within the CD247 ITAMs serve as high-affinity binding sites for the tandem SH2 domains of the ZAP-70 PMID:7509083 Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. |
| GO:0005886 plasma membrane | IDA PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell rece... | ACCEPT | Summary: Plasma membrane from TRIM adaptor study. Reason: Correct localization demonstrated experimentally. Supporting Evidence: PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain. |
| GO:0005886 plasma membrane | IDA PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc... | ACCEPT | Summary: Plasma membrane from CD16-CD3ΞΆ association study. Reason: Correct localization in NK cells demonstrated experimentally. Supporting Evidence: PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. |
| GO:0032395 MHC class II receptor activity | IDA PMID:1323144 Activation-induced ubiquitination of the T cell antigen rece... | MARK AS OVER ANNOTATED | Summary: MHC class II receptor activity - likely incorrect or over-annotated. Reason: CD3ΞΆ does not have intrinsic MHC binding activity. The TCR complex recognizes peptide-MHC but CD3ΞΆ is the signaling component, not the receptor binding component. Supporting Evidence: PMID:1323144 Activation-induced ubiquitination of the T cell antigen receptor. |
| GO:0042105 alpha-beta T cell receptor complex | IDA PMID:31461748 Structural basis of assembly of the human T cell receptor-CD... | ACCEPT | Summary: Alpha-beta TCR complex from cryo-EM structure study. Reason: Definitive structural evidence from cryo-EM structure of complete human TCR-CD3 complex. Supporting Evidence: PMID:31461748 Structural basis of assembly of the human T cell receptor-CD3 complex |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:1323144 Activation-induced ubiquitination of the T cell antigen rece... | ACCEPT | Summary: TCR signaling from ubiquitination study. Reason: Core function demonstrated experimentally. Supporting Evidence: PMID:1323144 Activation-induced ubiquitination of the T cell antigen receptor. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:7509083 Sequential interactions of the TCR with two distinct cytopla... | ACCEPT | Summary: TCR signaling from Lck/ZAP-70 kinase study. Reason: Core function demonstrated experimentally - CD3ΞΆ sequentially interacts with Lck then ZAP-70 for signaling. Supporting Evidence: PMID:7509083 Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases |
| GO:0002250 adaptive immune response | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | ACCEPT | Summary: Adaptive immune response from TCR signaling review. Reason: Correct. Review article on TCR signaling regulatory mechanisms. Supporting Evidence: PMID:29789755 Regulatory mechanisms in T cell receptor signalling. |
| GO:0005886 plasma membrane | ISS GO_REF:0000114 | ACCEPT | Summary: Plasma membrane from sequence similarity. Reason: Correct localization. |
| GO:0005886 plasma membrane | IDA PMID:31461748 Structural basis of assembly of the human T cell receptor-CD... | ACCEPT | Summary: Plasma membrane from cryo-EM structure study. Reason: Structural evidence confirms membrane localization. Supporting Evidence: PMID:31461748 Aug 28. Structural basis of assembly of the human T cell receptor-CD3 complex. |
| GO:0042105 alpha-beta T cell receptor complex | ISS GO_REF:0000114 | ACCEPT | Summary: Alpha-beta TCR complex from sequence similarity. Reason: Correct component. |
| GO:0042105 alpha-beta T cell receptor complex | IPI PMID:31461748 Structural basis of assembly of the human T cell receptor-CD... | ACCEPT | Summary: Alpha-beta TCR complex from protein interaction in cryo-EM study. Reason: Structural evidence for complex formation. Supporting Evidence: PMID:31461748 Aug 28. Structural basis of assembly of the human T cell receptor-CD3 complex. |
| GO:0046631 alpha-beta T cell activation | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | ACCEPT | Summary: Alpha-beta T cell activation from review article. Reason: Correct. CD3ΞΆ signaling is essential for T cell activation. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md activating downstream signaling cascades that drive T cell proliferation, cytokine production, and effector functions PMID:29789755 Regulatory mechanisms in T cell receptor signalling. |
| GO:0050852 T cell receptor signaling pathway | NAS PMID:29789755 Regulatory mechanisms in T cell receptor signalling. | ACCEPT | Summary: TCR signaling from regulatory mechanisms review. Reason: Core function from review article. Supporting Evidence: PMID:29789755 Regulatory mechanisms in T cell receptor signalling. |
| GO:0002250 adaptive immune response | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: Adaptive immune response from gamma-delta T cell review. Reason: Correct - CD3ΞΆ also functions in gamma-delta T cells. Supporting Evidence: PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. |
| GO:0005886 plasma membrane | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: Plasma membrane from gamma-delta T cell review. Reason: Correct localization. Supporting Evidence: PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. |
| GO:0042106 gamma-delta T cell receptor complex | NAS PMID:16418397 Stoichiometry of the murine gammadelta T cell receptor. | ACCEPT | Summary: Gamma-delta TCR complex - CD3ΞΆ also component of gamma-delta TCR. Reason: Correct. CD3ΞΆ is shared component of both alpha-beta and gamma-delta TCR complexes. Supporting Evidence: PMID:16418397 Stoichiometry of the murine gammadelta T cell receptor |
| GO:0046629 gamma-delta T cell activation | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: Gamma-delta T cell activation - CD3ΞΆ signaling in gamma-delta T cells. Reason: Correct. CD3ΞΆ signaling is required for gamma-delta T cell activation. Supporting Evidence: PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. |
| GO:0050852 T cell receptor signaling pathway | NAS PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. | ACCEPT | Summary: TCR signaling in gamma-delta T cells. Reason: Core function in gamma-delta T cells. Supporting Evidence: PMID:30976362 T cell receptor signaling for Ξ³Ξ΄T cell development. |
| GO:0004888 transmembrane signaling receptor activity | IC PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: Transmembrane signaling receptor activity inferred from TCR assembly study. Reason: Correct molecular function. Supporting Evidence: PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:35271814 Cholesterol inhibits TCR signaling by directly restricting T... | ACCEPT | Summary: TCR signaling from cholesterol regulation study. Reason: Core function demonstrated experimentally. Supporting Evidence: PMID:35271814 Epub 2022 Mar 9. Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility. |
| GO:0051259 protein complex oligomerization | EXP PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell ... | ACCEPT | Summary: Protein complex oligomerization - CD3ΞΆ ITAM-mediated oligomerization. Reason: Correct. CD3ΞΆ cytoplasmic domain can oligomerize through ITAM interactions. Supporting Evidence: PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain |
| GO:0051259 protein complex oligomerization | IPI PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell ... | ACCEPT | Summary: Protein complex oligomerization - duplicate with protein interaction evidence. Reason: Same function with different evidence code. Supporting Evidence: PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain and of other proteins containing the immunoreceptor tyrosine-based activation motif. |
| GO:0038094 Fc-gamma receptor signaling pathway | IDA PMID:8478617 Physical and functional association of p56lck with Fc gamma ... | ACCEPT | Summary: Fc-gamma receptor signaling - CD3ΞΆ associates with CD16 in NK cells. Reason: Correct. CD3ΞΆ associates with FcΞ³RIII (CD16) in NK cells to mediate ADCC signaling. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md CD247 also participates in Fc-gamma receptor III (CD16) signaling in NK cells PMID:8478617 Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. |
| GO:0033001 Fc-gamma receptor III complex | IDA PMID:28652325 Transmembrane features governing Fc receptor CD16A assembly ... | ACCEPT | Summary: Fc-gamma receptor III complex - CD3ΞΆ component of CD16 complex in NK cells. Reason: Correct. CD3ΞΆ homodimer or CD3ΞΆ-FcΞ΅RIΞ³ heterodimer associates with CD16 transmembrane domain. Supporting Evidence: PMID:28652325 Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules |
| GO:0042803 protein homodimerization activity | IDA PMID:28652325 Transmembrane features governing Fc receptor CD16A assembly ... | ACCEPT | Summary: Protein homodimerization - CD3ΞΆ forms homodimers. Reason: Core structural feature. CD3ΞΆ homodimerization is essential for TCR and CD16 complex function. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The CD247 protein exists as a disulfide-linked homodimer PMID:28652325 Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. |
| GO:0033001 Fc-gamma receptor III complex | IDA PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and ass... | ACCEPT | Summary: Fc-gamma receptor III complex from site-directed mutation study. Reason: Correct. Study demonstrated CD3ΞΆ association with CD16. Supporting Evidence: PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation. |
| GO:0042803 protein homodimerization activity | IDA PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and ass... | ACCEPT | Summary: Homodimerization from CD16 assembly study. Reason: Correct structural feature. Supporting Evidence: PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation. |
| GO:0046982 protein heterodimerization activity | IDA PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and ass... | ACCEPT | Summary: Protein heterodimerization - CD3ΞΆ can form heterodimers with FcΞ΅RIΞ³. Reason: Correct. CD3ΞΆ can heterodimerize with FcΞ΅RIΞ³ chain in NK cells. Supporting Evidence: PMID:1825220 Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma |
| GO:0005515 protein binding | IPI PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc... | REMOVE | Summary: Protein binding from CD16-CD3ΞΆ co-association study. Reason: Generic "protein binding" is uninformative. Specific CD16 interaction captured by GO:0033001. Supporting Evidence: PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. |
| GO:0042803 protein homodimerization activity | IDA PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc... | ACCEPT | Summary: Homodimerization from NK cell study. Reason: Core structural feature. Supporting Evidence: PMID:2532305 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. |
| GO:0007166 cell surface receptor signaling pathway | IC PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: Cell surface receptor signaling inferred from TCR assembly study. Reason: Correct general term. Supporting Evidence: PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. |
| 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: Alpha-beta TCR complex from TCR assembly study. Reason: Correct component demonstrated in assembly study. Supporting Evidence: PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. |
| GO:0065003 protein-containing complex assembly | IDA PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e... | ACCEPT | Summary: Protein complex assembly - CD3ΞΆ required for TCR complex assembly. Reason: Correct. CD3ΞΆ is required for complete TCR-CD3 complex assembly and surface expression. Supporting Evidence: file:human/CD247/CD247-deep-research-perplexity.md The CD247 homodimer incorporates as the final signaling module PMID:9485181 Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202165 | ACCEPT | Summary: Plasma membrane from Reactome ITAM phosphorylation pathway. Reason: Representative Reactome annotation for plasma membrane localization during TCR signaling. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202168 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202174 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202216 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202245 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202248 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202344 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029268 | ACCEPT | Summary: Plasma membrane - Reactome TCR downstream events. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029270 | ACCEPT | Summary: Plasma membrane - Reactome CD28 costimulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029271 | ACCEPT | Summary: Plasma membrane - Reactome CD28 costimulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029272 | ACCEPT | Summary: Plasma membrane - Reactome CD28 costimulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029273 | ACCEPT | Summary: Plasma membrane - Reactome CD28 costimulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029451 | ACCEPT | Summary: Plasma membrane - Reactome PD-1 signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029452 | ACCEPT | Summary: Plasma membrane - Reactome PD-1 signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029453 | ACCEPT | Summary: Plasma membrane - Reactome CTLA-4 signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029457 | ACCEPT | Summary: Plasma membrane - Reactome immunoregulatory signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029458 | ACCEPT | Summary: Plasma membrane - Reactome checkpoint signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029459 | ACCEPT | Summary: Plasma membrane - Reactome TCR checkpoint. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029467 | ACCEPT | Summary: Plasma membrane - Reactome TCR regulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029476 | ACCEPT | Summary: Plasma membrane - Reactome TCR complex regulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2197697 | ACCEPT | Summary: Plasma membrane - Reactome adaptive immunity. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389758 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855381 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664261 | ACCEPT | Summary: Plasma membrane - Reactome PD-L1 pathway. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664270 | ACCEPT | Summary: Plasma membrane - Reactome checkpoint signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664271 | ACCEPT | Summary: Plasma membrane - Reactome checkpoint inhibition. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664273 | ACCEPT | Summary: Plasma membrane - Reactome immunomodulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664275 | ACCEPT | Summary: Plasma membrane - Reactome immune regulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664278 | ACCEPT | Summary: Plasma membrane - Reactome T cell regulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666425 | ACCEPT | Summary: Plasma membrane - Reactome CAR-T signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666426 | ACCEPT | Summary: Plasma membrane - Reactome CAR signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666428 | ACCEPT | Summary: Plasma membrane - Reactome chimeric receptor signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666430 | ACCEPT | Summary: Plasma membrane - Reactome CAR-T pathway. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666435 | ACCEPT | Summary: Plasma membrane - Reactome CAR activation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9666458 | ACCEPT | Summary: Plasma membrane - Reactome CAR-T cell activation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-164943 | ACCEPT | Summary: Plasma membrane - Reactome TCR receptor complex. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-198955 | ACCEPT | Summary: Plasma membrane - Reactome TCR formation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: Plasma membrane - Reactome TCR assembly. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202233 | ACCEPT | Summary: Plasma membrane - Reactome TCR complex assembly. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202291 | ACCEPT | Summary: Plasma membrane - Reactome TCR complex formation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202307 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling initiation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5685600 | ACCEPT | Summary: Plasma membrane - Reactome TCR phosphorylation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5685602 | ACCEPT | Summary: Plasma membrane - Reactome ITAM phosphorylation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6793275 | ACCEPT | Summary: Plasma membrane - Reactome TCR-CD3 complex. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850326 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling cascade. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850356 | ACCEPT | Summary: Plasma membrane - Reactome T cell signaling. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8852200 | ACCEPT | Summary: Plasma membrane - Reactome T cell activation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664268 | ACCEPT | Summary: Plasma membrane - Reactome TCR signaling modulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9664406 | ACCEPT | Summary: Plasma membrane - Reactome T cell signaling regulation. Reason: Reactome pathway annotation confirming plasma membrane localization. |
| GO:0042802 identical protein binding | IDA PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell ... | ACCEPT | Summary: Identical protein binding from homodimerization study. Reason: Core structural feature - homodimerization. Supporting Evidence: PMID:14967045 Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain and of other proteins containing the immunoreceptor tyrosine-based activation motif. |
| GO:0005515 protein binding | IPI PMID:23858057 CD81 controls sustained T cell activation signaling and defi... | REMOVE | Summary: Protein binding from CD81 study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:23858057 Jul 15. CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses. |
| GO:0005515 protein binding | IPI PMID:11978774 BY55/CD160 acts as a co-receptor in TCR signal transduction ... | REMOVE | Summary: Protein binding from CD160 co-receptor study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:11978774 BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem S... | ACCEPT | Summary: Protein tyrosine kinase binding - CD3ΞΆ ITAMs bind ZAP-70 kinase. Reason: Core molecular function. Phosphorylated CD3ΞΆ ITAMs bind ZAP-70 tandem SH2 domains. Supporting Evidence: PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem SH2 domains form a 1:3 complex in vitro |
| GO:0005515 protein binding | IPI PMID:26783323 A novel human autoimmune syndrome caused by combined hypomor... | REMOVE | Summary: Protein binding from ZAP-70 mutation study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:26783323 A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70. |
| GO:0005737 cytoplasm | IDA PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell rece... | KEEP AS NON CORE | Summary: Cytoplasm localization. Reason: CD3ΞΆ cytoplasmic tail extends into cytoplasm. Primary localization is plasma membrane. Supporting Evidence: PMID:11390434 The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain. |
| GO:0042101 T cell receptor complex | IDA PMID:8176201 Differential expression of ZAP-70 and Syk protein tyrosine k... | ACCEPT | Summary: T cell receptor complex from ZAP-70/Syk expression study. Reason: Correct. Study examined TCR complex and associated kinases. Supporting Evidence: PMID:8176201 Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. |
| GO:0005886 plasma membrane | IDA PMID:1390434 Five novel antigens illustrate shared phenotype between mous... | ACCEPT | Summary: Plasma membrane localization from epitope study. Reason: Correct localization. Supporting Evidence: PMID:1390434 Five novel antigens illustrate shared phenotype between mouse thymic stromal cells, thymocytes, and peripheral lymphocytes. |
| GO:0005515 protein binding | IPI PMID:11891219 A novel Src homology 2 domain-containing molecule, Src-like ... | REMOVE | Summary: Protein binding from SLAP-2 adaptor study. Reason: Generic "protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:11891219 2002 Mar 12. A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling. |
| GO:0042101 T cell receptor complex | TAS PMID:3785426 A new subunit of the human T-cell antigen receptor complex. | ACCEPT | Summary: TCR complex from original CD3ΞΆ discovery paper. Reason: Historic paper establishing CD3ΞΆ as TCR component. Supporting Evidence: PMID:3785426 A new subunit of the human T-cell antigen receptor complex |
| GO:0005886 plasma membrane | TAS PMID:3785426 A new subunit of the human T-cell antigen receptor complex. | ACCEPT | Summary: Plasma membrane from original discovery paper. Reason: Correct localization from foundational paper. Supporting Evidence: PMID:3785426 A new subunit of the human T-cell antigen receptor complex. |
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